Sunscreens Regulations and Commercial Development Third Edition Cosmetic Science and Technology Series PDF

DK3046_half-series-title 2/1/05 9:45 AM Page A
Suncreens
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COSMETIC SCIENCE AND TECHNOLOGY
Series Editor
ERIC JUNGERMANN
Jungermann Associates, Inc.
Phoenix, Arizona
1. Cosmetic and Drug Preservation: Principles and Practice,

edited by Jon J. Kabara
2. The Cosmetic Industry: Scientific and Regulatory
Foundations, edited by Norman F. Estrin
3. Cosmetic Product Testing: A Modern Psychophysical
Approach, Howard R. Moskowitz
4. Cosmetic Analysis: Selective Methods and Techniques,
edited by P. Boré
5. Cosmetic Safety: A Primer for Cosmetic Scientists,
edited by James H. Whittam
6. Oral Hygiene Products and Practice, Morton Pader
7. Antiperspirants and Deodorants, edited by Karl Laden
and Carl B. Felger
8. Clinical Safety and Efficacy Testing of Cosmetics,
edited by William C. Waggoner
9. Methods for Cutaneous Investigation, edited by
Robert L. Rietschel and Thomas S. Spencer
10. Sunscreens: Development, Evaluation, and Regulatory
Aspects, edited by Nicholas J. Lowe
and Nadim A. Shaath
11. Glycerine: A Key Cosmetic Ingredient, edited by
Eric Jungermann and Norman O. V. Sonntag
12. Handbook of Cosmetic Microbiology, Donald S. Orth
13. Rheological Properties of Cosmetics and Toiletries,
edited by Dennis Laba
14. Consumer Testing and Evaluation of Personal Care
Products, Howard R. Moskowitz
15. Sunscreens: Development, Evaluation, and Regulatory
Aspects. Second Edition, Revised and Expanded,
edited by Nicholas J. Lowe, Nadim A. Shaath,
and Madhu A. Pathak
DK3046_half-series-title 2/1/05 9:45 AM Page C
16. Preservative-Free and Self-Preserving Cosmetics

and Drugs: Principles and Practice, edited by
Jon J. Kabara and Donald S. Orth
17. Hair and Hair Care, edited by Dale H. Johnson
18. Cosmetic Claims Substantiation, edited by Louise B. Aust
19. Novel Cosmetic Delivery Systems, edited by
Shlomo Magdassi and Elka Touitou
20. Antiperspirants and Deodorants: Second Edition,
Revised and Expanded, edited by Karl Laden
21. Conditioning Agents for Hair and Skin, edited by
Randy Schueller and Perry Romanowski
22. Principles of Polymer Science and Technology in
Cosmetics and Personal Care, edited by
E. Desmond Goddard and James V. Gruber
23. Cosmeceuticals: Drugs vs. Cosmetics, edited by
Peter Elsner and Howard I. Maibach
24. Cosmetic Lipids and the Skin Barrier, edited by
Thomas Förster
25. Skin Moisturization, edited by James J. Leyden
and Anthony V. Rawlings
26. Multifunctional Cosmetics, edited by Randy Schueller
and Perry Romanowski
27. Cosmeceuticals and Active Cosmetics: Drugs Versus
Cosmetics, Second Edition, edited by Peter Elsner
and Howard I. Maibach
28. Sunscreens: Regulations and Commercial Development,
Third Edition, edited by Nadim Shaath
DK3046_half-series-title 2/1/05 9:45 AM Page i
Sunscreens
Regulations and Commercial Development
Third Edition
edited by
Nadim Shaath
Alpha Research and Development
White Plains, New York, U.S.A.
Boca Raton London New York Singapore

Published in 2005 by
Taylor & Francis Group
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Preface
The sunscreen industry is achieving remarkable worldwide prominence by

responding to the growing need for skin protection with fast-paced innovation.
Increased consumer awareness of the harmful effects of sunlight has fueled the
demand for improved photo protection. The need for broad-spectrum protection
from both UVA and UVB rays has inspired scientists worldwide to research new
cosmetic formulations and delivery systems. More effective sunscreen actives,
emollients and novel cosmetic and functional ingredients have been regularly
added to the formulator’s repertoire. Creativity in innovation has been hindered
only by regulatory agencies and patent restrictions worldwide. Familiarity with
the current restrictive regulations and patent law infringements has become
integral to any research effort attempting to provide improved protection to
individuals affected by the sun’s damaging effects.
This book is designed to help the reader keep pace with the dramatic
changes in the sunscreen industry. It provides state-of-the-art research on sun-
screen development, evaluation, formulation and regulatory issues with a particu-
lar emphasis on the development of consumer sun care products. It features a
variety of chapters written by prominent scientists and practitioners from appro-
priately varied disciplines including academia, industry, the medical community,
marketing, the press, scientific organizations and regulatory agencies. These dis-
tinguished contributors have shared their latest innovations and knowledge of this
ever expanding field in a way that is pertinent to professionals and laymen alike.
The book has 48 chapters that are organized into nine major sections:
I. Introductory chapters on the evolution of sunscreens, photo

biological aspects, the need for photo protection, the safety of sun-
screens and a historical perspective on sun protection.
II. The Regulatory Aspects of sunscreens including a chapter from
the FDA, European COLIPA, Australian, USA and Japanese
iii
iv Preface
sunscreen regulations, a summary chapter on regulations of sun-

screens worldwide and a chapter on the United States Pharmacopeia
(USP).
III. The Ultraviolet Filters features a chapter on the chemistry and
mechanism of action of ultraviolet filters, two chapters on the phys-
ical inorganic particulate UV filters, one on the new sunscreen
actives and a chapter on the photo stability of ultraviolet filters.
IV. Cosmetic Formulations including water proofing strategies, SPF
modulation, broad-spectrum formulations, fragrancing sunscreen
products, the role of emulsifiers and emollients, natural sun care
products and surfactant free sunscreens.
V. Consumer Products with UV filters for the beach, daily use, babies
and kids, recreational and occupational hazard protection. A
chapter on fabrics as UV-radiation filters and another on sunless
tanning and tanning accelerators.
VI. Other Actives in the Sun Care Industry including antioxidants,
green tea polyphenols, botanicals and anti-aging ingredients.
VII. Commercial Production and Quality Control procedures for the
manufactured sun care products as well as the QC of ultraviolet
filters and a chapter on the modern analytical techniques in the
sunscreen industry.
VIII. Analytical Testing Procedures include in vivo and in vitro testing
procedures of sunscreen cosmetic formulations. The US FDA proto-
col, the European COLIPA and the International protocols for deter-
mining sun protection factors (SPF) are fully described. Balancing
UVA and UVB protection, dosimetry of UV radiation and spectral
standardization of sources used for sunscreens, in vitro models of
sunscreen performance and prediction of SPF are discussed.
IX. Marketing and Information with chapters on the role of industry
publications and technical information as well as recent sunscreen
market trends.
This is the first manuscript of its kind on sunscreens that covers technical,
regulatory, testing, consumer and commercial aspects of the industry. It gathers
information on the production of sunscreen consumer products, safety and the
need for photo protection, worldwide regulations, modern analytical techniques
for SPF and QC testing, recent trends in research on cosmetic formulations
and new ultraviolet filters, actives and cosmetic vehicles. It is a comprehensive
manual that incorporates novel advances and newly acquired knowledge in
sunscreen research. This assembly of contributing researchers and prominent
leaders in the field of sun care protection has produced the most up-to-date and
reliable reference guide in sun care available today.
Nadim A. Shaath, Ph.D.

Alpha Research & Development, Ltd.
Acknowledgment
This reference manual has consumed my contributors and I for the last 18
months. To each one of them and their institutions I say, “Thank you.” To my
wife for actively supporting me and standing beside me since my early teen
years I say, “I love you.” To my daughter Mona who has co-authored a
chapter in this manuscript and has embarked with me on a series of joint publi-
cations I say, “You have made me really proud. God bless you.” I would also like
to thank Mohammad Zureiqi from Alpha Research & Development, Ltd. for his
editing, typing and endless communications with my contributors. Finally, a
thank you is due to the editors of Marcel Dekker and Taylor & Francis for
their patience and continued support.
v
About the Editor
Dr. Nadim A. Shaath is President of Alpha Research & Development, Ltd.,

White Plains, New York. He is a frequent speaker and moderator at many
scientific meetings and is the author and editor of numerous articles in scientific
journals and books. Dr. Shaath is a member of the American Chemical Society,
the American Institute of Chemists and the Society of Cosmetic Chemists. He
received his B.Sc. (Honors) in Chemistry from the University of Alexandria,
Egypt and his Ph.D. degree in Organic Chemistry from the University of
Minnesota, Minneapolis. Upon serving three years as a Postdoctoral Fellow in
the Medicinal Chemistry Department at the University of Minnesota, he joined
the Chemistry faculty at the State University of New York and served as the
chairman of the department at SUNY-Purchase. After joining Felton Worldwide
as Executive Vice President and Technical Director responsible for the Sunarome
sunscreen line, he formed a fragrance, essential oil and sunscreen company,
Kato Worldwide/Nickstadt Moeller. Recently he founded Alpha Research &
Development, Ltd., a research and consulting firm in the fields of sunscreens
and essential oils.
vii
Contributors
Patricia P. Agin Schering-Plough HealthCare Products Inc., Memphis,

Tennessee, USA.
Nancy Allured Allured Publishing Corporation, Carol Stream, Illinois, USA.
Craig A. Bonda CPH Innovations (an affiliate of the C.P. Hall Company),
Chicago, Illinois, USA.
Mike Brown The Boots Company plc, Nottingham, UK.
Stefan Bruening Cognis Corporation, Ambler, Pennsylvania, USA.
Felix Buccellato Custom Essence Incorporated, Somerset, New Jersey, USA.
Ratan K. Chaudhuri EMD Chemicals, Inc., Hawthorne, New York, USA.
Curtis A. Cole Johnson & Johnson Consumer Products Worldwide, Skillman,
New Jersey, USA.
Christopher Corbett L’Oréal USA Products, Inc., Clark, New Jersey, USA.
Gerd Dahms Institüt für Angewandte Colloidtechnologie, Duisberg,
Germany.
B. L. Diffey Newcastle General Hospital, Newcastle, UK.
John C. Dowdy Rapid Precision Testing Laboratories, Cordova,
Tennessee, USA.
Craig A. Elmets Department of Dermatology, University of Alabama at
Birmingham, Birmingham, Alabama, USA.
Howard Epstein Kao Brands—The Andrew Jergens Company, Cincinnati,
Ohio, USA.
ix
x Contributors
Lawrence Evans III United States Pharmacopeia, Rockville, Maryland, USA.

Frederick Flores International Flavors and Fragrances, New York, New York,
USA.
Minoru Fukuda Shiseido Research Center, Yokohama, Japan.
Art Georgalas TRI-K Industries, Northvale, New Jersey, USA.
Paolo U. Giacomoni Clinique Laboratories, Melville, New York, USA.
Anthony D. Gonzalez Avon Products, Inc., Suffern, New York, USA.
Kathryn L. Hatch Agricultural and Biosystems Engineering, The University
of Arizona, Tucson, Arizona, USA.
Bernd Herzog Ciba Specialty Chemicals Inc., Grenzach-Wyhlen, Germany.
Julian P. Hewitt Uniqema Health & Personal Care, Wilton, Redcar, UK.
Matthew R. Holman Division of Over-The-Counter Drug Products, Center for
Drug Evaluation and Research, Food and Drug Administration, Rockville,
Maryland, USA.
Dietmar Hueglin Ciba Specialty Chemicals Inc., Basel, Switzerland.
Ulrich Issberner Cognis Deutschland GmbH & Co. KG, Duesseldorf,
Germany.
Robert E. Kalafsky Avon Products, Inc., Suffern, New York, USA.
Henry T. Kalinoski L’Oréal USA Products, Inc., Clark, New Jersey, USA.
Timothy Kapsner Aveda Corporation, Minneapolis, Minnesota, USA.
Santosh K. Katiyar Department of Dermatology, University of Alabama at
Rolf Kawa Cognis Deutschland GmbH & Co. KG, Duesseldorf, Germany.
Kenneth Klein Cosmetech Laboratories, Inc., Fairfield, New Jersey, USA.
Peter J. Lentini The Estee Lauder Companies, Melville, New York, USA.
Edwin D. Leonard, Jr. Patriot Distributors, Inc., DeLand, Florida, USA.
Mark Leonard Cognis Corporation, Ambler, Pennsylvania, USA.
Kelly Lewellen Tanning Research Laboratories, Inc., Ormond Beach, Florida,
USA.
Regina Lim Product Quest, Inc., Daytona Beach, Florida, USA.
Karl Lintner Sederma, Paris, France.
Contributors xi
Dennis L. Lott Tanning Research Laboratories, Inc., Ormond Beach,

Florida, USA.
Kenneth Marenus Estee Lauder Companies, Melville, New York, USA.
Romano E. Mascotto L’Oréal Research, Asnière, France.
Peter Matravers Aveda Corporation, Minneapolis, Minnesota, USA.
Timothy Meadows Farpoint, Inc., Dallas, Texas, USA.
Toni F. Miller Essex Testing Clinic, Verona, New Jersey, USA.
Emalee G. Murphy Kirkpatrick & Lockhart LLP, Washington, DC, USA.
Masako Naganuma Shiseido Scientific Research Department, Tokyo, Japan.
Malcolm R. Nearn Kentlyn, New South Wales, Australia.
Christopher G. Nelson, Jr. St. Petersburg, Florida, USA.
Uli Osterwalder Ciba Specialty Chemicals Inc., Basel, Switzerland.
Irwin Palefsky Cosmetech Laboratories, Inc., Fairfield, New Jersey, USA.
Patricia Peterson Aveda Corporation, Minneapolis, Minnesota, USA.
James P. SaNogueira Playtex Products, Inc., Allendale, New Jersey, USA.
Cheryl M. Sanzare L’Oréal USA Products, Inc., Clark, New Jersey, USA.
Robert M. Sayre Rapid Precision Testing Laboratories, Cordova, Tennessee
and University of Tennessee Center for the Health Sciences, Memphis,
Tennessee, USA.
David Schlossman Kobo Products, Inc., South Plainfield, New Jersey, USA.
Richard J. Schwen PAREXEL International, Inc., Waltham, Massachusetts,
USA.
Mona Shaath Alpha Research & Development, Ltd., White Plains, New York,
USA.
Nadim A. Shaath Alpha Research & Development, Ltd., White Plains,
New York, USA.
Yun Shao Kobo Products, Inc., South Plainfield, New Jersey, USA.
Daiva Shetty Division of Over-The-Counter Drug Products, Center for Drug
Evaluation and Research, Food and Drug Administration, Rockville, Maryland,
USA.
William Shields CCI, Rockledge, Florida, USA.
xii Contributors
Ko-ichi Shiozawa Aveda Corporation, Minneapolis, Minnesota, USA.

Joseph W. Stanfield Suncare Research Laboratories, LLC, Winston Salem,
North Carolina, USA.
David C. Steinberg Steinberg & Associates, Inc., Plainsboro, New Jersey,
USA.
John P. Tedeschi Bath & Body Works, Reynoldsburg, Ohio, USA.
Andrea Tomlinson Cognis UK, Waltham Cross, UK.
Christopher D. Vaughan SPF Consulting Labs, Inc., Pompano Beach,
Florida, USA.
Ismail I. Walele Finetex, Elmwood Park, New Jersey, USA.
Glenn Wiener Tanning Research Laboratories, Inc., Ormond Beach, Florida,
USA.
Carolyn B. Wills Mary Kay Inc., Dallas, Texas, USA.
James M. Wilmott Ridgefield Drive, Shoreham, New York, USA.
Nabiha Yusuf Department of Dermatology, University of Alabama at
Contents
Introduction
1. Sunscreen Evolution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Nadim A. Shaath
2. Photoprotection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Christopher G. Nelson, Jr.
3. A Perspective on the Need for Topical Sunscreens . . . . . . . . . . . . 45

B. L. Diffey
4. Safety Considerations for Sunscreens in the USA . . . . . . . . . . . . . 55

Richard J. Schwen
5. Sunprotection: Historical Perspective . . . . . . . . . . . . . . . . . . . . . . 71

Paolo U. Giacomoni
Regulatory Aspects
6. The Role of FDA in Sunscreen Regulation . . . . . . . . . . . . . . . . . . 85

Matthew R. Holman and Daiva Shetty
xiii
xiv Contents
7. The Final Monograph . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95

Emalee G. Murphy
8. Regulatory Aspects of Suncreens in Europe . . . . . . . . . . . . . . . . . 117

Romano E. Mascotto
9. Regulation of Sunscreens in Australia . . . . . . . . . . . . . . . . . . . . . 127

Malcolm R. Nearn
10. Legal and Regulatory Status of Sunscreen

Products in Japan . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
Minoru Fukuda and Masako Naganuma
11. Regulations of Sunscreens Worldwide . . . . . . . . . . . . . . . . . . . . . 173

David C. Steinberg
12. Sunscreen Products: The Role of the US

Pharmacopeia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
Lawrence Evans III
Ultraviolet Filters
13. The Chemistry of Ultraviolet Filters . . . . . . . . . . . . . . . . . . . . . . . 217

Nadim A. Shaath
14. Inorganic Ultraviolet Filters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239

David Schlossman and Yun Shao
15. Inorganic Particulate Ultraviolet Filters

in Commerce . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281
Nadim A. Shaath and Ismail I. Walele
16. New Sunscreen Actives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291

Bernd Herzog, Dietmar Hueglin, and
Uli Osterwalder
17. The Photostability of Organic Sunscreen

Actives: A Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321
Craig A. Bonda
Cosmetic Formulations
18. Formulating Sunscreen Products . . . . . . . . . . . . . . . . . . . . . . . . . 353

Kenneth Klein and Irwin Palefsky
Contents xv
19. SPF Modulation: Optimizing the Efficacy

of Sunscreens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 385
Julian P. Hewitt
20. The Role of Surfactants in Sunscreen Formulations . . . . . . . . . . . 413

Gerd Dahms
21. Role of Emollients and Emulsifiers in

Sunscreen Formulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 449
Stefan Bruening, Mark Leonard, Rolf Kawa,
Ulrich Issberner, and Andrea Tomlinson
22. Surfactant-Free Sun Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 461

James M. Wilmott
23. Fragrancing of Sun Care Products . . . . . . . . . . . . . . . . . . . . . . . . 493

Felix Buccellato
24. Formulating Natural Sun Care Products . . . . . . . . . . . . . . . . . . . . 507

Timothy Kapsner, Peter Matravers,
Ko-ichi Shiozawa, and Patricia Peterson
Consumer Products with Ultraviolet Filters
25. Recreational Sunscreens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 525

James P. SaNogueira
26. Daily Use Sunscreens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 535

Peter J. Lentini
27. Valuable Properties for Baby and Kids Segments . . . . . . . . . . . . . 541

Dennis L. Lott, Kelly Lewellen,
and Glenn Wiener
28. Fabrics as UV Radiation Filters . . . . . . . . . . . . . . . . . . . . . . . . . . 557

Kathryn L. Hatch
29. Sunless Tanning and Tanning Accelerators . . . . . . . . . . . . . . . . . . 573

Anthony D. Gonzalez and Robert E. Kalafsky
Other Actives in the Sun Care Industry
30. Role of Antioxidants in Sun Care Products . . . . . . . . . . . . . . . . . . 603

Ratan K. Chaudhuri
xvi Contents
31. Photoprotection by Green Tea Polyphenols . . . . . . . . . . . . . . . . . 639

Craig A. Elmets, Santosh K. Katiyar,
and Nabiha Yusuf
32. Botanicals in Sun Care Products . . . . . . . . . . . . . . . . . . . . . . . . . 657

Howard Epstein
33. Antiaging Actives in Sunscreens . . . . . . . . . . . . . . . . . . . . . . . . . 673

Karl Lintner
Production and Quality Control
34. The Manufacture of Suncare Products . . . . . . . . . . . . . . . . . . . . . 699

Timothy Meadows
35. Quality Control of Finished Sunscreen Products . . . . . . . . . . . . . . 719

Henry T. Kalinoski
36. Quality Control of Ultraviolet Filters . . . . . . . . . . . . . . . . . . . . . . 735

Nadim A. Shaath
37. Modern Analytical Techniques in the

Sunscreen Industry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 751
Nadim A. Shaath and Frederick Flores
Analytical Testing Procedures
38. US FDA Protocol for Determining Sun

Protection Factor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 769
Toni F. Miller
39. SPF Testing in Europe . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 779

Mike Brown
40. Balancing UV-A and UV-B Protection in Sunscreen

Products: Proportionality, Quantitative Measurement
of Efficacy, and Clear Communication to Consumers . . . . . . . . . . 807
Patricia P. Agin, Curtis A. Cole, Christopher Corbett,
Cheryl M. Sanzare, Kenneth Marenus, John P. Tedeschi,
and Carolyn B. Wills
41. Dosimetry of Ultraviolet Radiation: An Update . . . . . . . . . . . . . . 827

B. L. Diffey
Contents xvii
42. Spectral Standardization of Sources Used for

Sunscreen Testing: 5 Years of Compliance . . . . . . . . . . . . . . . . . . 843
Robert M. Sayre and John C. Dowdy
43. In Vitro Techniques in Sunscreen Development . . . . . . . . . . . . . . 853

Joseph W. Stanfield
44. Prediction of Sun Protection Factors

and UV-A Parameters by Calculation of UV
Transmissions Through Sunscreen Films
of Inhomogenous Surface Structure . . . . . . . . . . . . . . . . . . . . . . . 881
Bernd Herzog
Marketing and Information
45. Single Sunscreen Application Can Provide

Day-Long Protection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 903
Robert M. Sayre, John C. Dowdy,
and William Shields
46. The Role of Publications in the Industry . . . . . . . . . . . . . . . . . . . 913

Nancy Allured
47. Technical Information in the Expanding

Sunscreen Field . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 919
Regina Lim, Christopher D. Vaughan, and
Edwin D. Leonard, Jr.
48. Recent Sunscreen Market Trends . . . . . . . . . . . . . . . . . . . . . . . . . 929

Nadim A. Shaath and Mona Shaath
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 941
Introduction
1
Sunscreen Evolution
Nadim A. Shaath
Alpha Research & Development, Ltd., White Plains, New York, USA
Historical Background 4
Skin Cancer and the Solar Spectrum 5
Sunscreen Products 6
Issues and Challenges Facing the Sunscreen Industry 6
Regulatory and Safety Issues 6
Sun Protection Factor 7
The Region in the UV Spectrum 7
Water Resistance 7
Photostability and Photoreactivity 7
Safety and Stability 8
Manufacturing and Quality Control 8
Cosmetic Formulation Issues 9
Formula Types 9
Formula Optimization 9
Active Ingredients 9
Other Ingredients 10
Marketing Issues 12
Sunscreen Products for the 21st Century 12
UV Filters 12
Natural Ingredients 13
Biologically Active Ingredients 14
Cosmetic Formulations 14
Conclusions 15
References 16
3
4 Shaath
HISTORICAL BACKGROUND
In Ancient Egypt the cult of the sun god Ra provided a sun-centered cosmology
where Egyptians bowed in worship to the powerful effects of the life-giving sun.
The Ancient Egyptians were well aware of the dangers of the sun. Their lands
were scorched with heat. Women protected their skin, preferring light skin to
dark in their cultural hierarchy of beauty (1). Recent discoveries written on
papyri and the walls of several tombs unearthed ingredients and formulations
in use in Ancient Egypt specifically addressing issues of sun damage to the
hair and skin (2,3).
. Tirmis or lupin extract was used to block the rays of the sun and is still
used to date to lighten the color of the skin.
. Yasmeen or jasmin was used to heal the sun-damaged skin. Recent
evidence reveals that jasmin aids in DNA repair at the cellular level.
. Sobar or aloe was used to heal sun-damaged skin.
. Zaytoon or olive oil was used as a hydrating oil for both skin and hair
damaged by overexposure to the sunlight.
. Aquatic lotus oil was used for protection of the skin from the sun.
. Loze or almond oil was applied before and after sun exposure to hydrate
the sun-damaged skin, improving elasticity and texture.
. Calcite powder and clay were used as ultraviolet (UV) filters similar to
the modern day inorganic particulates zinc oxide and titanium dioxide.
. Rice bran extracts were used in sunscreen preparations. Today, gamma
oryzanol extracted from rice bran has UV absorbing properties.
. A number of cosmetic ingredients were used to mask and protect the
skin and hair from the ravishing rays of the sun (2,3). These included
kohl (to darken eyes in order to combat sunlight impairment to the
retina in the glare of the desert sun), red ochre (to redden and impart
a rosy glow in women’s makeup mimicking the effect of the sun on
the skin), and henna oil (to dye the lips and nails, darken the color of
the hair and skin, and protect light skin from the sun). It is interesting
to note that lawsone, the active principle of henna, was a Food and
Drug Administration (FDA) Category I sunscreen molecule!
In modern times, the first reported use of commercial sunscreens in the

world was in 1928 in the USA with the introduction of an emulsion containing
two sunscreen chemicals, benzyl salicylate and benzyl cinnamate (4). In the
early 1930s, a product containing 10% salol (phenyl salicylate) appeared on
the Australian market (5). In the USA, lotions containing quinine oleate and
quinine bisulfate appeared in 1935. p-Amino benzoic acid (PABA) was first
patented in 1943, leading the way for the incorporation of several para-amino
benzoates in sunscreen formulations (6). During World War II, red petrolatum
was used by the US military, which led to extensive use of both inorganic parti-
culates and organic UV absorbers after the war. The US military specifications
Sunscreen Evolution 5
(7) issued on July 10, 1951, listed approved sunscreen compounds and the
recommended concentrations, namely, glyceryl PABA (3%), and escalol 75A
(5%), 2-ethyl hexyl salicylate (Sunarome WMO, 5%), digalloyl trioleate (3%),
homomenthyl salicylate (8%), and dipropylene glycol salicylate (4%).
The reader is referred to the chapter written by Giacomoni (8) for a histori-
cal perspective on sun protection (also, an interesting perspective on the need for
photoprotection).
SKIN CANCER AND THE SOLAR SPECTRUM

According to the Centers for Disease Control and Prevention in Atlanta, the death
rate in the USA from melanoma has been growing by 4% a year. The American
Cancer Society reports that there are about 1.5 million new cases of skin cancer
diagnosed each year, with about 47,000 cases of melanoma resulting in over
10,000 skin cancer deaths. Of all the reported new malignancies, 80% were
basal cell carcinoma, 16% were squamous cell carcinoma, and 4% were malig-
nant melanoma. Most of these cases are a direct result of overexposure to UV
radiation (9).
There are three types of UV solar radiation. The most energetic rays are the
UV-C (200 – 280 nm), which are generally filtered out by the ozone layer prevent-
ing those deadly rays from reaching the earth’s surface. Any significant depletion
of the earth’s ozone protective layer would pose a hazard that is unimaginable.
The second type of UV rays are termed UV-B and they represent a narrow
band of rays from 280 to 320 nm with the maximum intensity peaking at
307 nm. These rays are sufficiently energetic and have been termed as
“burning” or “erythemal” rays since they are primarily responsible for the
redness associated with sunburn. The third type of UV rays are the UV-A rays,
which extend from 320 to 400 nm and by convention have been further sub-
divided into the shorter UV-A rays, UV-A II (320 – 340 nm), and the longer
UV rays, UV-A I (340 –400 nm). See Chapter 13 on the “Chemistry of UV
Filters” (10) for the depiction of the solar spectrum and the radiations emitted.
These rays have been referred to as the tanning rays since they penetrate deep
into the dermis layer of the skin thereby stimulating the formation of melanin,
the body’s natural defense protective layer. Until the 1970s, they were considered
relatively harmless and in many cases were associated with the formation of a
healthy tan. Recent evidence, however, has implicated these energetically
weaker, yet more penetrating, rays with the higher incidence of skin cancers.
Researchers have implicated UV-A radiation with molecular and tissular
effects, sagging of the skin, and the introduction of nicks in cellular DNA.
Most of the UV-A damage seems to implicate the presence of oxygen and
trace metals, hence the increased popularity of using antioxidants and singlet
oxygen free radical scavengers.
Protection from UV radiation is paramount. This can be achieved by the
avoidance of sun exposure whenever possible, by the wearing of sun protective
6 Shaath
clothing (11), hats, and UV filtering sunglasses along with the use of adequately
formulated sunscreen cosmetic or dermatological preparations. To help the con-
sumers select products that best suit their needs, the FDA and most major country
regulatory organizations have adopted several measures and standards (12). In
addition to the dissemination of information concerning the harmful effects of
prolonged sun exposure, the sun protection factor (SPF) system alerts consumers
to the degree of protection required. The water resistance labeling addresses
sweating, rub off, and effect of bathing in reducing the efficacy of the product.
Also, the UV-A/UV-B labeling system rates products for the type of radiation
it reduces. The reader is referred to the next two chapters and the many references
cited therein for additional information on the need for photoprotection.
SUNSCREEN PRODUCTS
Sunscreen products worldwide can be classified into three major categories:
1. Daily wear and long-term protective products
2. Tanning products
3. Recreational products
The reader is referred to section entitled “Products with Ultraviolet Filters”
in this book for the chapters written on the earlier-mentioned categories and to the
chapter by Shaath and Shaath on “Recent Sunscreen Market Trends”. Note that
the sun care market includes fabrics with UV filters [read Chapter 28 by Hatch
(11)] as well as a multitude of after-sun, medicated sunburn treatment products
that are outside the scope of this book.
ISSUES AND CHALLENGES FACING THE SUNSCREEN INDUSTRY

A number of issues and challenges face the formulator of cosmetic and pharma-
ceutical products that contain UV filters.
Regulatory and Safety Issues

In the USA, the FDA has been regulating this industry since August 25, 1978,
with the publication of the Advance Notice of Proposed Rulemaking. Sunscreens
are considered drugs and cosmetics and therefore must be governed by the
FDA-OTC monograph. The final monograph was issued on May 21, 1999, and
was to be finalized in May 2001; however, that date has been extended to on
or before December 31, 2005 (13).
The regulatory issues that should be addressed include claims, labeling,
manufacturing, and quality control for compliance.
Sun Protection Factor

This is an important, but not the only, criterion by which a sunscreen product is
evaluated. An in vivo test in compliance with the monograph condition has to be
met. The many in vitro techniques developed are very useful for honing in on the
correct formulation, but are not considered legal for compliance with the FDA’s
monograph protocols (refer to section entitled “Analytical Testing Procedures”
for all the in vivo and in vitro testing procedures). Current FDA regulations
allow labeling of sunscreen products to a maximum of 30þ, despite the many
products currently available with numbers as high as 100. From a cosmetic for-
mulation point of view, increasing the SPF number in a product is governed by
simple chemical principles (refer to section entitled “Cosmetic Formulations”).
The Region in the UV Spectrum

The next two chapters deal with the need for photoprotection and have adequately
covered the issues dealing with UV-A, UV-B, and broad-spectrum protection,
including protection from the visible and infrared regions. The protection of
the UV-B region is well documented with all the biological in vivo analyses avail-
able today. UV-A protection testing, on the other hand, is still not yet finalized by
the FDA, even though a number of analytical procedures are being discussed and
submitted to the FDA by the Cosmetics, Toiletries & Fragrance Association
(CTFA), individual companies, and interested scientists.
Water Resistance
The old statements on waterproof sunscreens have been eliminated in favor of
water-resistant or more water-resistant claims. The use of polymers and UV
filters that have minimal or no water solubility is basic in any formulation addres-
sing this issue. Formulation changes are also necessary to increase its water
resistance including favoring water in oil over oil in water formulations.
Photostability and Photoreactivity

A new issue has risen over the last decade questioning the photostability of a few
UV filters. The dibenzoyl methane type of sunscreen agents were implicated due
to their interconversion between its keto and enol forms; they are known to be
less photostable than other molecules in the monograph. This, however, has
led to a whole new class of photostabilizers known as triplet –triplet quenchers
(14) and a number of patents, most notably by L’Oreal, for the photostabilization
of dibenzoyl methane derivatives with octocrylene. It should be noted that any
molecule that can photochemically interconvert (cis –trans, keto – enol, or other
types of photoisomerizations) is subject to some degree of photoinstability.
Most derivatives lose some of their efficacy over extended periods of sunlight
exposure, even the popular octinoxate and padimate-O. Combinations of octinox-
ate and avobenzone in particular have also been known to be less photostable.
8 Shaath
The benzophenones, octocrylene, the salicylates, and the inorganic particulates

are generally photostable molecules.
Photoreactivity is concerned primarily with the inorganic particulates.
Among the attributes of metals and their oxides has been their ability to catalyze
reactions. Hence, questions relating to the photoreactivity of both zinc oxide and
titanium dioxide have recently surfaced. Suppliers have scrambled to assure
manufacturers and regulatory agencies of the safety of their products. In
general, titanium dioxide is more photoreactive than zinc oxide; however, predis-
persions and specialized coatings with silica, organics, and aluminum salts have
improved these products significantly.
Safety and Stability

Issues of safety are very well defined in the FDA’s monograph, COLIPA
(Europe) regulations, and other countries’ specific regulatory bodies including
those of Japan, South Africa, Australia, and New Zealand (12). Basically, a
product is in compliance if a UV filter is used at the permissible levels as
approved by the regulatory agency in question. All new UV filters must submit
New Drug Applications (NDA) to the FDA for approval or file for a Time and
Extent Application (TEA) if the ingredient has been in use for more than
5 years in five foreign countries. The finished cosmetic products must be
tested, like any other cosmetic or pharmaceutical product, for safety and stability
(15). The safety of all ingredients present, their potential interactions with one
another, and the packaging must be evaluated.
Sunscreen stability is a major factor contributing to the success of the
sunscreen formulation. Thorough long-term stability testing of the experimental
formulation needs to be conducted prior to product launch. Degradation of pro-
ducts on exposure to sunlight is a serious problem but the base and packaging
materials can also affect sunscreen stability. The solubility of most liquid UV
filters is similar to that of the polymers used in many packaging materials.
This can result in the UV filter migrating into and degrading the plastic while
also reducing the potency of the formulation left behind. The containers must
be selected to suit the formulation of the sunscreen. Opaque high-density poly-
ethylene is probably the best container, but there is no universal rule. PET is
good for clear products that do not contain certain filters and ingredients.
Manufacturing and Quality Control

Since the FDA classifies all sunscreen products as drugs, the manufacturing
sites have to comply with all the applicable regulations and current good
manufacturing practices (cGMP) (16). The formulation needs to be submitted
for the appropriate battery of tests for SPF and water resistance. The percentage
of each active ingredient in every batch manufactured has to be tested and veri-
fied by instrumental techniques (GC or HPLC).
Cosmetic Formulation Issues

An entire section of this book (Section V), including nine separate chapters, has
been included to address potential problems with formulating sunscreen products
containing UV filters.
Formula Types
The vehicle for the UV filter and the delivery system may pose unique problems.
Special applications of creams, milks, or lotions require either oil in water (O/
W) or water in oil (W/O) emulsions. Other applications include gels, balms,
foams, ointments, oils, sprays, or impregnation into fabric, clothing, or polymer
applications.
Formula Optimization
The optimization of the formula’s SPF, water resistance, and photostability may
require the use or avoidance of specific UV filters, polymers, and other ingre-
dients. The mildness, elegance, and cost-effectiveness of a sunscreen product
may dictate the selection or elimination of specific ingredients.
Active Ingredients
The heart of any sunscreen product is of course the UV absorber, but other ingre-
dients may well affect the efficacy and performance of sunscreen products. The
UV filters permitted in the USA, Europe, Japan, and Australia are listed in
Section II of this book.
UV filters may be classified according to the type of protection they offer as
inorganic particulates, organic chemical absorbing molecules, or new organic
particulates:
1. Inorganic chemical particulates: The use of the phrase “physical
blockers” should be avoided. These ingredients are chemicals that
reflect or scatter the UV radiation. Examples include zinc oxide and
titanium dioxide (red petrolatum is no longer in the final FDA mono-
graph). The inorganic chemical particulates, if present in sufficient
quantities, will absorb and reflect most UV, visible, and IR rays.
They are currently used in conjunction with organic chemical absor-
bers to achieve high SPFs. Micronized forms of these metal oxides
are currently available, claiming to enhance sun protection without
imparting the traditional opaqueness that is aesthetically unappealing
in cosmetic formulations. Other attempts have been made to change
the physical form of the inorganic powders or to complex them with
organic substances. These metal oxides are marketed in a variety of
particle sizes, coatings, dispersions, and suspensions and are currently
10 Shaath
widely used in cosmetic formulations. For a review refer to the two

chapters on inorganic particulates (17,18).
2. Organic chemical absorbers: The term “organic” here should not be
confused with organically grown essential oils or other plant derived
ingredients. These organic chemical filters absorb the harmful UV
radiation. Chemical absorbers are classified into either UV-A or UV-
B blockers depending on the type of radiation they protect the skin
from. UV-A absorbers are chemicals that tend to absorb radiation in
the 320– 380 nm region of the UV spectrum (benzophenones, meradi-
mate, and avobenzone). UV-B absorbers are chemicals that absorb
radiation in the 290 – 320 nm region of the UV spectrum ( para-
amino benzoates, salicylates, cinnamates, and camphor derivatives).
The best classification of chemical UV absorbers is the one based on
the chemical properties of sunscreens (10).
3. Organic particulates: For a discussion of this new category of UV
filters, the reader is referred to the chapter entitled “New Sunscreen
Actives” (19).
Other Ingredients
Sunscreen products, depending on their intended use, contain a multitude of other
ingredients. The other types of ingredients that enter into sunscreen products are
listed as follows:
1. Sunless tanners and bronzers: The only color additive currently
approved by the FDA is dihydroxy acetone (DHA). Other tanning
accelerators such as tyrosine and its derivatives or tyrosinases are
not approved by the FDA as cosmetics. Canthaxanthine marketed as
a tanning pill is not allowed by the FDA. It is only approved as a
color additive in foods. The reader is referred to the chapter entitled
“Sunless Tanning and Tanning Accelerators” (20).
2. Antiaging, antiwrinkle, and healing products: The reader is referred to
the chapter on antiaging products (21) for a discussion of the ingredi-
ents that address the problems associated with aging of the skin,
wrinkling, blemishes, acne, chapping of lips and that also contain
UV filters. The use of analgesics, aloe, botanicals, antioxidants, essen-
tial oils, and extracts in post-sun healing lotions is expanding rapidly.
3. Sunscreens for hair : Sun damage to the hair causes the fading of the
hair color. It may also cause brittle and dry hair shafts as well as split
ends. Products with UV filters have demonstrated their usefulness in
addressing some of the problems associated with hair damage. The
FDA Category I UV filters are generally used; however, a number of
cosmetic ingredient companies supply specialized UV filters specifi-
cally designed for the hair. If no SPF is claimed on hair products,
non-Category I ingredients may be used, so long as their safety and
efficacy have been demonstrated. Over two decades ago, the concept of
quaternary ammonium compounds such as salicylates or cinnamates,
that are substantive to the hair and are chemically bonded to UV
filters, was introduced. Today, a number of companies offer these pro-
ducts to the industry.
4. Antioxidants: Recent research has revealed that free radical scaven-
gers may play an important role in reducing the damage to the skin,
especially as it relates to the excessive exposure of UV-A radiation.
A multitude of antioxidants, including polyphenols found in green
tea and a number of essential oils and plant extracts, are currently
being used or suggested for use in many presun, postsun, and during-
sun exposure products. The reader is referred to the three chapters in
section entitled “Other Actives in the Sun Care Industry” of this book.
5. Natural ingredients: It should be noted, at the outset, that any claims
of SPF on a product labeled natural sunscreen must contain Category I
approved UV filters and be in compliance with all the FDA regulations
governing sunscreen products. The use of natural ingredients in the
health, aromatherapy, and beauty markets is rapidly expanding.
Their use is not only encouraged, they impart substantial benefits to
many sunscreen products as well. The reader is referred to the
chapter written by the Aveda group (22) for an in-depth discussion
of the natural ingredients that improve and boost the SPF, improve
solubility of actives, impart aroma therapeutic odors, and address
preservation with natural ingredients. It should also be noted here
that the term “organic” should refer only to those essential oils or
plant derivatives that have been grown organically and are approved
by the USDA and its certified organizations.
6. Film formers: A number of very powerful film formers are currently
used in sunscreen products to insure water resistance, make them
sweat proof, and provide rub-off resiliency. Excellent waterproofing
ingredients exist today including the PVP/eicosene copolymer, the
octadecene/MA copolymer, and the acrylate copolymers.
7. Other ingredients for emulsions: Most of these ingredients are gener-
ally not listed under the category of active ingredients. Their presence
of course is mainly cosmetic to impart elegance, feel, and functional-
ity, yet their effect on the sunscreen’s efficacy may be quite significant.
Many studies have demonstrated the effect of emollients in boosting
SPF (23). Thickeners, humectants, and emulsifiers have a major
effect on the spreading ability of the product on the skin, affecting the
thickness of the layer of sunscreen on the skin and its functionality

(a) International Federation for Organic Agriculture Movements (IFOAM), Bundestraus, Gorres-
strasse 15, 53113 Bonn, Germany; (b) Organic Farming Research Foundation, PO Box 440, Santa
Cruz, CA 95061, USA.
12 Shaath
(24). The proper choice of preservative is important not only for insur-
ing safety, microbial elimination, and extension of shelf life, but also
for its compatibility with UV actives. For example, formaldehyde
donors are not compatible with avobenzone. The reader is referred
to the chapter by Klein and Palefski (25) and that by Wilmott (26)
on sunscreen products without emulsifiers.
Marketing Issues
Marketing of sunscreen products and skin care products with UV filters poses a
serious challenge, considering the rapid advancements in technology, formu-
lations, ingredients, regulations, and information on the causes of skin cancers
and the aging process.
The current trends in the marketing of sunscreen products include a
shift from tanning to protection, from seasonal products to year-round products,
and from beach wear to daily wear. Specific growth trends include products
with high SPF, sunless tanning, products for children and kids, products with
new biologically active ingredients, and natural ingredients in sunscreen
products (27).
SUNSCREEN PRODUCTS FOR THE 21ST CENTURY

The products for sunscreen, lip care, or antiaging that contain UV filters are
closely governed by the Final Rule of the FDA in the USA, COLIPA in
Europe, and specific country regulations. In the USA and Australia, these
products are OTC drugs, whereas in Europe and Japan, they are considered
cosmetics. Methods of testing the efficacy of these products have become
almost standardized worldwide despite the differences in the protocols between
the US FDA and the European COLIPA methods. The UV-A testing procedure,
however, is still not finalized in the USA, but in the UK they seem to be content
with the Boots star rating system. The challenges of marketing a single product
that is sold worldwide still remain due to the slightly differing regulations, most
notably on the ultraviolet actives and the testing procedures.
In the last three decades, our knowledge of the chemistry of UV filters and
formulations has improved dramatically, enabling the cosmetic chemists to for-
mulate unique and effective sunscreen products. A review of the most important
ingredients in the formulation of sunscreen products reveals the areas where we
can expect to witness alternative approaches for producing and marketing new
and improved products for the 21st century.
UV Filters
Despite the fact that in the USA we only have 16 approved UV filters, several
have been recently introduced and improved. The introduction of both zinc
oxide and avobenzone has addressed this seriously deficient UV-A protection
area. The new micronized forms of both zinc oxide and titanium dioxide, along
with the many types of coatings and predispersions, have had a major impact on
improving UV-A protection in particular and making more natural claims in
some protection products. The photostability of a few of the ingredients, most
notably avobenzone, has been significantly improved with well-designed cos-
metic formulations and the use of new additives and other quenching ingredients.
The fact still remains that in the USA the process of pursuing an NDA is
extremely tedious, time-consuming, and prohibitively costly. The new FDA’s
TEA establishes criteria and procedures by which OTC conditions may
become eligible for consideration on the OTC drug monograph system and
that speed up the process of adopting new ingredients or filters approved for
use in Europe or other countries. Already three UV filters (amiloxate, enzacmene,
and octyl triazone) that have been extensively used in Europe have been
considered for approval under this TEA application process. Approval of these
three new UV filters in the USA is imminent.
The regulations for approving new UV filters in Europe and Australia are
far more progressive than those found in the USA. Recently, a number of new UV
filters that address both UV-A and UV-B protection have been introduced in
Europe. Among them are filters based on the following chemistry: terphthalidene
dicamphor, benzotriazole, phenyl dibenzimidazole, and hydroxy phenyl triazine.
The design of many of these new filters has taken on a novel approach for design-
ing more efficient UV-A and broad-spectrum filters while overcoming some of
the safety issues such as a few UV filters of low molecular weight (originally
designed for maximum solubility in cosmetic formulations) having the tendency
to be absorbed in the skin. These new molecules have multiple chromophores
with high molecular weight exceeding 500 Da and are thus delivered in cosmetic
formulations as insoluble organic particulates, analogous to the delivery of the
inorganic particulates of today.
Natural Ingredients
The FDA currently does not recognize natural ingredients and plant extracts
possessing UV filtering properties as Category I sunscreen ingredients. Today
we can demonstrate that a number of highly effective sunscreen products
can be formulated with predominantly natural ingredients, with or without the
inorganic particulates. There is a major green movement sweeping the country,
hence the need for cosmetic products that are formulated predominantly with
natural, organically grown plant ingredients from sustainable and renewable
resources. The FDA should take note of this development in view of the fact
that the Monograph had been almost finalized in the late 1970s of the last
century when the natural and green movement was not yet in bloom. Currently
available ingredients that qualify to yield SPF protection and boost existing
SPF formulations include extracts of galanga, green coffee, licorice, oat,
annatto, and many more natural actives that improve the solubility of UV
14 Shaath
filters, naturally preserve the formulations, and improve the feel and elegance of
natural cosmetics.
Biologically Active Ingredients

Sunscreen products for the 21st century should not only address protection from
sunburn, erythema, and redness, but also provide protection from the cellular
damage that is causing alarmingly increasing rates of skin carcinomas and
melanomas. Today there exist a number of ingredients and protocols, albeit
experimental and requiring substantial research, that address a multitude of
cellular damage issues, including DNA damage by UV-A, photoaging, immuno-
compromised skin, free radical generation in the skin, and inflammatory cellular
reactions. Their use in daily regimens against the long-term damage of the sun to
the skin is crucial.
The ingenious cosmetic chemist has to make do with an extremely limited
number of approved UV filters. Despite the fact that 21 ingredients were orig-
inally permitted, in reality, only eight of them were adequate or available for
use. Yet the cosmetic chemist was called upon to produce diverse products
that address a number of protection issues, cosmetic elegance, new vehicles,
superior performance, higher-SPF products targeted to new sectors of consumers,
such as babies, children, teens, sport-oriented individuals, or those seeking self
tanners or tanning accelerators. Commercially, the work and the knowledge
gained during the last 30 years can be demonstrated by the almost annual
double-digit growth of sunscreen, tanning, antiaging, and lip care products.
Unfortunately, skin cancer rates continue to rise, and even though this cannot
be blamed on the lack of ingenuity or poor cosmetic formulations, it nevertheless
begs the issue of relaxing the current regulations to allow for the introduction of
new and improved ingredients and sunscreen cosmetic products. The cosmetic
chemist in the USA in most of the last century had to make do with only two
UV-A filters, namely, oxybenzone (benzophenone-3) and meradimate, both woe-
fully inadequate for efficient UV-A protection. A third ingredient, titanium
dioxide, yielded mostly opaque products and has been used predominantly by
lifeguards, skiers, mountain climbers, and when brightly colored, for novelty
and children’s products. Toward the end of the last century several improvements
occurred, most notably the introduction of micronized forms of titanium dioxide
and zinc oxide (approved in 1998) allowing for more elegant cosmetics that offer
clear, nonopaque formulations. Also, Parsol 1789 (avobenzone) was approved in
1996 (it was available since the 1980s exclusively with an NDA approval to
Herbert Labs and an amended NDA in the 1990s to Schering-Plough only).
Problems of avobenzone with its photoinstability may be partially resolved
with quenchers and emollients. More importantly, information regarding the
chemistry of the ultraviolet filters, cosmetic formulations, and interactions was
widely disseminated since the 1980s, which allowed for more efficient formu-
lations maximizing its SPF potential by the proper selection of emollients, emul-
sifiers, thickeners, solvents, and other additives (28). The effect of these “other
ingredients” on the SPF, and hence the performance of the sunscreen product,
was dramatic. Products emerged with SPF labels exceeding 30, utilizing fewer
UV filters than their lower SPF counterparts of the 1970s and 1980s. New
vehicles (mousse, sprays, gels, towelettes, etc.), new types of emulsions (O/W,
W/O, and emulsions that reverse phases), improved thickeners, emollients,
emulsifiers, film formers, preservatives, and functional botanical ingredients
have all emerged improving the performance and attributes of future sunscreen
products.
The issue of new ingredients requiring approval also plagues the sunless
tanning and tanning accelerator industry despite the fact that this category is
the fastest growing sector in the recreational sunscreen industry. Consumers
fearing exposure to sunlight are using tanning accelerators to artificially color
their skin and give it the perceived healthy glow. The only approved artificial
tanner today is DHA. Ingredients that are safe for developing and stimulating
natural melanin or color need to be approved and adopted in the near future to
cater to this growing segment of the population.
CONCLUSIONS
The cosmetic industry and dermatologists face major challenges in the future to
educate the public about the dangers of excessive exposure to sunlight and to for-
mulate new strategies to address the spiraling incidence of skin cancer and signs
of premature aging of the skin (Dan Rather, who normally delivers the news on
television, became the news when he dramatically announced to his viewers
recently that he is being treated for basal cell carcinoma). Foremost in those
strategies would be to formulate safer yet more effective products that reduce
significantly the dangers of overexposure to harmful UV radiation.
International regulations need to be eased and harmonized allowing for a
single standard worldwide to permit the speedier introduction of new and
improved ultraviolet filters and sunscreen products worldwide.
The academic community should actively participate in this domain and
form partnerships with dermatologists and sunscreen manufacturers to research
the underlying causes of skin cancer from a cellular and molecular biology per-
spective, unearth markers for early detection, and ultimately assist marketers in
producing superior, more natural sunscreen products. New formulations should
contain ingredients to address both the direct damage to the skin from sunlight
(DNA dimer formation and [6-4]photoproduct formation) and the indirect
damage resulting from reactive oxygen species and free radicals.
Analytical and instrumentation scientists are encouraged to develop
newer and more advanced techniques for early diagnosis and for more reliable
methods of SPF, UV-A, and water resistance testing. The new techniques of
16 Shaath
photochemistry that are based on the remarkable work of the 1999 Nobel Prize
laureate in femtochemistry, Dr. Ahmed Zewail, are now being applied by
many scientists for insights into the photostability of DNA and other UV filters.
The botanist working closely with organic chemists should actively
research old remedies and new botanical sources for natural sunscreen protection
and eventually create better UV filters and other natural ingredients leading to
superior sunscreen products.
Ultimately, it is the responsibility of the marketers, the press and the
specialized organizations and professional societies to better communicate to
the consumer both the dangers of the damaging rays of the sun and the anticipated
new discoveries leading to better products and protection. With millions of new
cases of skin cancer reported each year due to the excessive exposure to sunlight,
we can ill afford to sit idly by while the quality of our lives and its very existence
is threatened.
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2005:321 –349.
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Sunscreens: Regulations and Commercial Development. 3rd ed. New York:
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2005:699– 718.
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2005:239– 279.
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19. Herzog B, Hueglin D, Osterwalder U. New sunscreen actives. In: Shaath NA, ed.
Sunscreens: Regulations and Commercial Development. 3rd ed. New York: Marcel
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2
Photoprotection
Christopher G. Nelson, Jr.

St. Petersburg, Florida, USA
Why Do We Need Photoprotection? 20

The Solar Spectrum 20
Acute Solar Damage 21
Introduction 21
Mechanism of Acute Photodamage 22
Histology of Acute Photodamage 22
Chronic Solar Damage 23
Introduction 23
Mechanism of Chronic Damage 23
Histology of Chronic Damage 24
Other Effects of Photoexposure 24
Photosensitive Reaction 24
Phototoxicity 26
Photoallergy 27
Photosensitivity Skin Disorders 27
Lupus Erythematosus (290 –330 nm) 27
Xeroderma Pigmentosum (290 – 340 nm) 27
Chronic Actinic Dermatitis (290 – 360 nm) 27
Polymorphous Light Eruption (290 –365 nm) 29
Hydroa Vacciniforme (290 –400 nm) 29
Persistent Light Reaction (290 –400 nm) 29
Solar Urticaria (290 – 515 nm) 29
19
20 Nelson
Porphyrias (400 – 410 nm) 29

Miscellaneous Dermatoses 29
Carcinogenesis Related to Photoexposure 30
Mechanism of Carcinogenesis 30
Opportunities to Interrupt the Pathway 31
Initiation 31
Promotion 31
Progression 33
Immunopathology of Skin Cancer—An Apparent Paradox 33
Strategies to Block UV Light 34
Sun Exposure Avoidance 34
Sun Protective Clothing 34
Sunscreens 36
Sunscreening Agents 37
Organic Sunscreening Agents 37
Inorganic Sunscreening Agents 37
Proper Use of Sunscreens 38
Suggestions for the Future 38
References 39
WHY DO WE NEED PHOTOPROTECTION?

The incidence of sunlight-induced premature aging of the skin and skin cancer is
increasing annually. Last year in the USA, over one million new cutaneous
malignancies were diagnosed. Approximately 80% of these were basal cell
carcinoma, 16% were squamous cell carcinoma, and 4% were malignant mela-
noma. An estimated 10,250 people died from skin cancer in 2004, of which
7910 died from malignant melanoma. This represents a 4.6% increase over 2003.
In 1930, the lifetime risk of an American developing malignant melanoma was
1 in 1500; by 2004, this risk has increased to 1 in 37 (1). The most important pre-
ventive factor is protection from ultraviolet (UV) exposure. Most people sustain
80% of their lifetime damage from the sun before age 18; however, UV exposure
later in life also contributes by producing cutaneous alterations that allow malig-
nant and premalignant lesions to develop from previous damage, as well as
causing damage that leads to premature aging (“photoaging”) of the skin (2).
THE SOLAR SPECTRUM

Solar radiation encompasses the entire electromagnetic spectrum, including
short, high-energy cosmic and gamma rays, longer lower-energy UV rays,
Photoprotection 21
visible light, infrared (IR) radiation, microwaves, and finally radio waves. High-
energy waves (l , 10 nm) displace electrons from molecules to form ions, and
are thus considered ionizing radiation. UV, visible, and short IR waves lack the
energy required for this process, and are classified as nonionizing radiation.
The UV spectrum is divided into vacuum UV (l ¼ 10 –100 nm), UV-C
(l ¼ 100 – 290 nm), UV-B (l ¼ 290– 320 nm), and UV-A (l ¼ 320– 400 nm).
Further, UV-A is divided into UV-A1 (l ¼ 340 –400 nm), and UV-A2
(l ¼ 320 – 340 nm).
While the solar spectrum represents a wide range of potential energies and
wavelengths, nearly 30– 40% of this radiation, including the most harmful por-
tions, is absorbed in the upper layers of the earth’s atmosphere by the ozone
layer (3). Of the solar radiation reaching the earth, approximately 50% is
visible (l ¼ 10– 400 nm). The ozone layer eliminates virtually all UV radiation
below 290 nm. Thus, vacuum UV, UV-C, and the shortest UV-B wavelengths are
blocked; conversely, minimal UV-A is filtered. The UV radiation that penetrates
the ozone layer and reaches the earth is 10% UV-B and 90% UV-A at midday
(solar noon). The UV-B intensity is highest at solar noon, and declines thereafter.
The UV-A intensity remains relatively constant throughout the day (4).
ACUTE SOLAR DAMAGE

Introduction
When exposed to UV radiation, human skin undergoes several changes.
The first response, immediate pigment darkening (IPD), is a transient,
brownish-gray coloration of the skin after exposure to UV-A. It begins within
60 s and lasts up to 30 min. Proposed mechanisms of IPD include photo-
oxidation of existing melanin and changes in the distribution of epidermal
melanocytes (5).
Persistent pigment darkening (PPD) is a longer lasting response of indivi-
duals with pigmented skin after exposure to UV radiation. Not only is the
melanin, which is already present, further darkened, but the production of new
melanin is also enhanced. PPD begins within hours and may last for days to
weeks. The proposed mechanism of PPD is UV-A exposure, and while UV-B
may have a role, the action spectrum for PPD is not defined for wavelengths
shorter than 320 nm (6).
An erythema response may be induced by both UV-A and UV-B. The
UV-A response is variable in individuals, and ranges from undetectable to
marked. UV-B produces delayed erythema, which appears 3– 4 h after exposure
and intensifies for 12– 24 h. It is often accompanied by pain, pruritus, and the
formation of bullae. The minimal erythema dose (MED) is defined as the minimal
dose of UV-B needed to produce barely perceptible erythema in a given individ-
ual. The 307 nm wavelength is the most efficient for producing erythema (7). The
dosage of UV-A to produce erythema (20 – 70 J/cm2) is 600 –1000 times that
22 Nelson
required for UV-B (20 – 1000 mJ/cm2). Although the intensity of UV-A at noon
is typically 10 times that of UV-B, the latter is responsible for 98 –99% of
delayed erythema development (8).
Mechanism of Acute Photodamage

The biological effects of UV and visible radiation, both acute and long-term, are
produced by the absorption of radiation by molecules called chromophores. These
molecules have highly characteristic absorption spectra that are dependent upon
their structures. After being irradiated, chromophores become “energized” and
undergo either molecular reorganization or interaction with nearby molecules.
These chemical changes cannot take place unless the specific wavelength for the chro-
mophore is absorbed. The major chromophores of the skin include DNA, proteins,
porphyrins, and urocanic acid. Other endogenous chromophores that may absorb
UV radiation include NADH/NADPH, tryptophan, riboflavin, and melanin (9).
The action spectra of these chromophores may be influenced by the addi-
tion of exogenous photochemically active chromophores (e.g., 8-methoxypsoralen)
or by internal entities such as medications or disease states. In fact, organic sun-
screens are actually exogenous chromophores that work by attenuating erythemo-
genic UV radiation.
Current theories for acute photodamage emphasize the importance of DNA
absorption of UV radiation. The absorption spectrum for DNA peaks at 260 nm
(UV-C), but it also absorbs UV-B and to a lesser degree, UV-A. When UV radi-
ation is absorbed, DNA forms characteristic lesions such as cyclobutane pyrimi-
dine dimers. It has been shown that the action spectra for pyrimidine dimer
formation and erythema in human skin are very similar, suggesting that DNA
absorption of UV radiation is responsible for acute erythema (10).
Histology of Acute Photodamage

After acute damage by UV radiation, typical histologic changes occur including
slight epidermal spongiosis, increase in nuclear diameter and nucleolar size of the
keratinocytes, depletion of Langerhans cells, induction of sunburn cells, hyper-
keratosis, parakeratosis, acanthosis, and migration of inflammatory cells into
the exposed areas (11,12). The inflammatory infiltrate may be mediated by
both lipoxygenase products and cytokines such as interleukin-1 (IL-1) (13,14),
IL-3 (15), IL-6 (16), granulocyte-macrophage colony stimulating factor (17),
and tumor necrosis factor alpha (TNF-a) (18).
Following UV exposure and damage, so-called sunburn cells develop.
These sunburn cells are actually necrotic keratinocytes in the epidermis. They
are recognized on hematoxylin and eosin staining by their round shapes, pyknotic
nuclei, and shrunken glassy eosinophilic cytoplasm. Sunburn cells share many
histologic features with apoptotic cells. Apoptosis is an innate programmed
cell death pathway, and is important for normal development and tissue homeo-
stasis. Apoptosis plays an important role in eliminating damaged, dysfunctional
Photoprotection 23
cells (19). The similarities between apoptotic cells and sunburn cells support the
theory that DNA is affected by UV exposure, and also supports the speculation
that sunburn cells are an indicator of photocarcinogenic potential (20,21).
CHRONIC SOLAR DAMAGE

Introduction
Chronic exposure to UV radiation accentuates and accelerates many of the
changes of intrinsic aging including telangiectasia, blotchy pigmentation, and
atrophy as well as loss of the elasticity of the skin. Although hypertrophy of
the epidermis is a short-term effect of sun exposure, the consequence of
chronic exposure is an exacerbation of age-related atrophy.
Mechanism of Chronic Damage

Tanning of the skin is a consequence of chronic UV radiation exposure, resulting
in increased melanin production in melanocytes. While both UV-A and UV-B
can cause erythema and tanning, UV-A is much less efficient. UV-B induces
tanning by increasing the binding of circulating melanocyte stimulating
hormone (MSH) to melanocytes, leading to proliferation, dendritic arborization,
and pigment production. Interestingly, these changes occur not only on exposed,
but to a lesser extent covered areas of the body (22). Melanin absorbs, reflects,
and scatters UV radiation, in addition to functioning as a free radical trap.
Melanin is produced from tyrosine through several enzymatically controlled
reactions. The rate-limiting step is the conversion of tyrosine into dihydroxyphe-
nylalanine (DOPA) by tyrosine hydroxylase. After its formation, the melanin is
incorporated into organelles called melanosomes, which are distributed to sur-
rounding keratinocytes. Some melanosomes remain intact in the keratinocytes
as they migrate to become stratum corneum, and others are degraded enzymati-
cally into an amorphous form that deposits in the intercellular spaces. It is this
amorphous melanin that undergoes oxidation in the IPD reaction previously men-
tioned (23). Persons of all skin types have approximately the same number of
melanocytes; however, more melanosomes are produced by darker-skinned
people accounting for the pigmentation difference. Black-skinned persons have
approximately 400 melanosomes per basal epidermal cell, about four times the
number in a typical pale Caucasian. The increased number of melanosomes in
black skin reduces the penetration of UV-A and UV-B by a factor of 5 and is
responsible for a 30-fold increase in MED. Tanning of Caucasian skin induces
an increase in melanosomes and a resultant increase in sun protection factor
(SPF) between 2 and 4 units. While this increase does afford some photoprotec-
tion, the skin is still susceptible to a significant amount of UV radiation induced
damage. It is significant that UV-A at high doses (e.g., tanning salons) can
produce erythema and melanogenesis, but does not provide the same degree of
protection as a naturally acquired UV-B sun tan. The increased melanogenesis
24 Nelson
induced by UV-A occurs primarily in the basal cell layer without distribution of
the melanosomes throughout the entire epidermis as occurs with UV-B. There is
therefore no associated SPF increase.
Chronic UV-B exposure causes stratum corneum hypertrophy; it can
increase up to six times its original thickness by increased synthesis of basal
keratinocytes. The stratum corneum is naturally hypertrophied on the palmar
and plantar surfaces, explaining their relative resistance to sun damage.
Thickened stratum corneum absorbs or reflects 90 –95% of incident UV-B,
greatly decreasing the amount that reaches the basal keratinocytes, melanocytes,
and superficial dermis (24). It is interesting to note that chronic UV-A exposure
does not cause thickening of the stratum corneum, further contributing to the lack
of photoprotection offered by a UV-A tan.
Histology of Chronic Damage

Late histologic changes caused by UV radiation include the typical changes of
photoaging. Staining with hematoxylin and eosin demonstrates hypertrophy of
the stratum corneum and atrophy of the epidermis. The upper dermis displays
basophilic degeneration of the dermal collagen, which is separated from the epi-
dermis by a thin band of normal collagen. Within the areas of basophilic degener-
ation, the bundles of eosinophilic collagen are replaced by amorphous basophilic
granular material. With elastic tissue stains, the areas of basophilic degeneration
stain like elastic tissue. This elastotic material usually consists of aggregates of
thick, interwoven bands in the upper dermis. In severe solar degeneration, the
elastotic material becomes more amorphous and may extend into the deeper
dermis (25). Damage to the dermal extracellular matrix proteins results in
deterioration of the tensile strength of the skin. The exact mechanism of these
changes to the collagen and elastic tissue remains elusive, and the exact wave-
lengths and the respective action spectra for these changes remain to be
determined.
OTHER EFFECTS OF PHOTOEXPOSURE

Photosensitive Reaction
A photosensitive reaction is a chemically induced alteration in the skin that
makes an individual more sensitive to UV radiation. Following absorption of a
specific wavelength, an oral, ingested or topical agent may be chemically
altered to produce a reaction ranging from macules and papules, vesicles and
bullae, edema, urticaria, to an acute eczematous reaction (26). The two main
types of photosensitive reactions are photoxic and photoallergic. Agents that
can cause photosensitivity are listed in Table 2.1.
Photoprotection 25
Table 2.1 Agents that may Cause Photosensitivity
Anticancer drugs Sulfisoxazole (Gantrisin; and others)

Dacarbazine (DTIC-Dome) Tetracycline (Achromycin; and others)
Fluorouracil (Fluoroplex; and others) Antiparasitic drugs
Methotrexate (Mexate; and others) Bithionol (Bitrin)
Procarbazine (Matulane) Chloroquine (Aralen)
Vinblastine (Velban) Hydroxychloroquine
Antidepressants Pyrvinium pamoate (Povan)
Amitriptyline (Elavil; and others) Quinine
Amoxapine (Asendin) Oxybenzone
Desipramine (Norpramin: Pertofrane) PABA esters
Doxepin (Adapin; Sinequan) p-Aminobenzoic acid
Imipramine (Tofranil; and others) Others
Isocarboxazid (Marplan) Amiodarone (Cordarone)
Maprotiline (Ludiomil) Bergamot oil, oils of citron, lavender,
Nortriptyline (Aventyl; Pamelor) lime, sandalwood, cedar (used in
Protrityline (vivactil) many perfumes and cosmetics; also
Trimipramine (Smontil) topical exposure to citrus rind oils)
Antihistamines Benzocaine
Cyproheptadine (Periactin) Captopril (Capoten)
Diphenhydramine (Benadryl; and Carbamazepine (Tegretol)
others) Chloradiazepoxide (Librium)
Antimicrobials Coal tar and derivatives
Antifungals (Fentichlor, (containing acridine, anthracene,
Multifungin, Jadit) naphthalene, phenanthrene
Demeclocycline (Declomycin; phenols, thiophene)
and others) Contraceptives, oral
Doxycycline (Vibramycin; and others) (Norethynodrel)
Griseofulvin (Fulvicin-UF; Cyclamates (calcium cyclamate,
and others) sodium cyclohexylsulfamate)
Methacycline (Rondomycin) Antipsychotic drugs
Minocycline (Minocin) Chlorpromazaine (Thorazine;
Nalidxic acid (NegGram) and others)
Oxytetracycline (Terramycin; Chlorprothixine (Taractan)
and others) Fluphenazine (Pernitil: Prolixin)
Sulfacytine (Renoquid) Haloperidol (Haldol)
Sulfadoxine-pyrimethamine Perphenazine (Trilafon)
(Fansidar) Sulfamethizole (Thiosulfil; and others)
Sulfaguanidine Sulfamethoxazole (Gantanol;
Sulfamethazine (Neotrizine; and others)
and others) Sulfamethoxazole – trimethoprim
Sulfanilamide (Bactrim, Septra; and others)
Sulfapyridine Thiothixene (Navane)
Sulfasalazine Trifluoperazine (Stelazine;
Sulfathiazole and others)
(continued )
26 Nelson
Table 2.1 Continued
Triflupromazine (Vesprin) Promethazine (Phenegran; and others)

Trimeprazine (Temaril) Thioridazine (Mellaril)
Diuretics Naproxen (Naprosyn)
Acetazolamide (Diamox) Phenylbutazone (Butazolidin;
Amiloride (Midamor) and others)
Bendroflumethiazide Piroxicam (Feldene)
(Naturetin; and others) Sulindac (Clinoril)
Benzthiazide (Exna; and others) Sunscreens
Chlorothiazide (Diuril; and others) 6-Acetoxy-2,4-dimethyl-m-dioxane
Cyclothiazide (Anhydron) (preservative in sunscreens)
Furosemide (Lasix) Benzophenones
Hydrochlorothiazide Cinnamates
(HydroDIURIL; and others) Diethystilbestrol
Hydroflumethiazide (Diucardin; Disopyramide (Norpace)
and others) Dyes (acridine, acriflavine,
Methyclothiazide (Aquatensen; anthraquinone, eosin, erythrocine,
Enduron) fluorescein, methylene blue,
Metolazone (Diulo; Zaroxolyn) methyl violet, orange red, rose
Polythiazide (Renese) bengal, toluidine blue,
Quinethazone (Hydromox) trypaflavin, trypan blue)
Trichlormethiazide (Methahydrin; Furocoumarins: psoralens
and others) (trioxsalen, methoxsalen, psoralen)
Hypoglycemics Gold salts (Myochrysine; Solganal)
Acetohexamide (Dymelor) Hexachloraphene (pHisoHex;
Chlorpropamide (Diabinese; Insulase) and others)
Glipizide (Glucotrol) Isotretinoin (Accutane)
Glyburide (DiaBeta; Micronase) 6-Methylcourmarin (used in
Tolzamide (Tolinase) perfumes, shaving lotions, and
Tolbutamide (Orinase; and others) sunscreens)
Nonsteroidal anti-inflammatory drugs Mestranol
Benoxaprofen (Oraflex) Musk ambrette (used in perfumes)
Ketoprofen (Orudis) Quinidine sulfate and gluconate
Piperacetazine (Quide) Saccharine
Prochlorperazine (Compazine; Tattoo dye (red or yellow
and others) cadmium sulfide)
Phototoxicity
Phototoxic reactions are the most common type of drug-induced photosensitivity.
They resemble an exaggerated sunburn and occur within 5 –20 h after the skin
has been exposed to a photosensitizing substance (either topically or systemi-
cally) and sufficient quantities of UV radiation of the proper wavelength. This
is not a form of allergy, and no prior sensitization is necessary. Theoretically,
this type of reaction can occur in anyone exposed to sufficient quantities of the
offending agent and light; the reaction is dose dependent for both. Phototoxic
Photoprotection 27
reactions are commonly caused by UV-A. These reactions may also cause ony-
cholysis (separation of the nail from the nail bed), as the nail bed is particularly
susceptible due to a lack of melanin protection (26). Many plants elaborate photo-
active substances (e.g., furocoumarins) that can induce phototoxic reactions.
These are listed in Table 2.2.
Photoallergy
Photoallergic reactions are mediated by an interaction of drug, light, and the
immune system. This is a less common form of drug-induced photosensitivity,
and is often caused by UV-B. Photoallergic reactions, unlike phototoxic
reactions, represent an immunologic reaction and require a latent period of
24 –48 h during which sensitization occurs. They are not dose related (26). If
the photosensitizer acts internally, it is called a photodrug reaction; if it acts
externally, it is a photocontact dermatitis. The clinical manifestations include
pruritus and an erythematous, often papulosquamous, eruption on exposed
areas of the skin.
PHOTOSENSITIVITY SKIN DISORDERS

There are several specific skin disorders which are triggered or exacerbated by
UV radiation; each has a specific triggering action spectrum, listed below in
parenthesis.
Lupus Erythematosus (290 –330 nm)

Lupus erythematosus may be exclusively confined to the skin without systemic
involvement, as in discoid lupus erythematosus. Systemic lupus may also
produce cutaneous manifestations. The clinical findings of both are more promi-
nent on sun exposed skin. Although the action spectrum appears to be predomi-
nantly UV-B, UV-A has also been shown to have a role in some individuals (27).
Xeroderma Pigmentosum (290 – 340 nm)

Xeroderma pigmentosum is an autosomal recessive disorder characterized by a
genetic defect in the ability to repair UV radiation induced DNA damage. This
reduced ability for DNA repair results in a high incidence of mutations,
leading to premature development of nonmelanoma skin cancer as well as malig-
nant melanoma. Typical changes of photodamage also occur, and appear much
earlier in life than in unaffected individuals.
Chronic Actinic Dermatitis (290– 360 nm)

Chronic actinic dermatitis is seen in older, mostly male patients and presents as
erythematous macules and plaques on sun exposed areas. These areas can evolve
into lichenified, hypertrophic lesions known as actinic reticuloid.
28 Nelson
Table 2.2 Common Plants and Lichens Causing Photodermatitis
Common name Botanical name Family
Lime Citrus aurantifolia Rutaceae

Citron Citrus medica (C. acida) Rutaceae
Bitter orange Citrus aurantium Rutaceae
Lemon Citrus limon Rutaceae
Bergamot Citrus bergamia Rutaceae
Gas plant; burning bush Dictamnus albus (D. fraxinella) Rutaceae
Common rue Ruta graveolens Rutaceae
Persian lime (Tahitian) Citrus aurantifolio, “Persian” Rutaceae
Phebalium argenteum
Cow parsley, wild chervil Anthriscus sylvestris Umbelliferae
Celery Apium graveolens Umbelliferae
Giant hogweed Heracleum mantegazzianum Umbelliferae
Parsnip (garden variety) Pastinaca sative (P urens) Umbelliferae
Cow parsley Heracleum sphondylium Umbelliferae
Parsnip (wild parsnip) Heracleum giganteum Umbelliferae
Fennel Foeniculum vulgare Umbelliferae
Dill Anethum graveolens Umbelliferae
Peucedanum ostruthium Umbelliferae
Wild carrot, garden carrot Daucus carota Umbelliferae
Masterwort Peucedaum ostruthium Umbelliferae
Ammin majus Umbelliferae
Angelica Angelica archangelica Umbelliferae
Figs Ficus carcia Umbelliferae
Milfoil, yarrow Achillea millefolium Composiate
Stinking mayweed Anthemis cotula Composiate
Buttercup Ranunculus spp. Ranunculaceae
Mustard Brassica spp. Cruciferae
Bind weed Convolvulus arvensis Convolvulaceae
Agrimony Agrimonia eupatoria Rosaceae
Goose foot Chenopodium spp. Cheopodiaceae
Scurfy pea, bavchi Psoralea corylifolia Leguminosae
St. John’s wort Hypericum perforatum Hypericaceae
Hypericum crispum Hypericaceae
Schinopsis quebrachocolorado
Red quebracho Schinopsia lorentzii Anacardiaceae
Lichens Parmelia spp. Lichen (symbiotic
Hypogymnia spp. association between
Pseudovernia spp. fungi and algae)
Cladonia spp. commonly grouped
Platismatia spp. with fungi
Physcia spp.
Umbilicaria spp.
Cetrania spp.
Photoprotection 29
Polymorphous Light Eruption (290 –365 nm)

Polymorphous light eruption is a common eruption that affects 10 –14% of the
Caucasian population, with a female predominance. Pruritic papules, macules,
vesicles, plaques, and erythema are produced within 2 h to 5 days after sun
exposure on unprotected skin.
Hydroa Vacciniforme (290 –400 nm)

Hydroa vacciniforme usually starts in the first decade, and has equal sex distri-
bution (28). After exposure to UV-A, a tingling sensation on exposed areas is
followed by the development of papules and bullae, which crust and heal with
vacciniforme scars. The condition tends to improve with adolescence.
Persistent Light Reaction (290 – 400 nm)

Most patients who develop a photosensitive dermatitis clear when the offending
agent is withdrawn. The subset of persistent light reactors continue to react for
months or even indefinitely following UV radiation exposure. The effective
mechanism is unknown and may be varied. The persistent nature of the reaction
could possibly be due to unknown constant exposure to an offending agent, irre-
vocable binding of the allergen to dermal protein, or idiopathic.
Solar Urticaria (290 – 515 nm)

Solar urticaria is a rare disease in which urticaria develops rapidly after exposure
to UV radiation. The reaction begins with pruritus within minutes of exposure
followed by erythema and urticaria, and usually runs its course in ,24 h.
Porphyrias (400 –410 nm)

Porphyrias are a group of diseases that are caused by inherited or acquired
abnormalities in the heme metabolic pathway. Photosensitivity manifests as
vesicles, bullae and hypopigmentation, as well as fragility and scarring of the
skin. Manifestations are variable depending on the type of porphyria.
Miscellaneous Dermatoses
In addition to xeroderma pigmentosum, other genodermatoses may have photo-
sensitivity, including Bloom’s syndrome, Cockayne’s syndrome, and Rothman –
Thomson syndrome.
Many other dermatoses may be aggravated by UV radiation exposure,
including bullous pemphigoid, chronic benign familial pemphigus (Hailey –
Hailey disease), cutaneous lymphocytoma, Darier’s disease, dermatomyositis,
disseminated superficial actinic porokeratosis, erythema multiforme, herpes
simplex, Jessner’s lymphocytic infiltrate, lichen planus, pellagra, pemphigus,
and transient acantholytic dermatosis (Grover’s disease).
30 Nelson
CARCINOGENESIS RELATED TO PHOTOEXPOSURE

Mechanism of Carcinogenesis
Carcinogenesis due to photoexposure can occur following acute or chronic UV
radiation exposure. Carcinogenesis is broadly considered to have three main
stages: initiation, promotion, and progression.
Initiation of carcinogenesis likely occurs at a young age in most patients, as
80% of an individual’s total lifetime damage is acquired before age 18. Initiation
is thought to be caused by DNA absorbing UV radiation, subsequently inducing
changes between adjacent pyrimidine bases on one strand of DNA. Cyclopyrimi-
dine dimers, particularly thymine dimers or less commonly, (6-4)-photoproducts
may be generated (29). The action spectrum for these changes is maximal at
260 nm (UV-C), although it extends through the UV-B and into the UV-A wave-
lengths (30,31). These DNA changes are constantly being repaired by nucleotide
excision (32). Whenever repair is incomplete, characteristic mutations persist,
and if the damage to the genome is great, p53 and its associated proteins will
induce apoptosis of the irradiated keratinocyte. If the UV-induced mutations
occur in the region containing p53, genomic replication control may be lost.
Clonal expansion of these defective keratinocytes may produce an actinic kera-
tosis (33). If the second p53 allele is also mutated, a squamous cell carcinoma
may arise. Finally, if the mutations occur in patched or other members of the
hedgehog signaling pathway, basal cell carcinoma may occur (34,35).
Promotion of carcinogenesis is thought to be mediated by further UV radi-
ation absorption by chromophores. This may lead to the release of reactive
oxygen species, singlet oxygen, hydrogen peroxide, and superoxide ion. These
reactive species may cause oxidation of lipids and proteins that in turn may
affect DNA repair, induce matrix metalloproteinase, produce dyspigmentation,
and result in skin aging and carcinogenesis (36). When compared with UV-B,
UV-A generates more oxidative stress (37), and is 10 times more efficient than
UV-B at causing lipid peroxidation (38). UV-A is more cytotoxic than UV-B
(39); it damages DNA by causing strand breaks and oxidation of nucleic acids
(39,40). UV-A can inhibit DNA repair (41) and induce matrix metalloproteinase
(MMP) synthesis (42), which augments the biologic aggressiveness of skin
cancer. UV-B also has an important role in tumor promotion. Following UV-B
exposure, fewer T helper-1 (TH-1), the cell-mediated immunity effector cells,
are activated and relatively greater numbers of T helper-2 (TH-2), the humoral
immunity or antibody-producing cells, are generated. This shifts the balance to
relative suppression of cell-mediated immunity, resulting in decreased fighting
of tumors, viruses, and bacteria. In addition, UV-B radiation interferes with the
presentation of antigen by Langerhans cells to TH-1 cells, but not to TH-2
cells. Furthermore, there is evidence that suppressor T cells activated by UV-B
cause the death of Langerhans cells (43). Signal transduction pathways are acti-
vated and synthesis of cyclooxygenase-2 leads to production of prostaglandin
E-2 (PGE-2). This produces inflammation, cellular proliferation, and further
Photoprotection 31
immunosuppression. Ornithine decarboxylase, the enzyme which downregulates

the rate-limiting step in the polyamine biosynthetic pathway, is activated by
exposure to UV radiation. Because polyamines regulate cellular proliferation,
this allows unregulated cellular proliferation to occur. Thus, UV radiation has
a dual role in the pathogenesis of nonmelanoma skin cancer. It not only produces
mutations in skin cells, but it facilitates the growth of neoplastic cells by impair-
ing tumor immune surveillance and allowing uncontrolled proliferation of cells.
Finally, in the progression of the premalignant cells to malignancy,
additional genetic changes occur, as well as alterations in transforming growth
factor beta (TGF-b). UV radiation depletes resident Langerhans cells, which
are replaced by macrophages. These macrophages, in turn, preferentially activate
T suppressor cells and appear to be responsible for long-term immunosuppression
(44). UV-A also generates singlet oxygen, which triggers a cascade including
transcription factors AP-1, AP-2, and NFkB. The AP-1 binding couplet contains
c-fos and c-jun, which activates matrix metalloproteinases that are capable of
destroying the connective tissue of the skin (45).
Opportunities to Interrupt the Pathway

Now that more of the mechanisms of photocarcinogenesis and photoaging have
been elucidated, numerous opportunities to interrupt these pathways are being
explored.
Initiation
The initiation stage of carcinogenesis is most effectively interrupted by protecting
DNA from UV radiation induced damage. However, small amounts of UV radi-
ation exposure are unavoidable, and even high-SPF sunscreens allow some UV
radiation penetration. Additionally, our DNA repair systems cannot be perfect,
and some mutant cells inevitably occur. The model for enzymatic repair aug-
mentation has been the easily sunburning, rapidly aging, and cancer prone DNA
repair-defective disorder xeroderma pigmentosum. Recently, a topical liposome-
encapsulated DNA repair enzyme preparation, T4 endonuclease V, has been
reported to dramatically reduce cutaneous malignancy in XP, apparently without
adverse effect (46), giving hope for augmenting the repair process by applying a
topical agent.
Promotion
Antioxidant therapy has been studied as a possible mechanism to modulate tumor
promotion. The skin relies on naturally occurring antioxidants to protect it from
oxidative stress generated by sunlight and pollution (47); these antioxidants are
both enzymatic and nonenzymatic and react in an interwoven complex
harmony. Normal molecular weight nonenzymatic antioxidants include
L -ascorbic acid in the fluid phase, glutathione in the cellular compartment,
vitamin E in membranes, and ubiquinol in mitochondria (48). Enzymatic
32 Nelson
antioxidants function predominately in cells. Glutathione peroxidase and gluta-

thione reductase reduce hydrogen peroxide and are important antioxidants in
peroxisomes. Copper –zinc superoxide dismutase and manganese superoxide
dismutase protect cells from superoxide; additionally, extracellular superoxide
dismutase protects the extracellular space from superoxide anion (48). A combi-
nation of antioxidants is much more effective than the sum of separate com-
pounds. This synergism is the result of the intricate connections between the
antioxidants themselves. If only one of the components is supported, another
will soon become the limiting factor. Too much of a single component could
even deplete some of the others, resulting in an overall negative effect. This is
the case, for example, for high levels of a-tocopherol, which can deplete gluta-
thione and ascorbate, or a large superoxide dismutase increase, which can
result in elevated levels of hydrogen peroxide. Providing several different key
antioxidants could enhance the complete mechanism (49). Another example is
ascorbate, which at high concentrations can act as a pro-oxidant, however, this
activity is dependent on the availability of free metal ions, of which the cellular
concentration is frequently low (49). In a guinea pig model the iron chelator,
2-furildioxime, in combination with a traditional sunscreen showed a significant
increase in SPF, from SPF 4 to SPF 30 when used in a 5% concentration (50). It is
also known that a-tocopherol can cause problems due to photoinstability. Its
absorption spectrum extends well into the UV range (295 nm) and when skin
with a high level of a-tocopherol is irradiated, large numbers of tocopheroxyl
radicals are formed that induce lipid peroxidation themselves and deplete other
antioxidants, especially glutathione and vitamin C (49). Protective effects
against sunburn have been reported for combinations of systemic ascorbic acid
(vitamin C) and D -a-tocopherol (vitamin E) (51); topical or oral administration
of an extract of Polypodium leucotomos, a fern which grows exclusively in the
jungles of Honduras, not only prevented sunburn, but also prevented depletion
of Langerhans cells (52). Topical green tea polyphenols are effective in prevent-
ing sunburn, Langerhans cell depletion and DNA damage (53). Isoflavone genis-
tein (soy) has been shown to inhibit UV-B-induced erythema and inhibited
chemical carcinogen-induced reactive oxygen species, oxidative DNA damage,
proto-oncogene expression, as well as the initiation and promotion of skin
carcinogenesis (54,55).
Another strategy for blocking the promotion stage of carcinogenesis is
blocking specific enzymes. Cyclooxygenase-2 is known to increase the pro-
duction of PGE-2, which leads to cellular proliferation and inflammation (56).
Cyclooxygenase can be blocked by nonsteroidal anti-inflammatory drugs
(NSAIDs). Diclofenac, one such agent, is available as a topical prescription,
approved by the US Food and Drug Administration (FDA) for the treatment of
actinic keratoses. As previously noted, ornithine decarboxylase downregulates
the rate limiting step in the polyamine biosynthetic pathway; polyamines func-
tion to regulate cellular proliferation. Thus, when UV radiation activates
ornithine decarboxylase the result is increased cellular proliferation (57).
Photoprotection 33
Ornithine decarboxylase can be blocked by various agents including eflornithine,

which is already an FDA approved topical for stopping growth of unwanted hair.
This agent also shows promise for treatment of actinic keratoses. Further UV
exposure during the promotion stage causes acceleration of all these processes,
and thus it is important to block UV radiation during this stage.
Progression
Finally, in the progression stage of carcinogenesis, UV radiation exposure causes
additional genetic changes, alternations in TGF-b, and further immunosuppres-
sion. Langerhans cell depletion has been shown to be blocked by several anti-
oxidants, as previously noted. The cascade that is set off by singlet oxygen and
results in increased matrix metalloproteinases can be partly blocked by retinoic
acid (58) and antioxidants (59). Blocking UV radiation exposure during the
progression stage is also critical.
IMMUNOPATHOLOGY OF SKIN CANCER—AN

APPARENT PARADOX
Most UV-induced skin cancers are highly immunogenic and stimulate a vigorous
inflammatory response. In spite of this, they are extremely successful at evading
host tumor immunosurveillance mechanisms. In experimental animal models,
skin cancers induced by UV-B grow rapidly and eventually kill the host. When
these same tumors are implanted into genetically identical mice that have not
been exposed to UV radiation, they are promptly rejected and the animals
survive. When the tumors are implanted in mice that have been exposed to sub-
carcinogenic doses of UV-B, this immunologic destruction does not occur (44).
Such findings are thought to be caused by a shift in the immunologic balance to
suppression of cell-mediated immunity following UV-A exposure, as fewer TH-1
cells are activated and relatively greater numbers of TH-2 cells are generated. Thus,
the immunologic balance is shifted to the relative suppression of the cell
mediated immunity. In addition, antigen presenting cells are destroyed. UV-B
radiation also stimulates the production of many different cytokines including
IL1-a, IL1-b, IL-6, IL-8, IL-10, IL-12, IL-15, and TNF-a. UV-B also causes
the induction of NFkB and it is through the activation of this signal transduction
molecule that production of IL-1, IL-6, and TNF-a occurs. IL-10 and TNF-a
have been implicated in UV-B-induced immunosuppression. UV-B also causes
the release of the neuropeptides substance p and calcitonin gene related
peptide (CGRP). It additionally increases the production of pro-opiomelanocortin
(PMC) peptides including alpha-MSH (a-MSH). a-MSH and CGRP have both
been implicated in UV-B-induced immunosuppression (60).
The minimal dose of UV radiation to cause suppression of cutaneous cell-
mediated immunity is much lower than MED. A single exposure of 0.25 and 0.5
MED suppressed contact hypersensitivity response (CHS) by 50% and 80%,
respectively (61).
34 Nelson
STRATEGIES TO BLOCK UV LIGHT

We know that blocking UV radiation is important to prevent or delay all three
phases of carcinogenesis: initiation, promotion, and progression. In reality,
there are three main lines of defense to block UV light.
Sun Exposure Avoidance

The first line of defense is to avoid sun exposure whenever possible. The
“sunwise precautions” are widely publicized and include limiting exposure
from 10:00 a.m. to 4:00 p.m., wearing sunglasses that block 99 – 100% of the
UV light, wearing a hat with a broad brim, seeking shade, and avoidance of sun-
lamps and tanning salons. The UV index has been developed to help consumers
judge the relative risk of exposure on any given day. It is measured on a scale of
1 –10, and is calculated by the National Weather Service using a computer algor-
ithm, which starts with a UV dose rate at the next “solar noon” and incorporates
such variables as amount of ozone, clouds, latitude, elevation, and time of the
year. This index is widely publicized on radio, television, and in the newspapers,
and can also be accessed at: www.epa.gov/sunwise.
Sun Protective Clothing

Our second line of defense is sun protective clothing. More protection is afforded
by tighter weaves, repeated laundering, darker colors, and artificial as opposed to
natural fibers. Less protection is provided by stretched wet fabrics that are close
to the skin. The tightness of the weave can be related with the “hole” effect. In
other words, the larger the spaces between the fibers, the more UV radiation
can penetrate the fabric. The thicker and closer the fibers, the less light can pene-
trate. Frequent laundering increases the protection of fabric by shrinking the
garment and “plumping up” the fibers. Color is also important; darker shades
absorb more UV, and thus black and dark-blue colors are more protective than
oranges and reds, which are more protective than pink and light blue. White is
the least protective color. The type of fiber is important; organic molecules in
synthetic fibers tend to absorb more UV radiation than do cellulosic fibers.
Wet fabrics transmit more UV radiation as a result of their refractive index, as
well as the reduced scattering effects of their water-filled interstices.
Photoprotection of fabrics is measured by UV protection factor (UPF) and
determined by the following formula (62):
S400
280 El Bl Dl
UPF ¼
S400
280 El Bl Tl Dl
where El is the solar spectral irradiance, Bl is the CIE relative erythemal effec-
tiveness values, and Tl is the spectral transmission.
Solar spectral irradiance values record the intensity of UV radiation at each
spectral wavelength that reaches the earth’s surface. These were measured in
Photoprotection 35
Albuquerque, New Mexico, on a clear day at noon in July. The relative erythemal
effectiveness values compare the effectiveness of each UV wavelength in produ-
cing sunburn; these were developed by the International Commission on Illumi-
nation (CIE) in 1987. It is important to note that UV-B is 1000 times more
erythemagenic than UV-A; therefore the UPF calculation is heavily influenced
by the UV-B portion of the spectrum.
Various methods to increase fabric UPF values have been demonstrated. In
one study of laundering and dyeing techniques, plain cotton T-shirt fabrics with a
low UPF were laundered five times in plain water only, resulting in an increase in
UPF from about 5 to approximately 7. Mercerized cloth (cotton treated with
sodium hydroxide) has a smaller initial fiber diameter and swells less in laundering.
Consequently, it had a lower baseline UPF and less of an increase when washed
in plain water. Laundering with plain detergent produced a similar increase in
UPF. Multiple washings with detergent plus a UV absorber induced notable
increases in the plain cotton T-shirt cloth (from 5 to over 20 UPF), whereas
the mercerized cloth increased from 3 to about 12 UPF. Dyeing was also
studied and blue dye caused a much greater increase in UPF than yellow.
Again, the increase in mercerized was more modest than in untreated cotton
fabric (63).
Additives can be utilized to increase the protection of fabrics. A patented
fabric has the sunscreen incorporated into the polymer of which it is made.
Several chemicals have also been patented and are available as laundry deter-
gents and rinses to add sun protection to fabrics. Furthermore, optical bright-
eners have been available for many years in most detergents to counteract the
yellowing caused by repeated launderings, but have recently been discovered
to increase the photoprotection of fabrics. Modern optical brighteners are
highly conjugated derivatives of stilbene or benzimidazole; they absorb UV
radiation and fluoresce blue. Different specific chemicals are best suited for
cotton, polyester, and nylon. The amount of UV radiation they absorb to
convert to blue light is significant as demonstrated in a study which showed
that repeated washings of both 100% cotton undershirts and knit polo shirts
with commercial products containing optical brighteners gave a significant
increase in their UPF (64).
Several studies have attempted to address the question of whether UPF
and SPF values correlate. When held directly on the skin, in vivo SPF tests of
fabric were lower than labeled UPF values (65). However, if the fabric is
held 1 mm away from the skin, SPF values correlate closely with those of
UPF (73). Simulated “in vivo” studies of T-shirts on a mannequin upon which
was placed a UV-sensitive film showed a variation of a factor of 2 or more
depending on location. Areas where the fabric was stretched and closer to the
skin such as the upper back and shoulders showed less UPF and areas where
the fabric was lax and further from the skin such as the lower back had a
higher UPF. In all cases, the UPF measured in this study was higher than the
in vitro published UPF (66).
36 Nelson
Sunscreens
Sunscreens are a very important part of photoprotection, and despite great
advances in sunscreen technology, are still an imperfect science. In reality, sun-
screens represent our third line of defense against UV radiation. In 1938, the
Federal Food, Drug, and Cosmetic Act was passed, establishing the Federal
FDA and empowering it with regulatory authority. Among these were the over-
sight of drugs, defined as anything that prevents or modifies a disease. In 1940,
the FDA ruled that sunburn was a disease and therefore sunburn preventives
would be regulated as over the counter drugs. For many years, companies were
not allowed to make claims of preventing sunburn, and only claims such as
“promotes an even tan” were permitted. By the 1970s, dermatologists were
beginning to realize the deleterious effects of UV radiation exposure and were
recommending sun protection. In 1978, the FDA published an advanced notice
of public rule making (ANPR) to regulate the fledgling sunscreen industry. In
1984, the SPF system was adopted, which measured a sunscreen’s ability to
block UV-B. This entails in vivo testing in which 2 mL/cm2 of sunscreen are
applied on an area of a subject’s skin and the relative MED increase is measured.
SPF is defined as the ratio between MED of skin with sunscreen vs. MED without
the sunscreen. In 1993, the FDA published a tentative final sunscreen monograph
(TFM), which included all of the agents approved as sunscreening chemicals,
along with their permitted minimum and maximum concentrations. The TFM
has had multiple drafts and revisions, and the deadline for its implementation
has been repeatedly extended. Previously, the target date of finalization had been
December 31, 2002, and of this writing the new target date is January 1, 2005.
As noted, the operational method for determining the UV-B protection is
well established and reproducible. However, with recent studies detailing the
integral role of UV-A exposure in carcinogenesis as well as photoaging, there
has been a great effort to establish a reproducible testing method to quantify
UV-A protection. The difficulty lies in the uncertainty of the action spectra for
tissue damage by UV-A, both for photodamage and carcinogenesis. No general
agreement on a useful end point for damage has been reached. Erythema,
which is usually visible on the skin, is weighted toward UV-B exposure. Further-
more, whatever end point is chosen, no single test has been shown to consistently
reproduce that biomarker. Among the proposed testing methods for UV-A are
assessment of IPD (68), PPD at 2 – 24 h (69), UV-A-induced erythema (70),
erythema induced after topical psoralen application and UV-A exposure (71),
UV-A protection factor (APF ) in which the smallest UV-A dose to produce
minimal erythema or tanning response is compared with and without sunscreen
(70), and in vitro spectroscopic methods (72) from which is derived the “critical
wavelength,” the wavelength below which 90% of the UV radiation is absorbed.
The American Academy of Dermatology recommends a critical wavelength
of 370 nm for sunscreens labeled “broad spectrum” (73). The inability to agree
on a single reproducible UV-A testing protocol has seriously delayed
Photoprotection 37
the implementation of the TFM, and remains a significant challenge for the
future.
SUNSCREENING AGENTS
Sunscreening agents can be divided into organics, which are more soluble and
absorb UV radiation, and inorganics, which are less soluble and reflect and
scatter the UV radiation.
Organic Sunscreening Agents

Fourteen organic sunscreening agents are listed on the most current version of the
TFM. They may be divided into two groups. The first, more efficient at absorbing
UV-B, include para-amino benzoic acid (PABA) and its esters, salicylates, and
cinnamates. Those that absorb better in the UV-A spectrum are benzophenones,
anthranilates, and dibenzoyl methanes. Other classes, which are not listed on the
TFM, are available outside of the USA. These aromatic compounds absorb
a specific portion of the UV radiation spectrum, which is then generally
re-emitted at a less energetic longer wavelength, often as heat or light, or may
be used in a photochemical reaction such as cis –trans or keto –enol photoche-
mical isomerization (74). The organic sunscreening agents are almost always
used in combination because no single agent used at currently allowed levels
can provide an adequate SPF. In addition, individual organic sunscreening
agents have relatively narrow spectra that can be broadened by the synergistic
interactions afforded by combinations. Most recently, the combination of
organic and inorganic agents has become increasingly popular in sunscreens.
Inorganic Sunscreening Agents

Materials such as titanium dioxide, zinc oxide, iron oxide, barium sulfate, and
magnesium oxide remain as particles when introduced into a vehicle because
their solubility is very low in acceptable cosmetic preparations. They differ
in their capacity to scatter and/or absorb specific wavelengths of light (75). Of
these, the two that are listed on the most current version of the TFM and are most
commonly used are titanium dioxide and zinc oxide. These agents are often used
together with other UV filters to enhance protection in the longer UV and the
adjoining visible light range (76). The main problem with such pigmentary
powders is that because they are opaque, they appear white on the skin. Iron
oxide is sometimes added to improve cosmetic acceptability, and this also has
the effect of improving protection in the UV-A and visible light ranges (76).
More recently, both titanium dioxide and zinc oxide have become available
as micronized powders. The smaller the particle size, the better the cosmetic
acceptability. Micronized titanium dioxide (particle size between 10 and 15 nm
as compared with 200 –500 nm in nonmicronized forms), creates a shift of photo-
protection from the longer UV-A and visible light range toward the UV-B.
38 Nelson
Micronized zinc oxide (particle size 60 –80 nm as compared with 200– 300 nm
for the nonmicronized form) protects mainly in the UV-A spectrum, but does
not provide the UV-B coverage afforded by micronized titanium dioxide (77).
As particle size is reduced, these agents become less reflective and more
absorbing. Their range of protection tends to shift down toward the UV-B. Micro-
nized zinc oxide is more protective than titanium dioxide in the area from 340 to
380 nm. Neither agent is very efficient at absorbing UV radiation above 380 nm
(77). Furthermore, titanium dioxide scatters visible light more efficiently, and
therefore appears whiter on the skin than does microfine zinc oxide (77). Both
agents’ ability to scatter light helps them to augment the efficiency of organic
sunscreens by effectively increasing the optical path length through the thin
layer of sunscreen that is applied to the skin.
Zinc oxide or titanium dioxide used in sunscreen preparations is often
coated with other materials such as silicones, fatty acids, or oxides of aluminum,
silicone, or zirconium to aid in dispersion. These coatings were developed by the
paint industry to reduce particle conglomeration, which improves the distribution
of particles when applied as a thin film on a surface. The proper coating provides
better compatibility between the particle and the dispersion medium which ulti-
mately improves aesthetics and decreases processing costs. Furthermore, coating
may reduce any potential photoactivity of the metal oxides (78).
PROPER USE OF SUNSCREENS

Even when used properly, high SPF sunscreens still transmit some UV radiation.
SPF values assume proper use of sunscreens. As previously noted, SPF is deter-
mined by a very specific operational method involving application of 2 mL/cm2
of sunscreen to the skin. Recent studies have shown that most people use less than
half of that amount, often only a quarter as much (79,80). At a thickness of
0.5 mL/cm2, an SPF of 50 yields a practical SPF of approximately 2 (81). In
fact, at 0.5 mL/cm2, it is impossible to achieve more than an SPF of 3, regardless
of the stated SPF of the sunscreen (81).
SUGGESTIONS FOR THE FUTURE

First and foremost, we need better, more efficient sunscreens. Stable molecules
are being developed that disperse energy harmlessly without degrading them-
selves. Better application systems are being developed along with film forming
agents to create a uniform layer of sunscreen on the skin in spite of the normal
“peaks and valleys” inherent on human epidermis.
It is also vital to educate the public on the proper use of sunscreens. Most
people do not apply enough sunscreen to achieve the stated SPF, and thus higher-
SPF sunscreens not used properly may do nothing more than give a false sense of
security while allowing enough UV radiation to penetrate to cause damage and
immunosuppression. People need to be educated on the proper use of sunscreens,
Photoprotection 39
how much to use, and how often to reapply it. The advice to reapply sunscreen
every 2 –3 h is often given, yet rarely followed. A recent regimen has been
described in which sunscreen is applied liberally to exposed areas 15 –30 min
before going out in the sun, followed by a reapplication of the sunscreen to
these same areas 15– 30 min after sun exposure begins. Further reapplications
are made as necessary after vigorous activity that could remove the sunscreens
such as swimming, toweling, sweating, rubbing, etc. This regimen has yielded
superior results (82), underscoring the importance of proper sunscreen
application.
Finally, despite all of our precautions, it is inevitable that some UV radi-
ation will penetrate and cause DNA damage and immunosuppression. If we
cannot avoid or block it out, other options include development of enzyme
repair systems, antioxidants used in the correct ratios and balance either topically
or systemically or both, and blocking of enzyme systems responsible for
increased cellular proliferation, inflammation, and ultimately, carcinogenesis.
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3
A Perspective on the Need
for Topical Sunscreens
B. L. Diffey
Newcastle General Hospital, Newcastle, UK
Observable Cutaneous Effects of Sun Exposure 45

Production of Vitamin D 46
Tanning 46
Sunburn 46
Skin Cancer 46
Photoaging 47
Sunscreen Use and the Sun Protection Factor 47
How Large Should the SPF Be to Prevent Sunburn? 48
How High Should the SPF Be to Give a Worthwhile Reduction in
Lifetime Risk of Skin Cancer? 49
Is Daily Use of Sunscreens of Benefit? 50
A Strategy for Sunscreen Use 51
References 52
OBSERVABLE CUTANEOUS EFFECTS OF SUN EXPOSURE

Ultraviolet (UV) radiation exhibits a number of effects on skin, both beneficial
and undesirable. The purpose of sun protection should be to minimize the
45
46 Diffey
likelihood of adverse effects without undue detriment to the beneficial effects.

The biological effects of UV on skin are summarized below.
Production of Vitamin D
The only well-established beneficial effect of solar UV on the skin is the pro-
duction of vitamin D3 . The skin absorbs UV-B radiation in sunlight to convert
sterol precursors in the skin, such as 7-dehydrocholesterol, to vitamin D3 .
Vitamin D3 is further transformed by the liver and kidneys to biologically
active metabolites such as 25-hydroxyvitamin D; these metabolites then act on
the intestinal mucosa to facilitate calcium absorption, and on bone to facilitate
calcium exchange. There is some suggestion that an enzyme involved in
vitamin D metabolism may protect against colon, breast, and prostate cancer (1).
Tanning
A consequence of exposure to solar UV, which still seems to be socially desir-
able, is the delayed pigmentation of the skin known as tanning, or melanin pig-
mentation. Melanin pigmentation of skin is of two types: (i) constitutive—the
color of the skin seen in different races and determined by genetic factors only
and (ii) facultative—the reversible increase in tanning in response to sun
exposure.
While vitamin D production and tanning are, or may be perceived to be,
a desirable consequence of sun exposure, the remaining three—sunburn, skin
cancer, and photoaging—are universally recognized to be adverse effects of
sun exposure.
Sunburn
Erythema, or redness of the skin due to dilatation of superficial dermal blood
vessels, is one of the commonest and most obvious effects of UV exposure
(“sunburn”). Following exposure to solar UV radiation, there is usually a latent
period of 2– 4 h before erythema develops. Erythema reaches maximum intensity
between 8 and 24 h after exposure, but may take several days to resolve comple-
tely. If a high enough exposure has occurred, the skin will also become painful
and edematous, and blistering may result.
Skin Cancer
The three common forms of skin cancer, listed in order of seriousness, are
basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and malignant
melanoma (MM). Around 90% of skin cancer cases are of the nonmelanoma
variety (BCC and SCC), with BCCs being approximately four times as
common as SCCs. Exposure to solar UV radiation is considered to be a major
etiological factor for all three forms of cancer (2).
Need for Topical Sunscreens 47
Photoaging
The clinical signs of a photoaged skin include dryness, deep wrinkles, accentu-
ated skin furrows, sagging, loss of elasticity, mottled pigmentation, and telan-
giectasia (3,4). Chronic solar exposure is the major environmental insult that
contributes to photoaging and is quite distinct from chronological, or intrinsic,
aging.
SUNSCREEN USE AND THE SUN PROTECTION FACTOR

Topical sunscreens act by absorbing or scattering UV radiation and are widely
available for general public use as a consumer product.
By far the most common reason for using sunscreens, cited by 80% of
people in one survey (5), was to protect against sunburn. Other reasons why
people use sunscreens are because they (6):
. Know the dangers of sun exposure
. Perceive themselves at high risk of skin cancer
. Know people who have had skin cancer
. Want Protection against aging and wrinkling
. Wish to extend time in the sun
. Have previously had skin cancer
Equally important, the reasons why people choose not to use sunscreens are
because (6):
. They have skin that does not burn easily
. They already have a “protective” tan
. They are not outdoors enough to warrant use
. Sunscreens are a nuisance and greasy to apply
. Sunscreens are expensive
. Sunscreens retard the desired tan
. They use other sun protective measures
. They forget
The protection provided by a sunscreen is expressed by its sun protection
factor (SPF). It is popularly interpreted as how much longer skin covered with
sunscreen takes to burn compared with unprotected skin (5). A more appropriate
definition of the SPF is that it is the ratio of the least amount of UV energy
required to produce a minimal erythema on sunscreen protected skin to the
amount of energy required to produce the same erythema on unprotected skin
(7). At the start of the 1990s most commercially available sunscreen products
had SPFs less than 10 but by 2000 most manufacturers produced products with
factors of 15– 30, and it is not uncommon to find products claiming a factor of
50 or higher.
48 Diffey
HOW LARGE SHOULD THE SPF BE TO PREVENT SUNBURN?

Sunscreens are used principally to prevent sunburn. The magnitude of sunscreen SPF
required to achieve this goal can be determined given knowledge of the local UV clima-
tology, the user’s behavior outdoors, and their personal susceptibility to sunburn.
Maximum daily ambient UV levels, expressed in units of standard
erythema dose (SED), under clear summer skies are about 70 in the tropics, 60
at midlatitudes approximating to those of southern Europe, and 45 for northern
European latitudes (8). The SED is a measure of erythemal UV radiation and
is equivalent to an erythemal effective radiant exposure of 100 J/m2 (9).
These maximum ambient exposures will not be received by people simply
because it would be unrealistic to lie in the unshaded sun all day without moving.
An extreme sunbather might spend half the time supine and half the time prone,
resulting in a maximum exposure on much of the body surface of 50% of
ambient. For upright subjects engaging in a variety of outdoor pursuits such as
gardening, walking, or tennis, the exposure relative to ambient on commonly
exposed sites, for example, chest, shoulder, face, forearms, and lower legs,
ranges from 20% to 60% (10). So, someone who is on vacation in southern
Europe, for example, would receive a daily exposure of no more than 20 SED
over much of the body surface. Since an exposure of 2 –4 SED is necessary
for a minimal erythema on the previously unexposed buttock skin in the most
common northern European skin types (II/III) (11), a photoprotective device
(sunscreen or clothing) need only possess an SPF of 10 or more to give a
sunburn-free vacation. And for tropical sun exposure, a protection factor of 15
or higher should be more than adequate for all-day exposure.
If then, sunscreens of SPF 15 are sufficient to protect against sunburn even
for all-day exposure in tropical sunshine, why are people who usually or always
use a high-factor (15) sunscreen more likely to report sunburn than those who
rarely or never use sunscreen (12,13)?
That the protection achieved is often less than that expected is explained by
a number of reasons (14):
. People normally apply much less sunscreen than the amount used in the
testing process to determine a product’s SPF.
. Sunscreen is normally spread haphazardly and not uniformly.
. So-called “physical” sunscreens containing mineral pigments like zinc
oxide can leave a white film on the skin and, as a consequence, people
may be encouraged to apply less.
. Sunscreens can be removed by water immersion, sand abrasion, and
toweling.
. Sunscreen may not be reapplied appropriately.
All of these factors mean that, as a rule of thumb, the protection achieved is
typically about one-third of the rated SPF (14). So, in order to achieve 15-fold
protection, an SPF50 rated sunscreen needs to be applied.
HOW HIGH SHOULD THE SPF BE TO GIVE A WORTHWHILE

REDUCTION IN LIFETIME RISK OF SKIN CANCER?
For people living in countries with large seasonal changes in ambient UV radi-
ation (both UV-B and UV-A), such as those in northern Europe, the northern
part of the USA, and Canada, exposure to sunlight is either adventitious
(generally summer weekdays and the six winter months) or elective (generally
summer weekends and summer vacation). The contribution to annual UV
exposure from these two types of exposure is typically 30% and 70%, respec-
tively (15).
Estimates of the risk of inducing skin cancer from exposure to UV radiation
require knowledge of dose – response relationships and the relative effective-
ness of different wavelengths (known as an action spectrum) in sunlight in
causing skin cancer. Data on dose – response relationships and action spectra
are available to some extent to allow quantitative estimates of the risk of
nonmelanoma skin cancer (NMSC) incidence, but presently not for malignant
melanoma. The best estimate for the action spectrum for NMSC resembles that
for erythema (16).
Application of multivariate analysis to population-based epidemiology of
NMSC has shown that, for a group of subjects with a given genetic susceptibility,
age and environmental UV exposure are the two most important factors in deter-
mining the relative risk. This has led to a simple power law relationship, in which
the lifetime risk can be approximated to (17):
Risk (annual UV dose)b
The symbol b is a numerical constant associated with the specific type of NMSC
and is normally derived from surveys of skin cancer incidence and ultraviolet
climatology.
If sunscreen use is limited to elective sun exposure, and it is assumed that
the protection achieved is one-third of the SPF rating, the lifetime risk of NMSC
relative to a non-sunscreen user is simply
f0:3 þ 0:7=½SPF=3gb
where SPF is the rated SPF. For the purpose of examining the predicted benefit of
sunscreen use on relative lifetime risk of NMSC, an exemplary value of 2 will be
used for b (18). If sunscreens rated at SPF5, SPF15, or SPF50 are used, the pre-
vious expression indicates that the corresponding reduction in lifetime risk of
NMSC, compared with no sunscreen use during elective exposure, is one-half,
one-fifth, and one-tenth, respectively. More sophisticated models of NMSC
risk are available than the simple approach used here, but in essence use of
these is unlikely to change dramatically these general estimates of the effect
that sunscreens used during intentional sun exposure can have in modifying
the lifetime risk of skin cancer.
50 Diffey
IS DAILY USE OF SUNSCREENS OF BENEFIT?

“Consumers want more and more UV protection in their daily skin care products
to prevent everything from wrinkles to cancer” (19). This quotation from a con-
sumer publication is now received wisdom by most beauty journalists and has
stimulated many cosmetic companies to incorporate UV absorbing chemicals
into facial moisturisers designed for daily use. Provided the daily use of
topical products containing UV filters does no harm and considering the potential
health benefits, manufacturers and others may argue that these products are in a
small but measurable way providing a positive impact.
There is limited evidence indicating that daily application of a high-factor
(SPF . 15) sunscreen may prevent SCC (20) and contribute to the prevention of
solar elastosis (21). However, these two studies were carried out in Queensland
and Texas, respectively, both areas of high insolation, and the conclusions may
not necessarily be transferable to people living in countries of low insolation,
such as those in northern Europe and the northern part of America. In a review
of sunscreen safety and efficacy (22), it was concluded that the current list of com-
monly used organic and inorganic active ingredients have favorable toxicological
profiles and do not pose a concern for human health. However, it is known that,
although uncommon, UV absorbers in sunscreens are now the commonest cause
of positive photopatch tests (23). Concern has been raised about systemic absorp-
tion of sunscreens after topical application (24), cellular toxicity (25,26), impact on
vitamin D synthesis (27), and estrogenic activity (28), although the significance of
these reports to human health consequences of sunscreen use remains circumspect.
A number of case – control studies on cutaneous melanoma showed signifi-
cantly higher risks among sunscreen users (6). Although these studies could be
taken to suggest an increase in the risk of melanoma due to sunscreen use,
they are difficult to interpret because of problems of positive confounding
(e.g., people who are at most risk of burning and most likely to develop mela-
noma are also most likely to use sunscreens) and negative confounding (e.g.,
sunscreen users may also use other methods of sun protection such as clothing).
While these concerns are insufficient to stop the use of sunscreens as part of
a sun protection strategy, they do suggest that perhaps there is an optimal use of
topically applied UV filters beyond which the benefit of further use may be both
unnecessary and unjustified, especially in the context of people living in countries
not known for their sunny climate.
In an analysis combining the relative exposures during different periods of
the year with topical sun protection used during one or more of these periods, it
was possible to estimate an “equivalent age” (29). This can be taken as the age by
which someone using no sunscreen during adulthood (from age 18 until age 70)
would receive the same cumulative sun exposure as another person engaging in a
specific sunscreen-use strategy throughout their adult life. Implicit in this calcu-
lation is that other sun protection measures (including none) are the same in both
the sunscreen users and the non-sunscreen users and that the protection afforded
by the sunscreen is assumed to be one-third of the SPF rating (see earlier). The
calculated equivalent ages are summarized in Table 3.1
The conclusion from these calculations is that, in terms of reducing the
cumulative UV exposure (assumed to be a surrogate for photoaging), a significant
benefit can be achieved by using a sunscreen during summer holidays and
outdoor leisure activities at summer weekends. For example, use of SPF15 sun-
screen products during holidays and summer weekends can reduce the lifetime UV
dose by an equivalent of almost 30 years of unprotected exposure. However,
whether the product is SPF15 or SPF30 makes little difference to chronic
exposure (although it would be expected to be important in reducing the risk
of sunburn). Supplementing this by daily use of a product incorporating UV
filters during summer weekdays may reduce the equivalent age by an additional
8 years or so. Virtually no benefit is gained from using UV protective products
from October to March in latitudes beyond 508.
A STRATEGY FOR SUNSCREEN USE

In summary, the following strategy is proposed for a rational approach to the
application of topical sunscreen agents for people living in countries not
known for their sunny climate:
. No need for UV protection in autumn and winter (October through
March in the northern hemisphere).
. Daily skin care (incorporating UV filters of SPF8 – 15) in spring and
summer (April through September) when exposure is largely adventi-
tious or unintentional.
. Sunscreen application (SPF . 30) on sunny holidays and long periods
outdoors on summer weekends.
Adoption of this strategy should lead to the following outcomes:
. Prevention of sunburn.
. Giving about the same lifetime UV exposure as a 35-year-old who behaves
in a similar way with regard to sun exposure but who uses no sunscreen.
Table 3.1 Calculated Equivalent Ages
Rated SPF
Cumulative use 8 15 30
Summer holiday 60 58 56
þSummer weekend 47 41 37
þSummer weekday 41 33 28
þOctober – March 38 28 23
52 Diffey
. Reduction in the risk of NMSC by at least fivefold relative to a nonuser

of sunscreen.
. Delay in the signs of photoaging.
. Ensuring a moderate exposure to sunshine, especially in late summer
and early autumn, to maintain vitamin D status during the winter
months.
Finally, it goes without saying that for white-skinned people living in
tropical and subtropical regions (roughly in the latitude band 308N to 308S)
there are sound climatological and biological reasons for adopting year-round
sun protection behavior, which would include the use of sunscreens.
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Battistutta D, Frost C, Lang C, Russell A. Daily sunscreen application and beta car-
otene supplementation in prevention of basal-cell and squamous-cell carcinomas of
the skin: a randomised controlled trial. Lancet 1999; 354:723 – 729.
21. Boyd AS, Naylor M, Cameron GS, Pearse AD, Gaskell SA, Neldner KH. The effects
of chronic sunscreen use on the histologic changes of dermatoheliosis. J Am Acad
Dermatol 1995; 33:941– 946
chem Photobiol 1998; 68:243 – 256.
23. Ibbotson SH, Farr PM, Beck M, Diffey BL, Ferguson J, George GA, Green C, du P
Menagé H, Murphy GM, Norris PG, Rhodes LE, White IR. Photopatch testing:
methods and indications. Br J Dermatol 1997; 136:371 – 376.
24. Hayden CGJ, Roberts MS, Benson HAE. Systemic absorption of sunscreen after
topical application. Lancet 1997; 350:863– 864.
25. Dunford R, Salinaro A, Cai L, Serpone N, Horikoshi S, Hidaka H, Knowland J.
Chemical oxidation and DNA damage catalysed by inorganic sunscreen ingredients.
FEBS Lett 1997; 418:87 –90.
26. Butt ST, Christensen T. Toxicity and phototoxicity of chemical sun filters. Radiat Prot
Dosim 2000; 91:283 –286.
27. Nowson CA, Margerison C. Vitamin D intake and vitamin D status of Australians.
Med J Aust 2002; 177:149 – 152.
28. Schlumpf M, Cotton B, Conscience M, Haller V, Steinmann B, Lichtensteiger W.
In vitro and in vivo estrogenicity of UV screens. Environ Health Perspect 2001;
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29. Diffey BL. Is daily use of sunscreens of benefit in the UK? Br J Dermatol 2002;
146:659–662.
4
Safety Considerations for
Sunscreens in the USA
Richard J. Schwen
PAREXEL International, Inc., Waltham, Massachusetts, USA
Requirements for Safety Testing of Sunscreens 55

Parameters Affecting Sunscreen Safety 56
Safety Programs Required for Sunscreen Products 57
Safety Testing Models for Sunscreen Products 58
In Vitro Models 59
In Vivo Dermal Safety Testing in Animals 61
In Vivo Systemic Safety Testing in Animals 64
In Vivo Dermal and Systemic Safety Testing in Humans 65
Risk Assessment and Safety Testing of Sunscreens 67
Conclusion 67
References 68
REQUIREMENTS FOR SAFETY TESTING OF SUNSCREENS

In the USA, sunscreens are classified as drugs based on their ability to prevent
injury to the skin after exposure to ultraviolet radiation (UVR). Because of
their proven safety and ease of use by consumers, the Food and Drug Adminis-
tration (FDA) has allowed them to be marketed over the counter (OTC), provided
they comply with the OTC monograph specifying active ingredients,
55
56 Schwen
concentrations, use, and labeling (1). These criteria are based upon safety and
efficacy data submitted by industry during the sunscreen monograph develop-
ment process initiated back in 1972. The 1978 Tentative Final Monograph
listed 21 ingredients, which changed to the current list of 16 with the 1996
approval of the New Drug Application (NDA) for avobenzone (2).
Importantly, any new sunscreen active ingredient, or even an old sunscreen
used inconsistent with the OTC monograph, technically results in FDA classifi-
cation of that product as an unapproved new drug. Clinical testing thus requires
an Investigational New Drug (IND), and marketing requires approval of an NDA
containing sufficient data on quality, safety, and efficacy. Due to the high cost of
such R&D programs, companies usually enter the sunscreen market with products
compliant with the OTC monograph. Indeed, only one new sunscreen active ingre-
dient (avobenzone) has been approved using the NDA process since the inception of
the OTC monograph process in 1972 (2). Thus, the regulatory classification of
sunscreens as drugs in the USA, while protecting the public, also effectively
represents an economic barrier to development of new active ingredients.
While the OTC monograph allows sunscreen marketing without a sub-
mission, the Food, Drug and Cosmetic Act still requires the marketer to
provide assurance that its products are safe in humans prior to marketing.
Indeed, safety concerns have led to the withdrawal of several OTC sunscreen
formulations and active ingredients. Unexpected interactions among formulation
components, skin irritation in certain subsets of patients, and unexpected sensit-
ization responses have unfortunately led to safety “surprises” in the marketplace.
Thus, confirmation of the safety of otherwise OTC-compliant products is needed
even though no additional data need to be filed with FDA prior to marketing. This
burden on the company to assure safety prior to marketing also applies to
“purely” cosmetic compounds, which are even less regulated compared to the
OTC monographed drugs like sunscreens.
The present chapter is a review of the safety issues associated with sun-
screen development, and a summary of the safety testing models available
(in vitro, animal, and human). This chapter also provides perspective on the devel-
opment and evaluation of safety data in terms of the risk/benefit of sunscreens.
PARAMETERS AFFECTING SUNSCREEN SAFETY

Sunscreen safety in the marketplace is affected by the chemical structure, as well
as environmental, and use factors that may affect their toxicity. Environmental
and use factors include those that have the potential to produce reactive species
(e.g., light exposure leading to phototoxicity), and those that may affect dermal
and systemic exposure. Factors known to affect dermal and systemic exposure,
and therefore toxicity of a sunscreen include actual applied dose, treatment fre-
quency, hydration of the skin, sites of the body treated, total body surface area
treated, treatment of compromised skin (e.g., abrasions, sunburn), effect of sweat-
ing, exposure of the skin to water during bathing, and the potential for concomi-
tant treatment with other topical products. Variables also include demographic
Safety Considerations for Sunscreens in the USA 57
differences in skin characteristics such as race, age, and gender (3). The impact of
any one of these variables upon a product’s toxicity is potentially significant. In
practice, safety programs usually address the primary and most significant
variables, and in the process generate a range of safety data that captures or
“brackets” the impact of other less significant variables upon the risk assessment.
This approach usually allows the less significant variables to be addressed via
“paper” arguments regarding their potential impact upon safety.
The convenient grouping of approved sunscreens into organic and inorganic
categories reflects not only their chemistry, but also their general mechanism of
efficacy and potential for toxicity. Organic sunscreens are the most popular types
with many ingredients approved for use in the OTC monograph (1). The mechan-
ism of action of the organic sunscreens relates to the activation of double bond
electrons in the molecule by UV-B radiation, followed later by emission of the
energy as low-energy and less-damaging light and heat (4). This same proposed
mechanism of efficacy against UV-B radiation, however, is also a concern from
the toxicology standpoint, since this same activation could theoretically lead to
generation of reactive intermediates. In practice, however, the approved organic
active ingredients show a high level of safety even with prolonged use.
On the other hand, the approved inorganic sunscreens (titanium dioxide and
zinc oxide) are largely biologically inert. These minimally absorbed, microfine
inorganic particles accomplish their efficacy by remaining on the surface of the
skin and reflecting UV light, thus acting as an effective sunblock. The action
spectrum shows that these inorganic compounds are most effective in the
UV-A range, thus they find common use in combination with UV-B-absorbing
organic sunscreens to provide broad-spectrum protection.
SAFETY PROGRAMS REQUIRED FOR SUNSCREEN PRODUCTS

Safety programs for sunscreen products usually fall into three main categories,
based upon intended use of the data from the program: (a) safety programs for
the company’s internal R&D decision-making, (b) traditional safety programs
to confirm safety of OTC monograph-compliant products, and (c) full safety
programs for new sunscreen active ingredients (full NDA programs). The predic-
tiveness, extent, and cost for these three types of programs can vary significantly.
Programs designed for internal decision-making often include in vitro models
used as part of a screening program for selection of ingredients and formula-
tions (see following text). These models may not be accepted by FDA as validated
predictors of safety in humans, and often carry a higher risk of false positives
and false negatives. The company usually uses these faster and cheaper models
to collect data to be used for optimizing the formulation, and often later conducts
the longer-term, more expensive, confirmatory safety studies using validated
FDA-accepted models.
On the other hand, safety programs for OTC monograph-compliant
products usually employ more predictive, traditional in vivo safety models to
confirm lack of key dermal toxicities: skin irritation, eye irritation, and delayed
58 Schwen
contact hypersensitivity. Typically the ingredients’ safety is already well charac-

terized, and the studies are conducted to confirm there are no unexpected toxici-
ties for that particular formulation. Similar programs are conducted for primarily
cosmetic products containing approved sunscreens (e.g., hair care products,
lipstick, and makeup). The obligation to confirm safety is still with the manu-
facturer, and the goal is to provide assurance that there are no surprises in the
marketplace.
The third category is more extensive since FDA considers new sunscreen
actives to be new drugs. In practice, these programs include assessment of
safety in several categories including genotoxicity, drug transport and disposition
(absorption, distribution, metabolism, and excretion; ADME), dermal safety,
systemic safety, and special safety (reproduction, teratology, carcinogenesis).
Important variables that affect toxicity are also addressed, including the exposure
to light (phototoxicity, photoallergy, photocarcinogenesis), the effect of skin
variability (age, gender, race), and parameters affecting drug transport (e.g., treat-
ment of compromised skin, location of treatment site). Studies typically proceed
in the order of in vitro, in vivo (animal), and in vivo (human), often with studies
conducted concurrently in order to expedite the overall program. Separate studies
are usually conducted on the drug substance (active ingredient) and drug product
(complete formulation) in order to assess intrinsic toxicity of the active as well as
toxic behavior in a more realistic exposure matrix. Study design often includes
placebo and positive controls in order to confirm the study validity and to “bench-
mark” the results with marketed products to help put the results in perspective.
For the special toxicity studies in the areas of reproduction, teratology, and
carcinogenesis, only the active ingredient is tested, and positive controls are
typically not included. Broader assessment of safety may include assessment
of accidental misuse or abuse situations (oral toxicity, eye irritation). Usage
studies include testing in large numbers of subjects who are provided “final”
labelled product with the instructions for use, with subsequent measurement of
product consumption and consumer comments. These studies help predict
actual variability in exposure (and safety) in the future marketplace, since sub-
jects often do not follow instructions on use.
For new sunscreen ingredients, the amount of safety data required for mar-
keting authorization varies by country and regulatory authority (5). One of the
realities is that some countries classify sunscreens as cosmetics, and require
less safety data for marketing authorization compared to the USA. If marketed
earlier outside the USA, the safety data collected from these markets may
subsequently be submitted to FDA under Material Time and Extent provisions,
in order to support marketing authorization in the USA (5).
SAFETY TESTING MODELS FOR SUNSCREEN PRODUCTS

Protocols for safety testing can be found in a variety of resources (6 – 8). Critical
for design of a safety program are: (a) specific objectives for the program, (b) the
regulatory requirements for the studies in the program, (c) the relevant scientific
and medical information related to the issue at hand, and (d) the corporate ethics
and acceptable risk/benefit for that product in the marketplace. A description of
the key models used to evaluate the safety issues common to sunscreen products
follows. Included are comments on their endpoints and relevance in a safety
program. As noted, compliance with the OTC monograph eliminates the need
to file data with the FDA, and studies are conducted mainly for internal confir-
mation. On the other hand, development of a new sunscreen active ingredient
in the USA would lead to conduct of not only in vitro, but the in vivo animal
and human studies listed below as well.
In Vitro Models
Sunscreen drug development programs usually employ in vitro models for safety
assessment due to significant savings in terms of cost and time when compared to
standard in vivo safety models. Common models are shown in Table 4.1. While
in vitro results are least relevant to safety assessment in humans, they play a par-
ticularly important role in the safety screening process since poor performing
ingredients can be eliminated early, thus avoiding unnecessary exposure to
animals and humans.
Sunscreens not only need to protect the consumer from the genotoxic
effects of UVR, but themselves need to be devoid of genotoxic effects. While
approved OTC sunscreens do not need to be tested, new sunscreen candidates
usually undergo a battery of tests, each with its own advantages, disadvantages
and limitations. In vitro models used to assess potential for genetic damage
include the reverse mutation (Ames) test in bacteria, and the mouse lymphoma
test in mammalian cells. The ability of a chemical or formulation to induce
broader scale genetic damage in chromosomes is assessed in the mouse micro-
nucleus assay, which measures the more macroscopic histological changes in
chromosomes after in vivo treatment of mice. A positive response suggesting
mutagenic potential is cause for concern and usually triggers either more exten-
sive testing or rejection of the new sunscreen candidate.
In addition to these classical genotoxicity tests, other more investigative
models have also been developed to screen for genotoxic potential, as well as
photogenotoxic potential. These models include direct incubation with DNA,
bacteria, and yeast, either with or without radiation (9). While not definitive
measures of safety, these models streamline the screening process and are
usually followed up with testing in the more validated, in vivo-relevant safety
models. Indeed the lack of correlation of some in vitro results with effects in
humans points to the need to interpret results from in vitro models with
caution. This is due to the fact that in vitro models cannot emulate the in vivo
dynamics of drug exposure, absorption, metabolism, and elimination from the
treatment site, all of which have the potential to affect toxicity.
60 Schwen
Table 4.1 Common In Vitro Safety Models
In vitro safety model Endpoint Rationale for use
Genotoxicity
Ames mutagenesis Point mutation Gene mutation test (bacterial,
(bacteria) in vitro)
Mouse lymphoma Point mutation and Gene mutation test
chromosomal (mammalian, in vitro)
abberations
(mammalian)
Mouse micronucleus Chromosomal Gross genetic damage
(in vivo) damage (in vivo)
Photogenotoxicity Mutagenicity (Ames) Measures light activation to
after exposure of a mutagenic species
product to light
Cytotoxicity Cell death in vitro via Detects general cell toxicity
neutral red uptake
Photocytotoxicity Cell damage after Detects potential for
exposure of cells to light-activation to
product and light acutely toxic species
In vitro ocular tolerance Cell toxicity as a In vitro models for potential
(cytosensor function of dose for eye irritation
microphysiometer, tissue and time
equivalent assay (TEA),
ex vivo rabbit eye or
bovine corneal models)
In vitro skin penetration Transport of chemical Drug transport will allow
through skin samples assessment of systemic
exposure
Investigative models have also been developed for prediction of a

compound’s potential for producing skin irritation, as assessed by direct cell
damage in vitro. Accordingly, in vitro cytotoxicity assessment is a relatively
quick means of obtaining data suggestive of irritation potential. The model
includes treatment of mammalian cells (fibroblasts or keratinocytes) in vitro
with the chemical, and measuring cellular uptake of a dye, which is indicative of
cell damage (10). Photocytotoxicity employs a similar model, with the inclusion
of exposure to UVR to simulate the solar spectrum. Indeed, use of this model has
found acceptance in the European Union, due to its strong correlation with in vivo
photoirritation (11). In order to identify the potential for ocular toxicity early in
the program, the cytosensor method, the tissue equivalent assay (TEA), or the
ex vivo rabbit ocular toxicity models may be used. The cytosensor method deter-
mines the metabolic rate via production of acid metabolites in murine fibroblasts,
whereas the TEA model measures mitochondrial metabolism in epithelial cells

via the dye stain MTT. In vitro corneal cell toxicity may also be assessed in
isolated bovine corneal cells (10).
An important element of any topical drug program, including sunscreens, is
the assessment of dermal drug transport. These models are used to measure
absorption and potential for systemic toxicity. Skin penetration, and potential
for systemic toxicity, is of course not a desired trait for sunscreens. Drug transport
can be assessed in vitro using skin samples from animals or humans, with the
transport ultimately depending upon many factors including the physical and
chemical characteristics of the drug (12). In the standard model, drug is
applied topically to a skin sample layered over a diffusion cell, and the amount
of drug passing through the skin sample and into the lower diffusion chamber
is quantified (13). Drug design for sunscreens includes considerations such
as molecular weight, lipophilicity, and polarity to minimize drug transport
through the stratum corneum, the rate-limiting factor in drug transport through
the skin. In vitro and in vivo assessment of drug transport is critical to the overall
risk assessment of the compound or formulation, since these are the data used
to make estimates of systemic exposure and toxicity in all of the organ
systems other than the skin.
For reliable use in a sunscreen development program, each of these in vitro
models should be first validated in terms of their ability to predict response in
man. Ultimately, this is accomplished through generation of data that establish
reproducible and consistent comparison of response. From a practical standpoint,
different compounds and classes of compounds are tested in each model. More
rigorous data will be required by FDA in the event screening models are used
in a drug submission. The search for validated methods is warranted however,
due to the benefits such systems may play in development programs in terms
of speeding the screening of candidates, and reduction of the need for testing
in animals and humans.
In Vivo Dermal Safety Testing in Animals

In vivo dermal safety testing in animals represents the next stage of safety assess-
ment, and is conducted to obtain data more relevant to humans. Key models
include those listed in Table 4.2.
In vivo assessment of new candidates for sunscreens typically includes
primary skin irritation in animals. The rabbit is the traditional animal model,
with both abraded and unabraded skin tested. The more expensive minipig may
be used since its skin characteristics model humans better than either rabbits or
rodents with thinner skin and higher hair density. Treatment duration can be
from a few days to several weeks, and it is important to prevent the animal
from removing the test product from the treatment site. Indeed, mice without
restraint can ingest the majority of a topically applied product in a matter of
minutes (14). In traditional topical skin irritation studies, animals are initially
62 Schwen
Table 4.2 In Vivo Dermal Safety Models—Animals
In vivo dermal Model

safety—animals (endpoint) Rationale for use
Skin irritation Rabbit patch testing In vivo model for acute

(erythema, edema, skin irritation
scaling)
Phototoxicity Rabbit patch model with Light activation to irritating
light activation (acute species
erythema, edema, scaling)
Delayed contact Local lymph node assay Potential for sensitization
hypersensitivity (LLNA) or guinea pig
maximization (erythema,
edema)
Photoallergy Sensitization models with Light activation to
inclusion of light potentially sensitizing
(erythema, edema) agent
Eye irritation Rabbit low-volume eye test Confirmation of in vitro
or rabbit Draize test positive results
(erythema, inflammation)
Subchronic dermal Rabbit or rodent dermal Assess topical and systemic
toxicity model, typically 28-day safety after repeat topical
study (dermal and doses
systemic safety endpoints)
Dermal carcinogenicity Rodent model and other new Confirmation of positive
in vivo models (onset and genotoxicity results
incidence of tumors).
Photocarcinogenicity Rodent model, typically Confirmation of positive
hairless mouse (onset and photogenotoxicity results
incidence of light-induced
tumor production)
shaved, treated daily, and skin irritation is assessed by grading on a visual scale
for erythema, edema, and scaling. Dose-ranging, by varying concentration or
volume applied, is included in order to identify the highest non-irritating dose.
As human data are obtained later in the program, the in vivo animal models
are reviewed to identify which is most predictive of humans for that particular
product. This “validated” model is then used in the future for further optimizing
the formulation.
Phototoxicity studies assess the potential of the light to produce irritating
species in mice previously treated with topical formulation. In the typical
model, hairless mice are treated topically, with one group subsequently
exposed to simulated solar light. The ability of light to shift the dose-response
curve for skin irritation (erythema, edema) is an index of whether light interacts
with the product to produce irritating species. Organic sunscreens, which actually
absorb UV light, have the theoretical potential to produce reactive species as they
release this energy into the surrounding dermal tissues.
For detection of delayed contact hypersensitivity, the mouse local lymph
node assay (LLNA) is now the preferred in vivo model of choice due to cost
and relevance of the data to humans (15). In LLNA, the test material is
painted on the ear of mice daily for three consecutive days. The local lymph
nodes are harvested on day 6 to determine if lymphocyte cell proliferation has
taken place above a predetermined stimulation index of threefold. In the
guinea pig maximization test, shaved guinea pigs are treated daily for 3 weeks
(induction phase) with the highest nonirritating dose previously determined in
separate skin irritation studies. After a 2-week rest phase, the animals are
dosed and graded for erythema and edema at 24 and 48 h (challenge phase),
with positive responders rechallenged after a second rest period to confirm the
result (16). Photoallergy is assessed in a similar model, except that exposure to
the compound and light is included during the induction phase. A positive
response during the challenge phase indicates that the compound has the
ability to produce photoreactive species that can induce a sensitization response.
Assessment of the potential for eye irritation is important for new actives
and formulations due to the potential for the eye to be accidentally exposed to
the product. The standard model is the Draize eye irritation test in rabbits,
using both rinsed and nonrinsed treatment groups. Irritation is graded using a
scale that takes into account several parameters. An improvement over the
Draize model is the low-volume eye irritation test, which is predictive of
responses in humans but less stress for the animals (17). As noted earlier, the
development of predictive in vitro methods for eye irritation have significantly
reduced the use of animals.
Subchronic dermal toxicity assessment is usually a later-stage toxicity
model, which assesses not only dermal but systemic toxicity as well. The
typical species is the rat, with treatment duration of 28 days or longer in the
standard toxicity protocol. Animals are shaved at intervals and treated daily,
with periodic assessment of dermal (erythema, edema, scaling) and systemic
toxicity (behavioral effects, food consumption, body weight). At the end of
the study, animals are sacrificed, and systemic safety is assessed by standard
parameters (gross pathology, organ weights, histopathology, hematology, serum
chemistry, urinalysis). As with other in vivo models, ingestion must be minimized
in order to attribute any observed toxicity to dermal exposure. Observations in
treated and control animals (placebo formulation) are compared to confirm any
drug-related toxicities.
Dermal carcinogenicity and photocarcinogenicity represent the late-stage
animal safety studies for new sunscreen actives. The need for these studies is
based upon the potential for chronic exposure of humans to the candidate sun-
screen. The typical animal model includes treatment of hairless mice daily for
2 years, with assessment of any dermal tumors in terms of onset and frequency,
64 Schwen
as well as assessment of tumor production at sacrifice. Photocarcinogenicity is

assessed in a similar model except with inclusion of simulated solar radiation.
Pilot studies are conducted to allow for selection of proper dose ranges and to
assure adequate survival in the main study to assure statistical validity. Protocols
for these very expensive and long-term studies are discussed with FDA in
advance, and as with other toxicity studies follow the relevant guidelines of
the International Conference on Harmonization (ICH) (18).
In Vivo Systemic Safety Testing in Animals

Sunscreens are selected for their efficacy properties as well as their dermal safety,
lack of systemic absorption, and lack of systemic toxicity. Virtually any systemic
toxicity of a sunscreen would present an unacceptable risk/benefit situation. This
is because the level of risk deemed “acceptable” is very low due to the fact that
other relatively safe products are already available, and since use will occur in an
uncontrolled OTC market environment. Subchronic dermal toxicity, as noted
earlier, is a model used to assess both local (dermal) as well as systemic safety
of the compound. Other key models for assessment of systemic safety of new
actives and formulations are given in Table 4.3.
Table 4.3 Key Models for Assessment of Systemic Safety—Animals
Systemic Model
safety—animals (endpoint) Rationale for use
Acute oral toxicity Rodent and nonrodent (acute Assess safety after
symptoms and lethality accidental ingestion or
after acute exposure) high systemic dose
Subchronic dermal or Rodent and nonrodent repeat Identifies target organ
oral toxicity dose studies (behavioral toxicities after prolonged
effects, gross pathology, high systemic exposure,
histopathology, serum and provides key data for
chemistry, urinalysis) the risk assessment
Teratology Rodent and nonrodent Determines potential for
models (malformations toxicity to the fetus and
in utero) offspring
Reproduction Rodent models (impairment Determines potential for
of reproductive capacity, toxicity to reproductive
using multiple endpoints) system of male and
female
Dermal pharmacokinetics Rodent and nonrodent (drug Determines systemic
and absorption, dermal transport, and exposure, fate of absorbed
distribution, distribution, metabolism, drug in the body, and key
metabolism, and and excretion) data for risk assessment
excretion (ADME)
Acute oral toxicity is typically assessed in mice or rats, and is a broad indi-
cator of the potential systemic toxic effects of the drug candidate. The classic
parallel-design LD50 model has been replaced with an increasing dose model
that is less demanding in terms of animal use. In a full toxicology program,
acute toxicity assessment is usually followed by subchronic oral toxicity,
which typically ranges in duration from 28 to 91 days and includes the systemic
parameters noted above for subchronic dermal toxicity studies.
Teratology and reproductive toxicity are two additional elements of a
program designed to assess the systemic toxicity of a new drug candidate on off-
spring and reproductive success. Teratology studies assess the effect of systemic
drug on the embryo and fetus, and are usually conducted in two species (rodent
and nonrodent). The number and types of malformations are compared in control
and treatment groups using a dose – response design. Reproductive toxicity
studies assess the effect of drug on male and female reproductive organs, and
reproductive performance. In peri- and postnatal toxicity studies, pregnant
females are treated prior to, during, and after pregnancy to assess effects on
the offspring. Protocols vary according to program needs, but all are designed
to identify a no-effect level in order to allow for a proper risk assessment.
Percutaneous drug absorption and its distribution, metabolism, and
excretion (ADME) are typically evaluated in rodents treated topically with
radiolabeled drug. Radiolabel is measured in urine, feces, treated site on the
skin, and in the organs of the remaining carcass to confirm the amount of
drug absorbed and tissue distribution. Metabolites in blood and urine are
usually quantified, and gross assessment of drug absorption is determined by
measuring percent of dose recovered in urine and feces. For many compounds,
percutaneous absorption in rodent models provides an overestimate of drug
transport in man, based on the rodent’s thinner skin and higher hair density.
As the program progresses, data are obtained in several species, including
humans, and the animal model most representative of exposure and metabolite
profiles in humans is identified. This species is then given special attention in
the risk assessment, since it is presumed to better reflect and predict potential
toxicities in humans due to these similarities.
In Vivo Dermal and Systemic Safety Testing in Humans

Safety testing of sunscreens in humans should normally be a confirmation of the
encouraging results obtained in prior in vitro and animal testing. While in vitro
and in vivo animal data are useful, they never completely predict responses in
humans. Studies in humans should not only confirm safety, but they should
also be designed to predict safety in the larger population. Accordingly, human
safety testing programs often include smaller-sized studies to confirm response,
followed by larger studies to detect low-frequency responses in key demo-
graphic groups (race, age, skin type). Larger numbers of subjects are required to
reliably detect low-frequency responses. Indeed, a frequency of 1% incidence of
66 Schwen
a significant toxicity such as delayed contact hypersensitivity (two responders in

a group of 200 subjects) would translate to 10,000 people affected per 1 million
users. The company is thus faced with design of larger studies to minimize sur-
prises and unnecessary risk in the future marketplace, where the costs associated
with termination of a program are much higher.
Key human safety models for sunscreens are shown in Table 4.4.
Acute and subchronic skin irritation are usually assessed over small areas
on the back or arms using both unoccluded (open) and occluded (patched)
treatment areas. Unoccluded sites resemble the actual use situation in the market-
place, where volatile formulation ingredients are allowed to evaporate. Occlu-
sion, on the other hand, represents a worst-case situation where the applied
material is allowed to better penetrate the stratum corneum via hydration of
the skin under the occluded patch. In both models, erythema, edema, and other
elevated responses are assessed as the primary indicators of skin irritation.
Delayed contact hypersensitivity (dermal sensitization) in humans is
assessed using the human repeat insult patch test (HRIPT). A 3-week induction
Table 4.4 Key Models for Assessment of Safety—Humans
Dermal and systemic Model

safety—humans (endpoint) Rationale for use
Acute skin irritation Acute patch testing under Confirm dermal nonirritating
occlusive or semiocclusive dose in humans
patches (acute erythema,
edema)
Subchronic skin 21-day cumulative patch test Confirm nonirritating dose
irritation (acute erythema, edema) after repeat dose in humans
Delayed contact Human repeat-insult patch Provides confirmation that
hypersensitivity test (HRIPT) (prolonged drug is of low sensitization
erythema and edema after potential in humans
challenge phase)
Human phototoxicity Acute patch model with Confirmation of lack of
simulated solar radiation phototoxicity in humans
(acute erythema, edema)
Human photoallergy HRIPT-type model with solar Confirmation of lack of
radiation (prolonged photoallergy in humans
erythema and edema after
challenge phase)
Human dermal Human dermal model Confirms actual systemic
pharmacokinetics (blood/urine levels of drug exposure in humans, and
and absorption, and key metabolites) provides key data for
distribution, systemic risk assessment
metabolism, and
excretion
phase, using a nonirritating concentration and occlusion, is followed by a 2-week

rest, then a challenge phase (7). A positive response is represented by a prolonged
erythema/edema at a naı̈ve treatment site. Typically, 100 – 200 subjects are used
in order to detect low-frequency positive responses.
Phototoxicity and photoallergy studies in humans employ similar models as
the skin irritation and HRIPT models described in the preceding text, except that
simulated solar radiation is included in the treatment phase. The models include
appropriate controls for the formulation excipients and the presence of light, so
that any positive response is due to light interaction with the drug.
RISK ASSESSMENT AND SAFETY TESTING OF SUNSCREENS

Results from the safety studies mentioned earlier allow for a risk assessment for
a new sunscreen candidate. This is done by calculating the no observable
adverse effect level (NOAEL) from animal studies, and comparing it to the
level of exposure estimated for humans. This NOAEL/human dose ratio is
the safety margin for the product, and it is calculated separately for each toxicity
endpoint. Although FDA has not defined a minimally acceptable safety margin,
this NOAEL/human dose ratio would traditionally be at least 100-fold. Of this,
a 10-fold margin is included to account for species variability between animals
and humans, with a further 10-fold margin added to account for variability in
response within the human population. Indeed, it is appropriate that FDA not
set a defined minimal acceptable ratio, since the appropriate ratio would vary
depending on the toxic effect, the frequency of the effect in the population,
the variability in actual dose applied in the marketplace, the benefit to the con-
sumer (i.e., risk acceptance), and many other considerations. However, for a
drug product in the sunscreen category, a conservative acceptable safety margin
ratio of 100-fold is reasonable since there are adequate sunscreens already
available on the market, with known and acceptable safety and efficacy. For
marketed active ingredients, the safety margins are actually much higher in
order to assure safety of subjects in an uncontrolled OTC market use situation.
For the safety models described, the validation of all models is critical
since false positives and false negatives can lead to missed opportunities or
unpleasant safety surprises in the market. Ideally, a properly validated model
should demonstrate a dose-response, and provide a rank-ordering of “actives”
that corresponds to the rank order of the safety of these compounds in humans.
CONCLUSION
By design, sunscreens provide protection from UV-B and UV-A by either absorb-
ing or reflecting this UV radiation. Accordingly, the risk assessment of a new
sunscreen candidate should include the benefits of blocking UV-A and UV-B, as
well as the actual safety profile of the sunscreen itself. FDA’s acceptance of
the safety of currently marketed sunscreens was determined during the OTC
68 Schwen
monograph process, which included a review of all available safety data on many
actives. For 15 of the existing actives, and one new active approved under an NDA,
the conclusion was that the risk to humans for these actives was very low in an
OTC use scenario. Most “new” sunscreen products actually include these
previously approved OTC active ingredients, thus safety testing is more limited,
does not need to be filed with FDA, and is performed by the company to
confirm there are no unexpected toxicities for their particular formulation.
On the other hand, a truly new sunscreen active ingredient must be sub-
jected to the extensive safety testing described in the previous sections, since it
would be classified as an unapproved new drug with IND and NDA filing require-
ments. From a toxicology perspective, this database provides the data needed for
a proper risk assessment to protect subjects during clinical testing, and to protect
consumers in the future marketplace. To date, R&D activity has shown that few
companies have been willing to pursue this expensive and long-term investment,
but perhaps the growing demand for safe and even more effective UV-A and
UV-B sunscreens will provide the needed financial incentive.
REFERENCES
1. Code of Federal Regulations Title 21, Section 352.10. Sunscreen active ingredients.
Revised as of April 1, 2003. Final Rule May 21, 1999.
2. Approved Drug Products with Therapeutic Equivalence Evaluations, US Department
of Health and Human Services, Food and Drug Administration, 1996.
3. Robinson MK. Population differences in acute skin irritation responses. Race, sex,
age, sensitive skin and repeat subject comparisons. Contact Dermatitis 2002;
46(2):86– 93.
4. Shaath NA, ed. Sunscreens: Regulations and Commercial Development. 3rd ed.
New York: Marcel Dekker, 2005.
2005:173 –198.
6. OECD Guidelines for the Testing of Chemicals. Vol. 1. Paris: Organization for
Economic Co-operation and Development, 1993.
7. Haschek WM, Rousseaux CG. Handbook of Toxicologic Pathology. New York:
Academic Press, 1991.
8. Niesink RJM, Vries J, Hollinger MA. Toxicology Principles and Applications.
New York: CRC Press, 1996.
9. Marrot L, Belaidi JP, Chaubo C, Meunier JR, Perez P, Causse C. An in vitro strategy
to evaluate the phototoxicity of solar UV at the molecular and cellular level:
application to photoprotection assessment. Eur J Dermatol 1998; 8:403 – 412.
10. Nohynek GJ, Schaefer H. Benefit and risk of organic ultraviolet filters. Regul Toxicol
Pharmacol 2001; 33:285 – 299.
11. Opinion concerning basic criteria for the in vitro assessment of percutaneous absorp-
tion of cosmetic ingredients. EU Scientific Committee on Cosmetic Products and
Non-Food Products Intended for Consumers. June 23, 1999.
12. Kasting GB, Filloon TG, Francis WR, Meredith MP. Improving the sensitivity of
in vitro skin penetration experiments. Pharm Res 1994; 11(12):1747– 1754.
13. Franz TJ. Percutaneous absorption and the relevance of in vitro data. J Invest
Dermatol 1975; 64(3):190– 195.
14. Schwen RJ. Drug development, quality of data, and meetings with the FDA. Presented
at the Australian Biotechnology Association Meeting, Brisbane, Australia, Nov 2002.
15. Kimber I, Dearman RJ, Basketter DA, Ryan CA, Gerberick GF. The local lymph node
assay: past, present and future. Contact Dermatitis 2002; 47(6):315 – 328.
16. Buehler EV, Newmann EA, Parker RD. Use of the occlusive patch to evaluate the
photosensitive properties of chemicals in guinea pigs. Food Chem Toxicol 1985;
23(7):689– 694.
17. Gettings SD, Lordo RA, Demetrulias J, Feder PI, Hintze KL. Comparison of
low-volume, Draize and in vitro eye irritation test data. I. Hydroalcoholic formu-
lations. Food Chem Toxicol 1996; 34(8):737 – 749.
18. New Horizons and Future Challenges. Sixth International Conference on
Harmonisation, Osaka, Japan, Nov 15, 2003.
5
Sunprotection: Historical Perspective
Paolo U. Giacomoni
Clinique Laboratories, Melville,
New York, USA
The Sun and Humans in the Past 72

Experimental Evidence of Beneficial and Harmful Effects of
Solar Radiation 74
UV-B, the Bad Guy 75
Experimental Evidence for UV-A Induced Damages 76
Why Anti-UV-A Sunscreens? 76
Anti-UV-B and Anti-UV-A Sunscreens 77
Beyond SPF 78
The Future: New Strategies for Defense 79
The Future: New Aggressors? 80
References 80
Life expectancy in Europe and North America has increased by a factor of 3 in

the last three centuries. One of the paradoxical consequences of increasing life
span has been that chronic exposure to small, not immediately life-threatening
insults accumulates as physiological changes later in life, which are unpleasant
at best and life-threatening at worst. This is particularly true for the changes
provoked by solar radiation.
71
72 Giacomoni
THE SUN AND HUMANS IN THE PAST

Some of the beneficial and harmful effects of solar radiation have been known
since antiquity, at least in the surroundings of the Mediterranean Sea. The
beneficial effects of the sun, its necessity for the survival of the human species,
were so clear to the humans in these regions, that the cult of the God Sun was
developed that lasted several thousand years in ancient Egypt. This cult perpetu-
ated itself, under different aspects, until the development of Mithraism and his
philosophical influence upon the newly born Christian religion.
One would think that the adoration of the sun was shared by the ancient
Greeks. They had a predilection for Apollo, the driver of the chariot of the
sun, and indeed, when thinking of ancient Greeks, the image comes to mind of
naked athletes or warriors, as sculpted in marble or painted on vases. A naive con-
clusion from these observations could be that ancient Greeks were not worried by
solar radiation. Yet, the observation of other paintings or the reading of Greek
literature convinces us that this is not the case.
First of all, tan was not palatable to ancient Greeks. Hera, the “first lady” of
the Olympos, is repeatedly described in the Iliad as having white arms.
In the description of Ulysses’ adventures, Homer says that while Princess
Nausicaa and her friends wait for the linen to dry, they swim in the sea. And after
the bath they apply olive oil to their bodies, have a sort of picnic, and then, after
having thrown away the veils covering their heads, they play ball.
This means that these young women want to be unimpeded when playing
ball, but that before the game, for the picnic, they had dressed themselves up and
had covered their heads because they knew that men prefer women with white
skin, as well as because they were aware of the scorching effects of the sun.
The care taken by women in ancient Greece to protect themselves against
the burning rays of the sun is apparent in Antigone’s words: “I see a woman. She
comes toward us, mounted on a young mare. On her head, a thessalian hat with
large brims covers her face to protect her against the sun”.
Vase paintings, too, reveal that ancient Greeks were aware of the dangers
linked to sun exposure. At the Metropolitan Museum of Arts in New York, one
finds documented evidence in favor of the above statement. On a vase of the 5th
century BC, the Trojan prince Paris is depicted as a young shepherd. He wears a
coat and a hat with a large brim. The other masculine figures in the painting are
also wearing full body-covering coats. This seems to indicate that when not
racing or fighting, men tended to cover their bodies. Yet, not all of the warriors
were necessarily naked. A painting of the 4th century BC portrays the combat of
Greeks and Amazons, with fully dressed warriors. In a more peaceful painting
from the 6th century BC the painter portrays the participants in a wedding pro-
cession as fully dressed men and women. Because of the mild climate of
Greece, those clothes were not intended to protect against the cold, so the last
interpretation we are left with is that those clothes and hats were meant to
protect against the sun.
Sunprotection: Historical Perspective 73
Similar paintings can be found on Greek vases in every archeological

museum.
The most concise, yet precise, description of the harmful effects of the sun
is given by Xenophon. Between 400 BC and 398 BC he was one of the officers
committed to bringing back to Greece a battalion of 10,000 Spartan mercenaries
from central Mesopotamia (today’s Iraq), where they were fighting an unsuccess-
ful war and were at risk of becoming slaves. Upon crossing a snow-covered
mountain in Armenia, he noticed the effects of freezing temperatures and of
the albedo of snow. He writes: “Soldiers who lost the use of the eyes, blinded
by the snow, or who lost their toes because of the cold, were abandoned. In
order to protect the eyes against the albedo from the snow, they kept a black
fabric before the eyes, and in order to protect their feet, they kept moving con-
tinuously”. From this we learn that as early as the beginning of the 4th century
BC, Greek mercenaries knew the cause –effect relationship between the albedo
of the snow and the impairment of the eye, as well as the possibility of avoiding
it by reducing the number of photons reaching the eye.
Etruscans were not afraid of working in the fields and chasing game under
the sun. They painted scenes of every day life with men wearing coats and hats.
They painted themselves as tanned men, but their women were always painted as
white. Only dancers were naked. The Romans, too, seem to have preferred white
skin for their loved ones (be they boys or girls). Yet, what remains of their writ-
ings, filtered by the Christian monks of the middle age, does tell us much about
their philosophical and political views but very little about how they protected
their skin against solar radiation.
The superficial researcher does not find much to read about sun protection
in the writings from the low Roman Empire through the Middle Ages and Renais-
sance until the late 18th century. The Interpretatio Arabicorum Nominum by
Andrea Alpago, first published in Venice in 1527 as an appendix to Avicenna’s
Canon does not contain one single word about ingredients able to protect against
the damage caused by the sun.
In the 500 pages or so of the two volumes of Hufeland’s Art of Increasing
Human Life Span, published in Jena (Germany) in 1796, avoiding exposure to
sunlight is not quoted as a way to improve, if not life span, at least the quality
of the skin. It has to be noted, though, that the skin was known to be an important
organ of the body and Hufeland uses about 10 pages in describing methods
for taking care of one’s skin. One of the possible reasons for not laying emphasis
on the consequences of excessive exposure to solar radiation is that at the end
of the 18th century in Germany, 80% of the human beings did not live beyond
the age of 30, and only 6% lived longer than 60 years: physiologists and
doctors had yet to understand the essence of microbial infection and were not
yet ready to tackle dermatological issues.
In these same times, British aristocrats and Swiss scientists discovered an
interest in gratuitous physical activity and the pleasure of climbing mountains.
The Mont Blanc became fashionable. In 1786 Paccard and Balmat reached the
74 Giacomoni
top of the Mont Blanc. Thirty years later, Countess Henriette d’Angeville
climbed the Mont Blanc. After having reached the top, she observed the
guides who helped her in the climbing: one’s lips were bleeding and his face
was covered with “droplets”, another had a visual impairment, a third one had
black lips, covered with blisters. Curious about her own situation, she took a
mirror from her bag and noticed that she had a swollen nose and lips, the
white of her eyes was all red and crossed by darker red veins, her skin was as
if grilled, and purple colored from the chin to the roots of the hair.
This is to say that by the end of the 18th century, centuries-long popular
knowledge and newly acquired aristocratic experience agreed on the fact that
exposure to solar radiation is harmful. What happened in the next century to
justify the craze about sunbathing which still lasts today?
EXPERIMENTAL EVIDENCE OF BENEFICIAL AND HARMFUL

EFFECTS OF SOLAR RADIATION
In the 19th century, the Industrial Revolution moved large amounts of the popu-
lation from the country to the cities, and the standards of living dropped dramati-
cally. In particular, instead of working or playing in the fields, children were
compelled to work hard in factories, lived in poorly equipped houses, and were
deprived of milk, and they developed rickets. The Polish physician Sniadecki
(1768–1838) realized that children living in rural areas around Warsaw did not
develop rickets. He concluded that it was the lack of exposure to sunlight that
caused the high incidence of rickets in Warsaw, and postulated that this was
also the cause for the high incidence of rickets in the highly industrialized
cities of northern Europe. It took 70 years for T.A. Palm, a British physician,
to draw the same conclusions in 1890, upon observing that children had a high
risk of developing rickets in the cities of Great Britain, whereas children living
in equally squalid yet sunlit conditions in India did not develop the disease. He
concluded that sunbathing could have beneficial effects in avoiding rickets,
and recommended it to the medical community. In 1919 the German physician
Huldschinsky treated rickets with radiation from a mercury lamp and suggested
that UV was responsible for the curative effect. [For a detailed account on rickets
and its cure, see Ref. (1).]
In the meanwhile, Finsen (the 1903 Nobel Prize winner) was experimenting
in treating phototherapy diseases as diverse as small pox, tuberculosis, and lupus
erythematosus. A strong positive image became associated with sunlight, irre-
spective of the observations by Dubreuilh or Unna indicating that farmers
develop skin cancer in sun exposed zones, whereas city dwellers are rarely
affected (2) or that sailors exposed a long time to sunlight develop “sailor’s
skin”, a condition characterized by erythema, pigmentation, and hyperkeratosis,
and have a chance of developing skin cancer (3).
At the turn of the century, in the time of the triumphant Belle Epoque,
British aristocrats and dandies “discovered” the French Riviera, invented
outdoor sports, praised physical activity, and as an accessory, developed a tan.

The Belle Epoque ended catastrophically with World War I. Men were sent to
the front and for many years all the work in farms and factories was performed
by women. This has greatly contributed to the social emancipation of women.
Could it be that it also pushed women into the sun, and won them over to the
psychological pleasure of displaying a tan similar to the one of dandies and aris-
tocrats? Whatever the reason, in the 1930s the tan became a must. According to
Driscoll (4), “the French fashion designer Coco Chanel is credited with promot-
ing suntanning as a fashion statement at this time. Thus, by the 1930s, it became
fashionable to wear more revealing swimming costumes to develop a slight tan,
which was also a statement that a tanned person was rich enough to afford a
holiday in the sun”. And to spread the fashion of tanning beyond the borders of
the affluent class, the French government promulgated in 1936 a law establishing
the principle of paid vacations: the employee was paid during the days off. France
has a few thousand kilometers of coasts and the rush to the sea was generalized.
So, about 65 years ago, exposure to solar radiation became a mass phenomenon in
Europe. Everybody immediately noticed what was first published by Widmark in
1889 (5), that exposure to ultraviolet provokes erythema, and the necessity for a
sunscreen was immediately felt.
UV-B, THE BAD GUY

The use of a specific glass type to filter ultraviolet radiation showed at least two
spectral regions called UV-A (wavelength above 320 nm) and UV-B (wavelength
below 320 nm) and that the UV-B part of the spectrum was responsible for
erythema [for details about this subject, see Ref. (6)].
The advent of molecular biology after World War II provided scientific
paradigms to understand the effects of ultraviolet radiation. Monochromatic
UV-C lamps (emitting ultraviolet radiation at 254 nm) were used to induce muta-
genesis in simple organisms, to study the photochemistry of DNA damage and
the enzymology of DNA repair. The absorption spectrum of DNA spans the
full UV-C and UV-B spectra, and UV-B itself was suspected of being carcino-
genic. Later, experiments with laboratory rodents confirmed that UV was to be
considered a full carcinogen, with UV-B playing the role of tumor initiator
because of its capability to generate cyclobutane-type and (6-4)pyrimidine
dimers, and UV-A playing the role of tumor promoter because of its capability
to promote irritations. Being unable to generate pyrimidine dimers, though,
UV-A was considered for many years to be harmless.
At that time, therefore, sunscreens only absorbed UV-B, known as erythe-
mogenic radiation. Many sunscreens were phototoxic and photounstable. Often
they were more damaging than protecting. To this, one can add the photosensi-
tizing concoctions prepared by unskilled merchants and self-appointed pharma-
cists. In the following 50 years, sunscreen technology improved and it not only
provided a protection against UV-B, but also paradoxically helped to point out
76 Giacomoni
that UV-A was also harmful to cells and tissues. The first hint of this conclusion
came from the epidemiologic observation that after years of exposure to solar
radiation notwithstanding the use of anti-UV-B sunscreens, the skin of sun
worshippers became severely damaged, sagging, elastotic.
EXPERIMENTAL EVIDENCE FOR UV-A INDUCED DAMAGES

Experiments performed with cultured cells in the 1960s and the 1970s seemed to
indicate that UV-A had the capability to introduce nicks in cellular DNA. Yet the
purist could always argue that the radiation used was contaminated by UV-B
radiation and that the calculation of the quantum yield of nicking was therefore
impossible. The advent of simple and double monochromators allowed the inves-
tigation of the biological effects of UV-A to proceed free of this criticism. At the
end of the 1980s, work with laboratory rodents indicated clearly that UV-A had
molecular and tissular effects. Bissett et al. (7) pointed out the role of repeated
UV-A irradiations in the sagging of the skin, which was not achieved with
UV-B radiation. Balard and Giacomoni (8) pointed out that ultraviolet from
solar simulators (UV-B þ UV-A) could induce the drop in the level of NAD in
the epidermis, which could not be obtained by the use of only UV-B radiation
on cells in culture. Last but not least, Brunet and Giacomoni (9) pointed out
that UV-A dramatically enhanced the small induction of heat shock genes
provoked in the epidermis by UV-B. A couple of years later it was understood
that DNA damage was inflicted by UV-A only in the presence of oxygen and a
transition metal (10). This damage, therefore, manifested itself as being oxidative
in nature. These results, therefore, paved the way to the use of antioxidants in
cosmetics and in sun care to avoid the indirect damages caused by UV-A, such
as oxidative nicking of DNA, peroxidation of lipids, production of singlet
oxygen, and so forth.
WHY ANTI-UV-A SUNSCREENS?

Oxidative damage is but one of the effects of UV-A. Studies with laboratory
rodents have opened the path to the understanding of UV-induced immune
depression, carcinogenesis, photodamage, and photoaging.
In 1977, Fisher and Kripke (11) observed that rodents did not reject a tumor
graft if they were previously irradiated with huge doses of UV. This seminal
paper marked the beginning of the era of photoimmunology. Besides the use
of ultraviolet to help in grafting tumors in laboratory rodents, it was observed
that a previous exposure to UV impaired the responses of contact hypersensitivity
and delayed-type hypersensitivity in mice and rats. The mechanisms involved in
these phenomena have been the objects of bitter disputes in the scientific commu-
nity over the years. It seems that one of the reasons for the conflicting results
could be found in the fact that, like erythema, the immune depression is a
threshold phenomenon, and that different mice strains have different threshold
values, the differences being as large as a factor of 4 (12).
Ultraviolet radiation impairs immune response in humans by increasing the
activity of suppressor T-cells (13). Although exposure to UV-B prior to vacci-
nation does not impair the production of antibodies at a normal rate (14),
exposure to UV-B impairs the delayed-type hypersensitivity response. Broad
spectrum (UV-B þ UV-A) sunscreen seem to protect the sensitivity response
better than only UV-B sunscreens, thus pointing out a role for UV-A in the estab-
lishment of immune suppression (15).
The depression of the immune response in humans is likely to be the con-
sequence of the reduction of Langerhans cell count in the epidermis successive to
exposure to UV. Indeed UV irradiation generates haptens and it can be expected
that antigen presenting cells just migrate to lymph nodes at a higher than normal
rate because of the large number of haptens they encounter. One could also
speculate that the impairment of the hypersensitivity response might well be
an evolutionary advantage because it reduces the risk of anaphylactic shock
induced by excess haptens. The interest in the immune depression provoked by
ultraviolet radiation was aroused by the fact that UV-B sunscreens were unable
to fully protect laboratory rodents, as well as human volunteers, against
immune suppression. From this phenomenon two things were to be learned:
first, that UV-A plays a role in photoinduced immune suppression and second,
that the threshold for triggering the immune suppression is smaller than the
threshold for triggering erythema. Thus, the protection factor afforded by a sun-
screen to the immune response is smaller than the protection factor afforded
against erythema.
ANTI-UV-B AND ANTI-UV-A SUNSCREENS

The large attention devoted to UV-A should not make one forget that UV-B is
mutagenic, immune-suppressive, and cancerogenic. To point out the important
role of the biological effects of UV-A, one does not need to lessen the dangers
of UV-B. The cell damaging potential of UV-B and its capability to produce
sunburn cells are instrumental in triggering an inflammatory response, now
recognized as one of the most important factors of skin aging (16). So, UV-B
should not only be feared because of its immune-suppressive, mutagenic,
cancerogenic, and erythemal (burning) properties, but also because it plays a
role in damaging the extracellular matrix and eventually all of the skin. The
quantum yield of DNA damage by UV-A is smaller than the one of UV-B, but
the count of UV-A photons in sunlight is 20 times larger than the count of
UV-B, and the damage to the extracellular matrix induced by UV-A (mostly
singlet oxygen driven) is incredibly larger than the one triggered by UV-B,
which is generally absorbed by the DNA in keratinocytes.
It is therefore necessary to couple anti-UV-B sunscreens with anti-UV-A
sunscreens. The sunscreens should also be associated with scavengers of
78 Giacomoni
singlet oxygen, which is now accepted as the major reactive species of oxygen
involved in the indirect damages provoked by ultraviolet (17,18). This recom-
mendation is all the more important because all sunscreens, being substances
able to absorb radiation around 300 –350 nm, have the unwelcome capability
to transfer their excitation energy to oxygen. By doing so, they increase the
level of singlet oxygen and the rate of production of oxidative damages.
BEYOND SPF
Notwithstanding all the progresses in biochemistry, molecular biology, and
dermatology, we still assess the protection offered by a sunscreen with methods
having two major potential flaws: the end point is the erythema, and the ultra-
violet radiation is UV-B.
Among the physiological responses to solar radiation, erythema is the
simplest to assess. Clinical observation is sufficient to differentiate between
erythemas of different degrees of severity. Erythema only appears if the delivered
UV dose is above a threshold. This contributed to the decision to use it as the end
point of choice for determining the protective effects of sunscreens. Indeed the
clinical analysis of erythema allows one to estimate with a certain precision,
the numerical factor by which a topically applied sunscreen is able to reduce
the delivered UV dose.
Methodologically, the use of the intensity of the erythema for evaluating
UV-protecting capabilities of specific compounds suffers from one major
flaw. Indeed, inhibitors of the erythemal response such as vaso-constrictive or
anti-inflammatory drugs could be believed to provide protection against
UV-induced damage, whereas they only inhibit the reaction triggered by the
damage, that is, erythema. This type of objection extends to all the proposed
methods to assess the protection offered by specific compounds against UV,
which rest on the quantitative analysis of a physiological reaction to damage
instead of on the assessment of the damage itself. Indeed, the inhibitors of the
response under scrutiny might be mistaken for protecting agents.
From a practical point of view, in the past, the use of erythema as an
endpoint has been a valuable tool in facilitating the evaluation of the efficiency
of new sunscreens. However, recent progress in photobiology indicates that,
irrespective of the methodological flaw discussed above, the exclusive use of
erythemal data might be dangerously misleading. Indeed, physiological responses
to solar radiation as crucial as UV-induced immune depression have threshold
values different from those relative to the onset of erythema, and DNA
damage is linearly dependent on UV dose, without the threshold effect.
Ideally, one should assess the protective effect of specific compounds by
evaluating the damages inflicted by the same dose of radiation (with identical
spectral distribution) in the presence or in the absence of the protecting agent.
The evaluation of the molecular damage inflicted by solar radiation on human
skin is of course a difficult task, which requires invasive techniques. The only
possibility one is left with is to assess the kinetic of removal of one easy-
to-measure damage and of a physiological response after exposure to UV in
the presence or in the absence of protecting agents.
THE FUTURE: NEW STRATEGIES FOR DEFENSE

Reducing the number of photons impinging on target organs is a way to reduce
photodamage and its consequences, but there is more to sun protection than just
wearing clothes or sunscreens. It should be possible to stimulate cellular
self-defense against outside aggressions. Fifteen years ago one of my graduate
students observed that messenger RNA for heat shock proteins accumulates in
epidermis after exposure to UV (9). We decided to point out in her
doctoral dissertation that “if the expression of these proteins has a beneficial
effect for UV irradiated epidermis, we could look for a gratuitous inducer of
their genes and thus prepare the epidermis to a subsequent irradiation to
protect it against deleterious effects of solar radiation”. In our minds, the
concept of “gratuitous induction”, so helpful 30 years earlier in the understanding
of the mechanism of negative control of gene expression, had found an appli-
cation in photobiology!
In the last 10 years or so it has been shown that the response of human cells
to UV is not limited to constitutive DNA repair and pigmentation, but also
encompasses poly-ADP-ribosylation, expression of heat shock proteins, accumu-
lation of p53 protein, induction of the cytochrome P-450 associated system of
detoxification, and expression of other defense proteins. One could therefore
propose treatments to “help” the cells induce their defense systems before
going out in the sun. It is essential, of course, that the induction of defense mech-
anisms be obtained by harmless treatments, as it is essential that the assessment of
the negative consequences of an aggression be obtained by measuring the
damage, not the defensive response to the aggression itself. Indeed, when protect-
ing agents are screened for their activity by measuring the extent of a particular
defense response, any inhibitor of that defense response can be mistaken for a
protecting agent.
By topical application of xenobiotics it is now possible to improve the
rate of repair of DNA and to stimulate melanin production. It is also possible
to induce the expression of heat shock proteins and of heme-oxygenase. It is
possible, too, to reactivate the Embden –Meyerhof pathway interrupted when
poly-ADP ribosylation depletes the cell of NAD, thus avoiding cell death
because of the lack of energy. UV-induced immune suppression deserves a differ-
ent approach. Boosting the immune response might have undesirable conse-
quences. It is therefore crucial that, when dealing with the impairment of
hypersensitivities, one confines oneself to the protection of specific targets and
to the repair of specific molecules, without inducing an overall boosting of the
immune system.
80 Giacomoni
THE FUTURE: NEW AGGRESSORS?

Last but not least, we might ask if we are sure to have searched all the spectrum
for harmful radiations. It is well known that the edge of violet light is harmful to
the retina, it is well known that blue light impairs catalase. Specific wavelengths
in the visible spectrum inhibit the synthesis of melatonin. Excess infrared might
enhance an inflammatory response. This is to say that it should not be excluded
that even the friendly visible light is endowed with harmful action. Of course,
there is no reason to panic, we have been living with visible and infrared radiation
for millennia, but learning about the molecular, enzymatic, and photochemical
effects of visible and infrared rays might be helpful to the progress of science
and beneficial for general health.
REFERENCES
1. Holick MF. A perspective on the beneficial effects of moderate exposure to sunlight:
bone health, cancer prevention, mental health and well being. In: Giacomoni PU, ed.
Sun Protection in Man. Amsterdam: Elsevier, 2001:11 – 37.
2. Dubreuilh W. Epitheliomatoses d’origine solaire. Ann Dermatol 1907; 8:387.
3. Unna PG. Die Histopathologie der Hautkrankheiten. Berlin: Verlag von August
Hirschwald, 1894.
4. Driscoll CMH. Artificial protection against solar radiation: fabrics. In: Giacomoni PU,
ed. Sun Protection in Man. Amsterdam: Elsevier, 2001:457 – 486.
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6. Urbach F. The negative effects of solar radiation: a clinical overview. In:
Giacomoni PU, ed. Sun Protection in Man. Amsterdam: Elsevier, 2001:39 – 67.
7. Bissett DL, Hannon DP, Orr TV. Wavelength dependence of histological, physical
and visible changes in chronically UV-irradiated hairless mouse skin. Photochem
Photobiol 1989; 50:763 – 769.
8. Balard B, Giacomoni PU. Nicotinamide adenosine dinucleotide level in dimethylsulfate-
treated or UV-irradiated mouse epidermis. Mutat Res 1989; 219:71–79.
9. Brunet S, Giacomoni PU. Heat shock mRNA in mouse epidermis after UV irradiation.
Mutat Res 1989; 219:217 –224.
10. Audic A, Giacomoni PU. DNA nicking by ultraviolet radiation is enhanced in the
presence of iron and of oxygen. Photochem Photobiol 1993; 57:508 – 512.
11. Fisher MS, Kripke ML. Systemic alteration induced in mice by ultraviolet light
irradiation and its relationship to ultraviolet carcinogenesis. Proc Natl Acad Sci
USA 1977; 74:1688 – 1692.
12. Kim TH, Ananthaswami HN, Kripke ML, Ulrich SE. Advantages of using hairless
mice versus haired mice to test sunscreen efficacy against photoimmune suppression.
Photochem Photobiol 2003; 78:37 – 42.
13. Hersey P, Haran G, Hasic E, Edwards A. Alteration of T-cell subset and induction of
suppressor T-cell activity in normal sujects after exposure to sunlight. J Immunol
1983; 131:171 – 174.
14. Sleijffers A, Garssen J, De Gruijl FR, Boland GJ, Van Hattum J, Van Vloten WA,
Van Loveren H. Influence of ultraviolet B exposure on immune response following
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15. Moyal DD, Fourtanier A. Efficacy of broad-spectrum sunscreens against the suppres-
sion of the elicitation of delayed-type hypersensitivity response in humans depends on
the level of ultraviolet A protection. Exp Dermatol 2003; 12:153 – 159.
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Biogerontology 2001; 2:219 – 229.
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Regulatory Aspects
6
The Role of FDA in Sunscreen
Regulation
Matthew R. Holman and Daiva Shetty

Division of Over-The-Counter Drug Products,
Center for Drug Evaluation and Research,
Food and Drug Administration,
Rockville, Maryland, USA
Differentiating Drug, Cosmetic, and Drug– Cosmetic Products 86

Regulatory Mechanisms for Marketing Sunscreen Drug Products 87
New Drug Application 87
OTC Drug Monograph System 89
Description of the OTC Drug Monograph System 89
Advisory Panel Review 90
Tentative Final Monograph 91
Final Monograph 91
Description of an OTC Drug Monograph 91
Amending an OTC Drug Monograph 93
Citizen Petition 93
Time and Extent Application 93
This chapter describes how the Food and Drug Administration (FDA) regulates
products containing sunscreen active ingredients. FDA regulates these products
based on the Code of Federal Regulations (CFR), which derives from the
85
86 Holman and Shetty
Federal Food, Drug, and Cosmetic Act (the Act), legislation enacted by
Congress. Discussion will begin with differentiation of drug and cosmetic pro-
ducts according to the CFR. Then, the remainder of the chapter will focus on
sunscreen drug products. The two mechanisms under which sunscreen drug
products can be regulated will be compared and contrasted. Because the most
common regulatory mechanism for marketing sunscreen drug products is the
over-the-counter (OTC) drug monograph system, the OTC sunscreen drug mono-
graph will be used to explain this system. Finally, two mechanisms by which an
OTC drug monograph can be amended will be described.
DIFFERENTIATING DRUG, COSMETIC, AND

DRUG –COSMETIC PRODUCTS
To understand whether a particular product is a drug, cosmetic, or drug – cosmetic
product, FDA refers to the definitions of a drug and a cosmetic stated in the Act.
In Section 201(g) of the Act, a drug is defined as follows:
(A) articles recognized in the official United States Pharmacopeia, offi-
cial Homeopathic Pharmacopeia of the United States, or official
National Formulary, or any supplement to any of them
(B) articles intended for use in the diagnosis, cure, mitigation, treatment,
or prevention of disease in man or other animals
(C) articles (other than food) intended to affect the structure or any func-
tion of the body of man or other animals
(D) articles intended for use as a component of any articles specified in
clause (A), (B), or (C)
In Section 201(i) of the Act, a cosmetic is defined as follows:
(1) articles intended to be rubbed, poured, sprinkled, or sprayed on, intro-
duced into, or otherwise applied to the human body or any part thereof
for cleansing, beautifying, promoting attractiveness, or altering the
appearance
(2) articles intended for use as a component of any such articles; except
that such term shall not include soap
These definitions define drug and cosmetic products, and FDA considers any
product that falls under both of these definitions as a combination drug – cosmetic
product.
Based on these definitions, FDA regulates all products containing a sun-
screen active ingredient and bearing a sunburn protection or prevention claim
as drugs. As described in 21 CFR 700.35, FDA regulates products containing a
sunscreen active ingredient but not bearing a sunburn protection or prevention
claim as cosmetics. For example, these products include those that contain a
sunscreen active ingredient to protect product color. Furthermore, some pro-
ducts regarded as drugs are also regulated as cosmetics by FDA. Combination
The Role of FDA in Sunscreen Regulation 87
drug – cosmetic sunscreen products are abundant because many sunscreen drug
products contain colorants, moisturizers, and other beautifying components and
bear cosmetic claims. For example, a product labeled with an SPF value and
labeled for the relief of dry skin is a drug –cosmetic (sunscreen –moisturizer)
product.
REGULATORY MECHANISMS FOR MARKETING SUNSCREEN

DRUG PRODUCTS
Because nearly all sunscreen drug products are sold OTC, this section will focus on
the mechanisms under which OTC sunscreen drug products can be marketed. An
OTC sunscreen drug product, whether it is also a cosmetic or not, can be marketed
under a new drug application (NDA) or the OTC drug monograph system, more
specifically, the OTC sunscreen monograph. Although nearly all sunscreen pro-
ducts in the marketplace are marketed under the OTC sunscreen monograph, it
is important to understand both mechanisms. Both mechanisms require that sun-
screen products be manufactured under current good manufacturing practices
(cGMPs) as defined in 21 CFR Part 210. In addition, all OTC drug products
must comply with the labeling content and format requirements of 21 CFR 201
Subpart C.
New Drug Application

Although there are some similarities in marketing under an NDA and the OTC
sunscreen monograph, many differences exist between the two routes
(Table 6.1). An NDA requires FDA approval before the sunscreen product can
be introduced into the OTC market. A drug manufacturer must submit data in
an NDA demonstrating that the product is safe and effective as a sunscreen for
use by consumers without the assistance of a healthcare professional. The data
are reviewed within time frames specified in the Prescription Drug User Fee
Amendments of 2002 (PDUFA III). For a standard NDA, FDA approval is
given within 10 months.
At the time that an NDA is submitted to FDA, the drug manufacturer must
submit a user fee. In 2003, the user fee for a typical NDA was $573,500. An NDA
is considered confidential by FDA. FDA does not release any information,
including the receipt of an NDA, until the review is complete. At this time,
FDA’s determination of approvability becomes public, but the data contained
in the NDA remain confidential.
Only after FDA approves a sunscreen product as safe and effective can a
drug manufacturer market the product. Moreover, the drug manufacturer can
only market the exact formulation that FDA has approved with the exact labeling
that FDA has approved. Any change in formulation, labeling, manufacturing
process, and so on, that deviates from that approved in the NDA must be approved
by FDA before the manufacturer can make the change. The manufacturer must
Table 6.1 Comparison of Two Regulatory Mechanisms for Marketing an OTC

Sunscreen Drug Product
OTC drug monograph NDA
No FDA pre-approval before marketing FDA pre-approval based on clinical trials

demonstrating adequate evidence of
safety and efficacy as well as detailed
manufacturing data are required before
marketing
No fees required to market product PDUFA user fees required when NDA
submitted
Any interested parties can market product Exclusivity and patent protection may
with the same active ingredients for the prevent other interested parties from
same indications marketing a product with the same
ingredients for the same indications
No deadline associated with publication Specific review deadlines
of a final monograph
Only considers active ingredients as long Based on the final formulation
as the inactive ingredients in a product
are safe and do not interfere with the
effectiveness of the active ingredients
(21 CFR 330.1(e))
Rulemaking process is public and Information submitted to FDA is
comments and data submitted to FDA confidential, but FDA reviews of the
are placed on public display in application are available to the public
Division of Dockets Management after approval
submit an NDA supplement supporting the desired change. NDA supplements do

not have user fees associated with them unless FDA has to review clinical data.
NDA products can be protected from competition from similar products by
patent protection, exclusivity, or both. NDA products can be patented, preventing
anyone except the patent holder from manufacturing a drug with the same active
ingredient(s) for the same indication(s). Patent protection is provided only for
those products that have been granted a patent by the U.S. Patent and Trade
Office. Under certain circumstances, FDA may protect an NDA product from
competition after patent expiration. FDA grants marketing exclusivity to com-
pensate for the significant amount of time that it can take to bring a drug into
the market from its initial discovery.
The description given above applies to all NDA products, including those
classified as “NDA deviations.” An NDA deviation is an NDA that uses an OTC
drug monograph to support its approval (21 CFR 330.11). The NDA deviation
allows a drug manufacturer to submit an NDA that only contains data related
to how the conditions of use of an OTC drug product differ from the applicable
OTC drug monograph(s). For example, a drug manufacturer could submit an
NDA for an OTC sunscreen product that complies with the sunscreen monograph
except that the product includes labeling not found in the monograph. The NDA
could reference the sunscreen monograph to support the safety of the active
ingredients and simply submit data supporting the additional labeling. An
NDA deviation can only reference a final monograph. Also, a product marketed
under an NDA deviation must follow the reporting requirements of the NDA
regulations.
OTC Drug Monograph System

Marketing a sunscreen product under the OTC drug monograph is significan-
tly different from marketing the product under an NDA (Table 6.1). Sunscreen
products marketed under the monograph do not require FDA approval
before marketing. Prior to marketing, a sunscreen manufacturer only has to list
its sunscreen product according to 21 CFR Part 207. FDA has a compliance
office that is responsible for ensuring that all OTC drug products comply with
the registration and listing requirements as well as cGMP and applicable OTC
regulations, including OTC drug monographs. For sunscreen products, the
compliance office monitors products for appropriate active ingredients at the
allowed concentrations, labeling consistent with the monograph, and accurate
SPF values according to the testing requirements of the OTC sunscreen drug
monograph.
As discussed later in this chapter, OTC drug monographs are based on
active ingredients and not on the final formulation. Thus, in contrast to OTC
drug products marketed under NDAs, OTC drug products marketed under
OTC drug monographs have the flexibility of changing formulations without
FDA pre-approval. There are two major requirements regarding ingredients:
1. The active ingredient(s) or combination of active ingredients must be
allowed under an OTC drug monograph.
2. The inactive ingredients must be safe and not diminish the effective-
ness of the active ingredient(s).
For this reason and because the rulemaking process to create an OTC drug mono-
graph is public, there is no exclusivity associated with products marketed under
an OTC drug monograph.
DESCRIPTION OF THE OTC DRUG MONOGRAPH SYSTEM

The OTC sunscreen monograph is used to illustrate the OTC drug monograph
system. In 1972, FDA created the OTC drug monograph system as a means to
examine all of the OTC drug products in the marketplace to determine whether
they were safe and effective. The OTC drug monograph system was designed
to be a public process in which all of the active ingredients, rather than the
final formulations, for a particular therapeutic category, such as sunscreen,
were evaluated for safety and efficacy. The basis of the OTC drug monograph
system is a three-step public rulemaking process:
1. Advanced Notice of Proposed Rulemaking (ANPR)
2. Tentative Final Monograph (TFM)
3. Final Monograph (FM)
As the process moves forward, each step builds upon and is a continuation of the
previous step. The development of the OTC sunscreen monograph will be used as
an example to explain this process.
Advisory Panel Review

In 1972, FDA appointed 17 independent advisory review panels consisting of
expert scientists, together with consumer and industry representatives, to
review the safety and efficacy of the marketed OTC drug products. Thus, the
OTC monograph system only included active ingredients present in products
on the market prior to its inception in 1972. FDA later changed this limitation
to include active ingredients present in products on the market prior to May
1975. An external Advisory Review Panel on OTC Topical Analgesic, Anti-
rheumatic, Otic, Burn, and Sunburn Prevention and Treatment Products (the
Panel) evaluated sunscreen drug products. The Panel was charged with deter-
mining whether each active ingredient in a sunscreen product was safe and effec-
tive for use as a sunscreen. To accomplish this task, the Panel assigned each
active ingredient to one of three categories:
. Category I: generally recognized as safe, generally recognized as effec-
tive (GRAS, GRAE)
. Category II: not generally recognized as safe, not generally recognized
as effective (not GRAS, not GRAE)
. Category III: more data need to be submitted; cannot determine safety
and effectiveness
A sunscreen active ingredient could fall into any of these categories during the
initial review. A separate assessment was made for efficacy and safety. For
example, the Panel found bornelone as safe (i.e., Category I for safety), but did
not have sufficient data to determine its effectiveness (i.e., Category III for effec-
tiveness). In addition, the panel recommended labeling, including therapeutic
indications, dosing, and warnings.
After the Panel met, FDA published the ANPR for OTC sunscreen products
in the Federal Register on August 25, 1978 (63 FR 38206). The ANPR
announced FDA’s intent to create the OTC sunscreen monograph. In addition,
the ANPR included the Panel Report, which contained the Panel’s conclusions
on whether each active ingredient was Category I, II, or III for safety and effec-
tiveness. The ANPR included a 90 day comment period, in which any interested
party could submit comments to FDA regarding the Panel’s conclusions.
Tentative Final Monograph

In the Federal Register of May 12, 1993 (58 FR 28194), FDA published an
advanced notice in the form of a Tentative Final Monograph for Sunscreen
Drug Products for OTC Human Use. This TFM was based on FDA’s evaluation
of the Panel’s findings and consideration of public comments submitted in
response to the ANPR. The TFM was FDA’s preliminary position regarding
the safety and effectiveness of particular active ingredients as well as acceptable
labeling and final formulation testing (i.e., SPF testing). Similar to the ANPR, the
TFM included a 90 day comment period. Regulations [21 CFR 330.10(a)(7)(iii)
and (iv)] also allow 12 months to submit new data and an additional 60 days to
submit comments on the new data.
Final Monograph
The Final Monograph for Sunscreen Drug Products for Over-The-Counter
Human Use was published on May 21, 1999. It was based on the FDA’s consider-
ation of public comments on the proposed TFM, and new data and information on
sunscreen drug products submitted to the FDA. Unlike a TFM, an FM typically
does not have a comment period. However, an FM has an effective date. In the
case of the OTC sunscreen FM, an effective date was included, but the FDA
later stayed the effective date, so the FM is not yet implemented. The FM was
stayed because it deals with UV-B protection and FDA wants to include UV-A
protection, which FDA will incorporate in a future rulemaking (Federal Register
66, pp. 67485 – 67487). Therefore, manufacturers can comply with the FM, but
they are not required to. After the FM becomes effective, any OTC sunscreen
drug product marketed in the USA under the monograph must meet all regulatory
specifications listed in the FM. Pre-approval by the FDA to market an OTC sun-
screen product is not required if the regulatory standards described in the mono-
graph are met.
Description of an OTC Drug Monograph

OTC drug monographs contain several components including, but not limited to,
the following:
. General provisions
. Active ingredients
. Labeling
– Indications for the product
– Warnings
– Drug interaction precautions
– Directions for use
– Specialized labeling
– Professional labeling
. Testing procedures
FDA refers to each of these components as conditions of use. The conditions of

use found in a monograph are those that FDA has found to be GRASE.
To understand the components of an OTC drug monograph, the OTC
sunscreen drug monograph will be described. The first section of the monograph
describes its purpose, certain definitions, and their abbreviations. The second
section of the monograph lists acceptable sunscreen active ingredients and
their concentrations that can be used in the finished OTC drug product. There
are a total of 16 sunscreen active ingredients listed in this section. Each of
these ingredients can be marketed within the concentration specified for each
ingredient, if the finished product provides a minimum SPF value of not less
than 2 as measured by the testing procedures specified in the monograph. This
section also identifies active ingredients that are allowed to be combined with
other active ingredients.
The labeling section describes the two parts of an OTC drug product label:
principal display panel (PDP) and Drug Facts panel. The PDP is the part of the
label that is most likely to be displayed or examined by consumers at a retail
site. Every manufacturer has the liberty of designing their labels. However,
there is certain information that is required to be displayed on the PDP. The
PDP of a sunscreen drug product is required to have a statement of identity or
the established name of the drug and must identify the product as a “sunscreen”.
The PDP must also list the product’s SPF value. If the product satisfies the water
resistant sunscreen product testing procedures as specified in the monograph, the
PDP must include a statement about its water resistance.
The Drug Facts panel must be displayed on the outer package of all OTC drug
products and is usually displayed on the back of the outer package. It has to meet
the requirements specified in the monograph as well as the requirements specified
in 21 CFR 201 Subpart C. The Drug Facts panel has a number of required headings:
. Active ingredient(s): This section must list all active ingredients, their
concentrations, and their statement of identity as a “sunscreen”.
. Uses: This section lists the indications for the particular product. The
only indication allowed under the monograph is the prevention of
sunburn. Also, sunscreen products that satisfy water resistance testing
have to list the time period of their efficacy after the water activity,
perspiration, or sweating.
. Warnings: This section contains a number of subheadings used to
describe contraindications, drug – drug interactions, as well as other
information about possible adverse events associated with the drug or
the condition that it treats.
. Directions: This section defines how to use the product, including the
amount of the drug to be used and the frequency. Specific instructions
are usually given for pediatric age groups.
Additional information on product performance may be added under the heading
Other information or anywhere outside the Drug Facts panel.
Following labeling, the FM specifies finished product testing procedures.

This is an important part of the FM and describes the conditions and procedures
for determining the SPF value and water resistance of a product. The testing pro-
cedures provide a detailed description of the standard (control) sunscreen compo-
sition and preparation, light source (solar simulator), sunscreen application,
subject irradiation, and calculations for determination of SPF value.
AMENDING AN OTC DRUG MONOGRAPH

A drug manufacturer or any other party may wish to alter the conditions of use in
an OTC drug monograph. For example, a manufacturer may wish to market a
drug product with an active ingredient concentration higher than the upper
limit listed in an OTC drug monograph. There are two mechanisms by which a
drug manufacturer or any other interested party can amend an OTC drug final
monograph:
. Citizen petition
. Time and extent application (TEA)
Neither of these mechanisms require that any additional fees other than the drug
registration and listing fee be paid to FDA. However, there are many differences
between these two mechanisms.
Citizen Petition
The citizen petition (petition) process is described in 21 CFR 10.30. A petition
can be submitted to FDA at any time to amend a TFM or FM for any OTC
drug category. A petition is used to submit data and comments after the
comment and data periods have expired following publication of an ANPR,
TFM, or FM. A petitioner can request that FDA amend any condition of use
allowed by an OTC drug monograph (see previous section). One limitation to
amending conditions of use allowed by an OTC drug monograph is that the
condition must have existed in the marketplace prior to 1975.
The FDA must issue a response to the petition within 180 days. However,
this response is often an interim response because FDA typically cannot complete
the review of a petition within this time frame. After FDA reviews a petition, it
either grants or denies the petition. If FDA grants a petition, the appropriate OTC
drug monograph is amended by the publication of a rulemaking in the Federal
Register. If FDA denies a petition, FDA sends the petitioner a letter explaining
why the petition was denied.
Time and Extent Application

The TEA is a regulatory process that allows conditions of use not found in
the OTC marketplace prior to 1975 to be considered for inclusion in an OTC
drug monograph. FDA created the TEA to allow conditions of use to meet the
marketing “for a material time” and “to a material extent” requirements of

Section 201(p) of the Act. These requirements must be met for a condition of
use to be GRASE. Thus, a TEA can be used in two situations:
. Conditions of use found in drug products sold in the USA under NDAs
. Conditions of use found in products sold outside the USA
The second situation can describe various types of products marketed as OTC
drug products or cosmetic drug products in other countries. Products regulated
as drug products in the USA may not be regulated as drug products in other
countries even though similar testing requirements are necessary for marketing
(e.g., sunscreens are regulated as cosmetics in the UK and as drug products in
the USA).
The basic requirement for submission of a TEA is that a condition of use
be marketed for a minimum of five continuous years in the same country and
in sufficient quantity (21 CFR 330.14). The TEA is essentially a two-step process:
1. TEA submission to determine eligibility
2. Submission of safety and effectiveness data and review of the data
by FDA
During the first step, an applicant submits information related to the marketing
experience of a condition. Initially, the TEA is considered confidential, similar
to an NDA. FDA reviews the marketing information to determine whether the
condition has been marketed for a material time and to a material extent. If the
condition does not meet these requirements, the applicant is sent a letter
stating that the condition is ineligible to be included in the OTC drug review
and explaining the reason(s) for this decision. In this case, the letter is put on
public display, but the TEA remains confidential.
If the condition is eligible to be included in the OTC drug review, FDA
publishes a notice of eligibility in the Federal Register and a request for data.
FDA’s review of the TEA and the redacted TEA are put on public display. This
leads to the second step in the TEA process, which are FDA review of safety
and effectiveness data. After FDA reviews the data, FDA publishes a rulemaking
in the Federal Register. The rulemaking contains FDA’s conclusions regarding
whether the condition is Category I, II, or III for safety and effectiveness. If
the condition is found to be GRASE (Category I), the applicable OTC drug
monograph(s) will be amended to allow the condition to be marketed.
7
The Final Monograph
Emalee G. Murphy
Kirkpatrick & Lockhart LLP,
Washington, DC, USA
History and Scope of the Regulation 96

Key Provisions of the Final Monograph 101
Permitted Active Sunscreen Ingredients 101
Ingredients Listed in 21 CFR 352.10 101
Active Ingredient Combinations 102
Sunscreen Active Ingredient Combination Pattern A 102
Sunscreen Active Ingredient Combination Pattern B 103
Ingredients for Combination Sunscreen – Skin Protectant Products 103
Combinations of Sunscreens and Skin Protectant Ingredients 103
Labeling Requirements 104
On the Principal Display Panel 105
In the Drug Facts Panel 106
Labeling Caveats 108
Antiaging/Antiphotoaging 109
Tanning Accelerators, Melanin and Antioxidants 109
Warnings for Tanning Products without Sunscreens 109
“Chemical-free”, “Natural”, and “PABA-free” Ingredients 110
Extended Protection Claims 110
Freckles and Uneven Skin Tone 110
Testing Sunscreen Efficacy 111
What of the Future? 111
FDA Requests for Information and Comment 112
Conclusion 114
95
96 Murphy
HISTORY AND SCOPE OF THE REGULATION

The US Food and Drug Administration (FDA) published the Final Rule for
Sunscreen Drug Products for Over-the-Counter Human Use on May 21, 1999,1
and the resulting regulation (or monograph) is codified in 21 Code of Federal
Regulations (CFR), Parts 352.1 –352.77, 310.545, 700.35, and 740.19. The
Rule establishes the conditions under which a sunscreen is “generally recognized
as safe and effective” and not misbranded for its intended use by identifying the
authorized monograph sunscreen active ingredients, their permitted combi-
nations, and any limitations on their use; establishes the required label statements
and format for all sunscreen drug products; and sets forth the official test method to
determine sun protection factor (SPF) values and performance claims such as
“water resistant/very water resistant”. A major regulatory advantage of compli-
ance with the Final Rule is that sunscreen products formulated and labeled in
accordance with the Final Rule and that also comply with other general require-
ments for over the counter (OTC) drug products and facilities2 may be placed
on the US market without further FDA review and are not subject to new drug
approval procedures.
The Final Rule is the result of over 20 years’ deliberation by FDA and
interested parties on the legitimate scientific and legal grounds for regulating sun
protection products, which at one time were viewed by many as no more in the
drug category than were sun bonnets. The evolution of the Rule, its scope, and
history, including the agency’s legal rationale for sunscreen drug regulations, are
best elucidated in the preambles to FDA’s Advance Notice of Proposed Rulemaking
(ANPR), the Proposed Rule, and its various amendments. Although some originally
questioned FDA’s classification of sunscreens as drugs,3 the agency’s rationale was
predicated on prior Trade Correspondence issued in the 1940s, in which it had
clearly differentiated sun tanning products as cosmetics and sunburn protection pro-
ducts as drugs.4 In the preamble to the Proposed Rule, FDA explained its decision to
apply the drug sunscreen requirements to cosmetic products bearing sunscreen
claims as well as to traditional “beach” sunscreens, stating,
Sunscreen products are marketed with various intended uses, such as (1)
beach products for occasional use to protect consumers from extreme
1
64 Fed. Reg. 27666 (May 21, 1999).
2
For example, Drug Establishment Registration and Drug Listing Requirements set forth at 21 Code of
Federal Regulations (CFR) 207; Current Good Manufacturing Procedures for Finished Pharma-
ceutical Products set forth at 21 CFR 211; OTC drug labeling requirements at 21 CFR 369; and
color additive regulations for drug products at 21 CFR parts 73 and 74.
3
See Cosmetic, Toiletry, and Fragrance Association comments, 1978 (Docket 78N-0038).
4
Trade Correspondence No. TC-61 (February 15, 1940) stated that a product promoted for prevention
of damage from the sun is a drug, and a product that is promoted solely for the purpose of acquiring an
even tan can be considered a cosmetic. The Final Rule includes a provision that revokes TC-61 as the
regulation supersedes the Trade Correspondence.
The Final Monograph 97
sunlight conditions, (2) tanning products to aid consumers in acquiring a

tan, and (3) non-beach products for daily use to protect consumers from
chronic exposure to sunlight (e.g., make-up preparations and lipsticks).
Although these intended uses are different, the agency considers each
one a drug use.
Beach products are considered drugs because they prevent sunburn,
protect the skin against harm from the sun, and prevent skin damage
through overexposure to the sun. In addition, consumers equate these pro-
ducts with mitigating harmful effects from the sun. For these reasons,
sunscreen beach products are drugs under section 201(g)(1)(B) [of the
Federal Food, Drug, and Cosmetic Act]. Such products are also drugs
under section 201(g)(1)(C) because they affect the body’s physiological
response to solar radiation (i.e., they lessen the erythema reaction).
Tanning products that contain sunscreens are drugs because they
prevent a sunburn . . . and affect melanogenesis . . . . Non-beach sun-
screen products are drugs because they prevent lip or skin damage . . . as
well as freckling, and uneven skin coloration . . . .5
FDA further clarified its view of sunscreen drug identity by stating,
When an ingredient can be used for either drug or cosmetic purposes, its
regulatory status is determined by objective evidence of the distributor’s
intent . . . this includes, but is not limited to, the representations made by
the manufacturer or distributor in the labeling or promotion of the
product. The agency believes that the inclusion of a sunscreen active
ingredient in a product that is intended or promoted to protect the consu-
mer’s skin from the harmful effects of the sun brings the product within
the statutory definition of a drug . . . . Such intent may be derived from
labeling, promotional material, advertising, and any other relevant
source [including] the consumer’s intent in using the product . . . . The
agency believes that all products containing a sunscreen active ingredi-
ent and claiming to protect the consumer from the sun or to enhance the
consumer’s ability to obtain an effect from sun exposure (i.e., a tan) must
be regulated as drugs in order to ensure the effectiveness of the sunscreen
ingredient . . . [with a few select exceptions . . .] such products may also
be regulated, but not solely, as cosmetics.6 (Emphasis added.)
Accordingly, products that contain one or more active sunscreen products
and are represented as intended to protect the skin from the sun, including the use
of words such as “sunscreen”, “sun block”, “sunshield” and phrases such as
5
56 Fed. Reg. 28194, 28195 (May 12, 1993). The Federal Food, Drug, and Cosmetic Act (FDC Act)
defines a drug as “an article intended for use in the diagnosis, cure, mitigation, treatment, or prevention
of disease” or “intended to affect the structure or any function of the body”. 21 USC 321(g) (2003).
6
56 Fed. Reg. 28204, 28205.
98 Murphy
“helps to acquire an even tan” and “protects against premature skin aging”, are
regulated as drugs. Furthermore, FDA concluded that references to “tanning”
in product labeling are so closely allied with sun protection that sun tanning
lotions without sunscreens are required to bear a warning statement, discussed
below. Shampoos, hair conditioners, hair sprays, nail polishes and similar pro-
ducts may contain a sunscreen for nontherapeutic use and will not be regulated
as drugs as long as the labeling clearly describes the nontherapeutic nature of
the sunscreen. For example, an appropriate explanatory phrase on the label
might state, “This product contains a sunscreen to protect the hair from
damage caused by the sun” or “Contains a sunscreen to protect product color”.
FDA issued the Final Rule as part of the agency’s ongoing review of non-
prescription drug active ingredients the OTC Drug Review.7 The procedures for
the Review started with an initial call for data in support of the safety and efficacy
of particular sunscreen active ingredients, which were evaluated by a specially
appointed panel of independent experts, the Advisory Review Panel on OTC
Topical Analgesic, Antirheumatic, Otic, Burn, and Sunburn Prevention Drug
Products. To be included in the OTC Drug Review program, the drug substance
must have been on the US market as a sunscreen agent prior to December 4, 1975.8
The Panel’s task was to assess the information voluntarily submitted by interested
parties and to give FDA its written views on the safety and effectiveness of each
active ingredient as a sunscreen agent. Importantly, the OTC Review Panel was
tasked to assess only the active sunscreen agents; inactive ingredients used in
OTC drug products are beyond the scope of the Review. Inactive ingredients
in OTC drug products are generally unregulated, except that they must be safe
and suitable for their intended use and must not interfere with the product effec-
tiveness or with analyses to determine the identity, strength, quality, or purity of
the active ingredient(s).9
The agency published the unaltered Panel Report as the ANPR to establish
a monograph for OTC drug sunscreen products in the August 25, 1978, Federal
Register,10 and provided interested parties the opportunity to comment. The pre-
amble to the ANPR is a valuable source of information on the products and active
sunscreens then on the US market, the studies and literature used by the Panel to
make its safety and effectiveness decisions (all of which are available from FDA
through the Freedom of Information Act procedures), and the initial discussions
of UV radiation characteristics and the most appropriate product sunscreen effi-
cacy testing methodology, for which at that time no uniform standard procedure
existed.
7
The review of nonprescription active ingredients was mandated by the 1962 New Drug Amendments
to the Federal Food, Drug, and Cosmetic Act which, in brief, required that all drug products be
evaluated for safety and effectiveness.
8
21 CFR 330.13(a).
9
21 CFR 330.1(e).
10
43 Fed. Reg. 38206 (August 25, 1978).
The subsequent Notice of Proposed Rulemaking for OTC Drug Sunscreen

Products (the Proposed Rule or Proposal) that was issued in the May 12, 1993,
Federal Register 11 reflects FDA’s initial response to the significant advances
in sunscreen marketing, safety, and technology developed during the years
between 1978 and 1993. In one of the agency’s most controversial decisions,
FDA proposed to limit the maximum SPF value to SPF 30. FDA also proposed
that the SPF value appear on the product principal display panel of all sunscreen
products and eliminated the minimum levels of active sunscreen ingredients,
except for sunscreen actives in combination with another sunscreen or any
other active ingredient.12 The Proposal also confirmed that all sunscreens
included in an OTC final monograph must be adequately and publicly character-
ized in a United States Pharmacopoeia (USP) monograph. FDA simplified sun-
screen labeling terminology; shortened and consolidated the required label
statements; and addressed claims such as “antiaging”, “premature aging of the
skin”, “accelerates tanning”, and other similar representations that had pro-
liferated in sunscreen labeling since the publication of the original ANPR. In
addition, the Proposal further clarified the methodology used to determine the
effectiveness of sunscreen products and sunscreen products represented as
“water resistant” or “very water resistant”.
The Proposal reflected FDA’s ongoing concerns about sunscreen safety and
effectiveness. For example, information pertaining to the safety of Padimate A
led to its deletion from the list of sunscreens in the Proposed Rule, while infor-
mation concerning the effect of nitrosating agents in sunscreens such as Padimate
O was investigated and resolved.13 During the 15 years between 1978 and the
long-awaited publication of the Proposal in 1993, FDA continued to address
issues such as sunscreen testing methodology in separate Federal Register
notices and at FDA-sponsored meetings.14 Following public comment on the
11
58 Fed. Reg. 28194 (May 12, 1993).
12
FDA eliminated the minimum levels of sunscreen ingredients for single drug category products
because the effectiveness of a sunscreen product is not measured merely by the amounts of active
in the product.
13
The Proposed Rule describes the methodology developed by FDA and the industry to identify and
determine the quantitative presence of the new nitrosamine, n-methyl-N-nitrosaminobenzoate octyl
ester (NMPABAO). As the presence of NMPABAO in sunscreen drug products containing Padimate
O also depends upon the presence of a nitrosating agent, such as the preservative 2-bromo-2-nitro-1,
3-propandiol, FDA concluded that Padimate O could be safely used in formulations without direct or
indirect nitrosating agents. Although FDA set no limits for the presence of NMPABAO in sunscreen
products, the agency suggested a maximum limit of 500 ppb and requested comment. The Final Rule
did not include any maximum limit for NMPABAO.
14
After having extended the comment period from November 24, 1978 to December 26, 1978, FDA
reopened the administrative record in March 1980 45 Fed. Reg. 18403 (March 21, 1980), to permit
consideration of information filed with FDA after the original submission period ended. Testing
methods for sunscreen finished products and claims were the most significant issues. FDA reopened
the administrative record once again in 1987 in order to hold a public meeting to discuss the
recommendations of the Panel on testing and claims issues. 52 Fed. Reg. 3598 (September 4, 1987).
100 Murphy
Proposed Rule, FDA reopened the administrative record in 1994 to solicit com-
ments on an amendment to the Proposal that would eliminate five sunscreen
active ingredients for which there appeared to be no public interest in develop-
ing USP monographs.15 Altogether, 6 of the original 21 ingredients proposed as
safe and effective in the ANPR did not appear in the Final Rule.16 In 1996,
FDA amended the Proposed Rule to add the ingredient avobenzone as a
single active sunscreen agent and in combination with certain other active
sunscreens,17 and in 1998, FDA proposed to include zinc oxide as a single
ingredient and in combination with any other proposed active sunscreen,
except avobenzone.18 Both avobenzone and zinc oxide are included in the
Final Rule.
In addition to modifying the list of proposed active sunscreen ingredients,
FDA also reopened the administrative record twice to consider issues related to
the safety and effectiveness of OTC drug sunscreen products and ingredients. The
agency announced a public meeting in 1994 to discuss ultraviolet A (UV-A) radi-
ation claims19 and again in 1996 to announce a public meeting on the photo-
chemistry and photobiology of sunscreens.20 FDA’s conclusions concerning
UV-A testing are not included in the Final Rule and, according to the agency,
will be discussed in future issues of the Federal Register. In the interim, the pre-
amble to the Final Rule indicates that UV-A labeling may continue in accordance
with the Proposed Rule.21 In that document, FDA suggested that in certain
circumstances, UV-A labeling may be appropriate if the ingredient(s) used in a
product has an absorption rate that extends to 360 nm or above in the UV-A
range. Although UV-A effectiveness and testing was beyond the scope of the
original Advisory Panel evaluation, the Panel did evaluate a combination of
lawsone with dihydroxyacetone, which it stated had been shown as effective
against both UV-B and UV-A radiation (to 400 nm). Because the agency believes
that information about UV-A protection is important to consumer health and
safety, it acknowledged that the lawsone/dihydroxyacetone combination could
bear claims to UV-A protection, as could any other monograph sunscreen
active ingredient able to demonstrate UV-A protection in the 360– 400 nm
Until May 26, 1988, FDA accepted comments on new information submitted in connection with the
public hearing discussion. FDA’s Proposed Rule appeared in the May 12, 1993 Federal Register. 58
Fed. Reg. 29194.
15
59 Fed. Reg. 29706 (June 8, 1994).
16
Padimate A (eliminated for safety reasons), digalloyl trioleate, ethyl 4-[bis(hydroxypropyl) amino-
benzoate], glyceryl aminobenzoate, lawsone with dihydroxyacetone, red petrolatum, and diethanola-
mine methoxycinnamate.
17
61 Fed. Reg. 48645 (September 16, 1996).
18
63 Fed. Reg. 56584 (October 22, 1998).
19
59 FR 16042 (April 5, 1994).
20
61 Fed. Reg. 42398 (August 15, 1996).
21
64 Fed. Reg. 27666 at 27667.
range.22 In its discussion of UV radiation claims, the agency noted that the
radiation that reaches the earth is in the UV portion (290 – 400 nm) of the sun’s
spectrum, and that any other claims to protection from visible light or infrared
light are inconsistent with this and would cause any product so represented to
be considered an unapproved new drug.
The public hearing announced by FDA in 1996 and the subsequent
discussion of the photochemistry and photobiology of sunscreens addressed,
among other issues, the safety and efficacy of micronized titanium dioxide and
the question whether the micronized version of the ingredient should be con-
sidered a new drug substance. FDA rejected the notion that the micronized ingre-
dient should be considered a new drug. Interestingly, data submitted to FDA in
connection with the public hearings on the subject indicated that micronized tita-
nium dioxide absorbs short-wavelength UV radiation and reflects and scatters
long wavelengths, thereby functioning similarly to chemical UV-B radiation
sunscreens.
KEY PROVISIONS OF THE FINAL MONOGRAPH

The key provisions in the Final Sunscreen Rule are the identification of permitted
active ingredients and combinations, uniform labeling of sunscreens, and clarifi-
cation of permitted performance claims and of the test methods to determine
sunscreen effectiveness against radiation in the UV-B range. This section
describes these provisions in summary.
Permitted Active Sunscreen Ingredients

Sunscreen active ingredients, as defined in the Final Rule, are those ingredients
listed in the regulation in 21 CFR 352.10 that “absorb, reflect, or scatter radiation
in the UV range at wavelengths from 290 to 400 nanometers”. The following
ingredients and maximum concentrations are permitted for use as sunscreen
active ingredients, provided that the finished product provides a minimum SPF
value of not less than SPF 2 as measured by the testing procedures set forth in
the monograph. These ingredients are the subjects of USP monographs, and
the new drug names indicated for some of the ingredients reflect the USP estab-
lished name of the ingredient. Any future sunscreen active ingredient listed in the
Final Rule must likewise be the subject of a monograph published in the USP.
Ingredients Listed in 21 CFR 352.10
(a) Aminobenzoic acid (PABA) up to 15%
(b) Avobenzone up to 3%
(c) Cinoxate up to 3%
(d) Reserved
22
58 Fed. Reg. 28194 at 28232.
102 Murphy
(e) Dioxybenzone up to 3%
(f) Homosalate up to 15%
(g) Reserved
(h) Menthyl anthranilate up to 5% (now Meridamate)
(i) Octocrylene up to 10%
(j) Octylmethoxycinnamate up to 7.5% (now Octinoxate)
(k) Octylsalicylate up to 5% (now Octisalate)
(l) Oxybenzone up to 6%
(m) Padimate O up to 8%
(n) Phenylbenzimidazole sulfonic acid up to 4% (now Enzulisole)
(o) Sulisobenzone up to 10%
(p) Titanium dioxide up to 25%
(q) Trolamine salicylate up to 12%
(r) Zinc oxide up to 25%
Active Ingredient Combinations

The following sunscreens may be combined with each other in a single product
when used in the prescribed concentrations. The Final Rule sets no minimum
concentration levels, but the amount of each active ingredient in a combination
must contribute a minimum SPF of at least 2 to the finished product. In addition,
the finished product must have a minimum SPF of not less than the number of
sunscreens in the combination, multiplied by 2.
Sunscreen Active Ingredient Combination Pattern A

Any of the following ingredients may be combined up to the indicated maximum
concentrations:
(a) Aminobenzoic acid (PABA) up to 15%
(h) Menthyl anthranilate up to 5%
(j) Octylmethoxycinnamate up to 7.5%
(k) Octylsalicylate up to 5%
(m) Padimate O up to 8%
(n) Phenylbenzimidazole sulfonic acid up to 4%
(p) Titanium dioxide up to 25%
(r) Zinc oxide up to 25%
Sunscreen Active Ingredient Combination Pattern B

The following ingredients may be combined up to the indicated maximum
concentrations:
(b) Avobenzone up to 3%
(j) Octylmethoxycinnamate up to 7.5%
(k) Octylsalicylate up to 5%
Ingredients for Combination Sunscreen–Skin Protectant Products

The Final Rule provided for combination sunscreen –skin protectant products
without specifying the specific permitted ingredient combinations allowed.
Since publication of the Final Sunscreen Rule, FDA has issued the Final Rule
for OTC Drug Skin Protectant Products for Human Use,23 which sets forth the
following permitted sunscreen –skin protectant combinations:
Combinations of Sunscreens and Skin Protectant Ingredients

Any sunscreen ingredient may be combined with any of the following skin
protectant ingredients:
(a) Allantoin, 0.5 – 2%
(d) Cocoa butter, 50 – 100%
(e) Cod liver oil, 5 – 13.56%, in accordance with Section 347.20(a)(1) or
(a)(2), provided the product is labeled so that the quantity used in a
24 h period does not exceed 10,000 U.S.P. units vitamin A and 400
U.S.P. units cholecalciferol
(g) Dimethicone, 1 –30%
(h) Glycerin, 20– 45%
(i) Hard fat, 50– 100%
(k) Lanolin, 12.5 –50%
(l) Mineral oil, 50 –100%; 30 – 35% in combination with colloidal
oatmeal in accordance with § 347.20(a)(4)
(m) Petrolatum, 30– 100%
(r) White petrolatum, 30 –100%
23
Final Monograph for Skin Protectant Drug Products, 68 Fed. Reg. 33362 (June 4, 2003), codified at
21 CFR 347.20(d).
104 Murphy
LABELING REQUIREMENTS
The Final Rule simplifies and consolidates the required labeling for sunscreen
products. The SPF value, which must appear on the principal display and front
panels of the sunscreen immediate and outer containers, is limited to SPF 30
“Plus” (or “ þ ”) and the original five product category designations (PCD)
have been reduced to three. Use of the PCD language in labeling is optional:
Chart 1—Product Category Descriptions
Minimal sun protection product (Provides an SPF value of 2 to

under 12)
Moderate sun protection product (Provides an SPF value of 12 to
under 30)
High sun protection product (Provides an SPF value of 30 or
above)
Permitted claims for products in the three PCD categories include:
Chart 2—Permitted Claims for Product Category Descriptions
SPF 2 to under 12 “Provides minimum/minimal protection against

sunburn/sunburn and tanning” or “For skin that
sunburns minimally”
SPF 12 to under 30 “Provides moderate protection against sunburn/
sunburn and tanning” or “For skin that sunburns
moderately”
SPF 30 or 30þ “Provides high protection against sunburn/
sunburn and tanning” or “For skin that sunburns
easily”
The Proposed Rule would have limited sunscreen SPF values to 30. Many com-
ments requested that FDA either set no limit on sunscreen SPF values or that the
limit be set at SPF 50. These comments suggested that higher SPF value products
are needed to protect the consumer from increased lifestyle and environmental
exposure to the sun, because sensitive-skinned persons may burn even with
SPF 30 products. Furthermore, comments suggested that higher SPF values
could be achieved through formulation changes rather than through increased
concentrations of active ingredients, although information available at that
time did not support any relationship between high SPF values and safety con-
cerns. Other comments noted that limiting SPF values would stifle sunscreen
product development and preventative health benefits, such as increased pro-
tection from UV radiation-induced photoimmunosuppression. On the other
hand, many argued that the proposal to limit SPF values to 30 would stop the
promotional “bidding war” surrounding high SPF value products.
FDA struck a compromise by permitting higher SPF formulations while

limiting the labeled SPF value to 30þ. While the agency agreed on the need for
higher SPF products and acknowledged the apparent lack of safety issues, it
was concerned that the testing methods developed to determine lower SPF
values might not be able to accurately and reproducibly determine higher
SPF values. Furthermore, the incremental increase in protection provided by an
SPF 30 product and an SPF 50 product is not easily evident to the consumer
due to the nonlinearity of the SPF rating system. Nevertheless, the agency
encouraged interested parties to continue development of test methods suitable
for assessing the effectiveness of high SPF products and to submit test data in
support of such methods to FDA. In fact, FDA has indicated that test methodology
and the related search for appropriate terminology to describe the benefits afforded
by higher SPF products will be the subject of a future Federal Register notice.
As previously stated, the Final Rule greatly simplified (and limited) the
general labeling requirements for OTC drug sunscreen products. In part, this
was undoubtedly in response to the publication of FDA’s regulation to standar-
dize all OTC drug labels by establishing a uniform format for the presentation
of required label statements.24 The drug facts panel format adopted by FDA
leaves little room for lengthy product descriptions and the final language of the
sunscreen monograph seems to be designed to accommodate this more restricted
labeling concept. Despite urgent requests by industry, with the exception of lip
products, FDA made no distinction in the Final Rule between labeling require-
ments for “beach” products and those for products normally marketed as
cosmetics and formulated with sunscreens for daily sun protection.
The exceptions for lipsticks and lip balms are limited and include provisions
to omit the otherwise required statements, “For external use only” and “When
using this product, keep out of eyes. Rinse with water to remove”. In addition,
the directions to apply the product “generously”, “liberally”, “smoothly”, or
“evenly” and to “ask a doctor about use for children under 6 months” are not
required for lip products. FDA also notes that the modified drug facts panel label-
ing permitted that certain small containers by 21 CFR 201.66(d)(10) be used for
sunscreen products labeled for use only on specific small areas of the face, such as
the lips, nose, ears, or around the eyes.
With these exceptions, all sunscreens must bear the following information
required by the Final Rule and other labeling regulations applicable to OTC drugs
generally.25
On the Principal Display Panel

1. The established name of the drug (if any) and the identification
“sunscreen”
24
64 Fed. Reg. 13254 (March 17, 1999), codified at 21 CFR 201.66.
25
21 CFR 201.1– 201.323, 21 CFR 310.
106 Murphy
2. The SPF value up to 30 (and for products with SPF values higher than
30), the designation 30 plus or 30þ
3. If applicable, the statement “Water/Sweat Resistant” or “Water/
Perspiration Resistant” or “Very Water/Sweat Resistant” or “Very
Water/Perspiration Resistant”
If a “water resistant” or a “very water resistant” claim is made for the product, the
labeled SPF must be the value obtained after the product has been tested using the
water- resistant or very water-resistant testing procedures outlined in the regu-
lation. There is no special test method for perspiration claims, as these are sup-
ported by data generated from the water resistance trials. Regardless of the
product’s properties, water resistance claims are optional even if the product
passes the testing.
In the Drug Facts Panel

1. Under the heading “Active Ingredient”, the name of the drug ingre-
dient and its percentage in the product and the purpose “Sunscreen”.
2. Under the heading “Uses”, the statements “Helps prevent sunburn”
and, for example, “Higher SPF gives more sunburn protection”. If
applicable, the statements “Retains SPF after [40]/[80] minutes of
activity in the water/sweating/perspiring”. In addition, the Uses
section of the panel may also include a reference to the SPF-related
Product Category Description claims (see chart 2 given earlier).
3. Under the heading “Warnings”, the statements “Keep out of reach of
children”, “For external use only”, “When using this product, keep out
of eyes. Rinse with water to remove”, and “Stop use and ask a doctor if
rash or irritation develops and lasts”.
4. Under the heading “Directions”, the statements, “Apply generously/
liberally/smoothly/or evenly [insert an appropriate time interval if a
waiting period is needed] before sun exposure and as needed”, and
“Children under 6 months of age, ask a doctor”. In addition, the Direc-
tions section of the panel may delete the phrase “as needed” above and
substitute “Reapply as needed or after towel drying, swimming/sweat-
ing/perspiring”.
5. The following optional statements may appear in the drug facts
panel under the heading “Other Information” or anywhere outside
the panel: a reference to the applicable product performance claim
(see chart 2) and/or the statement, “Sun Alert: Limiting sun exposure,
wearing protective clothing, and using sunscreens may reduce the risks
of skin aging, skin cancer, and other harmful effects of the sun”.
6. Under the heading “Inactive Ingredients”, a declaration of the
excipients in the product, listed in alphabetical order in the product,
except that in the case of products also regulated as cosmetics, the
ingredients should be declared in the order of predominance in the

product.26
7. Under the heading “Questions”, the panel may also include a telephone
number or address for further information.
Example Sunscreen Drug Facts Panel
DRUG FACTS
Active Ingredients Purpose
Titanium Dioxide (10%) Sunscreen
Zinc Oxide (5%) Sunscreen
Uses
B Helps prevent sunburn
B Higher SPF gives more sunburn protection
B Retains SPF after 40 minutes of activity in the water
B Provides moderate protection
Warnings
For external use only
When using this product
B Keep out of eyes. Rinse with water to remove
Stop use and ask a doctor if

B rash or irritation develops and lasts
Keep out of reach of children. If swallowed, get medical help or contact a
Poison Control Center right away.
Directions
B Apply generously and uniformly before sun exposure, repeat application
every two hours and after swimming.
B Children under 6 months of age: ask a doctor
Inactive Ingredients: LIST IN ALPHABETICAL ORDER
The Final Rule also addresses the labeling of products represented both as sun-
screens and as skin protectants and permits statements of identity, indications,
warnings, and directions for use applicable to each product type to be combined
to eliminate duplications. Where time intervals or age limits related to use of the
product as a sunscreen or skin protectant differ, the directions for the combination
product may not recommend any dosage that exceeds that of any individual
ingredient in the applicable monographs or provide for use by any age group
lower than the highest minimum age limit in an individual monograph. The
principal display panel of a combination sunscreen/skin protectant product
26
21 CFR 201.10.
108 Murphy
must include the required statements for both product types, for example,
“Sunscreen/Skin Protectant; SPF 20; Very Water-Resistant”.
Example Sunscreen/Skin Protectant Drug Facts Panel
DRUG FACTS
Active Ingredients Purpose
Titanium Dioxide (10%) Sunscreen
Zinc Oxide (5%) Sunscreen
Glycerin (30%) Skin Protectant
Uses
B Helps protect against sunburn
B Higher SPF gives more sunburn protection
B Retains SPF after 40 minutes of activity in the water
B Provides moderate protection
B Temporarily protects and helps relieve chapped or cracked skin
Warnings
When using this product
B Keep out of eyes. Rinse with water to remove
Do not use on
B deep or puncture wounds
B animal bits
B serious burns
Stop use and ask a doctor if

Brash or irritation develops and lasts more than 7 days or clears up and
occurs again within a few days
Keep out of reach of children. If swallowed, get medical help or contact a
Poison Control Center right away.
Directions
B Apply generously and uniformly before sun exposure, repeat application
every two hours and after swimming.
B Children under 6 months of age: ask a doctor
Inactive Ingredients: LIST IN ALPHABETICAL ORDER
LABELING CAVEATS
The Final Rule clarifies the agency’s position on specific other product performance
claims for sunscreens including claims for antiaging and photoaging effects; tanning
acceleration; melanin and antioxidant effectiveness; sunless tanning products;
“chemical-free”, “PABA-free”, and “natural” ingredient claims; extended protection
claims; and some claims that were previously included as acceptable indications in
the Proposed Rule, such as “protection from freckles and uneven skin tone”.
Antiaging/Antiphotoaging
The only statement permitted by the Final Rule related to antiaging and photo-
aging is the voluntary Sun Alert statement:
Sun Alert: Limiting sun exposure, wearing protective clothing, and
using sunscreens may reduce the risks of skin aging, skin cancer, and
other harmful effects of the sun.
Variations in the statement will cause the product to be misbranded. In
addition, an OTC sunscreen drug that uses “antiaging” language in the labeling to
suggest any unapproved therapeutic or physiologic effect would “likely be subject
to regulatory action as an unapproved new drug”.27 Products without sunscreen
ingredients or sunscreening claims but which use “antiaging” language in labeling
or in the product name would not fall within the OTC sunscreen drug category.
However, depending on the claims made and the circumstances of distribution,
FDA could also consider such a product to be an unapproved new drug. As a prac-
tical matter, FDA has tended to rigorously enforce use of unacceptable claims on
products clearly within established OTC drug categories, including sunscreens.
Tanning Accelerators, Melanin and Antioxidants

The preamble to the Final Rule addresses FDA’s view that products represented
to accelerate or stimulate the tanning process or to stimulate the production of
melanin in the body are unapproved new drugs because the intended use of the
product is to affect the structure or function of the body. Products represented
to contain melanin as a sunscreen ingredient are likewise unapproved new
drugs because melanin is not included in the Final Rule as a safe and effective
sunscreen ingredient. In addressing label references to antioxidants and free rad-
icals, FDA acknowledges protection claims attributed to antioxidants in some
cosmetic product labeling and intends to address them on a case-by-case basis.
Warnings for Tanning Products without Sunscreens

Products represented solely as cosmetics, such as sunless tanning products,
moisturizers for use during or after sun exposure, and “bronzers” to impart
color without tanning or to enhance tanning in some other way and which do
not contain sunscreens, must include the warning statement required under the
Final Rule by new section 21 CFR 740.19, namely:
Warning—This product does not contain a sunscreen and does not
protect against sunburn. Repeated exposure of unprotected skin while
27
64 Fed. Reg. 27666 at 27673.
110 Murphy
tanning may increase the risk of skin aging, skin cancer, and other
effects to the skin even if you do not burn.
“Chemical-free”, “Natural”, and “PABA-free” Ingredients

The terms “chemical-free”, “non-chemical”, and “natural” have been applied to
some products containing mineral sunscreens, such as titanium dioxide and zinc
oxide. FDA states in the Final Rule that all sunscreen products contain active and
inactive ingredients obtained through some chemical process or formulated into
the finished product by a chemical process. Therefore, the use of these terms to
describe either the sunscreen ingredient or the finished product is likely to be unac-
ceptable. However, FDA intends to review such claims on a case-by-case basis.
FDA agrees that consumers are familiar with the term “PABA” and might
not recognize the compendial (USP) name, “aminobenzoic acid”, and to eliminate
the term “PABA” from sunscreen labeling could cause some consumers to use a
product to which they have an allergy and to suffer adverse health effects. There-
fore, FDA concludes that wherever the ingredient “aminobenzoic acid” appears in
the labeling of an OTC drug sunscreen product, “including labeling that notes the
absence of this ingredient”, the descriptive term “PABA” must immediately follow
the established name. A product that is marketed as “PABA-free” is now required
to state that the product is “Aminobenzoic acid (PABA)-free”.
Extended Protection Claims

Some comments on the Proposed Rule suggested that the “very water resistant”
claim be expanded beyond the 80 min test period for products that can show such
extended efficacy. FDA acknowledges in the Final Rule that data submitted do
indicate that under testing conditions, some products may retain their SPF
values for up to 270 min. However, as no usage data were submitted to refute
the Advisory Panel’s contention that 80 min is an appropriate upper exposure
limit, FDA opted to retain the 80 min test protocol. Thus, a claim for extended
water resistance is outside the Final Rule and would be subject to review
under a new drug application. FDA noted that it would revisit the question
should it receive usage data indicating consumer patterns of more than 80 min
of water exposure. In addition, references to “prolonged exposure time”, orig-
inally present in the Proposed Rule, are omitted from the final product category
descriptions because, as FDA states in the preamble to the Final Rule, these
claims could send the wrong message about the dangers of even suberythmal,
nonburning sun exposure.
Freckles and Uneven Skin Tone

The Proposed Rule would have allowed sunscreen-containing makeup pre-
parations, lip products, and skin preparations to be represented as effective in the
prevention of “lip damage”, “freckling”, or “uneven skin tone”. However, these
indications have been dropped from the Final Rule on the basis that the SPF testing
predicts protection only from UV-B sunburn, and because freckling, skin tone and
lip damage may be attributable to UV-A, as well as to UV-B, radiation. FDA noted
that it would revisit the question of such claims when specific supportive data are
provided or a specific clinically relevant final formulation test is developed.
TESTING SUNSCREEN EFFICACY

The test methodology outlined in the Final Rule applies only to the efficacy of a
product in protecting against UV-B sunburn exposure and is considered relevant
only for sunscreens with lower SPF values. As stated in the Preamble to the
Final Rule, the proposed test method for measuring values up to SPF 30 “represents
at this time a straightforward, well-understood, and sound method for measuring
these values”.28 Nevertheless, FDA discussed its concerns that data from the test
methods currently authorized may not adequately assess the efficacy of sunscreens
with SPF values above 15. Because test methodology in this area is evolving, FDA
intends to work with interested parties in the development of accurate methods for
assessing high SPF value products and will, if appropriate, address this issue in a
future Federal Register proposal. FDA is also working with interested parties to
develop methodology to assess the effectiveness of UV-A sunscreens and to inves-
tigate whether sunscreens operative against UV-A radiation might also help to
protect against premature skin aging, photoaging, and wrinkling. The agency
intends to explore these issues in a future issue of the Federal Register when it
completes the UV-A portion of the sunscreen monograph.29
FDA recognizes that the formulation or mode of administration of some
products may require modification of the testing procedures and that alternative
methods, such as automated or in vitro methods, may be used. However, any
proposed modification or alternative procedures must be submitted to FDA as
a Citizen’s Petition30 and accompanied by data to support the modification or
data showing that the alternative methodology produces results of equivalent
accuracy. In the meantime, the testing procedure described in the Final Rule,
including procedures for determining “water resistant” and “very water resistant”
claims, will be used as the standard by which SPF value claims will be measured.
A detailed discussion of the UV-B sunscreen product test methodology is
included elsewhere in this volume.
WHAT OF THE FUTURE?

At the time of writing, FDA has indicated its intention to take action in several
unfinished areas. These include developing a test method for determining the
28
64 Fed. Reg. 27666 at 27680.
29
64 Fed. Reg. 27666 at 27677.
30
See 21 CFR 10.30 for the rules governing submission of Citizen’s Petitions.
112 Murphy
effectiveness of UV-A sunscreens and the appropriate claims for such products,
in particular, claims that might link premature skin or photoaging protection to
UV-A sunscreen use. At the same time, FDA has indicated that it will consider
whether a “negative” claim may be necessary to alert consumers about sunscreen
products that do not provide UV-A protection. FDA also continues to work on
developing a suitable test method for evaluating claims to high SPF protection
from UV-B radiation, which when completed, may allow for the use of SPF
values higher than 30þ in sunscreen product labeling. Other items open for
future consideration are the required specific reapplication directions to sun-
screen users and the extended protection claims based on data to indicate that
consumers stay in the water longer than 80 min, the current limit for “very
water resistant” claims.31
In order to address these and other issues, FDA has extended the effective
date of the Final Rule until December 31, 200532 (with the exception of those
parts that require the warning statement for cosmetic preparations that contain
sunscreen ingredients for nontherapeutic uses (21 CFR 700.35) and cosmetic sun-
tanning preparations that do not contain any sunscreen active ingredients).
In an earlier Federal Register notice also extending the effective date and
reopening the administrative record, FDA identified eight areas in which it is
seeking further data and information.33
FDA Requests for Information and Comment
1. Whether to adopt a specific spectral power distribution pattern and
require that solar simulators be filtered to provide a continuous emis-
sion spectrum from 290 to 400 nm with the following percentage of
erythema-effective radiation in each specified range of wavelengths.
This modification would be intended to eliminate conditions that
may cause overestimation of SPF value for high-SPF sunscreens.
Wavelength (nm) Percent erythema effectiveness

290 0.1
290– 310 46 – 67
290– 320 80 – 91
290– 330 86.5 – 95
290– 340 90.5 – 97
290– 350 93.5 – 99
31
See November 17, 2000 letter from Charles Ganley, MD, Director, Division of OTC Drug Evalu-
ation, CDER, FDA to Martin A. Weinstock, MD, PhD, Chairman, Skin Cancer Advisory Group
and Mary O’Connell, Director, Skin Cancer Initiatives (Docket 78N-0038).
32
66 Fed. Reg. 67485 (December 31, 2001).
33
65 Fed. Reg. 36319 (June 8, 2000).
2. Whether to replace the current specifications in Section 21 CFR 352.71

of the Final Rule limiting to 5% the amount of a solar simulator’s total
energy output that can be contributed by wavelengths longer than
400 nm and substituting a limit on the total radiation delivered to the
skin for all wavelengths. The purpose of the modification would be
to limit the total energy delivered to the skin so that skin temperature
does not reach a point that influences the UV dose reciprocity
relationship during the long exposure times needed to test high-SPF
sunscreens.
3. Additional data on the suitability of an analytical method related to
the use of one or more specific control preparations to test high-SPF
sunscreen drug products (SPF values of 15 and greater).
4. Whether the high-performance liquid chromatography assay is suitable
both for the currently authorized homosalate SPF 4 standard and
for SPF 15 standard, including a validation package documenting
specificity, accuracy, limit of detection, linearity, precision, and repro-
ducibility of the method. The purpose of the modification would be to
replace the spectrophotometric assay presently designated in Section
21 CFR 352.70(c) of the Final Rule.
5. Whether the number of currently identified SPF 20 –25 test subjects
should be increased in tests for SPF values over 30.
6. Whether the current exposure dose format for MED determination is
adequate for sunscreens with SPF values over 30. The current pro-
cedure is described as a series of seven exposures administered to
the protected test sites to determine the MED of protected skin, con-
sisting of a geometric series of five exposures, where the middle
exposure is placed to yield the expected SPF, plus two other exposures
placed symmetrically around the middle exposure. The purpose of the
inquiry is to solicit comment on the agency’s concern that widely
spaced geometric progression offers less accuracy in the upper SPF
range and may produce overestimated SPF values in high-SPF test
preparations.
7. Whether the labeled SPF limit of 30þ should be eliminated and
how to communicate in product labeling the level of sun protection
associated with high-SPF sunscreen drug products. FDA also
requested comments on the use of professional labeling for health
practitioners, about the value of high-SPF products, and about valid
indications.
8. Whether the practical limitations of current test equipment and subject
patience can be overcome, because testing high SPF preparations
necessitates the use of longer UV radiation exposure time, often
several hours. FDA asks what the total exposure times would be for
testing preparations with estimated SPF values of 60 and higher and
what the practical limit in terms of an SPF value might be.
114 Murphy
In the area of UV-A testing, FDA has received information related to

in vitro methodology to determine the potency of UV-A protection in sunscreens
and a recommendation for a UV-A Index representing the broadness and the
amplitude of UV-A protection for consumer labeling.34 Other comments to
FDA on UV-A testing and labeling advocate using a combination of both
in vitro critical wavelength testing (with a claim threshold of 370 nm) and an
in vivo method showing at least a fourfold increase in protection from persistent
pigment darkening or in the protection factor in the UV-A range. Products that
meet both test criteria would be labeled as “broad spectrum”.35
Other comments submitted to FDA express the need for prescription sun-
screen products,36 the need for photostability data for all sunscreen products,37
and the infringement of FDA on First Amendment Freedom of Speech ensuing
from the limit on SPF values and the restrictive nature of the uniform OTC
drug labeling regulation.38 The Cosmetic, Toiletry, and Fragrance Association
(CTFA) has requested exemption for topical products with no dosage limits,
such as sunscreens, from the proposed regulations requiring bar code labeling
on all drug products,39 and has requested off-label listing of inactive ingredients
in the case of small package OTC drug products, including, for example, lip
products containing sunscreens.40
CONCLUSION
Despite its official title, the 1999 Federal Register document is by no means a
“Final” Rule governing OTC drug sunscreen products. The comprehensive
monograph for both UV-B and UV-A sunscreen protection labeling and testing
that FDA had hoped to publish by the end of 2002 is now scheduled for the
end of 2005 and many of the issues and disagreements discussed above must
be resolved prior to publication. The history of the sunscreen monograph spans
more than three decades, if one begins with the 1972 commissioning of the orig-
inal Panel of Experts by FDA. During that time, perceptions of public health
priorities, technical advances, consumer practices, and marketing visibility
have changed. While at the time of writing there is still no truly “Final”
34
See November 12, 2002, letter to FDA from Beiersdorf AG (Docket 78N-0038).
35
See April 1, 2002, letter to FDA from the American Dermatology Association (Docket 78N-0083).
36
See Citizen Petition of February 13, 2003, to FDA from Robert Sayer, PhD and Ramon Fusaro, MD,
PhD and FDA’s June 13, 2003, response soliciting additional information on the potential use of the
New Drug Application procedures or OTC monograph professional labeling as possible methods for
adding additional sunscreen indications (Docket 03P-0067).
37
See Citizens Petition of August 13, 2003, from TRLI to FDA (Docket 78N-0038).
38
See October 28, 2002, letter to FDA from the Cosmetic, Toiletry, and Fragrance Association
(Docket 02N-0209).
39
See June 12, 2003, letter to FDA from CTFA, (Docket 02N-0204).
40
See September 2, 2003, letter to FDA from CTFA, (Docket 78N-021P).
Sunscreen Rule, FDA and sunscreen manufacturers, testers, and users have
created enough flexibility within the OTC Drug Review to consider and incorpor-
ate modifications to the original proposals that address these developments in an
ongoing manner. The most important challenge for the future will be to maintain
a similar flexibility in accommodating the addition of new ingredients, new indi-
cations, and new scientific insights, which are inevitable and foreseeable events.
Balancing FDA’s charge to protect public health by assuring safe and effective
drug products with the consumer’s “right to know” and the commercial interests
of industry remains the chief challenge for the future, not only as it relates to the
sunscreen monograph, but also for the entire OTC drug industry.
8
Regulatory Aspects of Suncreens
in Europe
Romano E. Mascotto
L’Oréal Research, Asnière, France
Definition of Ultraviolet Filters 117

The EEC Directive Published November 28, 1983 118
Non-EU Countries’ Regulatory Status 124
Sun Protection Measurements 124
Future 125
DEFINITION OF ULTRAVIOLET FILTERS

In Europe, sunscreen products are considered cosmetics, as their function is to
protect the skin from sunburn. The European Economic Community (EEC)
has issued a directive to its member states relating to cosmetic products.1
Article 1 says
A “cosmetic product” means any substance or preparation intended for
placing in contact with the various external parts of the human body or
with the teeth and mucous membranes of the oral cavity with a view
exclusively or principally to clean them, perfuming them or protecting
1
OJ of European Communities Number L262/170 (September 27, 1976).
117
118 Mascotto
them in order to keep them in good condition, change their appearance

or correct body odours.
Because of this definition there is a need to differentiate between the legal
status of sunscreen in European countries and that in the USA, Canada, and
Australia, where they are considered OTC products.
THE EEC DIRECTIVE PUBLISHED NOVEMBER 28, 1983

The Third Amendment2 gives the definition and a list of ultraviolet (UV) filters
that cosmetic products may contain. This list is divided into two parts: UV filters
that are fully permitted and those that are provisionally permitted. Through suc-
cessive Adapting Commission Directives3 the provisional list has been voided,
transferring the approved substances to the fully permitted list and adding new
permitted UV filters. It is no longer accepted by the European Commission to
provisionally register new UV filters.
The chemical nomenclature used is International Nomenclature for Cosmetic
Ingredients (INCI) and requires interpretation into trade names, which are
commonly understood by a cosmetic chemist. This is tabulated in Table 8.1.
The maximum concentrations, other limitations, and requirements and warnings
that must appear on the label are also listed in the table. The numbers prefaced
with “S” indicate COLIPA numbers (COLIPA—The European Cosmetic
Toiletry and Perfumery Association, representing the cosmetic industry in
those European countries that are members of the European Union). A definition
of UV filters is given in the preamble of the Annex VII ECC Directive:
UV filters are substances which, contained in cosmetic sunscreen pro-
ducts, are specifically intended to filter certain UV rays in order to
protect the skin from certain harmful effects of these rays. These UV
filters may be added to other cosmetic products within the limits and
under the conditions laid down in this Annex.
Other UV filters not listed in the table can be used for product protection (stabi-
lizing colors, and so forth).
The status of permitted UV filters has been reviewed by the EEC working
party dealing with the safety of cosmetic products, called the Ad Hoc Working
Party on Cosmetic Directive (AHWP). This group consists of member state gov-
ernments, as well as representatives from industry and consumer groups. As this
working party contains a mix of people, not necessarily scientifically trained,
they are being advised by the Scientific Committee on Cosmetology and Non
Food Products (SCCNFP) set up by the EEC Commission. Committee members
are independent eminent scientists, mainly dermatologists and toxicologists from
2
OJ of European Communities Number L332/38 (November 11, 1983).
3
SCCNFP/0690/03 Final (and annexes).
Table 8.1 UV Filters That Cosmetic Products May Contain
Maximum Other Conditions of

authorized limitations use and warnings
COLIPA EEC concentration and which must be Trade names, other chemical or
Ref. No. Ref. No. INCI name (%) requirements printed on the label trivial names
S1 1 PABA 5 PABA; Paramino l; Pabacidum;

Amben; Pabanol
S57 2 Camphor benzalkonium 6 (3-(40 -Trimethylammonium-
methosulfate benzylidene)-ibornan-2-one-
methylsulfate; mexoryl SO
S12 3 Homosalate 10 Homomenthyl salicylate;
3,5,5-trimethyl cyclohexyl
salicylate; Filtrosol A; benzoic
Regulatory Aspects of Suncreens in Europe
acid 2-hydroxy-3,3,5 trimethyl

cyclohexylester; Kemester
HMS
S38 4 Benzophenone-3 10 Contains oxybenzonea 2-Hydroxy-4-methoxy-
benzophenone; Uvistat 24;
Uvinul M40; Eusolex 4360;
Cyasorb UV-9; Spectrasorb
UV-9; benzophenone-3
(CTFA); Neo-Heliopan BB;
oxybenzone; Uvasorb Met
S45 6 Phenylbenzimidazole sulfonic 8 (as acid) Eusolex 232; Novantisol;
acid Neo-Heliopan Hydro/USP;
Parsol HS
(continued )
119
Table 8.1 Continued
120

S71 7 Terephthalylidene dicamphor 10 (as acid) Mexoryl SX; ecamsule

sulphonic acid
S66 8 Butyl methoxydibenzoylmethane 5 Parsol 1789; 4-t-butyl-40 -
methoxy dibenzoyl methane;
Eusolex 9020
S59 9 Benzilidene camphor sulfonic 6 (as acid) 3-(40 -sulfobenxylidene)
acid camphor; Mexoryl SL
S32 10 Octocrylene 10 (a) Uvinul N-539 T;. Eusolex OCR;
Escalol 597; Neo-Heliopan
303/USP
S72 11 Polyacrylamidomethyl 6 Mexoryl SW
benzylidene camphor
S28 12 Ethylhexyl methoxycinnamate 10 Parsol MCX; Neo-Heliopan AV;
p-methoxycinnamic acid
2-ethylhexyl ester; Sunarome
OMC; Uvinul MC80; Escalol
557 L
S3 13 PEG-25 PABA 10 Ethoxylated PABA ethyl ester;
Lusantan 25 (ethoxylated-
ethyl-4-aminobenzoate)
S27 14 Isoamyl p-methoxycinnamate 10 Isopentyl-4-methoxycinnamte;
Neo-Heliopan E 1000
S69 15 Ethylhexyl triazone 5 Uvinul T-150
Mascotto
S73 16 Drometrizole trisiloxane 15 Mexoryl XL
S78 17 Diethyl hexyl butamido triazone 10
S60 18 4-Methylbenzilidene camphor 4 3-(40 -Methylbenzylidene)-
D-1-camphor; Eusolex 6300;
Eusolex 8021 (part); Parsol
5000
S61 19 3-Benzylidene camphor 2 3-Benzylidene camphor;
Mexoryl SD; Ultren BK;
Ultraoyd
S13 20 Ethylhexyl salicylate 5 Octyl salicylate (CTFA) UV;
Sunarome WMO; benzoic
acid; 2-hydroxy-2-ethylhexyl
ester; Neo-Heliopan OS/BP;
Neo-Heliopan OS/USP
S8 21 Ethylhexyl dimethyl PABA 8 Sunarome PLUS-Arlatone
Regulatory Aspects of Suncreens in Europe
UV-B; octyldimethyl PABA;

Escalol 507, Padimate O;
Eusolex 6007; 2-ethylhexyl-
p-dimethyl amino benzoate;
Escalol 507
S40 22 Benzophenone-4 (acid) 5 (a) 2-Hydroxy-4 methoxy-
Benzophenone-5 (Na Salt) benzophenone-5-sulfonic acid
and salt Uvinul MS-40;
benzophenone-4 (CTFA);
Uval; Cyasorb UV-S-5;
Syntase 230
(continued )
121
122
Table 8.1 Continued

S79 23 Methylene bis-benzotriazoyl 10 Tinosorb M

tetramethylbutylphenol
S80 24 Disodium phenyl 10 (a) Neo-Heliopan AP
dibenzyimadazole
tetrasulfonate
S81 25 Bis-ethylhexyloxyphenol 10 Tinosorb S
methoxyphenyl triazine
S74 26 Polysilicone-15 10 Parsol SLX
S75 27 Titanium dioxide 25 Eusolex T-2000
Note: The zinc oxide (S76) dossier has been submitted in 2003 to the SCCNFP for evaluation; the use of the product is temporarily permitted.
a
The concentration corresponds to the acidic form.
Mascotto
Regulatory Aspects of Suncreens in Europe 123
different countries. They study and review the data provided to them from various
sources, including different government health boards, associations, industry,
hospitals, databases, and others. Their mission is to form an opinion on the safety
of chemical substances used in cosmetics under normal conditions of use and
then publish their findings and decision in a report which can be found in the
SCCNFP website.4
Meanwhile, the cosmetic industry, through the EU Countries Trade Associ-
ation, COLIPA, plays an important role in securing a reasonable list of permitted
UV filters and continues to collect, review, and present data and information on
usage.
The individual countries’ trade associations deal with the regulatory bodies
of their own governments. COLIPA has not only contributed to the preparation of
a sensible definition and list of UV filters but has also been collecting safety data
on the chemicals and presented them to the EEC commission in the required
format. COLIPA has a subcommittee on sun products that deals with sunscreens
and UV filters and teams working on sun protection factor (SPF) measurement,
water resistance, UV-A protection, and photostability methods.
There is a standard procedure for adding substances to the list of UV filters.
This procedure is laid down in Article 8 (2) of the EEC Cosmetic Directive,
which reads: “the amendments necessary for adapting Annexes II to VII to tech-
nical progress shall be adapted in accordance with the same procedure, after
consultation of the Scientific Committee for Cosmetology and Non Food
Products at the initiative of the Commission or of a member State”.
This, in practice, means that if a new cosmetic ingredient, for example, UV
filter, is discovered, the following action needs to be taken:
. COLIPA sends a written request to the EEC commission, supported by

file with safety data on the ingredient.
. EEC commission also submits the summary of the file to the working
party of Cosmetic Directive (AHWP).
. SCCNFP presents a written opinion to the EEC commission.
. This opinion is then circulated to all members of AHWP.
. The AHWP discusses the proposed addition to the list, usually in the
presence of an industry expert. This procedure takes time, usually
two or more meetings.
. In case of a favorable attitude by EEC member states’ delegates, the
EEC commission then prepares an official proposal for an amending
Commission Directive.
. The proposal is sent to the Committee for Adaptation for Technical
Progress (CATP), which is then convened by the EEC commission.
. CATP discusses the proposed amendment and approves or rejects it by
qualified majority voting.
4
See footnote 3.
124 Mascotto
. In case of approval, the EEC commission then prepares the amending

directive; this is signed by an EEC commissioner and officially distrib-
uted to all EEC member states and subsequently in the Official Journal
(OJ) of the European Communities.
In 2003 the European commission asked the SCCNFP to evaluate the
UV filters listed without a complete dossier, namely S1, S57, S12, S38, and
S45. The European and American industries responded positively and will
submit the complete status of the art safety information5 before the end of
2005 as requested.
NON-EU COUNTRIES’ REGULATORY STATUS

Most of the non-EU countries (e.g., Sweden, Turkey, and Switzerland) largely
follow the EU directive as a code.
SUN PROTECTION MEASUREMENTS

In 1994 Colipa published an SPF test method and introduced new techniques to
characterize and specify the emission spectrum of the UV source and to colori-
metrically select the skin type of the volunteers. COLIPA, the Japan Cosmetic
Industry Association (JCIA), and South Africa Cosmetic, Toiletry, and Fragrance
Association (CTFA) decided to harmonize and improve the SPF method at the
Malta Mutual Understanding Conference in 2000. Major changes to improve
the reproducibility of the measured SPF are
. Application procedure of the product on the skin including a training
CD-ROM for cream lotion and powder application
. Reading of the unprotected and protected minimal erythema dose
. Strict definition of the quality of the filtered UV spectrum
. Requirement for a periodical monitoring of the UV lamp by a qualified
expert
. Tightened %RCEE limits in the spectral range 290– 320 nm
(85 – 90%)
. Reduction of dose progression to 12% for SPF 25
. Reduction of the statistical criterion (95% CI +17%)
A joint agreement on the new “International Sun Protection Factor (SPF) Test
Method” was reached in October 2002.
A COLIPA new recommendation (No. 11) on SPF labeling has been pub-
lished in 2002; the limitation of the SPF numbers to be labeled is intended to
facilitate the understanding of the consumer.
5
See footnote 3.
Regulatory Aspects of Suncreens in Europe 125
The recommendation states

The mean value from the test is rounded down to any whole number in
the SPF Classification Table shown below, and this number is the
maximum SPF to be labeled. SPF test results should not be rounded
up to the nearest number in the classification table. The following
Categories and SPF numbers are recommended. Indication of products
Categories may be useful and should be optional.
Type SPF
Low 2– 4 – 6
Medium 8– 10– 12
High 15– 20– 25
Very high 30– 40– 50
Ultra 50þ
The maximum SPF labeled should be SPF 50þ (for a product to be labeled
as SPF 50þ the mean SPF measured must have been SPF 60 or above).
The SPF numbers labeled are restricted to those and only those shown in
the table. The term sunblock should no longer be used.
All labeling should comply by 31 December 2005.
COLIPA actively works on the UVA protection measurement method; the
mandate of the project team is to develop an in vitro method validated against
the in vivo persistent pigment darkening (PPD) method. In vivo PPD method
will be authorized as an alternative.
Future labeling will be based on a ratio between the in vivo SPF number and the
PPD result and the results will be expressed on labeling as a class in order not to intro-
duce a new number for UVA protection that can be misleading for the consumer.
FUTURE
In recent years, epidemiological evidence has accumulated data that indicate that
skin cancer and degenerative skin changes (e.g., aging) are partly related to
excessive exposure to UV rays. Cosmetic manufacturers tend to use UVA and
UVB filters in many products, not only those that are used to prevent sunburn.
This gives the cosmetic scientists reason to believe that UV filters and other
substances that have the ability to filter out UV light will become even more
important in reducing the risk of premature skin aging and skin cancer. Further
regulatory restriction would only harness flexibility and innovation. Guidelines,
rather than regulations, would be respected. The consumer’s safety is the main
obligation of a manufacturer and, therefore, the scientific and ethical approach
to sunscreens should be left with the experts.
9
Regulation of Sunscreens
in Australia
Malcolm R. Nearn
Kentlyn, New South Wales, Australia
Introduction 128
The Regulatory Framework 129
Test Methods 131
The Listing Process 132
New Chemicals 132
New Excipients (Nonactive Ingredients) 132
New Sunscreen Actives 133
Permitted Sunscreens Actives and their Maximum Allowed Dosages 135
Sunscreens Actives under Review 136
Licensing of Premises 136
Labeling of Sunscreens 137
Mandatory Requirements for Primary Sunscreens 137
Optional Requirements for Primary Sunscreens 137
Mandatory Requirements for Secondary Sunscreens 138
Optional Requirements for Secondary Sunscreens 138
Advertising of Sunscreens 138
The Cosmetic/Therapeutic Interface 139
Example 1 139
Example 2 139
Conclusions 140
127
128 Nearn
INTRODUCTION
Sunscreens are regulated as therapeutic goods in Australia. Given Australia’s
claim to have the highest incidence of skin cancer in the world, this seems
very reasonable. People from countries where UV-B radiation is less intense
and of shorter duration may consider this unnecessary; however, Australians
well understand the need to protect skin against sun exposure and they expect
their interests to be properly protected by the implementation of appropriate
controls of the quality of the sunscreens they buy and use. This is best achieved
in Australia by dealing with sunscreens as therapeutic goods.
Since 1983 the Australian Standard (later to become the Australian/New
Zealand Standard) entitled “Sunscreen Products—Evaluation and Classification”
(AS/NZS 2604)1 has provided descriptions of the techniques for measuring the
ability of sunscreens to protect skin against UV radiation. It also provides
performance standards that a product must achieve if it is to comply with the
Standard. Further, it states the requirements for the labeling of sunscreens that
comply with the Standard. Although compliance with Australian Standards is
voluntary, the Sunscreen Standard has been underpinned by regulations issued
by the Therapeutic Goods Administration (TGA) that make compliance with
the current edition, AS/NZS 2604:1998, enforceable in many respects. The
main regulatory framework for sunscreens is the Therapeutic Goods Act 1989,
the regulations of which are administered by the TGA. Generally, sunscreens
are “listed” therapeutic goods, meaning that the sponsor (usually the marketer)
must supply certain information and assurances before the TGA will grant
permission to market by issuing an Australian Listing (Aust L) number.
(However, there are some exceptions to this general rule; these exceptions are
explained below.) The onus is on the sponsor to ensure that the sunscreens
they make and distribute to the market meet the necessary standards of quality
and effectiveness. The TGA has the power to intervene if the marketed sun-
screens do not meet the required standards.
The regulation of sunscreens as therapeutic goods differs slightly from that
of other therapeutic goods, and in some respects is more flexible. For instance,
stability testing may be conducted according to “Guidelines for Stability
Testing of Sunscreens”.2 Also, there is a modified Code of Good Manufacturing
Practice for sunscreens that is available on the TGA website.3
1
Australian/New Zealand Standardw Sunscreen products—Evaluation and Classification. Standards
Australia, 286 Sussex Street, Sydney, NSW 2000, Australia and Standards New Zealand, Level 10,
Standards House, 155 The Terrace, Wellington 6001, New Zealand.
2
Guidelines for Stability Testing of Sunscreens April 1994. Compiled by the Australian Society of
Cosmetic Chemists (ASCC), the Cosmetic Toiletry, Fragrance Association of Australia (CTFA),
The Nutritional Foods Association of Australia (NFAA), and the Proprietary Medicines Association
of Australia (now the Australian Self-Medication Industry [ASMI]. www.asmi.com.au.
3
Australian Code of GMP for Therapeutic Goods—Sunscreen Products 1994. www.tga.gov.au/docs/
html/gmpsunsc.htm.
Regulation of Sunscreens in Australia 129
The regulations and their interpretation by officers of the TGA change from
time to time, so it is prudent to refer to the TGA’s very helpful website4 to remain
abreast of the current situation.
THE REGULATORY FRAMEWORK

In Australia the Commonwealth Government’s Department of Health and Ageing
is responsible for the safety and efficacy of therapeutic goods and devices (and
other matters). The Act of Parliament that covers these activities is the Thera-
peutic Goods Act 1989,5 which is a general statement of the requirements for
the manufacture and marketing of therapeutic goods. The objective of the Act
is to ensure the quality, safety, effectiveness, and availability of therapeutic
goods within Australia and for export from Australia and import into Australia.
The Therapeutic Goods Act is given effect by a series of regulations that are
updated from time to time in the light of changing needs. (One might add that
the implementation of the regulations, and particularly guidelines, is a matter
of individual interpretation of officers of the TGA, so that seemingly minor
changes can evolve in use.) The administration of these regulations is conducted
by the TGA.
Therapeutic goods may be either medicines or medical devices. Medicines
may be categorized as prescription only (meaning that to obtain them the custo-
mer must take a doctor’s prescription to a pharmacist who will dispense it) or
nonprescription. Nonprescription medicines may be “complementary medicines”
or “over-the counter (OTC) medicines”. Complementary medicines are
“traditional” or “alternative” medicines; they include vitamin, mineral, herbal,
aromatherapy, and homoeopathic products.
OTC medicines and complementary medicines may be either registrable or
listable. Registrable medicines must be registered with the TGA by completing
the necessary application forms and sending them to the TGA with the relevant
fees and evidence of safety, efficacy, stability, and specifications. This infor-
mation is then evaluated and the sponsor (person or company submitting the
information) is duly informed of the decision. On the other hand, applications
to market a listable product receive minimal evaluation by the TGA at the
time of application. The onus is on the sponsor to possess the information relating
to efficacy, stability, safety, and specifications. However, the TGA normally
checks that the labels comply with the relevant regulations before issuing market-
ing permission. Also, the sponsor must give a written (and legally binding) assur-
ance that the necessary data relating to efficacy have been obtained prior to
marketing. From time to time the TGA conducts an audit of such listing
4
www.health.tga.gov.au.tga.
5
Therapeutic Goods Act 1989, Act No. 21 of 1990 (includes amendments up to Act No. 3 of 1999).
www.dhs.vic.gov.au/nphp/publicvations/legislation/implement_opt/an2-7.pdf. (For further amend-
ments see the TGA website.)
130 Nearn
applications to determine if the necessary efficacy and other data have been
obtained. If the sponsor does not have the data then TGA can cancel the listing
(marketing permission) of that product and may suspend or cancel the license
of the sponsor to manufacture and market that product, or indeed any therapeutic
product.
All prescription-only, registrable, and listable therapeutic goods must be
manufactured in premises that have been licensed by the TGA (see figure).
Therapeutic Good
Medicine Medical device
Prescription Nonprescription
(Requires full registration dossier)
Complementary medicine OTC medicine
Listable Registrable
Generally, sunscreens are listable therapeutic goods in Australia:

1. Listable sunscreens are those sunscreens or moisturizers containing
sunscreens that make SPF claims where the SPF ¼ 4 or greater, and
do not make prohibited claims. Labels must comply with the Thera-
peutic Labeling Order TGO 69, the Therapeutic Goods Advertising
Code, and the current edition of the Sunscreen Standard AS/NZS
2604. For further details see the section on labeling of sunscreens.
Sunscreens having SPFs of less than 4 (i.e., 3 or 2) are listable if
they contain certain ingredients of animal origin (the reason for this
is concern about the potential to transmit transmissible spongiform
encephalopathies).
2. Sunscreens must be registered with the Australian Register of Thera-
peutic Goods (ARTG) if they are included in the Schedule of Pharma-
ceutical Benefits (PBS). The PBS is a scheme whereby the
Government provides a subsidy for a medicine that is included in
the PBS when a doctor’s prescription is provided by the patient to the

dispensing pharmacist. Currently, the patient will pay up to A$23.10 or
A$3.70 for holders of concession cards (e.g., pensioners). Sunscreens
must also be registered if in addition to making sunscreening claims
they make other therapeutic claims. A sunscreen product must be
registered if it contains a sunscreen active that is not included in the
current list (see later). Registration is far more onerous (and expensive)
because a full registration package must be submitted for evaluation by
the TGA.
3. Sunscreens are exempt from the need for listing or registration and
manufacture in licensed premises when the SPF is 3 or less and the
product does not contain certain ingredients of animal origin.
However, these sunscreens are still medicines and must comply with
the TGA regulations for labeling of therapeutic goods.
4. Tinted, unmedicated lip preparations, including lipsticks, are excluded
(i.e., not therapeutic) even if they make sunscreen claims but do not
make other therapeutic claims. Other cosmetics without therapeutic
claims (other than “with sunscreen”) and without SPF claims or equiv-
alent on the label are also excluded. Excluded sunscreens are regulated
as cosmetics by the National Industrial Chemicals Notification and
Assessment Scheme (NICNAS) and The Australian Competition and
Consumer Commission.
TEST METHODS
The test methods for sunscreen efficacy are set out in the Australian/New
Zealand Standard AS/NZS 2604. The SPF test method has much in common
with the COLIPA method, although there are subtle differences. It may be
purchased from Standards Australia.6
In addition to the SPF test method three methods are described for measur-
ing UV-A transmission between 320 and 360 nm. Method 1—solution method is
applicable to products that dissolve completely in a solution of dichloroethane
(12.5%), cyclohexane (37.5%), and isopropanol (50%). Following serial dilution
the absorbance of the sunscreen in a 1 cm path length UV – VIS spectropho-
tometer cell should be equivalent to 8 mm of the undiluted product. Method
2—thin film method is applicable to products that do not dissolve in the
solvent. An 8 mm of sunscreen product is sandwiched between two quartz
plates and this assembly is positioned adjacent to the measuring device of a
UV –VIS spectrophotometer. Method 3—plate method is applicable to all sunsc-
reens. The transmittance of a 20 mm layer of the sunscreen product is measured
using a UV – VIS spectrophotometer with integrating sphere. The broad-spectrum
6
See footnote 1.
132 Nearn
requirement for the sunscreen Standard AS/NZS 2604-1998 is that the sunscreen
sample must not transmit more than 10% of any wavelength between 320 and
360 nm when tested by methods 1 or 2 and not more than 1% when tested by
method 3.
All three methods tend to grossly exaggerate UV-A protection because
they do not take into account the roughness of the skin—the true film thick-
ness of the sunscreen on skin is much lower. Method 2 also has another
defect that is due to the failure of an ordinary spectrophotometer to capture
light that is scattered after passing through the sample. Method 1 also has
another defect because it does not take account of spectral shifts due to
solvent effects.
THE LISTING PROCESS

Sunscreens may be listed on the ARTG either by completing a written application
or electronically through the Electronic Listing Facility (ELF).7
ELF allows the sponsor to create applications and draft applications, and
to list a sunscreen product on the ARTG. When preparing the entry you can
view the label checklist to ensure that you are not making a prohibited
claim. You can also find out whether the ingredients you propose to use are
already included in the ARTG (and thus permitted). Currently, ELF is not
entirely foolproof, and the use of a local regulatory affairs consultant may
make the process easier. Also, TGA currently has a local ELF Help Desk
(1800 773 312).
NEW CHEMICALS
New chemicals for listable or registrable sunscreens must be included in the
ARTG. Many are already registered, but if a new material is to be registered
an application for inclusion, together with the appropriate information (and
fees, of course), must be sent to the Business Unit of the OTC Medicines
Branch of the TGA. The information is reviewed by OTC Medicines toxicolo-
gists and then by an independent expert committee, the Medicines Evaluation
Committee.
New Excipients (Nonactive Ingredients)

Before a new excipient (i.e., one that is not currently included in the ARTG) can
be used in a sunscreen it must be cleared for use by TGA. The sponsor should
7
Electronic Listing Facility. www.health.gov.au/tga/docs/html/elfuserg.htm (for guidance and
training on the use of ELF).
provide the following information:8

1. Evidence that it is included in the CTFA International Cosmetic
Ingredient Dictionary (page number and reference should be
quoted).
2. Assurance that it is not included in the current edition of Annex II of
the EEC Cosmetic Directive 76/768. This is the list of substances that
an EEC cosmetic may not contain.
3. Assurance that the excipient has been approved by the relevant
regulatory agency in one or more of the following countries:
Sweden, Canada, USA, Canada, UK, or Netherlands, or (less
desirably).
4. Assurance that there have been market-place sales of comparable pro-
ducts containing the excipient in one of the above countries for at
least 2 years.
5. Acute oral toxicity: LD50—animal or alternative equivalent.
6. Irritation study—skin, animal, or alternative method.
7. Sensitisation study—skin, animal, or alternative method. In addition,
the following may be required in individual cases:
8. Eye irritation study
9. In vitro mutagenicity (Ames) test
10. In vitro percutaneous absorption test
That is, to register a new excipient the sponsor will have to provide the infor-
mation set out in (1) – (7) and may be required to provide in addition the infor-
mation set out in (8) –(10). In principle, you may be able to market a product
containing the new excipient if the information set out in (1) – (4) is provided
and the sponsor undertakes to provide the information in (5) – (7) within 6
months, but this is considered to be inadvisable, particularly if evaluation by
the TGA of the data in (5) – (7) leads them to ask for any or all of the data in
(8) – (10).
Other sources of information that will be considered are publications in the
Cosmetic Ingredient Review and acceptance by NICNAS. (New chemicals other
than therapeutic ingredients must be cleared by NICNAS.)
New Sunscreen Actives

The data needed to support the approval of a new sunscreen active are based
on those needed for the approval of a new sunscreen active in the EU. TGA
has adopted the European guidelines for each test method. However, subtle
8
Australian Regulatory Guidelines for OTC Medicines (ARGOM.) Published by TGA July 1, 2003.
10.9–10.10. www.tga.gov.au/docs/html/listguid.htm.
134 Nearn
differences in interpretation often mean that the EU registration dossier will

not suffice to achieve registration in Australia. In particular, the TGA takes
the view that it is not possible to interpret toxicology data without properly
designed and conducted toxicokinetic studies. It is possible that absorption
of the active by the oral route may be lower than absorption by the dermal
route. Thus, a substance may be systemically toxic by the dermal route but
not by the oral route.
Another point of difference concerns skin penetration. If it is sufficiently
low in practice the EU may waive the need for certain tests. But how do they
decide what is “sufficiently low”? Furthermore, the toxicologists in TGA take
the view that in vitro skin penetration studies may not duplicate in vivo
studies. On the other hand, TGA is aware of the need for new improved sunscreen
actives and will accept sound arguments for not conducting certain tests, such as
carcinogenicity tests.
Details of the requirements for registration of a new sunscreen active
are given in the Australian Regulatory Guidelines for OTC Medicines.9 Below
is a summary of the guidelines. (Note that these are not intended to be prescriptive.)
– Photostability—UV absorbance spectra. The sunscreen active must be

photostable and in addition it may be necessary to show that the new
active does not interact with (e.g., destabilize) other sunscreen
actives with which it might be used. The TGA probably has in mind
the interaction between methoxycinnamates and avobenzone.
– Acute toxicity (oral and dermal).
– Skin irritation; relevant human studies are acceptable.
– Phototoxicity.
– Eye irritation.
– Skin sensitization; relevant human studies are acceptable.
– Photosensitization.
– Toxicokinetics (oral, dermal, and ADME [absorption, distribution,
metabolism, and excretion] studies).
– Repeat dose toxicity (oral and dermal)—3 – 6 month data.
– Genotoxicity and photomutagenicity (tests in bacteria and mammalian
cell lines, photomutagenicity in bacteria, photomutagenicity in a
chromosomal aberration test and an in vivo chromosome aberration
assay).
– Reproductive toxicity, including assessment for fertility and develop-
mental effects, and endocrine disruption assays.
– Carcinogenicity and photocarcinogenicity—or a justification for not
supplying the data.
– Interaction potential—that is, it may be necessary to show that the new
active does not interact with other approved sunscreens.
9
See footnote 8.
PERMITTED SUNSCREENS ACTIVES AND THEIR MAXIMUM

ALLOWED DOSAGES
Australian approved Maximum

name (AAN) Other names concentration (%)
Aminobenzoic acid 4-Aminobenzoic acid (PABA) 15
Isoamyl Isopentenyl-4-methoxycinnamate; 10
methoxycinnamate isoamyl-4-methoxycinnamate
Butyl methoxy 1-(4-tert-butylphenyl)- 5
dibenzoyl methane 3-(4-methoxyphenyl)propane-1,
3-dione; avobenzone
Cinoxate 6
Dioxybenzone Benzophenone 8 3
Ethoxylated ethyl-4-aminobenzoic acid; 10
PEG 25 PABA
Padimate O 2-Ethylhexyl-4-dimethylaminobenzoate 8
Octyl Octinoxate 10
methoxycinnamate
Octyl salicylate 2-Ethylhexyl-salicylate, octisalate 5
Homosalate Homomenthyl salicylate 15
Menthyl anthranilate Menthyl 2-aminobenzoate, meradimate 5
4-Methylbenzylidene 3-(4-Methylbenzylidene)-D -L camphor 4
camphor
Octocrylene 2-Cyano-3,3-diphenyl acrylic acid, 10
2-ethylhexyl ester
Octyl triazone 5
Alpha-(2-oxoborn-3-ylidene)toluene- 6 (as acid)
4-sulfonic acid and its salts
Oxybenzone Benzophenone-3 10
Phenylbenzimidazole Ensulizole 4
sulfonic acid
N,N,N-Trimethyl-4-(oxoborn-3- 6
ylidenemethyl)anilinium methyl sulfate
Benzophenone-4 Sulizobenzone 10
Sulisobenzone sodium, benzophenone 5 10
Ecamsule Terephthalylidene dicamphor sulfonic acid 10
Titanium dioxide 25
Triethanolamine Octisalate 12
salicylate
a
Zinc oxide
Methylene Tinosorb M 10
bis-benzotriazolyl
tetramethylbutyl
phenol
Drometrizole Mexoryl XL 15
trisiloxane
a
An upper limit of 20% had been set, but it is understood that this limit may be removed.
136 Nearn
SUNSCREENS ACTIVES UNDER REVIEW

The following sunscreen actives are under review and cannot be used until that
review is complete.
Maximum
AAN Other names concentration
Benzophenone To be determined
Benzophenone-2 To be determined
Isopropylbenzyl salicylate To be determined
Salicylic acid salts Salicylic acid salts (K, Na, time and To be determined
extent application [TEA])
LICENSING OF PREMISES
Premises where therapeutic goods are processed, including manufacture, filling,
labeling, sterilizing, QC testing, packing, storage, or release, must be licensed by
the TGA. Application forms can be downloaded from the TGA website.10 If the
production process is conducted at several different premises, each of them must
be licensed, except where the production involves the same kinds of goods under
the same management, including QA management. Another exception relates to
temporary storage of raw materials or work-in-progress in other locations before
returning to the (licensed) warehouse. If the sunscreen is manufactured overseas
the premises must also be licensed; the requirements are described in the
Standard for Overseas Manufacturers.11 The license is normally granted for a
limited number of applications. For instance, a license to manufacture a sun-
screen would not entitle the company to manufacture sterile goods unless other
conditions are met.
If a sunscreen manufactured outside Australia is to be imported into
Australia, it must have been manufactured in therapeutic premises that are satis-
factory to TGA. However, this does not apply to sunscreen actives—the onus is
on the manufacturer of sunscreen formulations to ensure that the sunscreen
actives they use in listable and exempt sunscreens have been made to appropriate
standards.
In the application for a license all steps in the process must be des-
cribed in general terms. Also, the range of dosage forms and devices must be
described.
10
Application for a License to Manufacture Therapeutic Goods. http://www.health.gov.au/tga/docs/
pdf/gmpapp.pdf.
11
Guidelines on Standard for Overseas Manufacturers. 13th ed., July 2003. http://health.gov.au/tga/
docs/pdf/gmpsom13.pdf.
LABELING OF SUNSCREENS
The labels of listed, registered, and exempt sunscreens must comply with the
following:
– The Labelling Order (TGO 69). This 48 page document can be down-
loaded from the TGA website.12 TGO 69 deals with the general require-
ments for labeling all medicines. Of relevance to sunscreens are
W Application and exemptions
W Interpretation
W Label requirements, particularly 3(1) General, 3(2) Particulars to be
included on the label, 3(3) Particulars to be included on the main
label, 3(9) Preparations for skin or mucous membranes, 3(14)
Directions for use, 4 Expression of quantity, 7 Permitted storage
conditions, First schedule. Note that these requirements also
cover goods imported into Australia.
– The Therapeutic Advertising Code13 (see later).
– AS/NZS 2604/1998, which is the current version of the Australian/New
Zealand Standard “Sunscreen Products—Evaluation and Classification”.
It may be bought from Standards Australia.14 AS/NZS 2604 dis-
tinguishes between primary sunscreens, the main purpose of which is
to protect against the harmful effects of ultra violet rays, and secondary
sunscreens, for which the main purpose is moisturizing or some other
nontherapeutic function and sunscreening is secondary. For each
category there are mandatory requirements and secondary requirements.
Mandatory Requirements for Primary Sunscreens

– Label protection factor (SPF as it appears on the pack) cannot be higher
than the measured SPF rounded down to the nearest whole number, and
it cannot be greater than 30þ.
– The label protection factor must appear clearly on the main label.
– Clear and adequate directions for use must appear on the container.
– The names of all actives must be given on the container.
Optional Requirements for Primary Sunscreens

– Category description (as appropriate to the label SPF).
– Broad spectrum on the main label (but if you claim broad spectrum the
sunscreen must pass the appropriate test for broad spectrum).
12
Therapeutic Goods Order TGO 69. www.tga.gov.au/docs/html/tgo69.htm.
13
Therapeutic Goods Advertising Code. Published by the Therapeutic Goods Advertising Code Council
(TGACC), Private Bag 938, North Sydney, NSW 2059, Australia. www.tgacc.com.au/code_gloss_
files/Code_2003-07-16.pdf.
14
See footnote 1.
138 Nearn
– Water resistant on the main label (but if you claim water resistant the
sunscreen must pass the appropriate test for water resistant).
Mandatory Requirements for Secondary Sunscreens

– Label protection factor (SPF as it appears on the pack) cannot be higher
than the measured SPF rounded down to the nearest whole number, and
it cannot be greater than 30þ.
– The label protection factor must appear clearly on the pack, but not
necessarily on the main label.
– Clear and adequate directions for use must appear on the container.
– The names of all actives must be given on the container.
Optional Requirements for Secondary Sunscreens

– Category description (as appropriate to the label SPF).
– Broad spectrum (but if you claim broad spectrum the sunscreen must
pass the appropriate test for broad spectrum).
– Water resistant (but if you claim water resistant the sunscreen must pass
the appropriate test for water resistant).
ADVERTISING OF SUNSCREENS
Advertising (and labeling) of sunscreens must comply with the Therapeutic Goods
Advertising Code15 which is issued by the Therapeutic Goods Advertising Code
Council. This Code sets out the general requirements and restrictions on advertis-
ing therapeutic goods. Advertisements for therapeutic goods are required to be
approved, and this is undertaken before the advertisement is made public. For
sunscreens (and certain other therapeutic goods) the proposed advertisement is
sent for clearance to Advertising Services, Australian Self-Medication Industry.16
There are some items that specifically relate to sunscreens:
– For most therapeutic goods advertisements should not lead people to
believe that harmful consequences may result from the therapeutic
good not being used. Sunscreens are specifically exempt from the
provisions of this clause.
– In general, an advertisement for therapeutic goods must not be directed
to minors. Sunscreens (and certain other products) are exempt from
this restriction.
– In general, any representation regarding the treatment, cure, or preven-
tion of a neoplastic disease (e.g., cancer) is a prohibited representation.
15
See footnote 11.
16
Advertising Services, Australian Self-Medication Industry Level 4, 140 Arthur Street, North Sydney
2060, Australia.
However, prevention of skin cancer through the use of sunscreens is

not a prohibited representation.
– SPF 30þ broad-spectrum sunscreens can make the following claims:
W “Can aid in the prevention of premature aging of the skin” or words
to that effect.
W May assist in preventing some skin cancers; may reduce the risk of
some skin cancers—provided that the need for avoidance of pro-
longed exposure to the sun and the importance of protective hats,
clothing, and eyewear are highlighted.
THE COSMETIC/THERAPEUTIC INTERFACE

The National Coordinating Committee on Therapeutic Goods has published
“Cosmetic Claims Guidelines”.17 These set out a series of examples of claims
that can be regarded as cosmetic, claims that are unacceptable for a cosmetic
(but not necessarily unacceptable for a medicine), and claims that are borderline
(unacceptable unless sufficiently modified to provide a cosmetic implication).
Two examples are particularly relevant to sunscreens.
Example 1
It is acceptable to claim that a cosmetic may cover up age spots and dark pigmen-
ted areas, but any reference to fading of age spots (depigmentation, bleaching of
skin) would be regarded as a therapeutic claim. Claims that the product may tem-
porarily reduce the depth of wrinkles by moisturization would require further
explanation to demonstrate the cosmetic nature of the claim. (In these contexts
the reader should bear in mind that any therapeutic claim in addition to a
normal sunscreening claim would require that the product be submitted for full
registration.)
Example 2
Allowable cosmetic claims include that the product gives the skin a bronze (sun-
tanned) appearance; that it prevents, protects against drying effects of the sun;
and that it moisturizes the skin; “with sunscreen” is only acceptable for a cos-
metic if there is no statement of SPF number, sunscreen category description,
or other therapeutic claim. The following are therapeutic claims: helps protect
the skin from the harmful effects of the sun; SPF; accelerates/activates suntan;
pretan accelerator; allows you to stay in the sun x times longer; screens
(blocks) (filters) out some of the sun’s UV (UV-A/UV-B/UV-C) (harmful)
rays. (Most of these are claims that are allowed for a listable sunscreen, of
course, but a claim of tan acceleration may well require that the product be
17
National Coordinating Committee on Therapeutic Goods Australia (NCCTG). Cosmetic Claims
Guidelines. 3rd ed., May 9, 1997. www.health.gov.au/hsh/tga/tga.htm.
140 Nearn
submitted for registration.) A claim that the product gives the darkest tan with
less time in the sun, or that it enhances tan, may be regarded as therapeutic
unless otherwise qualified to show that it is a cosmetic.
The features that distinguish acceptable cosmetic claims are either that they
refer solely to a cosmetic property (such as moisturizing) or that they relate to the
illusion of a property (look, feel). The probable justification for these allowed
claims is that cosmetics are supposed to be designed to disguise, cover up, or
otherwise superficially change the appearance of skin (and hair or teeth). If the
effect that is claimed implies a physiological response from the skin it is more
likely to be considered to be a therapeutic claim.
CONCLUSIONS
Sunscreens in Australia are regulated as therapeutic goods. Although the process
of listing them on the ARTG is quick, because the onus is placed on the sponsor
(marketer) to self-regulate (make sure that the sunscreen product and its labeling
and advertising comply with the relevant regulations), the TGA has the power to
determine whether the manufacturer and marketer are complying with the regu-
lations. These regulations are developing and evolving. Some of the changes that
are likely are as follows. Australia and New Zealand are harmonizing
their laws and regulations (Trans Tasman Harmonisation) relating to therapeutic
goods (and other areas), so that artificial barriers to trade can be minimized. The
Australian New Zealand sunscreen standard (AS/NZS 2604) has been reopened
to consider possible changes to the broad-spectrum part of the Standard. While
there are some areas of disagreement it is probably true to say that (a) there is
an acceptance that the current test methods are inadequate and (b) any new
method is unlikely to involve in vivo measurement of UV-A protectiveness.
Some people in the industry would like to see secondary sunscreens regulated
as cosmetics and are lobbying the authorities to this end, but other industry
bodies are opposed to this. Some of the industry guidelines are fairly old and
may need to be reviewed.
NICNAS is the body that registers all new chemicals, other than therapeutic
ingredients. Thus, it affects cosmetics rather than listed, registered, or exempt
sunscreens. Many people in the cosmetics industry believe that NICNAS
places a dead hand on Australian industry. By its insistence on registering
every new ingredient, even if it has been through a similar process in other
countries, it denies Australian industry the access to new ingredients and thus
the ability to create new products that can compete overseas. A working party
has been set up to consider the regulation of “chemicals of low concern” such
as cosmetic ingredients.
10
Legal and Regulatory Status of
Sunscreen Products in Japan
Minoru Fukuda
Shiseido Research Center,
Yokohama, Japan
Masako Naganuma
Shiseido Scientific Research Department,
Tokyo, Japan
Outline 142
Introduction 142
Japanese Skin Characteristics and Attitude to UV 143
The Sunscreen Characteristics Desired by Japanese 147
The Regulation of Sunscreen Products and the Development of
UV-Protective Agents 148
Development of Effectiveness, Labeling, and Testing of Sunscreen
Products in Japan 154
SPF Testing Methods in Japan 154
Measurement Standards for UV-A Protection Efficacy in Japan 157
Development of Sunscreen Labeling for UV Protection
Efficacy in Japan 164
Problems for the Future 167
References 169
141
142 Fukuda and Naganuma
OUTLINE
There is now worldwide awareness of the chronic and acute damage to human
skin caused by the ultraviolet (UV) rays in sunlight. Nevertheless, people of
different nationalities have differing skin responses, differing concerns about
the consequences of exposure, and differing attitudes to suntan and sunburn.
Surveys show that Japanese women are most anxious about pigmentation, so
their prime expectation of sunscreen products is to prevent skin pigmentation.
Pigmentation is caused by not only UV-B but also UV-A, so sunscreen products
for the Japanese market should have both UV-B and UV-A protective potencies.
The market for sunscreen products in Japan has been increasing year by
year, and the protective efficacy has also been improved. Sun protection factor
information (such as SPF) has been given on products in Japan since 1981.
Japan Cosmetic Industry Association (JCIA) standard SPF test methods were
issued in 1992, and revised in 1999, and it was decided that the highest SPF
which could be labeled on sunscreen products would be 50þ. The move
towards international harmonization of legal and regulatory requirements for cos-
metics has led to international agreement on unified SPF measurement methods
among Japan, EU and South Africa. The latest JCIA SPF measurement method in
2003 was based on this agreement.
In addition to UV-B, UV-A plays an important role in photoaging. In 1996
the JCIA measurement standards for UV-A protection efficacy came into effect.
In Japan, the regulation of cosmetics was changed dramatically in April 2001.
Allowed UV absorbers which can be used for preventing UV damage to skin
are limited to those in positive lists in the new regulation. The above changes
are discussed, together with prospects for sunscreen products in Japan.
INTRODUCTION
The chronic and acute damage to human skin caused by the UV rays in sunlight
has attracted attention both in Western society and in Japan, although to different
extents. The necessity of sunscreen to prevent such damage has always been
recognized in both cultures. However, Japanese and Caucasians differ in
skin color and sensitivity to UV rays and also in attitudes toward suntan and
sunburn. Therefore, their expectations of what sunscreen products should do
likewise differ. Further, legal and regulatory requirements covering the manu-
facture of sunscreen products differ from one country to another.
In this chapter, we will describe the response of Japanese skin to UV rays,
the attitude of Japanese people to UV exposure, and the characteristics they
expect of sunscreen products. The legal and regulatory framework for sunscreen
products, SPF testing methods, and PA (protection grade of UV-A) testing
methods in Japan will be introduced, and we will describe the labeling methods
adopted by the Japan Cosmetic Industry Association (JCIA). Furthermore, we
discuss the harmonization process leading to The International SPF Testing
Legal and Regulatory Status of Sunscreen Products in Japan 143
Method agreed upon by JCIA, The European Cosmetic Toiletry and Perfumery
Association (COLIPA), and Cosmetic, Toiletry and Fragrance Association of
South Africa (CTFA/SA), and comment on subjects for future discussion.
JAPANESE SKIN CHARACTERISTICS AND ATTITUDE TO UV

Billions of people live on the earth, and each has his or her own skin color. In
humans, skin color depends on the quantities of melanin and oxygenated or
reduced hemoglobin present in the skin, as well as on the skin’s thickness and
water content. Among these factors, the quantity of melanin, which is distributed
in the skin, determines its fairness or darkness, and greatly influences the human
complexion. At the same time, melanin plays a part in reducing the damage that
UV rays cause in the skin. This means that a person’s color determines his or her
degree of resistance to UV, which is one measure of the adaptability of people to
the earth’s environment. Moreover, skin color influences not only attitudes
toward UV, but also attitudes toward prevention of UV damage.
The so-called “sun belt zone” circling the equator, where people are
exposed to high levels of UV rays, is part of the torrid or subtropical zone; the
people who live there are generally dark-skinned. In the middle latitudes away
from the Equator, where sunlight contains moderate levels of UV, the majority
of inhabitants have yellowish skin tones. People with white skin live in high
latitudes, far from the equator.
The Japanese live in an island country, which extends from latitude 258N to
latitude 458N, and ethnically belong to the Mongolian peoples. They have yel-
lowish skin with moderately developed melanin productivity. The gradations
of skin color of the Japanese vary widely from fair to dark. Most of those with
fair skin have skin brightness and hue similar to those of Caucasians; those
with dark skin have aspects in common with Negroes (1). In our classification
of the back skin colors of the Japanese by visual evaluation in addition to the col-
orimetric parameters of value, chroma, and hue, the colors observed are divided
basically according to the parameters of value (V) and chroma (C), and arranged
within the spectrum from fair through dark skin (2) (Fig. 10.1). Naturally there
are differences in sensitivity to erythema and tanning between Japanese and
Caucasians, and even among Japanese individuals with various skin tones.
Figure 10.2 compares the process of tanning between Japanese and Caucasians
by means of measurement of the minimal erythema dose (MED)/minimal
melanogenesis dose (MMD) ratio using sunlight as the light source (2 – 5). The
results showed that the Caucasians tanned hardly at all even when erythema
had been induced to some degree by a single sunlight exposure; the Japanese
were more prone to tan than the Caucasians.
As regards the seasonal variation of facial skin color, skin color started
to become darker in spring and was darkest in August (Fig. 10.3) (6). It became
fairer from autumn to winter and was brightest in March. At the same time, the
pigmentation at various sites on the same person were determined. Interestingly,
Figure 10.1 Distribution of skin color in Japanese people.
the extent of variation was larger on the pigmented than on the nonpigmented sites,
though the variations were the same between pigmented and nonpigmented sites.
Therefore, pigmented sites stood out from the surrounding skin color.
The skin types of Japanese are shown in Fig. 10.4 (7). This survey was con-
ducted by companies belonging to the JCIA on 2500 persons (1258 females and
1242 males). The skin type was investigated using modified Fitzpatrick skin type
(8) by means of questionnaires. The ratios of skin types I, II, and III are 18.2%,
28.0%, and 29.8%, respectively. About 76% persons thought that their skin first
turned red, and 76% of them thought it then became dark.
Furthermore, in a questionnaire on skin troubles in Japanese females,
pigmented spots and freckles occupied the top spot and wrinkles came second.
Figure 10.5 shows the results of a survey of 5211 Japanese women in 1995. In
addition, Yoshii (9) reported that the ratio of pigmentation or pigmented spots
among Japanese females reporting skin troubles was 69% and the ratio of wrin-
kles was 53%. On the other hand, the ratio of pigmentation was 20– 40% and the
ratio of wrinkles was 40 – 60% in the USA, UK, and Germany. There was no
difference in the ratio of persons who were troubled with wrinkles. Japanese
females were characteristically very worried about pigmentation. Since Japanese
women have higher levels of melanin productivity and they have medium-
colored skin, pigmentation is relatively prominent on their skin.
Next, we investigated the attitude of Japanese women to UV (Fig. 10.6) in
2002. The level of awareness of UV was divided into five grades: very concerned,
moderately concerned, no opinion, slightly concerned, unconcerned. The ratios
Figure 10.2 Tanning capacity of Japanese of various skin colors and Caucasians.
62
60
L*
58
Non-pigmented area
±SE
Pigmented area
56
Feb. Mar. Apr. May June Jul. Aug. Sep. Oct. Nov. Dec. Jan.
Figure 10.3 Monthly change in L in pigmented and nonpigmented areas on Japanese

women’s faces.
Skin type VI 0.3%

Skin type V 7.2%
Skin type I
Skin type IV
18.2%
16.2%
Skin type II
28.0%
Skin type III
29.8%
Figure 10.4 Distribution of skin types in Japanese people (data from JCIA for 2500
persons).
of very concerned and moderately concerned were 38.2% and 47.9%, respect-
ively. Therefore, over 90% of Japanese females were concerned about UV
exposure. The main reasons for this were given as follows: (1) UV elicits pigmen-
tation or pigmented spots (57%) and (2) UV induces tanning (13%). Only 8.1% of
persons mentioned skin cancer, which is the main concern of Caucasians.
In Japan, fair skin has been considered from ancient times to be an essential
factor in beauty. There is an old saying, “A fair complexion hides seven defects”.
Following this traditional aesthetic sense, skin coloration and UV reactivity in
terms of pigmentation and pigmented spots are the focus of Japanese women’s
thinking about UV.
Pigmented spots and freckles

Wrinkles around eyes
Roughness of lip
Dullness of skin color
Suppleness of skin
Irregular texture
Pimple and acne
Reddish cheek
0 10 20 30 40 50%
Figure 10.5 Skin troubles in Japanese women. A total of 5211 Japanese women were
surveyed by means of questionnaires in 1995.
Less concerned Unconcerned
No opinion
Very concerned
Moderately
concerned
Figure 10.6 The attitude of Japanese women to UV.
THE SUNSCREEN CHARACTERISTICS DESIRED BY JAPANESE

Cosmetic products with a UV-protective effect first appeared in Japan in 1981.
Before then, partly as a result of advertising posters showing beautifully
tanned women in swimsuits, it had been fashionable to get a tan by sunbathing
at the beach. However, young women often became excessively sunburned or
pigmented in their eagerness to become tanned in a short time. At the same
time, many people disliked tanning on the face. In this situation, product labeling
enabled consumers to use sunscreens to the best effect for their own purposes and
according to their particular skin sensitivity to UV.
Later, it was realized that not only UV-B, but also UV-A damaged the skin,
and also that skin exposed to UV rays showed early photoaging phenomena. In
particular, UV-A aggravated and induced pigmented spots and freckles. There-
fore, many products that had both UV-B and UV-A protective effectiveness
appeared on the Japanese market. Since 1996, both SPF and PA have been
labeled on the packaging of sunscreen products. Protection of the body in
addition to the face became of increasing concern. Annual cosmetics sales for
the last 10 years are shown in Fig. 10.7. The sales of total skin care products
have increased only slightly, whereas those of sunscreen and suntanning products
have increased rapidly.
In 1998, the favorable mention of sunbathing disappeared from the advice
for mothers and babies supervised by the Ministry of Health, Labor and Welfare.
Furthermore, material to educate the public about the need for UV protection was
published in 2003 by the Ministry of the Environment. Consequently, sunscreens
for babies and children have become available. This means that the consumers of
sunscreen products cover the whole range of age. In addition, there are special
70 2.5
Sunscreen and tanning products

Skin care products Million Yen
60 Sunscreen and tanning products
2.0
Skin care products
50
1.5
40
30 1.0
20
0.5
10
0 0
91
92
93
94
95
96
97
19 8
99
00
01
02
9
19
19
19
19
19
19
19
19
20
20
20
Year
Figure 10.7 Sales of sunscreen and suntanning products and total skin care products in
the Japanese market.
sunscreen products such as sunscreens for acned skin which do not contain
comedogenic ingredients and sunscreens for sensitive skin or babies’ skin which
do not contain UV absorbers, perfume, paraben, or coloring materials.
Thus, with the popularization of UV protection and due to warnings by
dermatologists that daily exposure to UV rays can accelerate aging of the skin,
UV care has become part of the daily routine throughout the year. Accordingly,
nowadays UV-protective products include daily milky lotions and other basic
cosmetics and makeup products, in addition to sunscreens. The report showed a
high ratio of users of foundation in Japan compared with Caucasian females (9).
Virtually all foundations for summer use now have a function for UV protection.
In Japan, seasonal changes in climate are very distinct (Fig. 10.8). The
Japanese summer is characterized by high temperature and humidity. Therefore,
people prefer more astringent cosmetics and foundation cakes for wet or dry use.
Perspiration and sea bathing require a high level of water resistance. Two-layer
emulsions with high SPF and high water resistance have been introduced as
sunscreens. The use of products with high water resistance has been accompanied
by the development of special cleansing products.
In addition, Japanese skin is more sensitive to stimulation by cosmetics and
other products than is that of Caucasians. This is an important point that should be
taken into account in the design, development, and sale of sunscreens.
THE REGULATION OF SUNSCREEN PRODUCTS AND THE

DEVELOPMENT OF UV-PROTECTIVE AGENTS
The regulatory requirements for sunscreens differ from country to country. In the
USA, Canada, and Australia, sunscreens are over-the-counter drugs. On the other
Figure 10.8 Seasonal variations in UV radiation, temperature, and humidity.
hand, they are treated as quasi-drugs in China, Korea, and Taiwan. Furthermore,
they are cosmetics in Japan under The Pharmaceutical Affairs Law, as is the case
in Europe. The Pharmaceutical Affairs Law underwent major revision on April 1,
2001. Before this time, cosmetic manufacturers made cosmetics by using only
ingredients that were permitted by the government. However, since then it is
permitted to combine any ingredients in cosmetics except for materials in three
groups, and materials on a negative list, which includes active drugs, hormones,
and so on. The three groups are UV absorbers, coal-tar dyes, and preservatives,
and in these categories, only ingredients on the positive list can be used. UV
absorbers on the positive list are shown in Table 10.1.
There are 27 UV absorbers and 1 mixture of two UV absorbers on the posi-
tive list. Before 1990, the material most popular with Japanese manufacturers on
the basis of safety and effectiveness was octyl dimethyl PABA. However, some
problems with safety were reported, and it rapidly disappeared from the Japanese
market. Now octyl methoxycinnamate is the most widely used UV-B absorber
and butyl methoxydibenzoylmethane (avobenzone: Parsol 1789) (10) is the
most widely used UV-A absorber.
The UV absorbers initially developed absorbed UV under 320 nm. Many
of the absorbers in Table 10.1 are UV-B absorbers. The Japanese have also
shown an interest in the harmful effects of UV-A, especially in its tanning
effect. UV-A rays penetrate the skin more deeply than UV-B rays (11), and
reach the earth in high doses (12,13). Normally, our skin is exposed to
greater amounts of UV-A than UV-B rays. Several experiments have proved
that chronic exposure of skin to UV-A rays causes abnormalities in the connec-
tive tissue of the dermis (14,15) and accelerates the harmful effects of UV-B,
such as carcinogenesis (16). Furthermore, it has become clear that the UV
150
Table 10.1 Positive List for UV Absorbers in Japan (Revised Version in 2002)
Maximum concentration (%)
Groups UV absorber Japan COLIPA FDA Brand name
PABA derivatives PABA p-aminobenzoic acid 4 5 15

Octyl dimethyl PABA 10 — 8 Escalol 507
Pentyl dimethyl PABA 10 — — Escalol 506
Cinnamic acid Octyl methoxycinnamate 20 10 7.5 Parsol MCX
derivatives NeoHeliopan AV
Escalol5 57
Eusolex 2292
Uvinul MC80
Octanoate 10 — — Sunguard B
Cinoxate 5 — 3
Diisopropyl methyl cinnamate 10 — —
Isopentyl trimethoxycinnamate 7.50 — — Sun shelter SP
trisiloxate
Ferulic acid 10 — —
Benzophenone Benzophenone-3 Oxybenzone 5 10 6 Neoheliopan BB
derivatives Escalol 567
Eusolex 4360
UvinuI M40
ASL24
Benzophenone-5 10 — —
Benzophenone-4 10 — 10 Uvinul MS40
Fukuda and Naganuma
(Sulisobenzone)
Benzophenone-6 10 — — Uvinul D49
Benzophenone-9 10 — — Uvinul DS49
Benzophenone-1 10 — — Uvinul 400
Benzophenone-2 10 — — Uvinul D50
4-(2-beta-glucopyranosiloxy) 5 — —
propoxy-2-hydroxybenophenone
Salicylic acid Homomenthyl salicylate (Homosalate) 10 10 15
derivatives Octyl salicylate (2-ethylhexy salicylate) 10 5 5 NeoHeliopan OS
Escalol 587
dibenzoylmethane Butyl Methoxydibenzoylmethane 10 5 3 Parsol 1789
derivatives Eusolex 9020
Terephthalylidene sulfonic acid 10 10 (as acid) — Mexoyl SX
Phenylbenzimidazole Sulfonic Acid 3 8 (as acid) 4 Parsol HS
NeoHeliopan Hydro
Eusolex 232
2-ethylhexyl dimethoxybenzylidene 3 — — Softshade
dioxoimidazolidine propionate
Others 1-(3,4-dimethoxyphenyl)-4,4-dimethl- 7 — —
1,3- entanedione
Octocrylene 10 10 (as acid) 10 NeoHeliopan 303
Escalol 597
Legal and Regulatory Status of Sunscreen Products in Japan
Uvinul N539
Octyl triawne 5 5 — Uvinul T150
Drometrizole trisiloxate 15 15 — Mexorvul XL
151
rays which induce chloasma, a source of concern for Japanese women, cover the
range from UV-A to UV-B, and that the main causative wavelength lies in the
UV-A region (17). Some attempts have been made to develop effective UV-A
absorbers, and butyl methoxydibenzoylmethane was introduced into Japanese
sunscreen products in 1986 (18). Recently, Mexsoryl SX has been added to
the positive list.
Some of the requirements for applications to add a newly developed UV
absorber to the positive list are shown in Table 10.2. The requirements include
data on origin, background of discovery, use in foreign countries, physical and
chemical properties, and safety. Submitted materials will be discussed in a
council, which will approve an absorber, if they consider that it is safe and
useful. Then the applicant can use it in sunscreens or other cosmetics.
The foregoing discussion has dealt with UV absorbers. Next, we will con-
sider UV-scattering agents in the form of inorganic powders as UV-protective
cosmetic materials. The scattering effects of several kinds of inorganic
powders are shown in Fig. 10.9. Superior UV-preventive effects were observed
with titanium oxide, ferrous oxide, and zinc oxide. As ferrous oxide is colored,
it cannot be used in large amounts in sunscreens. It is advantageous that inorganic
powders are not allergenic and do not have absorption peaks at visible wave-
lengths. However, they scatter not only UV, but also visible light. Therefore,
skin to which inorganic powder has been applied looks pale or white.
Table 10.2 Data Required in Application for Approval of UV Absorbers for the
Positive List
Data on origin, background of Data on origin and background of discovery

discovery, use in foreign Data on use in foreign countries
countries, etc. Data on characteristics and comparison with
other UV absorbers
Data on physical and chemical Data on determination of structure
properties Data on physical and chemical properties
Data on safety Data on acute toxicity
Data on subacute toxicity
Data on reproductive effects
Data on skin irritation
Data on chronic toxicity
Data on skin sensitization
Data on phototoxicity
Data on photosensitization
Data on eye irritation
Data on genotoxicity
Data on human patch test
Data on absorption, distribution, metabolism,
excretion
Figure 10.9 UV protective effect in vitro of UV scattering agents.
In order to improve the texture of cosmetics using these inorganic powders,

while taking advantage of their UV-protective effect, attempts have been made to
change the forms of the powders or to prepare complexes of several inorganic
powders or combinations of inorganic powder and organic substances (19). The
UV-protective effect of inorganic powder varies with the diameter of the particle.
Titanium oxide, with a particle size of under 0.05 mm in diameter, has a high
UV-protective effect and does not block visible rays (20). It does not have a conspic-
uous color when applied to the skin, which is an advantage. Since titanium oxide has
poor spreadability, procedures such as adding spherical nylon particles were devised
in order to overcome this drawback (21). An oxide complex of silicon and titanium
was also developed; this complex has a superior UV-intercepting effect and
improved transparency to visible rays. Moreover, it is possible to process inorganic
powders containing UV absorbers to optimize the UV-protective effect.
Recently, zinc oxide powders have been used in sunscreens (19). Zinc
oxide powders are good protectors against UV-A without blocking visible light
(22). This has the advantage that treated skin does not look white. Furthermore,
various formulations have been tried. Figure 10.10 shows zinc oxide particles in
the form of petals. The use of wet preparation methods allows control of the
Figure 10.10 Newly developed zinc oxide formulation (left) and carnations (right).
diameter of particles and figures, and the petals are formed as secondary agglom-
erations. Primary particles of the zinc oxide have weak cohesive force, and when
they are applied on the skin they spread uniformly over the skin. This character-
istic improves the passage of visible light and the protective efficacy against UV.
The development of UV-protective agents, including scattering powders, has
made rapid progress, and every year new sunscreens using new protective agents
appear on the market in Japan.
As mentioned earlier, safety and a potent UV-protective effect are essential
factors for sunscreens sold in Japan. Therefore, UV absorbers and UV-scattering
agents are usually incorporated in sunscreens in various combinations rather than
as a single ingredient in large amounts.
DEVELOPMENT OF EFFECTIVENESS, LABELING, AND TESTING OF

SUNSCREEN PRODUCTS IN JAPAN
SPF Testing Methods in Japan
Since the US FDA released “Sunscreen Drug Products for Over-the-Counter
Human Use” in 1978 (8), many sunscreen products labeled with the SPF value
have been put on sale in the USA and Europe. In Japan, Shiseido first introduced
sunscreens labeled with Sun Care Shi-Suu 2,4,6, which means SPF, as an indi-
cator of UV protection efficacy into the market in 1981.
In 1991 JCIA established the Standard SPF Test Method (23) based on the
concept that the SPF value indicated on sunscreen products should be standar-
dized, permitting product comparison. The method served as a criterion for
product selection based on extensive measurement of UV-protective effects,
and was designed to be as consistent as possible with the worldwide trend
toward uniformity in UV protection efficacy evaluation. The JCIA Standard
SPF Test Method came into effect in January 1992.
Since then, labeled SPF values have tended to increase from year to year
(Fig. 10.11) (24). In 1999 the highest SPF number of a product on the Japanese
140
120
Maximum Value of SPF
100
+
80 SPF50+
60
40
20
0
90 91 92 93 94 95 96 97 98 99 2000
Year
Figure 10.11 Annual changes in maximum labeled SPF in the Japanese market.
market was 123. A variety of products appeared bearing extremely high labeled
SPF values, which were beyond the range expected when the JCIA Standard Test
Method was implemented, and it became evident that there was a possibility of
large disparities in measured SPF.
The Expert Committee on SPF of the JCIA set out to revise the JCIA
Method in October 1997. They concluded that the conditions of measurement
should be revised to increase the accuracy at high SPF values, and the
international situation should be taken into account, considering that an upper
limit had been imposed on labeled SPF values in the USA, Australia, and
New Zealand. As a result, the conditions of SPF measurement were partially
revised, and the upper limit of labeled SPF values was set at SPF50þ. There
are two reasons for the decision to fix SPF50þ as the upper limit of the labeled
values: (1) measurement errors become greater when a certain magnitude of meas-
ured values is exceeded and (2) a sunscreen product with SPF of 50 is considered
sufficient for protecting the skin from sunburn. Taking into account persons with
hypersensitivity to UV and regions where people are exposed to very strong UV,
however, it was decided that SPF50þ may be labeled on products that clearly
have a higher UV protection efficacy than SPF50. The JCIA’s Standard SPF
Test Method, which was established in November 1991, was changed to the
1999 Revised Version (25), to take effect from January 1, 2000. From 2000
the maximum SPF label number has remained at 50þ in the Japanese market.
Today the idea of SPF labeling has been accepted throughout the world.
The USA, Australia, New Zealand, Europe, South Africa, China, South Korea,
Taiwan, South America, and Japan all have similar SPF testing methods. Never-
theless, some differences of detail, for example, in testing conditions, remain. Are
these important? If Shiseido of Japan wants to export sunscreen to the USA or
Europe, it is necessary to do SPF testing and SPF labeling of the sunscreen all
over again, using the US FDA method and COLIPA method, respectively. The situ-
ation is similar when a US or European company wants to export to Japan. This
wastes time and resources for retesting and relabeling of SPF on sunscreen products.
To find out how the different testing conditions for SPF determination
among the countries would affect the SPF values of sunscreen products, 15 lab-
oratories under JCIA, COLIPA, and CTFA/Australia (CTFA/AS) measured SPF
values of the same two standard sunscreens using their own testing methods. This
was the so-called international ring test (26). Interestingly, the SPF values of each
of the standard sunscreens obtained by the various testing methods were not
statistically significantly different.
Table 10.3 shows the results from one laboratory that measured SPF values
of the two sunscreens in Caucasian volunteers and Asian volunteers (Japanese
and Chinese) living in the USA. Untreated MED of Caucasian people is about
30% smaller than that of Asian peoples with the same skin type II. However,
the differences in SPF values of 8% homosalate lotion (SPF4 standard) and
Sunscreen A between Caucasians and Asians were not significant.
These data suggest that existing differences in the precise SPF testing
conditions, including the races of volunteers, may not need to be taken into
account in setting an international framework for SPF testing.
Then JCIA, COLIPA, CTFA of America (CTFA), CTFA/AS, and
CTFA/SA got together at the International SPF Harmonization Conference
held in April 2000 in the Republic of Malta (27). The representatives called for
a thorough scientific examination of the feasibility of developing an International
SPF Test Method. Representative experts of JCIA, COLIPA, CTFA, and
CTFA/SA gathered in Brussels in September 2000, and started to discuss con-
cretely every detail of the SPF test methods.
By way of meetings in Tokyo (October 2001), Brussels (February 2002),
and Tokyo (August 2002) and three international teleconferences, basic agree-
ment on an International SPF Test Method was reached between JCIA,
COLIPA, and CTFA/SA in October 2002, at a meeting in Johannesburg.
Table 10.3 SPF and MED of Two Types of Sunscreen for Caucasians and Asians
Living in the USA
8% HMS Untreated
(SPF 4) Sunscreen A MED (J/cm2)
Skin
type n SPF SD SPF SD MED SD
Caucasians I– III 20 3.6 0.5 11.9 2.8 0.98 0.12

II 18 0.98
Asian II– III 20 3.7 0.6 10.4 1.6 1.5 0.28
(Japanese 19 þ II 8 1.3
Chinese 1)
Note: HMS is homomenthyl salicylate.

Finally, the International SPF Test Method was promulgated in English in March
2003 (28).
In Japan, we translated the English version into Japanese as the “Japan
Cosmetic Industry Association SPF Test Method—2003 Revised Version,”
adding some further local requirements, for example, the expiry date and labeling
method of SPF value. This new method came into effect in Japan on June 1, 2003
(29). Table 10.4 compares the major testing conditions between the International
SPF Test Method (JCIA Standard SPF Test Method—2003 Revised Version), the
JCIA Standard SPF Test Method (1999 version), and the US FDA SPF Test
Method (1999). A major feature of the International SPF Test Method is that it
specifies clearly the SPF test conditions which the JCIA method 1999 version,
COLIPA’s method, the US FDA’s method, and the AS/NZ method had adopted.
Measurement Standards for UV-A Protection Efficacy in Japan

UV-A causes darkening of the skin immediately after exposure [immediate
pigment darkening IPD)], and in the event of exposure to large amounts of
UV-A, this darkening seems to be transformed to delayed pigment darkening.
There are also reports that UV-A increases the sensitivity of the skin to UV-B.
In addition to these acute responses, UV contributes to skin cancer and to
aging of the skin, typified by blotches and wrinkles. The relative contributions
of UV-A and UV-B to these various reactions are not known, but the effects of
the deep penetration of UV-A cannot be ignored.
Japanese are more prone to tanning than Caucasians. While Americans and
Europeans expect sunscreens to allow them to tan safely, Japanese expect them to
prevent tanning, exactly the opposite expectation.
At present, SPF is the only universal parameter that is used for judging the
effect of sunscreens in the markets. This SPF, however, indicates the protective
effect against erythema mainly caused by UV-B, but not that against tanning,
which is the most serious problem for Japanese women. Under these circum-
stances, the labeled “UV Protection” in product claims is not always adequate,
so there is a need to clarify whether a product protects against UV-A or UV-B,
and to what extent it protects against each.
Throughout the world, the SPF value acts as an index that the consumers use
for product selection. With respect to an index or measurement method for UV-A
protection, however, a uniform measurement method has not yet been established
on a national or industry-wide level, although several papers on the subject have
been published, and studies are under way in various countries. Throughout the
world, products display various numerical values or marks indicating their efficacy
for UV-A protection, but because there was particular concern that a uniform
measurement method had not been established in Japan and these numerical
values might cause confusion among consumers in their product selection, it has
been decided not to display the level of UV-A protection on sunscreens.
158
Table 10.4 SPF Test Methods: International Method, JCIA Methods (2003 Revised Version and 1999 Version), and FDA Method
(1999 Version)
International method and JCIA method JCIA method (1999

(2003 revised version) version) US FDA method (1999 version)
1 Selection of Questionnaire; medical check by Questionnaire Questionnaire

volunteers professional; World Medical
Association Declaration of Helsinki
2 Skin type and test Phototype, colorimetric method; back Phototype; back Phototype; back
area
3 Number of test Minimum 10, maximum 20 (a maximum of Minimum 10 Minimum 20 (maximum subjects
subjects 5 results may be excluded) 25)
4 Statistical criterion 95% CI , 17% of mean SPF SE less than 10% by
mean SPF
5 Standard sunscreen P1 (DIN standard SPF 4) 2 , SPF , 20: choose P7
P2 (CTFA recommended SPF 12) P3 or P7
P3 (JCIA standard SPF 15) SPF . 20: choose P3
P7 (FDA and JCIA standard SPF 4)
2 , SPF , 20: can choose all
SPF . 20: choose P2 or P3
6 Acceptance limits 3.9 , P1 , 4.4 11.8 , P3 , 18.6 3.191 , P7 , 5.749
of standards 10.7 , P2 , 14.7 3.2 , P7 , 5.0 The 95% confidence interval for
13.2 , P3 , 17.4 the mean SPF must contain the
3.8 , P7 , 4.7 value 4.
7 Product quantity 2.00 mg/cm2 + 2.5; CD-ROM 2 mg/cm2 or 2 m/cm2 2 mg/cm2
and application
8 Drying time Start exposure sequence between 15 and Quickly after 15 min At least 15 min
Fukuda and Naganuma
30 min after application

9 Test areas Minimum 30 cm2, maximum 60 cm2 (1 cm Minimum 20 cm2 (1 cm Minimum 50 cm2
between adjacent application sites) between adjacent
application sites)
10 Solar simulator Xenon lamp; %RCEE acceptance limits Xenon arc solar Solar simulator which emits
,290 nm: ,1.0% simulator with a continuous spectrum from 290 to
290– 300 nm:2.0– 8.0% continuous spectrum 400 nm similar to sunlight at sea
290– 310 nm:49.0– 65.0% similar to sunlight level from the sun at a zenith
290– 320 nm:85.0– 90.0% angle of 108
290– 400 nm:100% ,290 nm:,1% of its total energy
Total irradiance without an excessive .400 nm:,5% of its total energy
feeling of heat or pain
11 Criteria for solar Recommend to check with UV radiometer and Spectroradiometer system, or
simulator spectroradiometric measurement. erythema response equivalent instrument
12 Uniformity of beam Within 10% for a large-beam UV source — Good uniformity (within 10%)
13 Exposure subsites Minimum 0.5 cm2 more than 1 cm2 Minimum 0.5 cm2, Minimum 1 cm2
is recommended .8 cm between more than 1 cm2 is
each exposure subsite recommended
14 Number of subsites Minimum 5 No mention 7
15 Incremental Expected SPF , 25: 1.25 Expected SPF ,20:1.25 Untreated: 1.25
progression of Expected SPF . 25: 1.12 Expected SPF ,30:1.50 ,8:0.64, 0.80, 0.90, 1.0, 1.1,
UV Smaller ratio may be used Expected SPF .30:1.10 1.25, 1.56
.8, ,15:0.69, 0.83, 0.91, 1.0,

1.09, 1.20, 1.44
.15:0.76, 0.87, 0.93, 1.0, 1.07,
1.15, 1.32
(continued )
159
160
Table 10.4 Continued

International method and JCIA method JCIA method (1999
(2003 revised version) version) US FDA method (1999 version)
16 MED The lowest UV dose that produces the first The minimum UV dose The first perceptible redness reaction
perceptible unambiguous erythema with that produces a with clearly defined borders
defined borders appearing over most of minimally 22 – 24 h
the field of UV exposure, 16 –24 h after perceptible erythema
UV exposure in almost the entire
field of radiation (2/3
or more) 16– 24 h
after irradiation
17 MED assessment MEDu, MEDp, and MED of standard MEDu and MEDp are MEDu, MEDp, and MED of
sample are evaluated on the same day in recommended to be standard sample are evaluated on
a blind manner evaluated on the the same day in a blind manner
same day by some
evaluators
18 Expression of MED mJ/cm2 or MED unit or time (s) No mention J/m2
19 SPFi and SPF SPFi ¼ MEDpi/MEDui SPFi ¼ MEDpi/MEDui SPFi ¼ MEDpi/MEDui
SPF is calculated as the arithmetical SPF is calculated as the SPF is calculated as the arithmetical
mean of all SPFi arithmetical mean of mean of all SPFi
Fukuda and Naganuma
all SPFi
20 Labelling SPF No mention Integral numbers, Maximum value less than 95%
discarding fractions confidence interval
of the mean; the
upper limit of SPF
labeling is 50; SPF
50þ if the SPF is 50
or more and the
lower limit of the
95% confidence
interval is 51.0 or
more
21 Reporting Information to be included in test report is No mention No mention
shown
22 Rejection of test In case the MED could not be determined No mention In case the MED could not be
data determined
161
UV-A protection has so far been studied mainly for the purpose of clinical
treatment of patients sensitive to UV-A (30) or in patients sensitized to UV-A by
oral or topical application of 8-MOP (31), trimethylpsoralen (32), or tetracycline
(33) for the treatment of psoriasis vulgaris and vitiligo.
However, although the methods used are effective in clinical practice, it is
not possible to compare the UV-A-protective effect of sunscreens quantitatively
when experimental facilities are different, due to differences in the sensitivity of
the subjects and in the action spectra. It may be dangerous to expose healthy vol-
unteers artificially photosensitized to UV-A by application of psoralen com-
pounds, and this would be ethically unacceptable.
We have attempted to use IPD as an indicator of UV-A protection efficacy
(34,35). IPD is a temporary brown-gray to brown-black coloration observed in
human skin immediately after exposure to UV-A. This reaction was originally
reported by Hauser (36). Thereafter, it was discovered that IPD is due to a
photo-oxidation reaction in which a colorless melanin precursor is oxidized to
generate a pigmented product (37). It was further discovered that IPD occurs
on exposure to visible light (36,38) and that this response is an effective index
for measuring UV-A protection in healthy human skin (10,18,34,35,39).
Because it occurs with a relatively small dose of UV-A and fades quickly, it is
believed that IPD is suitable as a response index for measuring UV-A protection
in Japanese subjects. However, we encountered the following problems:
1. Because it fades so rapidly, the darkening response immediately after
UV-A exposure varies widely among individuals, and stable PFA
(protection factor against UV-A) values are difficult to obtain.
2. When tests are performed on sunscreen, especially makeup products,
2 or 3 min elapse after UV-A exposure while the skin is wiped with
skin cleaner, and from a practical standpoint, observation immediately
after exposure is impossible.
3. Determination should be done by several experienced observers, but in
the periods of time required for two or three observers to make obser-
vations one after the other, the darkening response disappears.
When time course observations of IPD were made in an attempt to over-
come these problems using four types of UV-A light sources, it was discovered
that by 2 h or more after exposure the rate of fading slowed down and became
stable (Fig. 10.12) (40). It was then determined that stable values could be
obtained when PFA values were calculated by using the response at 2 – 4 h
after exposure as an index (40).
It is believed that the measurement of UV-A protection by using the
IPD response 2– 4 h after exposure as an index is a suitable method. It is not
appropriate to designate the response that occurs 2– 4 h after exposure as IPD,
because it is different from the immediate response after exposure. Therefore,
after considerable discussion it was decided that from the standpoint of a res-
ponse that ultimately persists, this response should be called persistent pigment
20
15
MMT (J/cm2)
10
Bio-SS
5 BLB
SS335
SS345
0
0 1 3 24 1 week
Hours after exposure
Figure 10.12 Time course of MMT determined with various types of light sources.
Bio-SS: biosolar simulator (Watanabe Shoukou) with UVA filter; BLB: fluorescent
lamp (Toshiba) with Schott WG335 (2 mm); SS335: solar simulator model 600 (Solar
Light Co.) with Schott UG11 and Schott WG335 (2 mm); SS345: solar simulator model
600 (Solar Light Co.) with Schott UG11 and Schott WG345 (2 mm).
darkening (PPD), and the minimum dose of UV-A necessary for inducing this
response should be called the minimal persistent pigment darkening dose (MPPD).
PFA values are obtained as a ratio of MPPD in protected skin to MPPD in
unprotected skin. We determined PFA values of standard sunscreen in Japanese
volunteers of various skin types. As shown in Fig. 10.13, the PFA values of
standard sunscreen showed no statistically significant differences among the
volunteers with the five skin types. However, we could not decide whether there
6 Test sample: Standard Sample

Observation time: 3 hours after exposure
5 Figure: subject number
Bar: standard error
4
PFA
3
2 32 32 7 2
2
1
I II III IV V
Skin type
Figure 10.13 Relationship between skin types of volunteers and PFA values of standard
sunscreen.
were differences in PFA between skin types II–IV and skin types I and V because
the number of volunteers with skin types I and V was too small.
The main differences in test conditions between the SPF test method and
the UV-A protection test method standardized by JCIA are summarized in
Table 10.5. The JCIA method for measuring UV-A protection efficacy seems
to be excellent. Its major advantages are (1) it is possible to obtain a test result
in a short time, (2) there is no injury to volunteers, (3) it is also safe for the
examiners, (4) it shows good reproducibility, and (5) it has high precision.
There were no obvious disadvantages.
Development of Sunscreen Labeling for UV Protection

Efficacy in Japan
Before 1986, the labeling of sunscreen products for UV protection efficacy was
only done in terms of expressions such as “excellent UV protection”, “strong
UV protection”, etc. in Japan. This was insufficient for consumers to select an
adequate sunscreen, and such labeling was regarded as unreliable by consumers.
Shiseido put the first sunscreen products labeled with the quantitatively
measured SPF and UV-A protection levels on sale in Japan. As shown in
Fig. 10.14, the former was expressed as Suncare-Shisuu in 1981 by Shiseido
and the latter as one of a set of protection grades, namely, A, AA, and AAA,
in 1986.
Other companies also followed in the footsteps of Shiseido. At that time
there were no Japanese standards for labeling or for testing, so some confusion
arose. Currently, we have the following standards of labeling on sunscreens for
SPF and PA.
The arithmetic mean of SPF values determined in subjects is the SPF value
for the sample. The SPF values are expressed in integral numbers, discarding
fractions. However, SPF is expressed as SPF 50þ if the SPF for the sample is
over 50 and the lower limit of the 95% confidence interval is 51.0 or more, or
as SPF 50 if the lower limit of the 95% confidence interval is ,51.0. The PFA
is a value that measures UV-A protection in terms of protection against skin dar-
kening 2 –4 h after exposure. The SPF uses the erythema response as the index of
protection, and in that respect it is quite different from the PFA. More especially,
because SPF is an index of the extent to which reddening can be controlled, it can
be regarded as giving an approximate guide to the effect in actual situations. In
the case of UV-A, however, even when we use darkening as an index, it is
impossible to prevent darkening through UV-A protection alone, and it is difficult
to link the response of the skin to a protective effect that can actually be seen by
consumers. Moreover, the values differ if the index is changed (35). For example,
when the immediate darkening, which occurs directly after UV-A exposure, is
used as an index rather than PPD, different PFA values are obtained. Neverthe-
less, although the values themselves may vary, it is believed that they all yield
similar results concerning the relative strength or weakness of the protection.
Table 10.5 JCIA Standards for SPF Test Method and UV-A Protection Efficacy Test Method
UVA protection efficacy

SPF test method (2003 revised version) test method
1 Selection of volunteers Questionnaire; medical check by professional; Questionnaire

World Medical Association Declaration of
Helsinki
2 Skin type and test area Phototype, colorimetric method; back Phototype; back
3 Number of test subjects Minimum 10, maximum 20 (a maximum of five Minimum 10
results may be excluded)
4 Statistical criterion 95% CI , 17% of mean SPF SE less than 10% by mean PFA
5 Standard sunscreen P1 (DIN standard SPF4) Cream containing 5% 4-tert-butyl
P2 (CTFA recommended SPF12) 40 -methoxydibenzoylmethane and
P3 (JCIA standard SPF15) 3% 2-ethylhexyl
P7 (FDA and JCIA standard SPF4) p-methoxycinnamate
2 , SPF , 20: can choose all
SPF . 20: choose P2 or P3
6 Product quantity and application 2.00 mg/cm2 + 2.5; CD-ROM 2 mg/cm2 or 2 m/cm2
7 Light source Solar simulator (xenon lamp); %RCEE Continuous UVA spectrum similar
acceptance limits to sunlight; ratio of UVA/
,290 nm: ,1.0% UVA ¼ 8 –20%.

290 – 300 nm: 2.0 – 8.0 % UV ray shorter than 320 nm shall
290 – 310 nm: 49.0 – 65.0% be excluded
290 – 320 nm: 85.0 – 90.0%
290 – 400 nm: 100%
Total irradiance without an excessive
feeling of heat or pain
(continued )
165
166

UVA protection efficacy
SPF test method (2003 revised version) test method
8 Incremental progression of UV Expected SPF , 25: 1.25 1.25,

Expected SPF . 25: 1.12
Smaller ratio may be used.
9 MED and MPPD The lowest UV dose that produces the first The minimum UV dose that
perceptible unambiguous erythema with produces slight darkening over
defined borders appearing over most of the field essentially the whole radiation
of UV exposure, 16 –24 h after UV exposure field within 2 to 4 h after
exposure.
10 SPF and PFA SPFi ¼ MEDpi/MEDui PFAi ¼ MPPDpi/MPPDui
SPF is calculated as the arithmetical mean of PFA is calculated as the
all SPFi arithmetical mean of all PFAi
11 Labeling Integral numbers, discarding fractions of the 2 , PFA , 4: PAþ
mean; the upper limit of SPF labeling is 50; 4 , PFA , 8: PAþþ
SPF 50þ if the SPF is 50 or more and the lower 8 , PFA: PAþþþ
limit of the 95% confidence interval is 51.0 PA shall be placed together
or more with SPF
12 Reporting Information to be included in test report is shown No mention
13 Rejection of test data In case the MED could not be determined In case the MPPD could not be
determined
Fukuda and Naganuma
Shiseido Sunscreen in 1981 Intercept Sunscreen in 1986

(Suncare-Shisuu 2,3,6) (UVA Protection Grade,A,AA,AAA)
Figure 10.14 First labeling products of the quantitative efficacies for UV-A and UV-B
protection in Japan.
Therefore, a classification scheme rather than numerical values was

adopted for expressing UV-A protection. The method of classification was
based on the following considerations:
1. The difference in UV-A protection must be clear from the measured
values. For expressing the effectiveness we chose cutoff points of
2, 4, and 8 based on the fact that the value “2 or more” differs by
at least three geometric progression increments (1.25 1.25
1.25 ¼ 1.95) from the value of “1” given for no effect, and in the same
manner each class differs from the next by at least three geometric
progression increments.
2. The meaning of the classification must be clear. The protection doubles
for each step of increase in the classification.
In recognition of the fact that the labels must be simple, clear, and easy for
consumers to understand, PA was selected as the expression for UV-A protection,
and the classes of protection are expressed by þ, þþ, and þþþ.
“PAþ” indicates that the product offers protection against UV-A, “PAþþ”
indicates that the product offers considerable protection against UV-A, and
“PAþþþ” indicates that the product offers the greatest protection against
UV-A. There are no sunscreens having only UV-A protection efficacy without
UV-B protection efficacy. Therefore, a restriction has been imposed such that
the labeling of the level of UV-A protection is combined with SPF values as
shown in Fig. 10.15.
PROBLEMS FOR THE FUTURE

One goal of cosmetics scientists is to be able to protect the skin against aging,
that is, to reduce or delay the signs of skin aging. Recovery and maintenance
Figure 10.15 Example of labeling of UV-A and UV-B protection efficacies in Japan.
of “fresh skin” is a common desire of all people. Aging phenomena in the skin
include pigmented spots, wrinkles, yellow skin, flabby skin, and tumors. These
skin changes are most commonly observed in the sites usually exposed to sun-
light, especially the face. They are collectively designated as photoaging, and
are considered to be caused mainly by cumulative UV exposure and external
stimulation. The most important countermeasure to photoaging of skin is
defense of the skin against UV rays. The simplest method is a change of life
style to avoid unnecessary sunburn and suntan. Measures such as wearing sun-
glasses, long-sleeved shirts, and a hat, putting up a parasol, and using sunscreens
are effective. Recent study has indicated that UV-B and UV-A accelerate skin
aging, and that both must be intercepted in order to prevent skin aging. Therefore,
the protective efficacy of sunscreens is a very important function for consumers.
Skin care cosmetics for daily use as well as those for leisure use are also
required to have a sun protective function. Accordingly, there is a continuing
need for new UV-A and UV-B absorbers which can be used in sunscreens in
appropriate amounts, and which at the same time are safe enough for use on
people with sensitive skin (41).
The dosages of sunscreens are determined not only by the safety levels of
UV absorbers, but also by the solubility of the absorbers in the base or solvent.
High solubility in cosmetics bases and solvents such as oil, alcohol, and water
is an essential factor for cosmetics ingredients.
Furthermore, UV absorbers must be water resistant. Since most sunscreens
are used on the beach or in the mountains in summer, UV absorbers would lose
their practical value if they were easily dissolved by seawater or perspiration. In
other words, UV absorbers have little practical value if they are not water
resistant, even if they have high UV absorbance. Therefore, development of
UV absorbers having superior water resistance as well as a UV-protective
EU Japan
SPF50+ SPF50+
No later than the end of 2005
Korea USA
China SPF30+
Taiwan
South Australia/ Mercosur

Africa New Zealand
SPF30+
International SPF Test Method
Figure 10.16 SPF test methods and upper limits of SPF labeling on sunscreen products
around the world.
effect, safety, and high solubility is highly desirable. The need for protection from
UV-A is evident from the established dermal toxicity of UV-A. Therefore,
measures on an international scale should immediately be taken to develop a
method of evaluating UV-A blocking and to identify UV-A absorbers.
Figure 10.16 shows the international status of SPF values and test methods.
The upper limits of labeled SPF numbers on sunscreen products in Japan, EU,
USA, and Australia/New Zealand are different. Further, although the differences
in SPF test methods among these countries and areas are not major, there are still
small differences in testing conditions, and differences in the ways of expressing
SPF also remain an issue.
These differences, which are scientifically insignificant, result in economic
loss and delay. In the near future, international harmonization of SPF test
methods and labeling methods should be promoted, including UV-A protection
and water resistance testing methods for sunscreen products.
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of photographic techniques for the differentiation of the location of melanin pigment
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tion. Tokyo: University of Tokyo Press, 1981:231 – 244.
2. Fukuda M, Nagashima M, Munakata A, Nakajima K, Ohta S. Effect of biological and
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4. Fukuda M, Naganuma M, Maeda K. Protection against cutaneous aging induced by
repeating sun exposure. In: Kligman AM et al., ed. Cutaneous Aging. Tokyo: Univer-
sity of Tokyo Press, 1988:589 – 605.
5. Fukuda M, Nakajima K. Sunscreen. J Jpn Cosmet Sci Soc 1981; 5:73 – 82.
6. Mizugaki M, Naganuma M, Fukuda M. Seasonal skin color variation of the pigmented
area on the female face measured by remote color sensing system. J Jpn Cosmet Sci
Soc 1997; 21:185– 189.
7. Fukuda M. Self-reported skin type of Japanese. J Jpn Cosmet Sci Soc 1991;
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8. Food and Drug Administration. Sunscreen drug products for over-the-counter-human
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9. Yoshii T. The survey about female attitude against their skin and the character of
their skin—the international comparison of surveys conducted in Japan, US, Europe
and Asia. J Jpn Soc Cutan Health. 2003; 50:68 – 74.
10. Fukuda M, Naganuma M, Iwai M, Nakayama Y. Protection to UVA-induced skin
reaction by ultraviolet absorbers. J Soc Cosmet Chem Jpn 1988; 22:5 – 9.
11. Everett MA, Yeargers E, Sayre RM, Olson RL. Penetration of epidermis by ultraviolet
rays. Photochem Potobiol 1966; 5:533– 542.
12. Fukuda M, Naganuma M, Nakajima K. Ultraviolet radiation of sunlight in Japan. Acta
Dermatol (Kyoto) 1987; 82:551 – 558.
13. Naganuma M, Hara E, Yagi E, Fukuda MM. Seasonal variation of solar UV dose.
J Soc Cosmet Chem Jpn 1991; 25:15– 20.
14. Kligman LH, Akin FJ, Kligman AM. The contributions of UVA and UVB to connec-
tive tissue damage in hairless mice. J Invest Dermatol 1985; 84:272 – 276.
15. Poulsen JT, Staberg B, Wulf HC, Brodthagen H. Dermal elastosis in hairless
mices after UV-B and UV-A applied simultaneously, separately or sequentially.
Br J Dermatol 1984; 110:531 – 538.
16. Stanberg B, Wulf HC, Klemp P, Poulsen T, Brodthagen H. The carcinogenic effect of
UVA irradiation. J Invest Dermatol 1983; 8l:517 – 519.
17. Toda K, Ohta M. Female facial melanosis. In: Fitzpatrick TB et al., ed. Biology and
Diseases of Dermal Pigmentation. Tokyo: University of Tokyo Press, 1981:225 – 229.
18. Fukuda M, Naganuma M, Nakajima K. Laboratories studies on UVA protection with
Parsol A. Nishinihon J Dermatol 1987; 49:88– 94.
19. Fukuda M, Takata S. The evolution of recent sunscreens. In: Altmyer P, Hoffman K,
Stucker M, eds. Skin Cancer and UV Radiation. Berlin: Springer-Verlag,
1997:266 –275.
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function. Fragr J 1986; 80:60 – 66.
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1999; 29(5):14– 19.
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Sunscreens and UV protection—SPF & PA. 1999 revised version. JCIA, 2000:1 – 59.
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Prot 2001; 11:93– 103.
28. CTFA/SA, COLIPA, JCIA. International Sun Protection Factor (SPF) Test Method.
2003.
29. Fukuda M, Asano H, Kawai M, Naganuma M, Hirose O, Matsue K, Mouri K.
Sunscreens and UV protection—SPF and PA. 2003 revised version. JCIA, July 25,
2003.
30. Rice EG. Dihydroxyacetone naphthoquinone protection against photosensitivity.
Dermatologica 1976; 153:38 – 43.
31. Jarratt M, Hill M, Smiles K. Topical protection against long wave ultraviolet A.
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topical psoralen treatment of vitiligo. Arch Dermatol 1971; 104:281 – 283.
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protection from longwave ultraviolet. J Invest Dermatol 1970; 55:164 – 169.
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In: Lowe NJ, Shaath NA, eds. Sunscreen: Development, Evaluation and Regulatory
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Soc Cutan Health 1992; 29:291– 298.
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39. Kaidbey K. Determination of UVA protection factors by means of immediate pigment
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11
Regulations of Sunscreens Worldwide
David C. Steinberg
Steinberg & Associates, Inc., Plainsboro, New Jersey, USA
Overview of Regulations and Permitted UV Filters 174

Active Ingredients 175
The USA 175
Japan 175
EU Permitted Filters 176
Australian Approved UV Filters 176
Summary of Actives 176
Approval Process for New Active Ingredients 176
USA 176
Japan 181
European Union 182
Australia 182
Testing of Sunscreens 183
Reference Standards 183
USA 183
European Union 188
Japan 190
Australia 190
UV-A Tests 190
USA 190
European Union 190
Japan 191
173
174 Steinberg
Australia 192
Water Resistance Tests 192
USA 192
Australia 192
The Labeling of Sunscreens 193
USA 194
European Union 196
Australia 196
Japan 197
Manufacture of Sunscreens 197
Sunscreens are regulated throughout the world either as cosmetics or as over-

the-counter (OTC) drugs that do not require a governmental preapproval, or as
OTC drugs that require a preapproval before they are placed on the market.
Regardless of how they are regulated, all of these product regulations are very
similar concerning sunscreens! Each country has a preapproved list of permitted
UV filters, an accepted method of running efficacy by SPF determination, and
regulated labels. Some countries have approved methods for UV-A claims and
water-resistance testing.
This chapter will cover the approved UV filters in the USA, EU, Japan, and
Australia, their maximum use level, correct ingredient designation, and how new
filters are approved. There is also a master cross-reference list by INCI desig-
nation. The different SPF test methods will be described along with the formu-
lations of reference standards, current approved UV-A methods, water-resistant
testing, labeling requirements, and finally a brief review of current Good Manu-
facturing Procedures (cGMPs) for the USA.
OVERVIEW OF REGULATIONS AND PERMITTED UV FILTERS

The USA regulates sunscreens as OTC drugs under the Final Monograph issued
May 21, 1999. For a complete copy see http://www.fda.gov/cder/otcmono-
graphs/Sunscreen/sunscreen_FR_19990521.pdf.
Japan regulates sunscreens as cosmetics as of March 31, 2002.
The European Union regulates sunscreens as cosmetics under the Cosmetic
Directive 76/768/EEC. These can found at http://pharmacos.eudra.org/F3/
cosmetic/pdf/vol_1en.pdf.
Australia regulates sunscreens as OTC drugs under the Therapeutic Goods
Act of 1989, which require preapproval before being allowed on the market.
There is an exemption of products that claim an SPF of 3 or less.
Regulations of Sunscreens Worldwide 175
ACTIVE INGREDIENTS
The permitted list of UV filters is the cornerstone for formulating sun protection
products. The USA permits the fewest UV filters with Japan, the EU, and
Australia having many more approvals.
The USA
As of October 1, 2003, there are 16 permitted filters in the USA. Table 11.1 lists these
by their drug name and the maximum permitted level. These actives must meet the
specifications found in the United States Pharmacopoeia. All sunscreens can be used
with any other sunscreen with the exception of avobenzone. This is permitted to be
used only with the following other permitted filters: cinoxate, dioxybenzone, octinox-
ate, octisalate, homosalate, oxybenzone, octocrylene, sulisobenzone, and trolamine
salicylate. If you use two or more UV filters in a product, each must add a
minimum SPF of 2 to the total. So a product with one filter must have a minimum
SPF of 2, for two filters it must be 4, for three filters it must be 6, and so on.
Japan
Japan changed their regulations in 2002 and moved sunscreens into the category
of cosmetics from quasi-drugs. They established a positive list for permitted UV
filters and permitted concentrations. These are allowed in four separate categories
of use: all cosmetics (Table 11.2), rinse-off no mucous membrane application,
Table 11.1 US Permitted Filters
Maximum
UV filter drug name concentration (%)
Aminobenzoic acid 15
Avobenzone 3
Cinoxate 3
Dioxybenzone 3
Homosalate 15
Meridamate 5
Octocrylene 10
Octinoxate 7.5
Octisalate 5
Oxybenzone 6
Padimate O 8
Ensulizole 4
Sulisobenzone 10
Titanium dioxide 25
Trolamine salicylate 12
Zinc oxide 25
176 Steinberg
Table 11.2 UV Filters Allowed in Japan in all Cosmetics
Maximum content
UV filter INCI name (per 100 g)
Homosalate 10
Glyceryl ethylhexanoate dimethoxycinnamate 10
PABA and its esters 4 total
Butyl methoxydibenzoylmethane 10
leave-on no mucous membrane application; and rinse-off and leave-on cosmetics

which can be applied to mucous membranes (Table 11.3).
EU Permitted Filters
All UV filters must be preapproved and listed in Annex VII (Table 11.4).
Australian Approved UV Filters

Australia has a permitted list of UV filters and also requires all filters to obtain an
Australian approved name (AAN) before use (Table 11.5).
SUMMARY OF ACTIVES
Table 11.6 summarizes by INCI name the approvals by country by concentration
for sunscreen application.
APPROVAL PROCESS FOR NEW ACTIVE INGREDIENTS

USA
Before 2002, the only method available to approve a new active was the very
complex and costly New Drug Application (NDA) process. Here, a manufacturer
would submit the new active in a formulation along with extensive safety and
efficacy testing. The FDA would approve this and send a letter to this submitter
allowing them to sell this new drug with the FDA’s stated rules, for this particu-
lar formulation only. If the manufacturer wanted to use this active in a different
formulation, they were required to submit a supplementary NDA. Only this
company could use this active. A producer of the active could obtain an NDA
but that would put them in the finished goods business! After at least 2 years
on the market, the holder of the NDA could then petition the FDA to reopen
the Final Monograph to allow this active. If the FDA approves this request,
then anyone could use this active in any Monograph compliant formulation.
Since 1978, with the original publication of the Proposed Rules for Sunscreens
Table 11.3 UV Filters Allowed in Japan Depending on the Type of Cosmetic
UV filter Type 1 Type 2 Type 3
Glucopyranoxy propylhydroxy 5 5 NAa

benzophenone
Ethylhexyl salicylate 5 10 NA
Diisopropyl methyl cinnamate 0.5 10 NA
Cinoxate 1c 5 5
Benzophenone-6 10 10 NA
1-(3,4-dimethoxyphenyl) 7 7 NA
4,4-dimethyl-1,3-pentanedioneb
Ethylhexyl dimethoxybenzylidene 3 3 NA
Benzophenone-2 10 10 0.05
Terephthalidene dicamphor sulfonic acid 10 10 NA
Ethylhexyl triazone 5 5 NA
Isopentyl trimethoxycinnamate trisiloxane 7.5 7.5 2.5
Pentyl dimethyl PABA 10 10 NA
Ethylhexyl dimethyl PABA 10 10 7
Isopropyl methoxycinnamate, diisopropyl 10 10 NA
methoxycinnamate esters (mixture)
Ethylhexyl methoxycinnamate 20 20 8
Benzophenone-3 1c 5 5
Benzophenone-4 10 10 0.1
Benzophenone-5 10 10 1
Phenylbenzimidazole sulfonic acid 3 3 0
Ferulic acid 10 10 NA
Octocrylene 10 10 NA
a
NA ¼ not allowed.
b
No INCI designation.
c
1 ¼ no limit.
Note: Categories of use: type 1—rinse-off, no mucous membrane application; type 2—leave-on, no
mucous membrane application; type 3—rinse-off and leave-on cosmetics which can be applied to
mucous membranes.
by the FDA, only avobenzone was approved by this very complicated method.
This has been a major issue between industry and the FDA.
In 1999, the FDA proposed new rules for allowing foreign safety and effi-
cacy data to be used for possible approval of any OTC drug active or to increase
the permitted level. This rule was finalized in January 2002. It is known as Time
and Extent Application (TEA).
TEA is a three-part process. The first part is a submission by either a user
or a seller of the active of a formal application showing a minimum of five
178 Steinberg
Table 11.4 UV Filters Permitted in the EU (Annex VII)
COLIPA Maximum
No. Chemical name as used in the directive concentration (%)
S 1 4-Aminobenzoic acid 5
S 3 Ethoxylated ethyl-4-amino benzoate 10
S 8 2-Ethylhexyl-4-dimethyl-aminobenzoate 8
S 12 Homosalate 10
S 15 2,4,6-Trianolino-( p-carbo-20 -ethylhexyl-10 oxy)- 5
1,3,5-triazone
S 16 Drometrizole trisiloxane 15
S 17 Benzoic acid, 4,40 -[[6-[[4-[[(1,1-dimethylethyl) 10
amino]carbonyl]phenyl] amino]1,3,5-triazine-
2-4-diyl]bis-bis(2-ethylhexyl)] ester
S 19 3-Benzylidene camphor 2
S 20 2-Ethylhexyl salicylate 5
S 27 Isopentyl-4-methoxycinnamate 10
S 28 2-Ethylhexyl-4-methoxy-cinnamate 10
S 32 2-Cyano-3,3-diphenyl acrylic acid, 2-ethylhexyl ester 10
S 38 Oxybenzone (warning label required—“contains 10
oxybenzone if over 0.5%”)
S 40 2-Hydroxy-4-methoxybenzo-5-sulfonic acid 5
S 45 2-Phenylbenzimidazole-5-sulfonic acid and 8
its potassium, sodium, and triethanolamine salts
S 57 N, N, N-Trimethyl-4-(2-oxoborn-3-ylidenemethyl) 6
anilinum methyl sulfate
S 59 alpha-(2-Oxoborn-3-ylidene)toluene-4-sulfonic 6
acid and its salts
S 60 3-(40 -Methylbenzylidene)-D -1-camphor 4
S 66 1-(4-tert-Butylphenyl)-3-(4-methoxyphenyl) 5
propane-1,3-dione
S 71 3,30 -(1,4-Phenylenedimethylene)-bis- 10
(7,7-dimethyl-2-oxobicyclo-[2.2.1]
hept-1-ylmethanesulphonic acid) and its salts
S 72 Polymer of N-f(2 and 4)-[2-oxoborn-3-ylidene) 6
methyl]benzylgacrylamide
S 74 Benzylidene malonate polysiloxane 10
S 75 Titanium dioxide 25
S 76 Zinc oxide 25
S 79 2,20 -Methylene-bis-(6-(2H-benzotriazol-2-yl)- 10
4-(1,1,3,3-tetramethylbutyl)phenol)
S 80 2,20 -(1,4-Phenylene)bis)-1H-benzimidazole-4,6-disulfonic 10
acid, monosodium salt
S 81 2,4-Bis-f[4-(2-ethyl-hexyloxy)-2-hydroxy]-phenylg- 10
6-(4-methoxyphenyl)- (1,3,5)-triazine
S 83 Benzoic acid, 2-[4-(diethylamino)-2-hydroxybenzoyl]- 10
hexyl ester (expressed as acid)
Table 11.5 UV Filters Permitted in Australia by Their Required Name
Maximum
concentration
AAN INCI name (%)
Aminobenzoic acid PABA 15

Isoamyl methoxycinnamate Isoamyl p-methoxycinnamate 10
Benzophenone-2 Benzophenone-2
Butyl Butyl 5
methoxydibenzoylmethane methoxydibenzoylmethane
Cinoxate Cinoxate 6
Dioxybenzone Benzophenone-8 3
Octyl methoxycinnamate Ethylhexyl methoxycinnamate 10
Octyl salicylate Ethylhexyl salicylate 5
Homosalate Homosalate 15
Isopropylbenzyl salicylate Isopropylbenzyl salicylate
Menthyl anthranilate Menthyl anthranilate 5

4-Methylbenzylidene camphor 4-Methylbenzylidene camphor 4
Octocrylene Octocrylene 10
Octyl triazone Ethylhexyl triazone 5
None Benzylidene camphor 6
sulfonic acid
Oxybenzone Benzophenone-3 10
Phenylbenzimidazole Phenylbenzimidazole 4
sulfonic acid sulfonic acid
None Camphor benzalkonium 6
methosulfate

Salicylic acid salts
Benzophenone-4 Benzophenone-4 10
None Benzophenone-5 10
Ecamsule Terephthalylidene 10
Dicamphor sulfonic acid
Titanium dioxide Titanium dioxide 25
Triethanolamine salicylate TEA salicylate 12
Zinc oxide Zinc oxide 20
Methylene bis-benzotriazolyl Methylene bis-benzotriazolyl 10
tetramethylbutylphenol tetramethylbutylphenol
Drometrizole trisiloxane Drometrizole trisiloxane 15
Notes: None—must apply for AAN before it can be used. The asterisks denote sunscreens currently
under review—no new products containing these will be permitted until the review is completed.
consecutive years of use of this UV filter (the rules for a TEA cover all drugs, not
just UV filters) as a nonprescription product in a foreign country. After this sub-
mission is reviewed and meets the FDA’s requirements, the FDA issues a notice
in the Federal Register that this first part has been approved. Rejected
180 Steinberg
Table 11.6 Cross-Reference of all UV Filters by INCI Designation
INCI designation USA Japan EU Australia
1-(3,4-Dimethoxyphenyl) 7
4,4-dimethyl-1,3-pentanedione
3-Benzylidene camphor 2
c
4-Methylbenzylidene camphor 4 4
Benzophenone-1 10
a
Benzophenone-2 10
Benzophenone-3 6 5 10 10
Benzophenone-4 10 10 5 10
Benzophenone-5 10 10
Benzophenone-6 10
Benzophenone-8 3 3
Benzophenone-9 10
Benzylidene camphor sulfonic acid 6 6
Bis-ethylhexyloxyphenol 10
Butyl methoxydibenzoylmethane 3 10 5 5
Camphor benzalkonium methosulfate 6 6
Cinoxate 3 5 6
Diethylamino hydroxybenzoyl 10
hexyl benzoate
Diethylhexyl butamido triazone 10
Diisopropyl methyl cinnamate 10
Disodium phenyl dibenzimidazole 10
tetrasulfonate
Drometrizole trisiloxane 15 15
Ethyl PABA 4
Ethylhexyl dimethoxybenzylidene 3
Ethylhexyl dimethyl PABA 8 10 8 8
Ethylhexyl methoxycinnamate 7.5 20 10 10
Ethylhexyl salicylate 5 10 5 5
c
Ethylhexyl triazone 3 5 5
Ferulic acid 10
Glucopyranoxy propylhydroxy 5
benzephenone
Glyceryl ethylhexanoate 10
dimethoxycinnamate
Glyceryl PABA 4
Homosalate 15 10 10 15
c
Isoamyl p-methoxycinnamate 10 10
Isopentyl trimethoxycinnamate 7.5
trisiloxane
(continued )

INCI designation USA Japan EU Australia
Isopropyl methoxycinnamate 10
Menthyl anthranilate 5 5
Methylene bis-benzotriazolyl 10 10
Octocrylene 10 10 10 10
PABA 15 4 5 15
PEG-25 PABA 10 10
Pentyl dimethyl PABA 10
Phenylbenzimidazole sulfonic acid 4 3 8 4
Polyacrylamidomethyl benzylidene 6
camphor
Polysilicone-15 10
TEAb-salicylate 12 12
Terephthalylidene dicamphor 10 10 10
sulfonic acid
Titanium dioxide 25 No limit 25 25
b
Zinc oxide 25 No limit 20
a
Under review, no new approvals are expected until this is complete.
b
Permitted as a color.
c
TEA (Time and Extent Application) submitted.
applications are not made public. After this announcement, there is a request for
submission of safety and efficacy data for the UV filter alone and this filter
formulated into sunscreens. This data can come from suppliers or users anywhere
it is permitted. After the FDA reviews these submissions, another announcement
is made in the Federal Register stating the intention of the FDA to amend the
Final Monograph to allow this new ingredient. After a comment period, this
then becomes an approved filter for everyone to use.
So far (as of October 1, 2003), three filters have been approved through step 1:
amiloxate (INCI isoamyl methoxycinnamate), enzcamene (4-methylbenzylidene
camphor), and ethylhexyl triazone (no drug name as of this writing).
Japan
Under the new cosmetic regulations, there is a positive list of UV filters. To be
approved and placed on this list requires a formal submission to the Minister
of Health, Labor and Welfare (MHW), Examination and Administration
Section, Medicine Bureau, who after reviewing your submission will approve
or reject or request additional data. The submission must include the chemistry
of the filter including the method of production and purity. You need to submit
data as to its efficacy and whether it is for UV-A, UV-B, or both. If the filter
has been approved in any other market, this information must be included
182 Steinberg
along with maximum use levels and any restrictions. If the chemistry is similar to
that of other sunscreens, this comparison is also required.
Safety testing includes single-administration toxicity, repetitive adminis-
tration toxicity, reproductive development toxicity, skin primary irritation,
continuous skin irritation, sensitivity, phototoxicity, photosensitization, eye irri-
tation, genetic toxicity, human patch test on Japanese subjects, and data on
absorption, distribution, metabolism, and excretion.
All data must be submitted on official forms in Japanese.
European Union
The Scientific Committee Cosmetics and Non-Food Products (SCCNFP)a reviews
submissions (usually coordinated by The European Cosmetic, Toiletry and
Perfumery Association [COLIPA]) and then makes recommendations to the
European Commission. If approved, they are added to the Cosmetic Directive
as an Adaptation of Technical Progress and the filter is added to Annex VII.
The test required for submission by SCCNFP can be found at http://europa.
eu.int/comm/food/fs/sc/sccp/out185_en.pdf.
Australia
The Medicines Evaluation Committee advises the Therapeutic Goods Administra-
tion (TGA) on the regulation of OTC medicines (including sunscreens) in Australia.
The following studies should be submitted:
Acute oral toxicity
Acute eye irritation
Skin sensitization
Acute dermal irritation
Toxicokinetics—an in vivo determination of dermal and oral absorption is
needed to establish systemic exposure via both routes and to enable the
interpretation of the toxicity studies
Genotoxicity testing—in bacterial and mammalian cell lines, photo-
mutagenicity test in bacteria, photomutagenicity in a chromosomal aber-
ration test, and an in vivo chromosome aberration assay
Reproductive toxicity testing—for assessment of developmental and ferti-
lity effects
Photostability
Subchronic oral toxicity
Carcinogenicity—in vivo carcinogenicity and photocarcinogenicity bioas-
says or justification for not providing these studies; a justification could
be based around issues such as
The expected pattern of use (identify possible low exposure)
a
This committee has been replaced in 2004 by the Scientific Committee on Consumer Products (SCCP).
Results of mutagenicity studies

Lack of similarity to existing molecules with known carcinogenic activity
Low persistence in the skin
Low in vivo absorption
Lack of photosensitization or phototoxic potential
Proven photostability
Lack of possible adverse effects on the skin (change to epidermis/dermis)
Another issue that should be addressed is the potential for interaction with
other commonly used UV filters, since sunscreen products generally contain
more than one active ingredient. These are new requirements as Australia use
to automatically allow any UV filter permitted in the USA or the EU.
TESTING OF SUNSCREENS
Sun protection factor (SPF) is the universal method to describe efficacy of sun-
screens. SPF is the ratio of the length of time you can be exposed to UV (mainly B)
radiation with the sunscreen divided by the same amount of radiation without the
sunscreen. The FDA in its Final Monograph describes the US method. COLIPA
and Japan Cosmetic Industry Association (JCIA) (trade associations) have
adopted methods for the EU and Japan. Australian methods are adopted by
TGA from the latest Australian/New Zealand Standards.
Table 11.7 compares these four methods.
REFERENCE STANDARDS
USA
The FDA in their Final Monograph establish the following as the reference
standard formulation:
Part A
Lanolin 5.00
Homomenthyl salicylate 8.00
White petrolatum 2.50
Stearic acid 4.00
Propylparaben 0.05
Part B
Methylparaben 0.10
EDTA disodium 0.05
Propylene glycol 5.00
Triethanolamine 1.00
Purified water 74.30
Procedure: Heat both phases to 77–828C with constant stirring until the con-
tents of each phases are solubilized. Add A to B slowly while stirring. Cool.
Table 11.7 Comparison of the Four Methods
184
Parameter EU USA Australia Japan
Date October 1994 May 21, 1999 1998 January 1992

UV definition UV-C 200– 280 UV-B 290 – 320 UV-B 290 – 320 UV-B 290– 320
UV-B 280– 320 UV-A 320 – 400 UV-A 320 – 400 UV-A 320– 400
UV-A 320– 400
Selection of Medical—informed consent Questionnaire, informed Questionnaire, personal Questionnaire
volunteers Technical – visual, consent interview
colorimetry
Exclusion Pregnant, lactating, Medical history, abnormal Photosensitizing medication, Photodermatitis,
criteria medication, dermatological skin response, medication skin disease, abnormal photosensitizing,
problems, abnormal response to UV, allergies medication
response, UV-A suntan
Skin type Phototypes Phototypes Phototypes Phototypes
I, II, III I, II, III I, II, III I, II, III
Test area Back Back Back Back
Age limitation 18–60 years — — .18 years
Frequency 5 times/12 month period — — —
Number of 10–20—statistical criterion 20 data ¼ 25 subjects ¼ 10 ¼ 10
subjects
Statistical 95% CI , 20% mean SPF — SEM ¼ 7% SPF SEM ¼ 10% SPF
criterion
Reference P1 2.7%OMC SPF ¼ 4 8% HS 8% HS 8%HS
standard P2 7% ODP, 3% OB, SPF ¼ 4.47 SPF ¼ 4 SPF ¼ 45
SPF ¼ 12 P3 3% OMC, 0.5% AVB, 5% AVB, 3% OMC
P3 3% OMC, 0.5% AVB, 2.78%PBIS For UV-A
2.78% PBIS SPF ¼ 15
SPF ¼ 15
Steinberg
Acceptance — +SD With 25% of nominal value, —
limits for 95% CI includes applicable to each subject
standards value of 4.0
Quantity 2.00 + 0.04 mg/cm2 2 mg/cm2 2.0 mg/cm2 or mL/cm2
applied +5%
Mode of Weight (by loss), fingercot, Fingercot (oil, lotion: syringe; Weight, fingerstall, validated Fingertip, weight or
delivery no loss, droplets, gentle gel, butter: warmed) method; uniform thickness volume – viscosity
rubbing
Test site 35 cm2 50 cm2 30 cm2 20 cm2
randomized randomized
Drying time As soon as possible after 15 min 15 min 15 min
15 min 20 – 258C air-conditioned
Solar simulator Continuous spectrum, Continuous emission ,1% energy ,290 nm; no Xenon arc; continuous
erythemal efficacy similar spectrum 290 – 400 nm, peaks in UV-B, continuous spectrum similar to
to that of standard Sun similar to sunlight at sea spectra in UV-A; Xe sunlight in UV-B;
level, 108 zenith angle, preferred (150 – 6000 W) energy ,290 nm
,1% energy ,290 nm þ WG 320/1 mm (2% at smallest
,5% energy .400 nm 300 nm) þ dichroic mirror
or IR filter
UV monitoring Radiometer (280 – 400 nm) Spectroradio metry — UV radiometer
Flux uniformity 15% (min—max)/subsite Within 10%/subsite — Constant and uniform
flux
Number of At least 5 3; 5 for MEDu, 7 for MEDp 5 —
exposure sites
(continued )
185
186

Parameter EU USA Australia Japan
Progression of 25% geometric 1.25 26% (geometric) 25% (geometric)

doses SPF ,8: 0.64– 1.56 exp. 12% for SPFe 25 smaller for high SPF
SPF X
SPF 8 – 15: 0.69 – 1.44 X
SPF .15: 0.76 –1.32 X
Exposure site: Minimum 0.5 cm2 1 cm2 1 cm2 0.5 cm2
minimum Recommended 1 cm2
size
Skin response erythema erythema erythema erythema
Observation 16–24 h 22 – 24 h 16 – 24 h 16– 24 h
time-post
exposure
Minimal First perceptible Smallest dose of energy that Minimum quantity of radiant Minimum UV dose
erythema unambiguous redness, with produces redness reaching energy to produce the first that produces
clearly defined borders site at 22 – 24 h detectable reddening of fair minimally
postexposure human skin perceptible
erythema at most
Steinberg
radiation fields
MED Simultaneous, paired, visual, Blind MEDus previous and Visual only, same observer Visually— one or two
determination or colorimetric evaluation same day and similar manner for trained evaluators.
MEDu and MEDp MEDu/MEDp
simultaneously or
not; same manner
MED Energy (mJ/cm2) or time (s) Eeff ¼ S Vi(l) I(l) Energy or time —
expression J/m2effective
Individual SPFi MEDpi/MEDui MEDps (J/m2)/ MEDp/MEDu MEDp/MEDu
definition MEDus (J/m2)
Validation of Not the lowest dose in the Rejection: no erythema/ SPFi– SPF of std 4 25% MED not recognized at
individual series ps or ms protected or
result Subject noncompliant unprotected site
SPF definition Arithmetical mean of SPFi Arithmetical SPF mean of SPFi, one Arithmetical mean x of
Variability and 95% CI with n mean x of SPFi decimal point, labeled to SPFi Lower integral
volunteers SD, A ¼ t.s./vn with n lowest integer (SEM 7% number
volunteers mean SPF)
Note: OMC ¼ Octyl methoxycinnamate; ODP ¼ Octyl dimethyl PABA; OB ¼ Benzophenone-3; AVB ¼ Butyl methoxydibenzoylmethane; PBIS ¼
Phenylbenzimidazole sulfonic acid; HS ¼ Homosalate.
187
188 Steinberg
This standard can be obtained from Cosmetech Laboratories (1-973-882-5151)

(www.Cosmetech.com).
European Union
COLIPA lists three different formulations as standards.
P1 Low SPF Standard:
Phase 1
Propylene glycol stearate, SE (Tegin P) 1.0
Mineral oil (liquid paraffin WPM 24) 5.0
Stearic acid 1.5
Octyl methoxycinnamate (Parsol MCX) 2.7
Cetearyl alcohol (Lanette O) 0.4
Propylparaben 0.1
Phase 2
Methylparaben 0.1
Triethanolamine 0.8
Glycerin (85%) 4.0
Carbomer (Carbopol 934P) 0.1
Water 84.3
Heat phases 1 and 2 to 758C. Add phase 1 to 2 with stirring. Cool to 308C.
SPF ¼ 4.0 –4.4.
P2 High SPF Standard (CTFA/JCIA Standard):
Phase 1
Lanolin 4.5
Cocoa butter 2.0
Glyceryl stearate, SE 3.0
Stearic acid 2.0
Octyl dimethyl PABA (Escalol 507) 7.0
Benzophenone-3 (Uvinul M40) 3.0
Phase 2
Water 71.6
Sorbitol 5.0
Triethanolamine 1.0
Methylparaben 0.3
Propylparaben 0.1
Phase 3
Benzyl alcohol 0.5
Melt Phase 1 and heat to 80– 858C. Heat phase 2 to 80– 858C. Add phase 1
to phase 2 with a homogenizer. Cool to 508C and add phase 3. SPF ¼ 11.5 –13.9
P3 High SPF Standard (Bayer Standard C202/101):
Ingredients Percentage w/w

Part 1
Cetostearyl alcohol BP (and) PEG-40 castor oil (and) 3.15
Sodium cetearyl sulfate
Note: As the source may affect the end product, this is Emulgade F (Henkel,
INCI—cetearyl alcohol [and] PEG-40 castor oil [and] sodium cetearyl sulfate)
Deceyl oleate 15.0
Octyl methoxycinnamate 3.0
Butyl methoxy dibenzoylmethane 0.5
Propyl hydroxybenzoate BP 0.1
(INCI—propylparaben)
Part 2
Water purified BP 53.57
(INCI-water)
Phenylbenzimidazole sulfonic acid 2.78
Sodium hydroxide (45% solution) BP 0.9
Methyl hydroxybenzoate BP 0.3
(INCI—methylparaben)
Disodium edetate BP 0.1
(INCI—disodium EDTA)
Part 3
Carbomer 0.3
Note: As the grade of carbomer used may affect the end product, the grade
equivalent to carbomer 934P should be used
Sodium hydroxide (45% solution) BP 0.3
Procedure: Heat part 1 to 75 –808C. Heat part 2 to 808C (if necessary boil
until solution is clear and cool to 75– 808C). Add part 1 into part 2 while stirring
part 2. Prepare part 3 by dispersing carbomer in water (by stirring with rotor/
stator dispersator), then add sodium hydroxide for neutralization. Add part 3 to
parts 1 and 2 while stirring and homogenize for about 3 min. Adjust pH to
7.8 –8.0 with sodium hydroxide or lactic acid while stirring until cooled to
room temperature.
190 Steinberg
The mean SPF + 2 standard deviations should fall between 12.5 and
18.5. This product should be stored below 208C and used within 1 year of
preparation.
Japan
Japan uses the COLIPA P2 as a standard.
Australia
Australia has two reference standards for SPF.
1. Homosalate Reference Product:
Part A
Wool fat BP 5.00
Homosalte 8.00
Paraffin soft white BP 2.50
Stearic acid 4.00
Propyl hydroxybenzoate BP 0.05
Part B
Methyl hydroxybenzoate BP 0.10
Disodium edetate BP 0.05
Propylene glycol BP 5.00
Triethanolamine BP 1.00
Procedure: Heat parts A and B separately to between 778C and 828C with
constant stirring until the contents of the bath are solubilized. Add part A to part
B while stirring. Cool down to room temperature. The mean SPF + 2 standard
deviations should fall between 4 and 5.
2. P3 Reference Standard:
This is identical to the COLIPA high SPF reference.
UV-A TESTS
USA
At the time of writing (October 1, 2003), the FDA had not issued proposed regu-
lations for UV-A testing and claims. These are expected in the Spring of 2005 and
will probably be finalized in 2006.
European Union
The EU has no COLIPA method or any recognized method. Companies are free
to substantiate their UV-A protection claims by any published method. Popular
method include the in vitro critical wavelength and the Boots Star System
methods.
Japan
The first country approved, official method to define UV-A protection is the
Japanese method, which came into effect on January 1, 1996. This method
states that SPF is a worldwide recognized method to give consumers a general
idea of protection against UV-B radiation. They have proposed another ratio
called PFA (protection factor of UV-A). This is an in vivo test.
To develop PFA values, testing is performed on a minimum of 10 human
subjects of skin types I, II, or IV (always burns easily, tans minimally; burns mod-
erately, tans gradually; burns minimally, always tans well, respectively).
The standard is a cream with 5% avobenzone and 3% octinoxate. The light
source is continuous spectra UV-A with a filter to prevent radiation below
320 nm. The radiation should be of a ratio similar to sunlight in the UV-A
range. This ratio is 8 –20% of UV-A II (320 –340 nm) to UV-A I (340 –400 nm).
There is a minimal persistent pigment darkening dose (MPPD), which is a
slight darkening over the field of 0.5 cm2, that persists or occurs within 2– 4 h of
exposure. This is read by at least two trained operators.
The PFA is defined as the ratio of the MPPD with protection over the
MPPD without protection:
MPPD protection
PFA ¼
MPPD without protection
The method to express this ratio is
2 to ,4 PA þ Protection against UV-A

4 to ,8 PAþþ Considerable protection
8 or more PAþþþ Greatest protection
Labels will look like the following:

1. SPF 10 PAþ
or
2. SPF 10 PAþ
The UV-A test standard formulation is
Part A
Water 57.13
Dipropylene glycol 5.00
Potassium hydroxide 0.12
Trisodium edetate 0.05
Phenoxyethanol 0.3
192 Steinberg
Part B
Stearic acid 3.0
Glyceryl stearate, SE 3.0
Cetostearyl alcohol 5.0
Petrolatum 3.0
Glyceryl tri-2-ethylhexanoate 15.0
2-Ethylhexyl p-methoxycinnamate 3.0
4-tert-Buty-40 -methoxydibenzoylmethane 5.0
Ethylparaben 0.2
Methylparaben 0.2
Heat A and B to 708C. Add B to A to emulsify.
Australia
Australia tests for UV-A protection using an in vitro method. The sunscreen is
dissolved in a solvent mixture of dichloromethane, cyclohexane, and isopropa-
nol. The transmission of the sample is run using a spectrophotometer from 320
to 360 nm. There must be at least 90% absorption to claim UV-A protection. If
the sunscreen is not clear in the solvent, an alternative method using a thin
film is used.
WATER RESISTANCE TESTS

The FDA has a published test and Australia Standards also has a method that is
required to be used there.
USA
The Final Monograph changed the water resistance testing from the Tentative
Final Monograph (TFM). The complete test can be found in the Final Mono-
graph. In general, the sunscreen is applied and then the subjects are put into
23 –328C water in a pool, whirlpool, or Jacuzzi. There is then a 20 minutes
immersion time with moderate activity followed by 20 minutes of rest (with no
toweling of the site of application). Another 20 minutes of immersion with mod-
erate activity is then followed by air drying and running of the SPF test. The SPF
that is found can then be put on the label and the product labeled “water resist-
ant”. For the claim “very water resistant” the immersion is four times 20 minutes.
Australia
Australia permits two methods for determining water resistance. The mean pro-
tection factor of the sunscreen is determined after immersion of the test subject
for not less than 40 minutes in either a swimming pool (method 1) or a spa bath
(method 2).
Method 1—swimming pool immersion:
This is for an indoor pool at temperatures between 238C and 288C and a pH
of 6.8 – 7.2. It should be protected from significant direct sunlight.
Procedure: The SPF is determined by the Australian method. The test
subjects are engaged in moderate swimming activity for not less than
40 minutes according to this schedule:
Moderate swimming 20 minutes

Rest period (no toweling of test sites) 5 minutes
Moderate swimminutesg 20 minutes
The time claimed does not include the rest periods. When time to be claimed
is .40 minutes, the schedule should consist of 20 minutes of activity followed
by 5 minutes of rest. After the conclusion of the swimming, the subjects should
dry themselves in the air for not less than 15 minutes. SPF is then run again.
Method 2—spa pool immersion:
The spa should be indoors and protected from direct sunlight and have a pH
between 6.8 and 7.2. The temperature should be maintained at 33 + 28C. For
every 20 minutes of immersion of test subjects, the water should be circulated
for 16 minutes and the air agitated for 4 minutes. The time should be the same
as for swimming pools, and the subjects should sit facing the center of the spa
and sit so that the water jets do not impinge directly on the test sites.
Tested SPF after immersion Maximum water resistance claimable

At least 2, but ,4 Should not be claimed
At least 4, but ,8 40 minutes
At least 8, but ,15 80 minutes
At least 15, but ,20 2 hours
At least 20, but ,25 3 hours
.25 4 hours
THE LABELING OF SUNSCREENS

It is critical to understand that no dual labeling of sunscreens is permitted in the
four major markets. The USA and Australia treat sunscreens as drugs while Japan
and the EU consider them as cosmetics. You cannot label a product a drug and
194 Steinberg
also label it as a cosmetic for a different market. So you may have the same for-
mulation, but you must use separate labels.
USA
The labeling of sunscreens in the USA includes front and back panel labels,
permitted and prohibited claims, and correct nomenclature.
Front panel
You are required to identify the product as a sunscreen and also state the
SPF. The maximum SPF permitted is 30þ.
You may list Product Performance Statements with these categories or
descriptions:
SPF 2 to under 12 (minimal or minimum sunburn protection)
SPF 12 to under 30 (moderate sunburn protection)
SPF 30 or above (high sunburn protection)
You are required to have the net contents on the front in the lower 30% of
the label.
The following claims are prohibited:
Shields from the sun
Blocks out the rays of the sun
Prevents or protects against freckling
Prevents or protects against wrinkling
Prevents or protects against redness or uneven coloring of the skin
Protects against UV-A/UV-B
Shields against specific factors that accelerate the signs of skin aging
Protects against premature aging, skin aging, skin lesions, and skin
cancer (with or without stating “due to the sun” in the labeling of the
product)
PABA-free
Sunblock
Natural
Chemical-free
Nonchemical
Extended wear
All-day protection
IR radiation protection claims
You may say: “aminobenzoic acid (PABA)-free”. You may claim on the
front label “Water resistant” or “Very water resistant” if your product passes
the FDA tests.
Back panel
You are required to have a “Drug Facts” panel.
Example:
Drug Facts
Active Ingredients ....................................................................... Purpose
Avobenzone 3.0% .................................................................................. Sunscreen
Octinoxate 5.2% ........................................................................................... ”
Octisalate 2.0% ............................................................................................. ”
Oxybenzone 2.8% ......................................................................................... ”
Uses
† helps prevent sunburn
† higher SPF gives more sun protection
† retains SPF after 40 minutes of activity in water
Warnings
When using this product keep out of eyes. Rinse with water to remove
Stop use and ask a doctor if rash or irritation develops and lasts
Keep out of reach of children, if swallowed, get medical help or contact a Poison
Control Center right away
Directions
† apply generously 30 minutes before sun exposure and as needed
† children under 6 months of age: ask a doctor
† reapply as needed or after towel drying, swimming or sweating
Other information
Sun alert: Limiting sun exposure, wearing protective clothing, and using sunscreen
may reduce the risk of skin aging, skin cancer, and other harmful effects of the sun
Inactive ingredients Water, Diethylhexyl Naphthalate, Glycerin, Polyglyceryl-3
Methyl Glucose Distearate, Butylene Glycol, Isopropyl Myristate, C30-38
Olefin/Isopropyl Maleate/MA Copolymer, Stearyl Alcohol, Disodium EDTA,
Carbomer, Triethanolamine, Phenoxyethanol, Methylparaben, Ethylparaben,
Propylparaben Butylpararben, Isobutylparaben
Questions?
1-800-123-4567 between 9 am and 5 pm EST
For information on Drug Facts labeling go to http://www.fda.gov/cder/

Offices/OTC/drugFacts.htm
or contact Hirschhorn & Young Graphics (1-212-246-4695) for their book
Simplified FDA OTC Label Requirements Guidelines.
Sunscreens must list their active ingredients using drug names followed by the
percentage in the formulation. The only permitted purpose is sunscreen. Under
196 Steinberg
“Uses” you are required to say “Helps prevent sunburn” or “Higher SPF gives more
sunburn protection”. Optionally, if you pass the water resistant (or very water resist-
ant) test, you can say, “Retains SPF after 40 (80) minutes of activity in the water”.
Finally you may list the Product Performance Statements mentioned earlier.
Required warnings and directions are spelled out in the Final Monograph.
Under other information you may state, using these exact words: “Sun alert:
limiting sun exposure, wearing protective clothing, and using sunscreens may
reduce the risks of skin aging, skin cancer, and other harmful effects of the sun”.
Inactive ingredients must be listed using INCI nomenclature in descending
order of predominance to 1%, provided you make cosmetic claims on the front
label. If you make no cosmetic claims whatsoever, you must list the inactive
ingredients by their drug name in alphabetical order. If the ingredient does not
have a recognized drug name, it is advisable to make some cosmetic claim and
follow the cosmetic labeling described earlier.
All sunscreens must have Drug Facts labels no later than May 16, 2005. Sun-
screens placed on the market after January 1, 2002, also should have Drug Facts
labels. Products on the market before this date and that make a UVA protection claim
are not required to have Drug Facts labels until the FDA announces it is required.
There are also a special exemption and special label requirements for pro-
ducts applied to a small area of the face such as lipsticks.
European Union
As sunscreens are regulated as cosmetics the labeling rules follow their cosmetic
regulations. You must have an address in the EU on your label. You must have an
ingredient declaration using INCI names in descending order of predominance—
note there are no “active” ingredients in cosmetics, nor can you state percentages.
Finally, you must substantiate all claims. So SPF, UV-A, or water-resistant
claims require proof in your Product Information Package.
Australia
Australia requires the listing of the actives using AAN and the maximum concen-
tration present. They also require listing of the preservatives used and their
percentages.
You must give your TGA approval number listing it like this: AUST L
(insert number). Other required information includes storage conditions, expira-
tion date (which is required for all products regardless of stability testing), batch
number, the name and address of the marketer of the product, and the SPF.
Optional claims permitted are “Broad spectrum”, providing the SPF is at
least 15 and you pass the Australian UV-A test; you are allowed to claim
water resistance up to 4 h providing you pass the Australian water resistant test.
For products with an SPF of 30þ you may claim “May assist in preventing
some skin cancers” or “Reduces the risk of some skin cancers”. You will also
need to include “The need for avoidance of prolonged exposure to the sun”, and
“The importance of wearing protective clothing, hats, and eyewear”.
You may make reference to protection against sun induced skin aging.
Japan
Besides the listing of UV-A claims as stated in the UV-A section, Japan requires
all cosmetics to now have complete ingredient disclosure in descending order of
predominance in Japanese symbols.
MANUFACTURE OF SUNSCREENS
Regardless of country, sunscreens must be produced under current cGMPs. In the
USA these can be found in 21 CFR Sections 210 and 211. The major require-
ments are listed below:
1. Quality unit: Quality control and quality assurance must be indepen-
dent of production. Approval or rejections of all procedures, raw
materials, packaging, labeling, and in-process materials of drug pro-
ducts must not be decided by anyone reporting to production. If the
product is produced outside your facility (contract manufacturer),
you must have independent QC supervision. All responsibilities
and procedures must be in writing.
2. Personnel: All personnel must be qualified by education and experi-
ence to comply with cGMPs. There must be adequate supervision and
training in cGMPs, skills, and Standard Operating Procedures (SOPs),
and there must be documentation of this training and effectiveness.
3. Facilities and utilities: The design and construction of the facilities
must be such that they ensure cGMP compliance. There must be
adequate space to prevent mix-ups and contaminations. Housekeep-
ing must be adequate with written procedures and adequate train-
ing. Special areas of concern include heating, ventilation and air
conditioning, dust control, and microbiological control.
4. Equipment: The equipment must be qualified for its intended use.
Written documentation of maintenance, calibration, and cleaning
and change procedures is needed. Cleaning procedures must be vali-
dated and monitored.
5. Control of materials: You should have specifications, vendor qualifi-
cations, incoming controls, QC release, shelf life, storage, and dispens-
ing controls.
6. Water: You need specifications, a validated system, and monitoring
procedures.
7. Master production and control records: These must be approved by
the Quality unit and must have adequate specificity of materials,
198 Steinberg
equipment, formulation, process steps, and parameters to ensure a

reproducible product.
8. Packaging and labeling controls: This is a major FDA inspection
concern. How do you prevent label mix-ups?
9. Investigations: How to handle deviations, out of specifications, and
corrective actions.
10. Prevention of contamination: Raw material qualifications, QC of
incoming materials, storage of materials, personnel controls such as
hygiene, clothing, and practices, process controls, equipment clean-
ing and verification, cleaning validation, facility design, environ-
mental controls, and housekeeping.
11. Laboratory controls: Specifications, sampling and testing procedures,
method validation, reference standards, instrument maintenance and
calibration, record keeping, and stability program.
The FDA does not require SPF be run on each batch. What is required is the analysis
of the actives for the level that was used to determine the SPF. The amount of each
filter must be 100 + 5% of the original amount. This is the same criterion as that for
determining expiration dating. If your formulation is stable for 3 years and the
actives are present again at the 100 + 5% level, you are not required to have an
expiration date. If you use accelerated stability testing for this, you should period-
ically compare this with real time retained samples.
12
Sunscreen Products: The Role of the
US Pharmacopeia
Lawrence Evans III

United States Pharmacopeia, Rockville, Maryland, USA
Introduction 200
The US Pharmacopeia 201
Mission 201
History 201
Legal Recognition 201
United States Pharmacopeia and National Formulary 201
USP Reference Standards 203
Standards-Setting Body 203
Monograph Development and Revision Process 204
Overview 204
Contributors 204
Revision Process 205
Guideline for Submitting Revisions 205
Pharmacopeial Forum 207
USP Monographs for Sunscreen Active Ingredients 207
USP Monographs for Active Ingredients Identified in 21 CFR 352.10 208
USP Monographs for Ingredients not Identified in 21 CFR 352.10 209
Conclusion 210
Appendix 210
References 212
199
200 Evans
INTRODUCTION
A major function of the United States Pharmacopeia (USP) is the development
of monographs containing public standards for articles such as prescription/
nonprescription drugs, dietary supplements, and excipients. These standards
help to ensure that the public receives quality medicines and supplements.
Since 1972, the Food and Drug Administration (FDA) has made a con-
certed effort to develop regulations for over-the-counter (OTC) drug products.
On May 21, 1999, their efforts came to fruition for OTC sunscreen products
with the publication of the final rule (1) (21 CFR 352.10). Often referred to as
the final monograph for sunscreens, it should not be confused with a USP mono-
graph. The regulation lists the active ingredients allowed in sunscreen products
and describes test specifications and label requirements. As part of the final
rule, FDA required that each active ingredient have a USP monograph.
Below is the list of sunscreen active ingredients (former titles in paren-
theses) included in part 352.10 of the final rule.
a. Aminobenzoic acid
b. Avobenzone
c. Cinoxate
d. [Reserved]
e. Dioxybenzone
f. Ensulizole (phenylbenzimidazole sulfonic acid)
g. Homosalate
h. [Reserved]
i. Meradimate (menthyl anthranilate)
j. Octinoxate (octyl methoxycinnamate)
k. Octisalate (octyl salicylate)
l. Octocrylene
m. Oxybenzone
n. Padimate-O
o. Sulisobenzone
p. Titantium dioxide
q. Trolamine salicylate
r. Zinc oxide.
Two positions are labeled “Reserved” for the possible addition of diethanolamine
methoxycinnamate and Lawsone with dihydroxyacetone, the inclusion of which
depends solely on the development of USP monographs.
This chapter describes the role of USP in the regulation of sunscreens,
beginning with the mission of USP, followed by a historical look at the organiz-
ation and ending with a review of USP monographs for the sunscreen active
ingredients. Each of these topics will be discussed to show how USP works to
provide public standards for sunscreen active ingredients. This information is
Sunscreen Products: The Role of the US Pharmacopeia 201
also broadly applicable to drug substances and products for various therapeutic
categories.
THE US PHARMACOPEIA
Mission
The mission of the USP is “to promote the public health and benefit practitioners
and patients by disseminating authoritative standards and information developed
by its volunteers for medicines, other health care technologies, and related prac-
tices used to maintain and improve health and promote optimal health care
quality” (2).
History
The US Pharmacopeial Convention is the only major nongovernment pharmaco-
peia in the world. It evolved from a group of 11 physicians who met in 1820 to lay
the foundation for the first United States Pharmacopeia, a compendium of 217
“well-established drugs” (3). Beginning in 1880, the pharmacopeia was trans-
formed from a book of recipes to one containing product standards (4). At that
time, USP published the pharmacopeia in 10-year intervals until 1942, after
which the organization switched to 5-year intervals. In 1975, USP acquired the
National Formulary and began publishing it with the USP as a single unit
titled the United States Pharmacopeia and National Formulary (USP – NF ) (5).
In 2002, USP reached another milestone by making USP –NF an annual
publication.
Legal Recognition
Federal laws recognize the USP and NF as official compendia of the USA. Early
acknowledgment was given in the Drug Import Act of 1848, when federal legis-
lation recognized the USP as an official compendia (6). Both the 1906 Federal
Food & Drugs Act and the 1938 Federal Food, Drug, and Cosmetic Act
(FD&C Act) mention USP and NF strength, quality, and purity as enforceable
standards (7,8). The FD&C Act uses the term “official compendium” in reference
to the official USP and the official NF and their Supplements. Also, the FD&C
Act made compliance with USP and NF compendial standards enforceable by
FDA under its adulteration and misbranding provisions. In order for a drug not
be declared adulterated and misbranded, it must conform to all of the require-
ments of its monograph and other relevant portions of the compendia. Any vari-
ations in strength, quality, or purity must be stated on the article’s label (8).
United States Pharmacopeia and National Formulary

USP – NF are the largest and most comprehensive compendia in the world. Com-
prising more than 3800 drug substance, drug product, dietary supplement, and
202 Evans
excipient monographs, USP – NF is organized into two primary sections, USP

and NF, each of which has similar subsections. USP is subdivided into seven
subsections:
. Front Matter (mission, preface, people, admissions, and a commentary)
. General Notices
. Monographs
. General Chapters
. Reagents, Indicators, and Solutions
. Tables
. Dietary Supplement Monographs.
The front matter of USP includes the organization’s mission statement and
the preface, which briefly gives the history and rules and procedures of the not-
for-profit organization. Also found in this section are lists of the people involved
(e.g., Expert Committee members, USP staff ), admissions to USP – NF, and a
commentary section. The admissions sections lists official title changes, revisions
appearing in the current edition not included in the previous edition, articles that
appeared in the previous edition but were not included in the current edition, and
articles admitted by Supplement. Supplements represent additional means of
publishing revisions to the USP – NF between its annual editions. The commen-
tary section includes responses to public comments and proposals.
The General Notices and Requirements section contains summaries of the
basic information regarding the interpretation and application of the standards;
tests, procedures, and acceptance criteria; and other requirements in the USP–NF.
When specific information is not given in a monograph, the requirements set forth
in the General Notices are applied. Exceptions to the general notices and chapters
are noted in the individual monograph and are given precedence.
Monographs make up the bulk of USP. Each monograph consists of the
specification plus additional information for an official article, that is, a substance
or preparation that can meet public standards for strength, quality, and purity.
A typical monograph consists of the official title, descriptive information,
definition, packaging and storage instructions, labeling instructions, reference
standards information, and the monograph’s specification, which includes the
monograph tests, procedures, and acceptance criteria.
General Chapters help reduce duplication of text by creating standard pro-
cedures and sometimes acceptance criteria applicable to a broad number of
monographs and other general chapters. They can be broadly classified as
either General Tests and Assays or General Information. The two can be distin-
guished by their assigned chapter number: General Tests and Assays are
numbered below 1000 (e.g., k831l Refractive Index). General Information
Chapters are numbered above 1000 (e.g., k1225l Validation of Compendial
Methods). The latter are interpretive documents that are not required in con-
formity testing, although they can become so if they (or a part of them) are refer-
enced in a monograph and/or they are adopted by reference in law or regulation.
They can also become mandatory if a manufacturer or compounding professional

includes them in internal product or process standards.
The reagents, indicators, and solutions section includes general tests for
reagents, reagent specifications, indicators required in monograph procedures,
and descriptions of test, buffer, colorimetric, and volumetric solutions. The
Tables section contains a number of reference tables provided as supplemental
information such as container specifications for dispensing capsules and
tablets, description and solubility information, and standard atomic weights as
recommended by the International Union of Pure and Applied Chemistry.
The final section of the USP is dedicated to dietary supplement mono-
graphs. Dietary supplement ingredient and product monographs follow the
same format as drug substance and product monographs.
The NF contains sections essentially identical to USP without the Dietary
Supplements section. Several sections of NF, such as the front matter, most
General Chapters, and the reagents sections, reference those of USP in order to
avoid duplication. The primary difference between USP and NF is the scope of
these monographs. The NF contains monographs for excipients. A minority of
these articles can also be drug substances and are cross-referenced to the USP.
USP Reference Standards

A reference standard is a highly characterized chemical that is suitable for use in
performing the test procedures that appear in USP – NF. They are used to test
compliance/noncompliance with monograph requirements. USP reference stan-
dards are developed through a collaborative effort involving USP, FDA, and
industry and/or academic laboratories. To guarantee integrity, the process
involves extensive testing by multiple groups, a rigorous approval process con-
ducted by the USP Reference Standards Committee, appropriate packaging,
and fulfillment of numerous quality control requirements prior to release for
distribution (7).
Standards-Setting Body
The standards-setting body of USP is the Council of Experts, consisting of 62
Expert Committee chairs who are elected at the USP quinquennial Convention
(2) from a pool of candidates developed by the Convention’s Nominating Com-
mittee. After the primary election, a further election occurs to populate each
Expert Committee with its members. Taken together, the Council of Experts
and its Expert Committees comprise approximately 650 volunteers who set the
standards in the USP –NF and also contribute value-added information for
the USP-DI. The Expert Committees are organized into divisions, each of
which has its own Executive Committee with responsibilities that differ from
those of the Council’s Executive Committee (2).
204 Evans
Monograph Development and Revision Process

Overview
The development of new monographs and revision of existing monographs are
exceptional processes that involve public comment and interaction between
USP and stakeholders. USP’s bimonthly journal of standards development and
official compendial revision, Pharmacopeial Forum (PF ), is the vehicle for
public review and comment. Manufacturers and interested parties voluntarily
submit proposals to USP for consideration by the appropriate Expert Committee
for review, after which the Committee approves the proposals for publication in
PF. If there are no adverse comments, the proposal becomes official in USP –NF.
If there are significant comments requiring revision of the proposal, republication
in PF is necessary. The process is a dynamic one that is governed by an unbiased
set of procedures developed to establish public standards.
Contributors
There are several contributors to the revision process, but the one constant is the
USP staff liaison in the Information and Standards Department at USP. Each
liaison is responsible for one or more Expert Committees. As the title implies,
liaisons serve as an interface for industry, government, the Expert Committees,
and other pharmacopeias (Fig. 12.1). Liaisons also are technical experts for the
numerous monographs for which they are responsible. Other contributors to
the revision process include stakeholders, FDA, and the public. Manufacturers,
contract laboratories, and trade organizations primarily make up the stakeholders
group and initiate the majority of the requests for revision submitted to USP.
At each of its centers, FDA has a person responsible for interactions with USP.
Figure 12.1 Contributors to the USP standard setting process.

The Center for Drug Evaluation and Research and Development is the only center
with a compendial staff that reviews proposals published in PF and submits
comments that reflect the views of the agency.
Revision Process
The procedures that govern the review process are depicted in the flow chart in
Fig. 12.2. The process is initiated upon receipt of a proposal to develop a new
monograph or revise an existing monograph. Prior to forwarding it to the
Expert Committee, the USP staff liaison reviews the submitted proposal to
ensure it is technically sound, includes all pertinent supporting information
(e.g., validation data), and is formatted in USP – NF style. Review of most of
the active sunscreen ingredient monographs falls under the responsibility of
the Pharmaceutical Analysis 6 (PA6) Expert Committee.
Once the Expert Committee concludes that the request for revision is
acceptable, approval is given to publish it in PF for public review and comment.
Significant comments are forwarded by the USP liaison to the Expert Committee
for review. If the Expert Committee concludes that the comments are not signifi-
cant and no additional revisions are required, the proposal becomes official and is
published in either an Interim Revision Announcement, a Supplement to the
USP – NF, or the USP –NF. If the Expert Committee concludes the comments
are significant, a revised proposal is published in PF, including comments and
response.
Guideline for Submitting Revisions

USP has available for complimentary download from its website (www.usp.org)
the Guideline for Submitting Requests for Revision to the USP – NF. The purpose
of the Guideline is to provide interested parties with a tool to help draft optimal
submissions and reduce delays in the process. The Guideline comprises an intro-
duction, glossary, addenda, and chapters describing the requirements for drug
substance and product monographs.
The Guideline outlines the procedures involved in the development of a new
monograph as well as the information to assist sponsors in submitting the needed
information. In an effort to make the process paperless, USP invites interested
parties to submit revision proposals electronically. In addition, an overview of
the Guideline’s organization is given to help navigate users through the
document. Arguably one of the most useful features of the Guideline is its glossary.
In an era when nomenclature varies globally and terms such as test, procedure, and
method sometimes are all used interchangeably in the same context, USP works to
promote consistency in nomenclature as a means of facilitating communication.
Chapters 1– 4 are core elements of the Guideline. Information needed to
submit revision proposals for noncomplex actives, which include drug substance
and products, biological/biotechnological-derived substances, excipients, and
vaccines, is given. Each chapter describes the requirements such as name,
206 Evans
Figure 12.2 Public review and comment process for standards development [from
Ref. (2)].
assay, test for impurities, identification of active moiety when applicable, and a
host of other requirements for each of the types of monographs mentioned. For
active ingredients used in sunscreen products, the requirements to revise this
class of actives are found in chapter one, Noncomplex Actives.
The Addenda section of the Guideline consists of templates for drug sub-
stance, tablets, capsules, and excipient monographs. These models are designed
to help a sponsor in drafting monograph proposals into USP – NF format and are
supplemental to the validation data supplied with a revision proposal. USP’s
intent with the Guideline is to provide another tool to increase the efficiency of
the revision process.
Pharmacopeial Forum
As mentioned earlier, PF is the vehicle for public review and comment. Each
issue of PF routinely includes sections that describe policies, give information
on reference standards, and list cancelled proposals, to name a few. Three sec-
tions of special interest are Previews, In-Process Revision, and Interim Revision
Announcements (IRAs). New monographs and revisions to existing monographs
can appear in any of these sections. However, each section represents a different
stage in the process of becoming official. Generally, there is a 60-day public
comment period for items published as In-Process Revision. Parties who are
unable to provide comments prior to this deadline can submit an “Intent
to Comment Form” that gives an intended date by which comments will be
submitted. Items appearing in Previews are not scheduled to become official
and may or may not advance to In-Process Revision status. Examples of items
often published in this section are:
. Proposed new monographs of articles that are available from multiple
sources
. Controversial items requiring an extended public comment period
. Items at an early stage of consideration, such as new technology.
USP plans to begin including a comment date in Preview proposals. Proposals
appearing as In-Process Revision are items scheduled for official implementation.
This usually includes proposals to revise new and existing monograph speci-
fications or proposals that have graduated from the Previews section. Interim
Revision Announcements are a mechanism to make revisions official between
Supplements to USP – NF. Published in PF with official dates of implementation,
they are the only items in this publication that are official. Thus PF is a valuable
source of immediate and future revisions relevant to industry, regulatory
agencies, and the public.
USP MONOGRAPHS FOR SUNSCREEN ACTIVE INGREDIENTS

In the tentative final monograph for OTC sunscreen products published in the
Federal Register in May 1993, FDA proposed 20 Category I (generally recog-
nized as safe and effective) ingredients for use in OTC sunscreen drug products,
of which several did not have USP monographs (10). A year later, FDA published
a proposal to amend the tentative final monograph to include only the 15 active
208 Evans
ingredients for which USP monographs existed or for which there was an
expressed interest in developing USP monographs (11). To achieve this goal,
FDA encouraged the Nonprescription Drug Manufacturers and the Cosmetic,
Toiletry, and Fragrance Associations to work with USP to develop monographs
for these ingredients. Nine ingredients were chosen by the associations as
materials of interest for USP monographs. No interest was expressed for the
five remaining ingredients (digalloyl trioleate, ethyl 4-[bis(hydroxypropyl)]
aminobenzoate, glyceryl aminobenzoate, lawsone with dihydroxyacetone, and
red petrolatum), and they were deleted from the tentative monograph (11).
Avobenzone and zinc oxide were later added to the list of active ingredients
by means of separate amendments (12,13). A USP monograph had already
been established for zinc oxide. Since the publication of the final monograph,
cinoxate was removed from USP 26 –NF 21 and is the lone active ingredient
on the list without a USP monograph (2).
In addition to the ingredients listed in 21 CFR 352.10, USP – NF contains
product monographs (e.g., aminobenzoic acid gel) that incorporate some of
these ingredients (2). There are also monographs in USP –NF for ingredients
not identified in 352.10 but which are used in sunscreen products outside the
USA (e.g., dihydroxyacetone).
USP Monographs for Active Ingredients Identified in 21 CFR 352.10

A USP monograph for a sunscreen substance follows a standard format. The defi-
nition of the substance appears under the name, followed by universal and
specific tests as needed. According to the Guideline, USP has adopted the Inter-
national Conference on Harmonisation (ICH) approach, which requires four
universal tests and additional specific tests depending on the article. The univer-
sal tests are Description, Identification, Assays, and Impurities Test. In current
USP monographs, impurities are generally handled by either the test for
Related Substances or Chromatographic Purity. In the Description and Solubility
section of USP – NF, some of the active sunscreen ingredients are described as
liquids and oils. Several others are described as powders, but only the mono-
graphs for avobenzone and aminobenzoic acid have a melting point specification.
Homosalate, meradimate, octocrylene, octinoxate, octisalate, padimate O, and
trolamine salicylate are liquids and oils that have a refractive index specification.
With the exception of sulisobenzone, all other ingredients described as powders
have either a loss on drying or loss on ignition test.
Most of the monographs for ingredients identified in 21 CFR 352.10 have
two identification test procedures, infrared (IR) absorption and ultraviolet (UV)
absorption. The monographs for octocrylene, sulisobenzone, and trolamine
salicylate have only the UV identification requirement, and homosalate requires
only an IR procedure. The monographs for zinc oxide and titanium dioxide incor-
porate chemical procedures.
The majority of the Assay test procedures for sunscreen active ingredients
are either titration or gas chromatography (GC). Although the monographs for
dioxybenzone and oxybenzone have UV assays, trolamine salicylate is the
only ingredient with a liquid chromatography assay procedure. Most ingredient
monographs with a chromatographic assay procedure also have a Chromato-
graphic Purity test. In addition to these tests, additional test requirements can
be found in the individual monographs.
Since their introduction into USP –NF, most of the sunscreen active ingre-
dient monographs have undergone little, if any, revision. Even fewer revisions
have occurred in the USP monographs of those ingredients that preceded the
final sunscreen monograph (e.g., zinc oxide). The most notable revision came
in the form of a name change for six ingredients. The revision, which had an
adoption date of September 1, 2002 (18 months after the official publication
date), included ingredients listed and not listed in 21 CFR 352.10. The United
States Adopted Names (USAN ) Council proposed simpler and more convenient
chemical names relative to those provided in the original proposals submitted to
USP. It is the policy of the USP Nomenclature and Labeling Expert Committee to
adopt such USAN names when available for the titles of USP monographs. The
names (former name in parenthesis) of the ingredients that changed were
amiloxate (isoamyl methoxycinnamate); ensulizole (phenylbenzimidazole sul-
fonic acid); enzacamene (methyl benzylidene camphor); meradimate (menthyl
anthranilate); octinoxate (octyl methoxycinnamate); and octisalate (octyl
salicylate) (14).
Octocrylene, octisalate, and octinoxate are the only ingredients listed in 21
CFR 352.10 for which monograph revisions have been made in recent years. A
significant revision to the octocrylene monograph was the addition of a Chroma-
tographic Purity test for individual and total impurities (15). A revision to Identi-
fication Test A was also included in the revision proposal. A subsequent proposal
to increase the individual impurity limit was published and was based on the
typical impurity level found in material in commerce (16). The monograph for
octisalate underwent similar revisions: Identification Test A was revised and a
test for Chromatographic Purity was introduced, later followed by a revision to
lessen the overly restrictive individual and total impurities limits that had been
previously enacted (17,18).
USP Monographs for Ingredients not Identified in 21 CFR 352.10

Amiloxate, enzacamene, and dihydroxyacetone are active sunscreen ingredients
not included in 21 CFR 352.10 but which have USP monographs. The mono-
graphs of each are very similar to those included in 21 CFR 352.10. Two identi-
fication tests are given for each, including IR tests. The dihydroxyacetone
monograph uses thin-layer chromatography (TLC) as the second identification
test, whereas UV is the second identification test in the amiloxate and enzaca-
mene monographs. GC is the technique of choice for assay in the amiloxate
210 Evans
and enzacamene monographs, but a conventional titration is used for dihydroxy-

acetone. TLC is used to determine impurities present in dihydroxyacetone,
whereas a GC procedure is employed in the amiloxate and enzacamene
monographs.
Aside from the nomenclature revisions, there have been no other revisions
to any of the three monographs mentioned in this section, probably because they
are not included in 21 CFR 352.10. This is likely to change because FDA has
made both amiloxate and enzacamene eligible for consideration based on infor-
mation provided in their respective Time and Extent Applications (TEAs) (19).
CONCLUSION
The objective of this chapter was to discuss the role of USP in helping to assure
the quality of sunscreen ingredients. The final FDA OTC sunscreen monograph,
the adjustment in names by USAN, and continuous improvement from USP’s
Council of Experts in sunscreen monographs offer a good example of positive
stakeholder interactions to make available valuable products for consumers,
patients, and practitioners. The combined approach conserves manufacturer
and regulator resources. It fulfills the general purpose of USP’s two official
compendia extending back in time almost 200 years. The role of the USP will
continue to expand as the number of active ingredients added to 21 CFR
352.10 continues to increase.
APPENDIX
Octinoxate Monograph (From Ref. 2)
Former title: Octyl Methoxycinnamate
C18H26O3 290.40
2-Ethylhexyl 3-(4-methoxyphenyl)-2-propenoate.
2-Propenoic acid, 3-(4-methoxyphenyl)-, 2-ethylhexyl ester. [5466-77-3].
Used with permission. Copyright 2003 The United States Pharmacopeial Convention, Inc. All rights
reserved.
Octinoxate contains not less than 95.0 percent and not more than 105.0 percent of
C18H26O3, calculated on the as-is basis.
Packaging and storage—Preserve in tight containers, in a cool place.

USP Reference standards k11l—USP Octinoxate RS.
Identification—
A: Infrared Absorption k197Fl.
B: Ultraviolet Absorption k197Ul—
Solution: 5 mg per mL.
Medium: alcohol.
Specific gravity k841l: between 1.005 and 1.013.
Refractive index k831l: between 1.542 and 1.548.
Acidity—Transfer 5 mL of Octinoxate to a suitable container, add 50 mL of
alcohol, and mix. Add 4 drops of phenolphthalein TS, and titrate with 0.1 N
sodium hydroxide: not more than 0.8 mL is consumed.
Chromatographic purity—
System suitability solution—Prepare a solution of benzyl benzoate and USP
Octinoxate RS in acetone containing about 50 mg of each per mL.
Test solution—Transfer about 5 mL of Octinoxate to a 100-mL volumetric
flask, dilute with acetone to volume, and mix.
Chromatographic system (see Chromatography k621l)—Proceed as
directed in the Assay, but chromatograph the System suitability solution.
Procedure—Inject a volume (about 1 mL) of the Test solution into the chro-
matograph, record the chromatogram, and measure the responses for all the
peaks. Calculate the percentage of each impurity in the portion of Octinoxate
taken by the formula:
100ðri =rs Þ;
in which ri is the peak response for each impurity; and rs is the sum of the
responses for all the peaks: not more than 0.5% of any individual impurity is
found; and not more than 2.0% of total impurities is found.
Assay—
Internal standard solution—Transfer about 25 mL of benzyl benzoate to a
500-mL volumetric flask, dilute with acetone to volume, and mix.
Standard preparation—Dilute an accurately measured quantity of USP
Octinoxate RS quantitatively, and stepwise if necessary, with Internal standard
solution to obtain a solution having a known concentration of about
50 mg per mL.
reserved.
212 Evans
Assay preparation—Transfer about 5 mL of Octinoxate, accurately

measured, to a 100-mL volumetric flask, dilute with Internal standard solution
to volume, and mix.
Chromatographic system (see Chromatography k621l)—The gas
chromatograph is equipped with a flame-ionization detector and a 0.32-mm
25-m column that contains coating G1. The carrier gas is helium, flowing at a
rate of about 2 mL per minute. The chromatograph is programmed as follows.
Initially the temperature of the column is equilibrated at 808, then the temperature
is increased to 3008 over a period of 10 minutes, and maintained at 3008 for 10
minutes. The injection port temperature is maintained at 2508, and the detector is
maintained at 3008. Chromatograph the Standard preparation, and record the
peak responses as directed for Procedure: the relative retention times are about
0.68 for benzyl benzoate and 1.0 for octinoxate; the resolution, R, between
benzyl benzoate and octinoxate is not less than 20; the column efficiency is not
less than 65,000 theoretical plates; and the relative standard deviation for repli-
cate injections is not more than 2.0%.
Procedure—Separately inject equal volumes (about 1 mL) of the Standard
preparation and the Assay preparation into the chromatograph, record the chro-
matograms, and measure the responses for the major peaks. Calculate the quan-
tity, in mg, of C18H26O3 in the portion of Octinoxate taken by the formula:
100CðRu =Rs Þ;
in which C is the concentration, in mg per mL, of USP Octinoxate RS in the
Standard preparation; and Ru and Rs are the peak response ratios of octinoxate
to benzyl benzoate obtained from the Assay preparation and the Standard
preparation, respectively.
REFERENCES
1. Office of the Federal Register, Federal Register, 64(98), Rules and Regulations, 1999:
27666– 27693.
2. The United States Pharmacopeia, 26th rev. and The National Formulary, 21st ed.
Rockville, MD: The United States Pharmacopeia Convention, 2003.
3. The United States Pharmacopeia, 1st rev. The United States Pharmacopeia
Convention, 1820.
4. The United States Pharmacopeia, 6th rev. The United States Pharmacopeia
Convention, 1880.
5. The United States Pharmacopeia, 20th rev. and The National Formulary, 15th ed.
Rockville, MD: The United States Pharmacopeia Convention, 1980.
6. Drug Import Act of 1848, 9 Stat., 1848.
7. Federal Food & Drugs Act of 1906, Public Law 59-384, 34 Stat. 768, 1906.
reserved.
8. Federal Food, Drug & Cosmetic Act of 1938, Public Law 75-717. 52 Stat. 1040, 1938.
9. USP: People, Programs, Policies, and Procedures, 2000– 2005. Rockville, MD: The
United States Pharmacopeia Convention, 2002.
10. Office of the Federal Register, Federal Register, 58(90), Proposed Rules, 1993:
28194– 28296.
29706– 29707.
48645– 48655.
56584– 56589.
14. Pharmacopeial Forum 2000; 26(3).
15. Pharmacopeial Forum 2001; 27(5):3028.
17. Pharmacopeial Forum 2001; 27(5):3027– 3028.
19. Office of the Federal Register, Federal Register, 68(133), Notices, 2003:
41386– 41387.
Ultraviolet Filters
13
The Chemistry of Ultraviolet Filters
Nadim A. Shaath
Alpha Research & Development, Ltd.,
White Plains, New York, USA
Introduction 218
The Electromagnetic Spectrum 218
Effect of UV Radiation on the Skin 220
Classification of UV Filters 221
PABA and p-Aminobenzoates 224
Salicylates 226
Cinnamates 227
Benzophenones 228
Anthranilates 229
Dibenzoylmethanes 230
Camphor Derivatives 230
Miscellaneous Compounds 231
Mechanism of Sunscreening Action 231
Effect of Vehicle on the Efficacy of UV Filters 232
pH Effects on UV Filters 233
Effect of Emollients on the Efficacy of UV Filters 233
Effects on the Extinction Coefficient 235
The Future of UV Filters 235
Conclusions 237
References 238
217
218 Shaath
INTRODUCTION
The recent evidence linking ultraviolet-A (UV-A) rays to serious damage beyond
the fashionable and sought-after tan is daunting (1). These and other important
findings have prompted the cosmetic industry to create new sunscreen products
that would afford the consumers more efficient protection. Since the cosmetic
industry began formulating a myriad of new sunscreen active agents into an
array of functional products, it has become necessary for the cosmetic chemist
to know more about the chemical structure and reactivity of UV filters and
their potential interaction with other ingredients in the sun care cosmetic
formulations.
This chapter first reviews the electromagnetic spectrum and the ultraviolet
rays responsible for most of the skin damage and its associated disease and dis-
comfort. The UV filters are then classified according to their structure – activity
relationship and the attributes of each are highlighted. The mechanism of sun-
screen action is presented and the effect emollients have on the functionality of
sun care formulations is discussed. Finally, the features of the UV filters of the
future are outlined.
THE ELECTROMAGNETIC SPECTRUM

Human skin and hair are constantly subjected to solar radiation (2). The radiation
emitted by the sun is of an electromagnetic character and differs from other forms
of electromagnetic radiant energy in its spectrum, as described by its energy (E ),
wavelength (l), or the frequency (n). Electromagnetic radiation is energy gov-
erned by the following relationship:
E ¼ hn
where E ¼ energy (ergs), h ¼ Planck’s constant ¼ 6.62 10227 erg/s, and n ¼
frequency (cycles per second [cps] or Hertz [Hz]).
An important physical relationship governing the properties of electromag-
netic waves is described by the following equation:
n ¼ c=l
By substituting the second equation into the first, we arrive at the all important
equation governing the action of sunlight on humans where the energy (E) and
the wavelength (l) have a reciprocal relationship as shown below:
E ¼ hc=l
where c ¼ speed of light ¼ 3.0 1010 cm/s and l ¼ wavelength (cm or m).
The above relationship reveals that the wavelength increases as the energy
associated with it decreases and vice versa. Thus, the UV-B region of the spec-
trum (290 – 320 nm) will have higher energies associated with it than the UV-A
region (320 –400 nm) (see Fig. 13.1). The significance of this relationship
The Chemistry of Ultraviolet Filters 219
Figure 13.1 The electromagnetic spectrum of radiant energy.
between energy and wavelength will become more evident when the effects of
UV radiation on the skin are discussed.
Solar radiation that is visible to the eye is only a very small segment of the
total range of the electromagnetic waves and can roughly be divided into three
regions:
. Electrical rays, which include wireless, Hertzian, radiowaves and

microwaves. These rays are generally longer wavelengths (measured
in meters) and have much lower energies associated with them than
the harmful UV rays.
. Optical rays, which are subdivided into infrared, visible, and UV rays.
. X-rays, gamma rays, and cosmic rays have short wavelengths mea-
sured in 1029 –10215 m and are obviously high in energy and
extremely damaging rays.
In the optical region, the UV rays have the shortest wavelengths and the
highest energies associated with them. These rays are sufficiently energetic to
cause photochemical reactions, resulting in both immediate and delayed
damage to the skin and hair, termed the photochemical effect. The visible
region or the light effect is where the rainbow of the colors of the spectrum is
exhibited (violet to red). The longest wavelength (hence, lower energy) is the
infrared (IR) region, which is responsible for the heat effect. The UV rays,
which have been demonstrated to be the most damaging to humans, can be
further subdivided into three regions, namely, the UV-A, UV-B, and UV-C.
The most damaging of the UV radiations is the UV-C, also called the ger-
micidal region, has the highest energy associated with it (the lower wavelengths,
200 –290 nm). Fortunately, the harmful rays of the UV-C and of course those that
are higher, namely, X-rays, gamma rays, and cosmic rays are filtered by the
stratospheric ozone layer; thus, none of these rays reach the earth’s surface.
The depletion of this layer through the continued use of chlorofluorohydro-
carbons (CFCs) poses a major threat to mankind if left unabated. Nevertheless,
artificial light sources (tanning salons, mercury arc, or welding arcs) do contain
some UV-C radiation and should be used only with adequate protection. It is the
UV-A and UV-B regions that are not completely filtered out by the ozone layer
and are sufficiently energetic to cause damage to the skin and hair.
220 Shaath
The UV-B rays, also called the burning or erythemal rays with wavelengths
ranging from 280 to 320 nm, is responsible for most of the immediate damage to
the skin, resulting in erythema or sunburn, and subsequent long-term damage if
the skin is left unprotected.
The UV-A region extends from 320 to 400 nm and is further subdivided
into UV-A I from 340 to 400 nm and UV-A II from 320 to 340 nm. Parish
et al. (3) list many reasons why the UV rays are extremely important and
should be dealt with:
1. The amount of solar UV-A reaching the earth’s surface is enormously
greater than that of UV-B.
2. Photosensitivity reactions (phototoxicity and photoallergy) are mostly
mediated by UV-A.
3. High doses of UV-A can cause redness to human skin; moreover,
UV-A may potentiate or add to the biological effects of UV-B.
4. The development of sunscreens that effectively block or diminish the
highly erythemogenic UV-B permits prolonged sun exposures; how-
ever, many of these sunscreens do not significantly alter the amount
of UV-A reaching the skin.
5. UV-A is transmitted by most window glass and many plastics that do
not transmit UV-B.
6. Recent studies suggest that UV-A can affect cells and microorganisms.
7. There is experimental and epidemiological evidence to suggest that
solar UV-A is one of the possible etiological agents for certain kinds
of cataracts in humans.
For these and more reasons protection from the UV-A rays is crucial in any
photoprotection regimen.
EFFECT OF UV RADIATION ON THE SKIN

The skin, which is the largest organ of the body, has several functions including
the regulation of body temperature, protection from the environment, partial
regulation of water loss and retention, and serves as a temporary storage site
for glucose when blood glucose is elevated. Other biochemical properties associ-
ated with the skin are melanin formation, epinephrine stimulation of the sweat
glands and the regeneration of viable epidermal cells (4).
The skin is composed of three layers: the epidermis, including the stratum
corneum, the dermis, and the hypodermis (see Fig. 13.2). The dermis contains
melanocytes, which generate the melanin pigment responsible for the color of
the skin. Exposure to rays with wavelengths in the UV-A region will stimulate
the formation of melanin, which acts as a protective layer on the skin. The
skin is shown along with the amount of UV radiation that penetrates each
layer. UV radiation near 300 nm (UV-B) penetrates both the stratum corneum
and the epidermis and is sufficiently energetic to cause severe burning (erythema)
Figure 13.2 Schematic representation of light penetration into the skin.
of the skin, especially in fair-skinned individuals. Radiation with wavelengths

longer than 350 nm starts penetrating the dermis thereby stimulating the for-
mation of melanin and producing a tan that protects the skin from immediate
sunburn. Although UV-A rays are of lower energy than the UV-B rays, the
fact that they can penetrate further into the hypodermis, causes elastosis (loss
of structural support and elasticity of the skin) and other skin damage, potentially
leading to the skin cancers we observe rising in epidemic proportions today.
CLASSIFICATION OF UV FILTERS
There are three types of UV filters:
1. Organic UV absorbers
2. Inorganic particulates
3. Organic particulates.
This chapter deals primarily with the organic UV absorbers. The inorganic
particulates are dealt with in Chapter 14 and the new organic particulates are dealt
with in Chapter 15.
The relationship between chemical structure and efficacy of UV filters is
clearly evident as documented in this chapter.
Sunscreens have originated from both academic and industrial research
laboratories with completely diverse uses. The cost, safety, and marketability
of the new filters have had a dramatic influence on the evolution of the current
approved list of sunscreen chemicals, regardless of their efficacy, degree, and
nature of their protection.
In the USA, the recently approved Category I list of sunscreen chemicals
(5) lists 16 UV filters, 14 of which are organic UV filters (that absorb UV
222 Shaath
rays) and two inorganic particulates (that both absorb and reflect UV rays). No
organic particulates have been approved as Category I ingredients in the USA.
The ingredients along with their approved percentage, the lmax and extinction
coefficient (1) are shown in Table 13.1.
Table 13.1 FDA-OTC Panel Category I Sunscreens
Extinction
lmax coefficient (1)
Sunscreen Approved % (ethanol) (nm) (ethanol)
A. Organic absorbers
UV-A absorbers
Avobenzone 3 357 30,500
Oxybenzone 6 325 9,400
Sulisobenzone 10 324 8,400
Dioxybenzone 3 327 10,440
Meradimate 5 336 5,600
UV-B absorbers
PABA 15 290 14,000
Cinoxate 3 305 11,000
Octocrylene 10 303 12,600
Ocinoxate 7.5 310 23,300
Octisalate 5 307 4,900
Homosalate 15 306 4,300
Padimate-O 8 307 27,300
Ensulizole 4 310 26,000
Trolamine salicylate 12 298 3,000
B. Inorganic particulates
Zinc oxide 25 Broad spectrum
Titanium dioxide 25 Broad spectrum
This list of UV filters, with the exception of avobenzone and the micro-
nized forms of zinc oxide and titanium dioxide, reflects the knowledge that
dates back to the early 1970s. They do not represent the most recent advances
in UV filter design. Currently, any sunscreen supplier wishing to introduce a
new UV filter must either go through a costly and time-consuming New Drug
Application (NDA) to the US Food and Drug Administration (FDA) or hope
for the reopening of the monograph for additional sunscreen approvals before
its anticipated adoption date in 2005. Unlike medical drugs, for which the
return on investment may be in the hundreds of millions of dollars, sunscreen
chemicals do not afford substantial returns to the companies producing them.
The cost to obtain an NDA is estimated to be several million dollars with a
waiting period exceeding 3 years. This is prohibitive for most manufacturers
embarking on research designed to produce new and innovative UV filters.
A promising alternative to the NDA process is the FDA’s Time and Extent
Application (TEA) (Chapter 6) that established criteria and procedures by which
over-the-counter (OTC) conditions may become eligible for consideration in the
OTC drug monograph system. Three new ingredients, namely amiloxate, enzaca-
mene, and octyl triazone are under review for potential inclusion in the list of
approved sunscreens in the USA.
The European Economic Community (EEC) member countries have estab-
lished a body called COLIPA (Chapter 39) that effectively regulates the sun-
screen industry. The cost in both time and the production of the necessary safety
toxicological data is reasonable, allowing for more new introductions and inno-
vations. Japan (Chapter 10) and Australia (Chapter 9) have similar, less costly
measures for the adoption and introduction of new sunscreen agents.
Seven new ingredients have been recently approved for use in Europe
(Chapter 16):
1. BEMT (bis-ethylhexyloxyphenol methoxyphenyl triazine [S81])
2. DTS (drometrizole trisiloxane [S73])
3. DBT (dioctyl butamido triazone [S78])
4. EHT (ethyl hexyl triazone [S69])
5. DHHB (diethylamino hydroxbenzoyl hexyl benzoate)
6. BDHB (bis-diethylhydroxybenzoyl benzoate)
7. BBET (bis-benzoxzoylphenyl ethylhexylimino triazine).
Many of the new UV filters being designed in Europe have followed a novel
new approach to the conventional organic UV absorbers. They generally contain
multiple chromophores and are occasionally grafted onto a polymer backbone.
The molecular weights of most of these molecules exceed 500 Da and a few of
them have been supplied as microfine organic particulates in 50% aqueous disper-
sions in the same manner as the new microfine inorganic particulates of today.
Herzog and coauthors have recently described the broad spectrum UV filter
(BEMT) (6). To illustrate the general new trends in the synthesis of new mol-
ecules, the molecular structure of BEMT is shown here:
OCH
3
OH N N OH
O O
224 Shaath
It is evident that broad-spectrum absorbance is attained due to the extended reson-

ance delocalization through the full aromatic molecule. The ortho substituents
extend the electron transfer through hydrogen bonding between the phenolic
group and the nitrogen in the heterocylic ring. The para-methoxy substituent in
BEMT with its electron-donating capability lowers the energy requirements even
further, thereby extending the absorption lmax into the longer UV-A. The water
resistancy in BEMT is achieved by the two hydrophobic ethyl hexyl substituents.
The organic chemical UV filters approved in the USA today can be classi-
fied as derivatives of the following classes of compounds:
1. PABA and p-aminobenzoates
2. Salicylates
3. Cinnamates
4. Benzophenones
5. Anthranilates
6. Dibenzoyl methanes
7. Camphor derivatives
8. Miscellaneous chemicals.
The above classes of organic molecules will be reviewed below to illustrate the
relationship between their chemical structures, the UV absorbance activity and
their physico-chemical properties.
PABA and p-Aminobenzoates

Para-amino benzoic acid (PABA) has an absorption maxima at 290 nm and a
moderate molar extinction coefficient of 14,000. Its chemical structure reveals
the presence of two reactive functional groups; namely, amino and carboxylic
acid moieties, substituted in a para orientation on the benzene nucleus as shown:
H O
••
N C
H OH
This particular configuration of an electron-releasing group (–NR2) substituted

para to an electron acceptor group (–COOH) allows for the efficient electron
delocalization shown here:
R O R -
••
+ O
N C N C
R OH R OH
Quantum chemical calculations have revealed that this electron delocalization

energy corresponds to the electronic transitions associated with the UV-B
region of the solar spectrum (7). Unfortunately, the presence of these two extre-
mely polar groups, the amino and carboxylic acid, situated away (para) from one
another contributes to a number of problems that render the use of this product
commercially less appealing, namely:
1. Free amines tend to oxidize rapidly in air and thereby produce off
colors.
2. Amines and acids are extremely polar groups that tend to hydrogen
bond intermolecularly as shown:
H
H O H O H
C N C N
O H O H
This intermolecular hydrogen bonding leads to the increased associ-

ation of the molecules, thereby producing a crystalline physical
state. This crystal structure poses various constraints on the liberal
use of the product in cosmetic formulations. A suitable emollient
will be required to ensure the rapid and continuous dissolution of
PABA in the formulation.
3. The presence of both the polar amine and carboxylic acid group pro-
motes the water solubility of the sunscreen chemical in the finished
cosmetic formulation owing to the excessive hydrogen bonding with
emollients.
4. Excessive hydrogen bonding between PABA and polar emollients,
leads to a dramatic solvent effect (7). This solvent effect will shift
the lmax by 27 nm from 293 nm in nonpolar solvents to 266 nm in
polar solvents. Such solvent effects have a major influence on the effi-
cacy of the UV filter in cosmetic formulations.
5. The carboxylic acid and amine substituents cause the molecules to be
subject to pH changes in the formulation.
In addition to the foregoing chemical limitations of PABA, several recent reports
have cast doubt on its safety as a UV filter (8) hence it has experienced a major
decline in its worldwide use as a sunscreen agent.
Researchers in the field of sunscreens responded to the consumers need for
better UV filters, and several sunscreens based on the strength of the PABA
moiety emerged. A sunscreen was designed to protect both the amino and
carboxylic acid grouping from pH changes and potential chemical reactions.
Padimate-O the only other PABA derivative that is on the Category I listing
was until recently the workhorse of UV filters. It represented the ultimate in sun-
screen design as the intermolecular association leading to the many of the undesir-
able properties listed above was decreased. This change in structure resulted in a
UV filter that is a liquid instead of a crystalline solid and also decreased the pro-
blems associated with the primary amine and the carboxylic acid group outlined
above. Its molar extinction coefficient is one of the highest found in a UV-B filter
226 Shaath
in the USA, reaching 27,300. The extinction coefficient is double that of PABA.
Even though it is still subject to solvent affects, the shifts reported are from 300 nm
in nonpolar solvents to 316 nm in polar solvents, values that are well within the
UV-B range. Reports of its photoinstability have been cited in the literature (9)
and its commercial use worldwide has decreased significantly.
H3C O R
N C
H3C O
Salicylates
Salicylates were the first UV filters ever used in sunscreen preparations (10).
Several of these derivatives have enjoyed substantial sales worldwide including
octisalate (S.-13 in Europe), homosalate (S.-12 in Europe), and the water-soluble
trolamine salicylate (S.-9 in Europe).
OR
C O
…
H
O
R ¼ 2-ethyl hexyl:octisalate
R ¼ homomenthyl:homosalate
R ¼ triethanolamine:trolamine salicylate
The salicylates as a group, are ortho-disubstituted compounds with a spatial
arrangement permitting internal hydrogen bonding within the molecule itself as
shown in the chemical structure, exhibiting a UV absorbance of about 300 nm.
The hydrogen bonding possible in the salicylates lowers the energy requirements
for the compound’s electrons to be promoted to its photochemically excited state
as shown here:
OR¢ OR¢
C C -
O O
¦
••
H + H
R O
••
R O
••
The salicylates have the ideal UV-B sunscreen range of 300 –310 nm, neverthe-
less, for precisely the same reason, namely the ortho relationship, they have a
much lower extinction coefficient. The ortho relationship of the phenolic group
to the bulky carboxylic ester grouping causes crowding and strain on the
molecule as a whole. To counterbalance this steric strain, the two groups
deviate ever so slightly from planarity. Any minor deviation from planarity of
the molecule causes a lowering of the extinction coefficient because the sym-
metry will dictate whether an electronic transition is allowed or forbidden. A dis-
cussion of such rules is beyond the scope of this chapter; however, the interested
reader is referred to the many excellent monographs on the topic (11).
The salicylates are excellent solubilizers of crystalline UV filters such as the
benzophenones and avobenzone. They are mild and stable ingredients with an
excellent safety record, despite their continued use for more than 50 years. This
is predominantly due to this unique ortho-disubstituted chemical structure. The
two active groups, the hydroxyl and the carboxylic acid groups, are intramolecu-
larily hydrogen bonded to one another rendering their electrons less available for
interaction with other ingredients or with biological substrates found on the skin.
For water-soluble sunscreens, trolamine salicylate is commercially avail-
able and approved for use worldwide. It is known to boost the sun protection
factor (SPF) of cosmetic formulations owing to their substantivity to the skin
and is also used in hair preparations.
Cinnamates
Cinnamates, most notably octinoxate, are currently the most popular sunscreens
protecting the UV-B rays of the electromagnetic spectrum. In fact, there were over
a dozen cinnamate derivatives on the European COLIPA lists and three are
approved for use in the USA. A fourth molecule, amiloxate, is currently under
review through the TEA process (Chapter 6). The structure following the next
paragraph reveals remarkable similarity to octinoxate where the ester is an
amyl grouping instead of the octyl group.
The cinnamates have an extra unsaturation conjugated to both the aromatic
ring and the carbonyl portion of the carboxylic ester. This configuration permits
the electron delocalization to occur throughout the octinoxate molecule. The
energy corresponding to this electronic transition has a wavelength of about
310 nm and a fairly strong molar extinction coefficient (.23,000). For practical
purposes, this molecule is insoluble in water, making it suitable for most water-
resistant sunscreen formulations.
R
O
C C R¢
CH O
H3CO
R ¼ H, R0 ¼ C2 H4 OC2 H5 Cinoxate
0
R ¼ H, R ¼ C8 H17 Octinoxate
0
R ¼ H, R ¼ C5 H17 Amiloxate
R ¼ CN, R0 ¼ C8 H17 Octocrylene
228 Shaath
Octinoxate, on the other hand, is subject to cis – trans isomerism and it is known
to lose some of its efficacy due to this photoinstability. Other reports also suggest
the lowering of the SPF values of formulations in combination with avobenzone.
Despite these reports, octinoxate has had an excellent safety record and remains
as the most popular UV filter in use worldwide.
Another cinnamate approved for use today is octocrylene (ethyl hexyl
cyano diphenyl acrylate) with a lmax of 303 nm and an extinction coefficient
of 12,600. It is approved for use in the USA at levels up to 10%. It found
increased use after L’Oreal published its findings that octocrylene increases the
photostability of formulations containing avobenzone (Chapter 17). The third
molecule, Cinoxate has had limited use in cosmetic formulations in the USA.
Benzophenones
The benzophenones are the only class of compounds that belong to the aromatic
ketone category. Avobenzone is a diketone with unique chemical properties and
the rest of the 14 Categtory I ingredients are esters, acids, or their salts. Reson-
ance delocalization in benzophenones as in all the other classes of compounds
discussed earlier, is aided by the presence of an electron releasing group in
either the ortho or para position or both. The electron-accepting group in this
case, the carbonyl group itself, participates in the resonance delocalization
process shown next,
H H
R¢ R¢
O O O O
C C
+
O O
H3C H3C
R R
0
R¼H R ¼H Oxybenzone
0
R ¼ H, R ¼ OH Dioxybenzone
0
R ¼ SO3 H, R ¼H Sulisobenzone
Aromatic ketones, unlike the esters encountered earlier, will resonate more
easily, thereby requiring a lower quantum of energy for the electronic transition
resulting in a higher wavelength (exceeding 320 nm) hence their use as UV-A
filters.
The drawback in using benzophenones as UV filters is due to various factors:
. Aromatic ketones are chemically different from esters. Metabolically,
esters unlike ketones may be hydrolyzed in vivo, producing by-products
that the body can metabolize (a detoxification mechanism). It has been

Even though dibenzoyl methane derivatives are arylakyl ketones, they exhibit their UV-filtering
effect through a keto–enol tatomerism, which is not possible in benzophenones.
reported that patients developed statistically more allergic reactions to

oxybenzone than to PABA (12).
. These products are, without exception solids, and are generally difficult
to handle and to dissolve in cosmetic formulations.
. Their UV absorption reveals two maxima, one around 290 nm (UV-B)
and the other is generally ,330 nm, which is a value barely into the
UV-A region.
Anthranilates
Anthranilates, or ortho-aminobenzoates, are an interesting class of UV filters.
Meradimate, is on the US FDA Category I listing.
O
C
O
NH2
Meradimate
This class of compounds offers an elegant example on the effect of chemical
structure on UV absorbance characteristics. This effect, termed here the ortho
effect, has been observed in numerous organic compounds. Meradimate, has a
lmax of 336 nm, whereas padimate-O, a para-disubstituted aminobenzoate has
a lmax of only 307 nm.
H
N O H
H
C N
O
C O H
O C H C8H17
10 19
Meradimate Padimate-O
ðlmax 336 nmÞ ðlmax 307 nmÞ
This dramatic 29-nm shift in the maximum absorption is clearly due to the ease in
electron delocalization in the ortho-disubstituted compounds for which the geo-
metry allows for this “through space” assistance. This also results in a lower
molar extinction coefficient in the anthranilates than that of the para-amino
benzoates, in a manner analogous to that described for the salicylates. Again,
the steric crowding in the ortho-disubstituted compound causes the molecule
to deviate from coplanarity, thereby reducing the intensity of the absorbance.
Anthranilates, as with salicylates, are stable and safe compounds to use
owing to this ortho-disubstituted relationship and, as in salicylates, do not
exhibit any significant solvent shift effects in cosmetic formulations (7).
230 Shaath
Dibenzoylmethanes
Dibenzoylmethanes, or substituted diketones, are a relatively new class of UV
filters. Only one has now received approval for use in the USA (avobenzone),
whereas three are approved for use in Europe.
This group of UV filters exhibits properties resulting from a keto –enol
tautomerism (Chapter 17). The keto form of these compounds actually has a
lmax of about 260 nm. However, the enol form has a lmax exceeding 350 nm,
making them suitable candidates for UV-A protection.
O OH O O
O O
Enol: lmax 350 nm Keto: lmax 260 nm

Butyl methoxydibenzoyl methane ðavobenzoneÞ
Dibenzoyl methane derivatives have exceptionally high molar extinction coeffi-
cients (.30,000). However, they suffer from possessing low photostability. In
several reports (13), the photoisomerization of various sunscreen chemicals
have been listed. Avobenzone is reported to be relatively photolabile if impro-
perly formulated in cosmetic vehicles. Triplet – triplet quenchers have been intro-
duced to stabilize the molecule (a patent by L’Oreal uses octocrylene for its
stabilization) and a number of emollients and ingredients are purported to stabil-
ize the more desirable enol form of the molecule.
Camphor Derivatives
Six bicyclic compounds are approved for use in the EEC member countries and
only one, Enzacamene is currently being considered for use in the USA through
the TEA process.
4-Methyl benzylidinecamphor ðenzacameneÞ

Most of the bicyclic derivatives are solids and have a high molar extinction
coefficient generally .20,000 and absorb in the UV-B range of 290– 300 nm.
They all owe their photostability (14) to the resonance delocalization in the
molecule, shown here:
O O
HC HC
+
R R
Miscellaneous Compounds
2-Phenyl benzimidazole-5-sulfonic acid (ensulizole) has some water solubility, is
a high melting white powder, is affected by pH changes and is used in limited
quantities in the USA. It has a moderate to high extinction coefficient of
26,000 and its lmax is about 310 nm.
HO S
3 N
Ensulizole
The inorganic particulates have currently received an inordinate amount of atten-
tion and we have devoted two chapters to review their chemistry and applications
(Chapters 14 and 15).
Also, several new organic particulates have recently been approved in
Europe and their chemistry is reviewed by Herzog et al. (Chapter 16).
MECHANISM OF SUNSCREENING ACTION

UV filters are generally aromatic compounds conjugated with an electron-
receiving group (e.g., a carbonyl group) or conjugated with a double bond (X)
and an electron-releasing group (an amine, a hydroxyl, or a methoxyl group)
that is substituted in the ortho or para position of the aromatic ring (7) as shown:
Y X C O C O
R R
Y
para-Disubstituted ortho-Disubstituted
UV absorbers UV absorbers
Chemicals of this configuration absorb the harmful short-wave (high-energy)
UV rays (200 – 400 nm) and convert the remaining energy into innocuous
232 Shaath
longer-wave (lower-energy) radiation (.400 nm). Quantum mechanical calcu-

lations have shown that the energy of the radiation quanta present in the UV-B
and UV-A regions lies in the same order of magnitude as that of the resonance
energy of electron delocalization in aromatic compounds. Thus, the energy
absorbed from the UV radiation corresponds to the energy required to cause a
“photochemical excitation” in the sunscreen molecule. In other words, the sun-
screen chemical is excited to a higher energy state from its ground state by
absorbing this UV radiation. As the excited molecule returns to the ground
state, energy is emitted that is lower in magnitude than the energy initially
absorbed to cause the excitation (longer wavelengths).
The longer wavelength radiation is emitted in one of several ways (see
Fig. 13.3). If the loss in energy is quite large, that is, the wavelength of the
emitted radiation is of sufficient length that it lies in the infrared region, then it
may be perceived as a mild heat radiation on the skin. This minuscule heat
effect is undetected because the skin receives a much larger heat effect by
being directly exposed to the sun’s heat. If the emitted energy lies in the
visible region, then it may be perceived as either a fluorescent or a phosphores-
cent effect. This is common in the imidazoline-type sunscreen for which a slight
bluish haze may be observed on the skin or in cosmetic formulations. In the
extreme case, the emitted radiation is sufficiently energetic (lower wavelength)
that it may cause a fraction of the sunscreen molecule to react photochemically.
Cis – trans or keto –enol photochemical isomerization has been observed in some
organic molecules, causing a mild shift in the lmax of the chemical (15).
Effect of Vehicle on the Efficacy of UV Filters

Cosmetic vehicles may have a profound effect on the efficacy of UV filters and
their formulations. The pH, lmax, and extinction coefficient (1) directly influence
the SPF and the stability of cosmetic formulations.
Figure 13.3 Schematic representation of the process in which a sunscreen chemical

absorbs ultraviolet radiation.
pH Effects on UV Filters
The UV absorption spectra of acidic and basic compounds may be affected by
pH. In acidic compounds, the use of alkaline conditions (pH . 9) will assist in
the formation of anions that tend to increase delocalization of electrons (16).
This electron delocalization would decrease the energy required for the electronic
transition in the UV spectrum; hence, a bathochromic shift is observed (longer
wavelength or lmax). For example, phenols in an alkaline environment will
experience this anticipated bathochromic shift owing to the formation of the
phenolate anion. This phenolate anion will participate in resonance delocaliza-
tion of electrons.
Acidic conditions (pH , 4) will assist in the formation of cations with
aromatic amines. A hypsochromic shift towards the lower wavelength occurs
because the protonation of the unbound loan pair of electrons with acid would
prevent any resonance delocalization of the electrons. Thus aniline, for
example, forms the anilinium cation at low pH and a considerable hypsochromic
shift occurs.
Thus, UV filters such as PABA, sulisobenzone, zinc oxide, and ensulizole
experience pH changes in their formulations. Care must be exercised when
handling cosmetic formulations containing these UV filters that are affected
by pH changes.
Effect of Emollients on the Efficacy of UV Filters

Solvent shifts in sunscreen chemicals due to their combinations with a variety of
emollients have been observed (7). The use of different emollients in cosmetic
formulations may profoundly influence the effectiveness of a sunscreen chemical.
The shifts in the UV spectrum are due to the relative degrees of solvation by the
emollient in the ground state and the excited state of the chemical. To predict the
effect the emollient has on a particular chemical, the interaction (mostly hydro-
gen bonding) between the emollient and the sunscreen chemical must be
understood.
The solvation of polar sunscreens (e.g., PABA) with polar solvents such as
water or ethanol will be quite extensive. This extensive solvation stabilizes the
ground state, thereby inhibiting electron delocalization. The net result would be
a hypsochromic shift to lower wavelengths as depicted in Fig. 13.4 (case A).
For less polar sunscreen compounds, such as padimate-O, the solvent – solute
interaction (hydrogen bonding) is different because the excited state is more
polar than the ground state. The net result is stabilization of the excited state
by polar solvents. This then lowers the energy requirements for the electronic
transition; hence, a higher lmax would be expected, and a bathochromic shift
occurs as shown in Fig. 13.4 (case B) and Table 13.2.
For sunscreen compounds such as salicylates and anthranilates, they are
subject to the “ortho” effect, which supersedes other resonance delocalization
effects for the observed UV transitions. The six-membered ring formation
234 Shaath
Figure 13.4 Energy diagram depicting the stabilization of the ground state and the
excited state.
reduces the energy requirements for the electronic transition in the molecule by
loosening the electrons in the carbonyl group that is conjugated to the aromatic
ring.
This lower-energy transition is reflected in a higher than usual lmax. Most
of the available electrons are involved in the six-member cyclic arrangement and
Table 13.2 Summary of UV Absorption Data of Sunscreens in Combination with Polar

and Nonpolar Solvents
l1 max l2 max Extinction

Sunscreen Dl (l2 2 l1) nonpolar polar coefficient (1)
PABA 227 293 266 14,000

Dioxybenzone 226 352 326 10,440
Sulisobenzone 210 334 324 8,400
Oxybenzone 28 329 321 9,400
Octisalate 22 308 306 4,900
Homosalate 22 310 308 4,300
Meradimate þ2 334 336 5,600
Avobenzone þ9 351 360 30,500
Padimate-O þ16 300 316 27,300
Ocinoxate þ23 289 312 23,300
are not available for interaction with the solvent molecules. Thus, salicylates and
anthranilates do not exhibit any significant solvent shifts.
Effects on the Extinction Coefficient

The value of the extinction coefficient (1) is the basis of how the effectiveness of
the sunscreen chemical is assessed. Therefore, chemicals with a high extinction
coefficient are more efficient in absorbing the energy of the harmful UV radiation
than chemicals with a lower extinction coefficient.
All the electronic transitions for any compound may be characterized as
symmetry allowed or symmetry forbidden (17). Symmetry-allowed transitions
generally have high extinction coefficients, and symmetry-forbidden transitions
have lower extinction coefficients. Nevertheless, trends in extinction coefficients
for sunscreen chemicals can be arrived at qualitatively by studying both the
spatial requirements and the electronic transition responsible for the observed
UV spectrum. The degree of resonance delocalization in a molecule gives a
clear indication as to its lmax and a qualitative prediction of its extinction coeffi-
cient is possible.
The more efficient the electron delocalization in a molecule, the higher its
extinction coefficient. Compare, for example, padimate-O and homosalate. In
padimate-O, the two substituents on the benzene ring are in a para relation,
whereas the two substituents in the homosalate are in a sterically hindered
ortho relation. In ortho-disubstituted aromatic compounds, the two groups are
close to one another, causing a deviation from planarity. The slightest deviation
from coplanarity will significantly reduce resonance delocalization; hence, a
lower extinction coefficient is observed in homosalate compared with
padimate-O. For the same reason, octisalate and homosalate (both ortho-
disubstituted) have lower extinction coefficients than the para-disubstituted
compounds. Increased conjugation, allowing for more efficient resonance
delocalization, will also result in higher extinction coefficients. For example,
the extinction coefficient of ethylene is 15,000, that of 1,3-butadiene is 21,000,
that of 1,3,5-hexatriene is 35,000, and for the highly conjugated molecule,
b-carotene, it is 152,000 (18). The new UV filters originating in Europe have mul-
tiple chromophores and therefore increased conjugation resulting in extinction
coefficients exceeding 40,000 (Chapter 16).
THE FUTURE OF UV FILTERS

The ultimate sunscreen chemical should ideally have the following
characteristics:
1. It should absorb the harmful UV radiation in the region 280– 380 nm.
If a broad-spectrum protection is not possible by using one sunscreen
chemical, then the use of two or more ingredients that filter the
236 Shaath
280– 320 nm (UV-B region) and the 320 – 380 nm (UV-A region)
radiation, may be necessary.
2. It should possess a large molar extinction coefficient (1) at its lmax.
Values exceeding 25,000 would be extremely desirable. This would
afford the maximum possible protection with the least amount of
sunscreen in the cosmetic formulations. The new molecules currently
designed in Europe have multiple chromophores with unusually high
extinction coefficients.
3. The UV filters should have good solubility in emollients. Solid sun-
screens such as the benzophenones, avobenzone, camphor derivatives,
and PABA require special care to solubilize in formulations and insure
that they do not crystallize out on the skin. To insure the stability of
the sunscreen formulation, the UV filters must remain dissolved
throughout allowing for a reasonable shelf life. Inorganic and
organic particulates with silicone backbones have to be suspended
properly in the formulation and the phase in which they are incorpor-
ated in is chosen carefully to allow for maximum stability.
4. The lmax and the molar extinction coefficient (1) should not be
affected by solvents. Excessively polar sunscreen chemicals are
stabilized by polar solvents, thereby lowering the energy require-
ments of the ground state of the sunscreen. This in turn will cause
a hypsochromic shift (to shorter wavelengths) in polar solvents. On
the other hand, sunscreens that are not too polar in their ground
state but more polar in their photochemical excited states, will experi-
ence a bathochromic shift (to longer wavelengths) in polar solvents.
The ideal sunscreen would be one in which the polarity of the ground
state and that of the photochemically excited state are similar in
nature. Hence, a hypsochromic shift (owing to the solvent stabiliz-
ation of the ground state) will be counterbalanced by the bathochro-
mic shift (owing to the solvent stabilization of the photochemically
excited state).
5. It should have excellent photostability and be photochemically inert.
If isomerization such as cis – trans or keto– enol, is possible in the
molecule, then the degradation quantum yields should be low, indi-
cating that the isomerization is reversible. The addition of specific
emollients or quenchers may be necessary to insure their photo-
stability in the formulation. Inorganic particulates should be produced
commercially with the least amount of photo-chemical reactivity
possible. This may include choosing the type of mineral carefully,
the specific coating and the type of dispersant.
6. For water-resistant formulations, the sunscreen should be practically
insoluble in water. Water-soluble sunscreens will still have a role to
play in the sunscreen formulations, such as in hair preparations or
when boosting the SPF is required.
7. It should not be toxic, comedogenic, sensitizing, or phototoxic.

8. It should be compatible with cosmetic vehicles and ingredients, and
be easy to use and handle.
9. Since UV filters constitute a significant portion of the cosmetic
formulation, occasionally exceeding 15% of the formula, then it
may also be desirable to have the sunscreen impart additional charac-
teristics such as emolliency, moisturizing, or possibly imparting a
pleasant aroma that can cover base notes in formulations that are
fragrance-free.
10. It should not discolor the skin, stain clothing, cause stinging sen-
sations, deposit crystals, cause drying of the skin, or produce off-
odors when applied to the skin or hair.
11. The UV filter should be available isomerically pure, be chemically
stable for prolonged storage, and be chemically inert to other cos-
metic ingredients.
12. The ideal sunscreen should be inexpensive to use.
13. It should be compatible with most packaging material.
14. Sunscreen molecules should be adequately protected with patents and
intellectual property. Patents should cover their combinations with
other UV filters, emollients, quenchers, or additives.
15. Ultimately, the UV filter should be approved worldwide by official
regulatory agencies with the fewest restrictions on levels used or
combinations that are disallowed.
The foregoing conditions are obviously a wish list for the theoretically ideal
sunscreen candidate. Unfortunately, no sunscreen chemical on the market
today can claim to possess all of these properties. Nevertheless, the sunscreen
chemicals available, whether through deliberate design or through serendipity,
have provided the cosmetic chemist with a reasonable arsenal of UV filters
that are effective, possess a number of the “ideal” properties and have only a
few undesirable effects.
CONCLUSIONS
Our understanding of how sunscreens absorb and/or repel the harmful UV rays is
extensive. The relationship of chemical structure and efficacy of UV filters was
clearly demonstrated through the review of all the currently available UV
filters, as well as recent reports on new chemicals possessing unique sunscreen
capabilities. The evolution of modern sunscreen chemicals, although still not
complete, has nevertheless produced an impressive array of UV filters that
have been incorporated into a multitude of products used in our daily lives
such as moisturizers, creams, lotions, towelettes, and shampoos.
The future will witness new applications for which sunscreens may be used
requiring more effective, substantive sunscreen chemicals that have fewer
238 Shaath
drawbacks and limitations. This calls for additional extensive research and
resources devoted to this effort by chemical and cosmetic institutions and com-
mercial firms, newer more effective testing procedures to ensure the safety of
UV filters at the anticipated expanded usage levels, and the reasonable relaxation
of regulations by governmental and regulatory agencies to allow for the speedier
adoption of novel UV filters.
REFERENCES
1. Gasparro F, Mitchnick M, Nash J. A review of sunscreen safety and efficacy. Photo-
chem Photobiol 1998; 68(3):243.
2. Parish J. The scope of photo medicine. In: Regan J, Parish J, eds. The Science of Photo
Medicine. New York: Plenum Press, 1982:3– 17.
3. Parish J, Anderson R, Urbach F, Pitts D. The Spectrum of Electromagnetic Radiation:
UV-A. New York: Plenum Press, 1978:5– 6.
4. Marzulli F, Maibach H. Dermatoxity. 2nd ed. New York: McGraw-Hill, 1983:32.
5. Federal Register, 27666 (May 21, 1999).
6. Mongiat S, Herzog B, Deshayes C, Konig P, Osterwalder U. Cosmet Toilet 2003;
118(2):47– 54.
8. Kligman AM. The identification of contact allergens by human assay: III. The
maximization test: a procedure for sunscreening and rating contact sensitizers.
J Invest Dermatol 1966; 47:393 –409.
9. Gasparro F. UV-induced photoproducts of para-aminobenzoic acid. Photo-
dermatology 1985; 2:151.
10. Patini G. Perfluoropolyethers in sunscreens. Drug Cosmet Ind 1988; 143:42.
11. Jaffe HH, Orchin M. Theory and Application of Ultraviolet Spectroscopy. New York:
John Wiley & Sons, 1964.
12. Davis D. Cosmet Insiders Rep 1988; 7:1– 2.
13. Beck I, Deflander A, Lang G, Arnaud R, Lemaire J. Study of the photochemical
behavior of sunscreens benzylidene camphor and derivatives. Int J Cosmet Sci
1981; 3:139 –152.
14. Beck I, Deflander A, Lang G, Arnaud R, Lemaire J. Study of the photochemical
behavior of sunscreens benzylidene camphor and derivatives II. Photosensitized iso-
merization by aromatic ketones and deactivation of the 8-methoxy psoralin triplet
state. J Photochem 1985; 30:215.
15. Liem DH, Hilderink LTH. UV absorbers in sun cosmetics 1978. Int J Cosmet Sci
1979; 1:341 –361.
16. Morrison R, Boyd R. Organic Chemistry. 7th ed. Boston: Pearson, Allyn and Bacon,
2003.
17. Streitwiezer A Jr. Molecular Orbital Theory for Organic Chemists. New York: John
Wiley & Sons, 1961.
18. Scott AI. Interpretations of the Ultraviolet Spectra of Natural Products. New York:
Pergamon Press, 1964.
14
Inorganic Ultraviolet Filters
David Schlossman and Yun Shao

Kobo Products, Inc., South Plainfield, New Jersey, USA
Evolution and Perspectives 240

Evolution of Inorganic Ultraviolet Filters 240
Titanium Dioxide and Zinc Oxide 241
Perspectives for Inorganic UV Filters 241
Physical and Chemical Properties of Titanium Dioxide and Zinc Oxide 242
General Properties 242
Titanium Dioxide 242
Zinc Oxide 243
Isoelectric Point 244
Photocatalytic Activity 244
Glycol Method 246
Vitamin Method 246
Optical Behaviors 246
Scattering 247
Absorption 247
Manufacturers of Inorganic Ultraviolet Filters 248
Production of Micronized Titanium Dioxide 249
Manufacturers of Micronized Titanium Dioxide 250
Typical Specifications of Micronized Titanium Dioxide 250
Production and Manufacturers of Micronized Zinc Oxide 250
Typical Specifications of Micronized Zinc Oxide 252
239
240 Schlossman and Shao
Surface Treatment 252

Background 252
Surface Properties of Micronized Pigments 253
Inorganic/Organic Surface Treatments 254
Popular Surface Treatments for Micronized Pigments 255
Surface Treatments of Micronized Titanium Dioxide or Zinc Oxide
for Use with Avobenzone 255
Hydrophilic Surface Treatments for Micronized Pigments 255
Selecting the Proper Surface Treatment 255
Influence of Particle Size on UV Attenuation by TiO2 and ZnO 256
Particle Size 256
Influence of Particle Size on UV Attenuation 257
Zinc Oxide 259
Characterization of TiO2 and ZnO Dispersions 261
Dispersion of Inorganic Ultraviolet Filters 264
Objectives of the Dispersion Process 264
Index of Agglomeration 265
Advantages of Dispersions 266
Incorporating Micronized Pigments and Dispersions into Formulations 266
Producers of Dispersions 266
Formulations 267
Guidelines 267
Emulsifiers and Additives 269
Determining Suitable Levels of Actives 269
Foundations and Daily UV Lotions 270
Formulating with Zinc Oxide 270
Obtaining Broad-Spectrum Protection 271
Sample Formulations 272
W/O Waterproof Sunscreen Formula SPF 30þ 272
O/W Sunscreen Lotion SPF 27 272
Sunscreen Cream Gel 273
Sprayable O/W Sunscreen SPF 15þ 274
Regulations, Claims, Toxicity, and Testing 275
Summary 276
References 276
EVOLUTION AND PERSPECTIVES

Evolution of Inorganic Ultraviolet Filters
The popularity of inorganic ultraviolet (UV) filters with consumers and formula-
tors results from their effectiveness and safety. It is disclosed in JP Application
Inorganic Ultraviolet Filters 241
No. 1981-161,881 that when 0.1– 40% of ultrafinely divided titanium oxide with
a particle size of 10 –30 nm, which has been rendered hydrophobic, is blended
into cosmetic base materials, it transmits visible light but reflects and scatters
the harmful UV rays (1).
There are no known allergies to physical sunscreens (2). Contrarily, there
has been much data gathered from clinical studies that some organic sunscreens
cause photoallergies, are skin sensitizers, and can penetrate through the dermis
into the blood stream. The photostability of organic sunscreens varies and they
may become degraded unless they are stabilized or encapsulated.
Physical sunscreens, particulates, inorganic UV filters, inorganic sunscreens,
micronized pigments, micro, nano, ultrafine and mineral pigments are all terms that
which will be used interchangeably in this chapter to describe attenuation grades of
titanium dioxide and zinc oxide. Nowadays, many global brands are formulated
with particulates as the sole sunscreen agent to attenuate UV radiation in baby
and infant care products, and they are frequently contained in combination with
organics in children’s products and daily wear products for the face, lips, and eyes.
Notwithstanding their safety, there are some drawbacks to formulating
sunscreens with inorganic pigments. The usual factors impairing demand are
higher formulation costs and poor esthetics, including diminished spreading,
moisturizing, besides the so-called whitening effect.
Titanium Dioxide and Zinc Oxide

Companies are permitted by the FDA to make a broad-spectrum protection label
claim with either titanium dioxide or zinc oxide (3). During the past few years,
there has been a shift to zinc oxide from titanium dioxide as more consumers
are paying attention to warnings from dermatologists about the harmful effects
of UV-A radiation and are favoring products with higher UV-A protection.
Studies have been published in dermatologic journals in the USA, which report
that micronized zinc oxide absorbs more UV light in the long-wave UV-A
spectrum (340–380 nm) than micronized titanium dioxide (4,5). It is also
popular because of its superior transparency since it has a lower refractive index
than titanium dioxide, 2.0 compared with 2.7. Schering-Plough introduced
during 2003, under their brand Coppertone KIDSw an SPF 50 UV-A/UV-B sun-
screen lotion with zinc oxide. The FDA permits up to 25% of titanium dioxide and
zinc oxide to be used in sunscreen products in the USA, however, these particulates
may not be formulated together with butyl methoxy dibenzoyl methane (avoben-
zone), an organic UV-A sunscreen (3). In Europe, the COLIPA has yet to rec-
ommend zinc oxide be listed as a sunscreen active (6). MHW permits
combinations of micronized pigments and avobenzone in Japan.
Perspectives for Inorganic UV Filters

Increased global competition in the personal care industry has enabled elegant
formulations to be developed internationally. Today’s micropigments as
supplied, are finer in particle size, contain a narrower particle size distribution,
have an improved physical and chemical stability, and are easier to disperse.
During his presentation at the 2003 Florida SCC Sunscreen Symposium, David
Steinberg remarked that the approval by the FDA of combinations of avobenzone
together with micronized pigments should be forthcoming in the new sunscreen
monograph (7). Demand for micropigments in the USA should increase after that.
The future demand for titanium dioxide and zinc oxide pigments will in fact be
influenced by the impending monograph, particularly the regulations on measur-
ing UV-A (and a broad-spectrum sun protection claim), and whether SPF 30þ
becomes the maximum amount of sun protection that can be claimed. Compe-
tition from new organic filters, broad spectrum organic particulates like methyl-
ene bis-benzotriazolyl tetramethylbutylphenol, and a further understanding of
UV damage on skin structures will also influence demand (8).
PHYSICAL AND CHEMICAL PROPERTIES OF TITANIUM

DIOXIDE AND ZINC OXIDE
General Properties
Titanium Dioxide
Titanium is the ninth most common element in the earth’s crust. In nature, it exists
only in combinations with other elements such as oxygen. Three titanium-
containing ores are of commercial importance: ilmenite, rutile, and anatase.
Ilmenite is a composite of oxides of iron and titanium and has a formula of
FeTiO3 or FeOTiO2 . Titanium dioxide content of ilmenite ranges from 45% to
60%. Important deposits are located mainly in Brazil, India, and Canada.
Naturally occurring rutile and anatase are not pure and contain various
amounts of metals including those that pose health hazards to humans. Therefore,
commercial TiO2 is always synthesized. Although rutile and anatase have the
same chemical identity, they are different in their crystalline structure. Anatase
has a regular octahedral crystal lattice while rutile has a tetragonal one.
Another type of titanium dioxide is called brookite, which forms an orthorhombic
crystal. However, brookite has no commercial importance.
Out of the aforementioned three forms of titanium dioxide, rutile is the
most thermally stable. When anatase and brookite are heated at a very high temp-
erature, they convert into rutile, in which unit cell the atoms are more densely
packed. Rutile and anatase have somewhat different physical and chemical prop-
erties, because of their difference in crystal lattice. Some of the properties are
listed in Table 14.1.
Chemically, titanium dioxide is very stable. It is stable towards acids and
bases except very concentrated strong acids. It is insoluble in all organic solvents.
Therefore, it is considered to be essentially inert in all of its applications. It is very
safe to use and has replaced many other white pigments, because of its inertness
and insolubility.
Table 14.1 Physical Properties of Titanium Dioxide
Parameter Rutile Anatase
Density (g/cm3) 4.2 3.9

Hardness (Mohs) 6–7 5.5– 6
Refractive index 2.76 2.52
Dielectric constant 114 48
Melting point (8C) 1855 Converts into rutile
Zinc Oxide
Zinc ranks 24th in abundance but never occurs free in nature. Zinc is never found
as the free metal but there are a number of important ores such as sphalerite (zinc
blende, zinc sulfide, ZnS), smithsonite (zinc carbonate, ZnCO3), zincspar (also
zinc carbonate, ZnCO3), and marmatite (zinc sulfide, ZnS, containing some
iron sulfide, FeS). Zinc is widespread around the world. Important deposits are
located in North America and Australia.
Pure zinc oxide (ZnO) is typically a white or yellow-white powder. Crystalline
zinc oxide has a hexagonal crystal structure. Zinc oxide is produced by oxidizing zinc
vapor in burners or by precipitation from zinc salt. The source of the zinc vapor is
either impure zinc oxide or purified zinc metal. Zinc vapor generated from purified
zinc metal will provide the highest purity zinc oxide that can be used in personal care
products (9–11). Physical properties of zinc oxide are listed in Table 14.2.
Unlike titanium dioxide, zinc oxide is slightly soluble in water. The reported
water solubility of zinc oxide ranges from 1.6 mg/L (298C) to 5 mg/L (258C).
An important conversion in water is the hydrolysis of zinc oxide to zinc hydrox-
ide. The reported water solubility of zinc hydroxide ranges from 2.92 mg/L
(188C) to 15.5 mg/L (298C). The rate of conversion of zinc oxide to zinc hydrox-
ide is dependent on various factors, the most important of which is temperature.
Although zinc oxide is not reactive in most conditions where practical
applications are employed, its reactivity needs to be noted to avoid misuse. It
can adsorb carbon monoxide and carbon dioxide and react with carbon dioxide
in moist air generating zinc carbonate. Zinc oxide and zinc hydroxide are ampho-
teric. They can react with acid to form zinc salts or with alkali to form zincates.
Table 14.2 Physical Properties of Zinc Oxide
Parameter Value
Density (g/cm3) 5.7

Hardness (Mohs) 4
Refractive index 1.99
Dielectric constant 1.7 –2.5
Melting point (8C) 1975
Isoelectric Point
When a pigment is dispersed in a liquid, the stability of the dispersion is affected
by the electrical charge on the pigment surface, which gives an electrostatic
repulsion to keep particles apart. The classic method to measure the surface
charge is zeta potential. This is typically done in a polar solvent and the zeta
potential is measured as the pH of the medium changes. Isoelectric point (IEP)
is obtained when a pH is such that zeta potential is zero, that is, the surface of
the particles is neutral. The IEP of pure titanium dioxide is 3.8 and that for
zinc oxide is 9. For various reasons, TiO2 is coated with alumina or silica. The
IEP is then altered and determined by the nature of the coating. With alumina
coating, the IEP shifts to a higher pH of 7. With silica coating, the IEP shifts
to a lower pH of 2.1, which renders the surface negatively charged in most appli-
cations. The surface charge can be greatly changed and increased by the adsorp-
tion of polymeric electrolytes. As a result, polymeric electrolytes are frequently
used in pigment dispersion.
In a nonaqueous medium, the surface charges of TiO2 and ZnO are much
less. Since TiO2 and ZnO are often coated with organic compounds when they are
dispersed in a nonaqueous medium, the effect of surface charge on the stability of
dispersion is less important and the steric repulsion becomes a predominant
factor in stabilizing the dispersed particulate.
Photocatalytic Activity
Both TiO2 and ZnO are semiconductors whose electrons can be excited with
energy and promoted from valence band to the conducting band in which the
electron can move around the atomic structure. The energy gap between the
two bands is 3.06 eV for rutile and 3.20 eV for anatase corresponding to a
long-wavelength absorption edge of 420 and 390 nm, respectively. Light with
a shorter wavelength has enough energy to excite the electrons in the valence
band and therefore can be absorbed by TiO2 . When the electrons are promoted
to the conducting band, they can migrate away from the original lattice and,
therefore, create hole – electron pairs. The electrons and holes react with dis-
solved oxygen, surface hydroxyl groups and absorbed water to form hydroxide
and superoxide radicals that can be responsible for many side reactions
(Fig. 14.1).
Figure 14.1 Reactions involved in the photocatalytic activity of TiO2 .

When O2 is excluded, reaction 2 cannot proceed. Instead reaction 4 will

take place. At such a state the electrons can absorb visible light and cause
graying. This phenomenon can occur to a TiO2 containing product that is
packed in an airtight, transparent package.
The band gap for zinc oxide is 3.35 eV, which corresponds to a wavelength
of 380 nm. Under UV irradiation, reactions 1 –3 listed in Fig. 14.1 for titanium
dioxide also take place in zinc oxide. Reaction 4 will not occur due to the nature
of the zinc chemistry. Therefore, graying caused by UV absorption does not
occur to zinc oxide.
Scientists at Kemira Corporation studied the difference in photocatalytic
activity between ultrafine rutile and anatase. The sample was dispersed in
melamine – formaldehyde resin and the drawdown of the paste was exposed to
UV light for 3 min. The relative photocatalytic activity was determined by
measuring the darkening of the paste induced by the reduction of Ti4þ to Ti3þ.
Based on data obtained, they concluded the following.
. Rutiles are much more light resistant than anatase crystals
. Calcination of crystals greatly improves light stability
. A heavy inorganic posttreatment is the key to improving their light
stability (Kemira Pigments, personal communication, 2003).
Kobayashi and Kalriess conducted a quantitative study on the photodecom-
position of gaseous acetaldehyde in the presence of various grades of TiO2 and
ZnO (12). The rate constant of the first-order reaction was calculated from
measured data and was used to indicate the level of the photocatalytic activity.
Some interesting data are presented in the Table 14.3.
The experimental data confirmed that rutile is much more photostable than
anatase. Zinc oxide is more stable than titanium dioxide, but the level of its
photocatalytic activity cannot be ignored.
Researchers at Sakai reported suppressed photochemical activity of their
micronized zinc oxide (SF-20) with an organosiloxane treatment. They found
that a 10% slurry of this zinc oxide in white petrolatum after 9 h exposure
under a 365-nm UV lamp had decreased yellowing (13). Reduced zinc ion
Table 14.3 Rate Constant of the First-Order Reaction
Sample Size (nm) Treatment Rate
TiO2 (anatase) 410 None 4.76

2% Methicone ,0.01
TiO2 (70% rutile) 21 None 3.70
TiO2 (rutile) 30– 50 Alumina 0.13
3% Lecithin 0.033
ZnO 15– 35 None 1.83
3% Methicone ,0.01
bleeding was reported by treating micro zinc oxide with silica by Showa Denka
under alkaline (1% ammonia, pH 11.7) or acidic (0.012% nitric acid, pH 2.7) con-
ditions. Once the soluble zinc concentration rises in a cosmetic formulation
containing fatty acids, the viscosity of the formulation increases and eventually
gelation occurs (14). The photocatalytic activity of zinc oxide can be almost com-
pletely suppressed if the pigment is coated first with an inorganic coating, and is
secondarily coated with an organic compound.
The test methods described above for measuring the photocatalytic activity
and many others reported in literature are often too complicated for a cosmetic
chemist to perform. A few industrial methods have then been developed
during the past few years. These methods are indeed very useful for quick com-
parison study to screen different types of titanium dioxide, although indirect and
not analytically quantitative.
Glycol Method
A sample of the inorganic sunscreen is mixed with propylene glycol. The mixture
is preferably milled on a Hoover Muller or a bench-top mill. The paste obtained is
placed on a white chart and is then covered with a glass plate. The edges of the
glass plates are sealed so that the paste is isolated from the air. The sample is then
exposed to sunshine or UV light for a certain period of time. The change of color
of the paste before and after the exposure can be assessed visually or quantified
instrumentally (15).
Vitamin Method
In this method, a sample of the inorganic sunscreen, 1% solution of ascorbyl
monopalmitate in decaglyceryl monolaurate, and propylene glycol monocapry-
late are mixed completely. The paste is drawn down on a white chart. The
color is then compared to the blank sample in which no ascorbyl monopalmitate
is added (15).
Optical Behaviors
When light hits a particle, it can be reflected, scattered, or absorbed. A simple
equation for the interaction of light with a particle is expressed in Fig. 14.2,
where It is intensity of transmitted light, I0 is the intensity of incident light; Ir ,
Is , and Ia are the intensities of the reflected, scattered, and absorbed light, respect-
ively. For submicrometer particles, the specular reflection is often very small.
Scattering and absorption are the major attenuation mechanism and the predomi-
nance is related to the particle size and the chemical composition.
Figure 14.2 Equation describing the interaction of light with a particle.

Scattering
The scattering from molecules and very tiny particles (,0.1 wavelength) is pre-
dominantly Rayleigh scattering. When the particle size is at the same magnitude
as the wavelength, Mie scattering predominates. This scattering produces a
pattern like an antenna lobe, with a sharper and more intensely forward lobe
for larger particles (Fig. 14.3).
For attenuation grade TiO2 , the scattering follows Mie theory and the inten-
sity of scattering (Is) can be expressed as in Fig. 14.4, where N is the number of
the particles, I0 is the intensity of the incident light, d is the diameter of the par-
ticle, l is the wavelength of the incident light, and m is the relative refractive
index, which is defined as the ratio of the refractive index of the particle over
that of the medium in which the particle is (16,17).
As shown in Mie’s equation, the intensity of scattering is proportional to
the sixth power of the particle diameter and therefore, a large particle is much
more efficient in scattering. At a given weight, Nd 3 is constant. Thus, scattering
is proportional to the third power of the particle diameter. As a result, in order to
reduce the scattering of visible light (the whitening effect), the reduction of the
top size in a distribution is important, even more so than to reduce the mean par-
ticle size. On other hand, when the size is reduced too much to minimize the
whitening, the dominance of scattering of UV light will give way to absorption.
Another important factor in Mie’s equation is the relative refractive index.
In most sunscreen products, the media (like oils) have a refractive index of 1.33 –
1.6. When rutile TiO2 with a refractive index of 2.76 is used, the relative refrac-
tive index is about 1.8. If ZnO is used instead, its lower reactive index of 1.99 will
result in a relative refractive index of about 1.3. According to the Mie’s law, TiO2
will be nearly three times effective in scattering light.
Absorption
As aforementioned, light with wavelength ,420 nm has enough energy to excite
the electrons in the valence band and therefore can be absorbed by rutile TiO2 .
The theoretical calculation has shown, however, the absorption of UV at
longer wavelength is weak and gradually reaches a plateau at 360 nm
(Fig. 14.5). TiO2 is not considered as an efficient UV-A, especially UV-A II,
Figure 14.3 Scattering patterns for Mie and Rayleigh scattering.

Figure 14.4 Equation of Mie scattering.
absorber, but is an efficient UV-B absorber. The attenuation of UV-A by TiO2

mainly takes places via scattering (18).
Since the band gap wavelength of zinc oxide is longer than that of titanium
dioxide, ZnO absorbs broader spectrum range of UV light than TiO2 . Moreover,
due to the difference in electron energy states (i.e., band structure), the UV cutoff
is sharper for ZnO than for TiO2 .
The absorption is a function of the number of atoms that interact with the
light in its pathway. For a single photon, the size has no effect on the absorption.
In reality, however, when the particle size is reduced, there will be more particles
that become available to interact and hence absorb the UV light. Due to this
increase in the interactions, smaller particle size will result in a stronger UV
absorption when the weight of TiO2 or ZnO is fixed (19). The limitation on the
particle size, however, is quantum behavior, which occurs when the size of the
particle is close or smaller than the exciton Bohr diameter (20), which is about
5 nm. Neither TiO2 nor ZnO on the market has a size even close to this dimension
yet, which means that the smaller the particle size, theoretically, the better the
UV absorption (Fig. 14.6).
MANUFACTURERS OF INORGANIC ULTRAVIOLET FILTERS

As mentioned earlier, commercial TiO2 is always synthesized. Tayca, ISK, Sumi-
tomo Cement, and Sakai, the dominant global manufacturers of micronized pig-
ments all have their factories in Japan. Kemira, another important producer of
micronized titanium dioxide, is located in Finland. Manufacturers are listed in
Table 14.4.
Figure 14.5 Calculated UV absorption curves for rutile and anatase TiO2 .
Figure 14.6 Particle size and transparency.
Production of Micronized Titanium Dioxide

Titanium dioxide pigments are typically made from one of two chemical pro-
cesses (21). The sulfate process is used by the majority of micro titanium produ-
cers including Tayca, the largest global supplier of rutile-based micronized
titanium dioxide (Tayca Corporation, personal communication, 2000). In this
process, the titanium ores are reacted with sulfuric acid resulting in a titanyl
sulfate intermediate. Sachtleben manufactures anatase grades of TiO2 from natu-
rally occurring ore. The ore is converted to a soluble form using highly concen-
trated sulfuric acid (22). The chloride process is newer. It produces pigments by
reacting titanium ores with chlorine gas at 9008C to obtain titanium tetrachloride.
Hydrolysis of these titanium salts and calcination are necessary production steps
to obtain a rutile pigment. Rutilization catalysts such as Al3þ and aluminum
chloride enable the process to occur at lower temperatures. This is important to
avoid excessive particle growth and pigment discoloration (21).
Tioxide Group PLC patented a particulate material consisting of a noncal-
cined titanium dioxide. The particles are acicular in shape within the range of
10 –150 nm. They are coated with an oxide or hydrous oxide layer of alumina
and silica and contain an organic dispersing agent selected from the family of
compounds consisting of substituted carboxylic acids and soap bases such as
polyhydroxy stearic acid (23).
Table 14.4 Manufacturers of Micronized Titanium Dioxide
Manufacturer Trade name Internet address
Degussa P-25 www.degussa.com

Ishihara Sangyo TTO www.iijnet.or.jp/itc-fmp/
Kaisha, Ltd.
Kemira Pigments Oy UV Titan www.kemira.com/pigments
Rhodia Mirasun www.rhodia.com
Sachtleben Hombitec www.sachtleben.de/h/e/hom/0000e.html
Showa Denka Maxlight www.sdk.co.jp/chemicals/index.html
Tayca Corporation MT Series www.tayca.co.jp/english/file/04/04_02.html
Titan Kogyo STT www.titankogyo.co.jp
Uniqema Solaveil, www.uniqema.com/pc
Tioveil
Alternatively, particles of titania can be prepared by decomposition or

hydrolysis of suitable titanium compounds. High-temperature hydrolysis of an
organic titanium compound such as titanium alkoxide can be used. Oxidation
or hydrolysis in the vapor state of titanium halides under appropriate conditions
can also be used (24). Degussa manufactures a fumed titanium dioxide of high
purity (see www.degussa.com).
Manufacturers of Micronized Titanium Dioxide

Kemira, ISK, and Sachtleben are manufacturers of both pigmentary and micronized
grades of titanium dioxide for personal care products. Micronized titanium dioxide
is supplied at a particle size of approximately 1/10 of the particle size of pigmentary
titanium dioxide (24). Commercially available micropigments range in particle size
of 10–60 nm and attenuate a broad range of UV light. Titan Kogyo and Showa
Denka both offer micronized titanium dioxide pigments larger than 100 nm (25,26).
ISK manufactures their micronized titanium dioxide by a proprietary
method, which is neither the sulfate nor the chloride process. Rutile, anatase,
and combinations of both are produced. ISK distinguishes their grades as made
by either the calcination or wet process. Wet process grades are superior in dis-
persibility, but calcined grades have superior physical and chemical stability
(ISK, personal correspondence, 1995). ISK also offers different shapes such as
spherical, dendrite, and spindle (27). They have also developed a titanium
dioxide balloon that consists of micronized titanium particles, but feels smoother
than micronized titanium dioxide (28). The shell wall was found to be too fragile
to permit any commercial applications besides loose powders (Toshiki Pigment
Co. Ltd., personal correspondence, 2000).
Kemira produces rutile grades by the sulfate process (Kemira Pigments,
personal correspondence, 2003). The optical properties are mainly developed
in the crystallization and/or calcination process steps during their manufacturing
process of 20 nm titanium dioxide (29). Rhodia, Sachtleben, Titan Kogyo, all
supply an anatase crystal and Degussa supplies a mixture of anatase and rutile.
Anatase reflects more UV light as opposed to a rutile crystal that absorbs more
UV light (30).
Typical Specifications of Micronized Titanium Dioxide

Consideration of the particle size and surface treatment are important in selecting
a grade of micronized titanium dioxide for a given application. Popular grades are
included in Table 14.5.
Production and Manufacturers of Micronized Zinc Oxide

The different production techniques to produce nanosized zinc oxide can be sum-
marized as follows:
. Vapor techniques (e.g., combustion synthesis, gas condensation,
plasma synthesis)
Table 14.5 Micronized Titanium Dioxide—Typical Specifications
TiO2 Crystal Primary particle size Surface

Supplier Grade (%) form (surface area—BET) treatment
Degussa P-25 99.5 Anatase 21 nm (50 + 15 m2/g) None

EMD Eusolex 76– 82 Anatase 10 – 15 nm Alumina,
T-2000 dimethicone
ISK TTO S-4 .82 Rutile 15 nm AHSAa
ISK TTO S-3 .82 Rutile 15 nm Alumina
ISK TTO V-3 .82 Rutile 10 nm Alumina
Kemira UV Titan .75 Rutile 14 nm Alumina,
M170 methicone
Kemira UV Titan .85 Rutile 20 nm Alumina,
M262 dimethicone
Sachtleben Hombitec 75– 85 Anatase (80 – 160 m2/g) Silica, silicone
L5
Showa Maxlight 64 Unknown 35 nm Silica
Denka TS-04
Tayca MT-100T .80 Rutile 15 nm AHSAa
Tayca MT-500B .96 Rutile 35 nm Alumina
Tayca MT-100Z .73 Rutile 15 nm AHSAa
Titan STT 65C-S 96.5 Anatase (64 m2/g) None
Kogyo
a
Aluminum hydroxide and stearic acid.
. Liquid techniques (e.g., chemical precipitation, hydrothermal proces-

sing, sol –gel processing)
. Solid state techniques (e.g., mechanochemical processing).
Manufacturers are listed in Table 14.6.
According to Innes et al., the major issues to overcome in the production of
nanopowders are controlling the growth of the particles and then stopping the
newly formed particles from agglomerating once formed. Hard agglomerates
of zinc oxide are formed when they are manufactured by vapor techniques.
This is because the nanoparticles are created by the rapid solidification of a
liquid or vapor into a gaseous medium. The particles will have a higher
surface energy than particles made by other methods and will be more reactive.
These more reactive surfaces will aid the formation of hard agglomerates and
thus individual particles will be more difficult to disperse (21).
Advanced Nano Technologies’ mechanochemical processing uses a high-
energy dry milling to induce chemical reactions during ball – powder collisions
to form nanoparticles in a solid state matrix. Agglomeration is minimized by
ensuring the particles are encapsulated on formation by a solid diluent (typically
NaCl). The mean particle size is 25 nm with a standard deviation of 3.3 nm (31).
Nanophase manufactures micronized zinc oxide by a vapor technique (see
www.nanophase.com).
Table 14.6 Manufacturers of Zinc Oxide
Manufacturer Trade name Internet address
Advanced Nano Zinclear www.ant-powders.com/zinclear.htm

Technologies
BASF Z-Cote www.basf.com
Elementis Specialties Nanox www.elementis-specialties.com
Zinc Corporation USP-1 www.zinccorp.com
of America
Nanophase NanoGuard www.nanophase.com
Sakai Finex www.sakai-chem.co.jp
Showa Denka Maxlight ZS www.sdk.co.jp/chemicals/index.html
Sumitomo Cement ZnO series www.socnb.com/index_e.html
Tayca Corporation MZ Series www.tayca.co.jp/english/file/04/07_03.html
Haarmann and Reimer ZnO Neutral www.symrise.com
Manufacturers of micronized zinc oxide are included in Table 14.6. The

most popular grades that are sold are ZnO-350 in Japan, manufactured by Sumi-
tomo Osaka Cement, and Z-Cote HP-1 supplied by BASF in the USA.
Typical Specifications of Micronized Zinc Oxide

As with micronized titanium dioxide, particle size and surface treatment of
micronized zinc oxide are important factors in selecting a grade to formulate.
Popular grades supplied to the personal care market by the leading manufacturers
are listed in Table 14.7.
SURFACE TREATMENT
Background
The physical and chemical stability of micronized pigments were discussed in the
section titled “Physical and Chemical Properties of Titanium Dioxide and Zinc
Oxide.” Therefore, it should be of no surprise that surface treatments add
value to micronized pigments. As a matter of fact, multiple coatings have
become a standard industrial practice and are known to be very effective. They
are of paramount importance for compatibility in formulation, photostability
for years, and mechanical properties (32). Surface treatments are produced by
micropigment manufacturers and by companies specializing in organic surface
treatments. Treatment specialists include Daito Kasei and Miyoshi Kasei in
Japan, and US Cosmetics and Kobo Products in the USA. Several popular treat-
ments are listed in Table 14.8. It is imperative to use a coated TiO2 or ZnO for a
sunscreen application to ensure the stability of the product.
Table 14.7 Micronized Zinc Oxide—Typical Specifications
ZnO Primary particle size Surface

Supplier Grade (%) (Surface area—BET) treatment
ANT Zinclear – 25 nm Stearic acid

BASF Z-Cote 98 ,200 nm None
Elementis Nanox 200 .99 60 nm (17 m2/g) None
Sakai Finex SF-20 .99 60 nm (20 m2/g) None
Showa Denka ZS-032 80 31 nm Silica
Sumitomo ZnO-350 .99 35 nm None
Cement
Tayca MZ-700 .99 10 – 20 nm None
Surface Properties of Micronized Pigments

Small particle size TiO2 or ZnO are preferred for beach and daily wear appli-
cations, to reduce skin whitening accordingly. The photocatalytic activity,
however, becomes much greater since the surface area of the pigment particle
Table 14.8 Popular Surface Treatments of Micronized TiO2 and ZnO
Manufacturer/
supplier Grade Type Surface treatment Description
BASF Z-Cote HP-1 ZnO Trimethoxy caprylyl Hydrophobic

silane
Degussa T-805 TiO2 Trimethoxy caprylyl Hydrophobic
silane
EMD Eusolexw T-2000 TiO2 Alumina, dimethicone Hydrophilic
EMD Eusolexw T-S TiO2 Alumina, stearic acid Lipophilic
Ishihara TTO S-4 TiO2 Aluminum hydroxide, Lipophilic
stearic acid
Ishihara TTO S-3 TiO2 Alumina Hydrophilic
Ishihara TTO 51-C TiO2 Aluminum hydroxide, Lipophilic
(calcined) stearic acid
Kemira M170 TiO2 Alumina, methicone Hydrophobic
Kemira M262 TiO2 Alumina, dimethicone Hydrophobic
Kobo ZnO-XZ-MS4 ZnO Methicone Hydrophobic
Kobo R10-TiO2-TTS7 TiO2 ITT/TCS crosspolymer Lipophilic
Sachtleben Hombitec L5 TiO2 Silica, silicone Hydrophobic
Sakai Finex-K2 ZnO Zinc silicate, silica Hydrophilic
Showa Denka Maxlight TS-04 ZnO Silica Hydrophilic
Showa Denka Maxlight ZS-032 ZnO Silica Hydrophilic
increases one magnitude faster with a drop in size (33). Therefore, the surface of a
micronized or ultrafine pigment must be treated to suppress this activity to mini-
mize or eliminate potential side reactions that can occur to other ingredients in a
formula. The anatase form of titanium dioxide is more reactive than the rutile
form, and calcined grades less reactive than wet processed grades as reviewed
earlier. Rhodia reported anatase to be a better substrate for an optimal surface
treatment (34).
A separate issue with decreasing particle size to be discussed further is
agglomeration. The larger specific surface areas are thus the reactive surface
area for the formation of aggregates, agglomerates, and flocculates (and also
adsorption processes). The forces of attraction that cause aggregates are
explained more fully in the section on particle size under the heading “Influence
of Particle Size on UV Attenuation by TiO2 and ZnO.”
TiO2 surface properties have been summarized by Sachtleben Chemie
GmbH as follows:
1. Primary particle size or specific surface area
2. The presence of acidic and basic hydroxyl groups
3. The moisture absorbed
4. The surface charge (resulting from defects, dopings, unsaturated valen-
cies and the adsorption of ions).
The surface of untreated titanium dioxide pigments is polar or hydrophilic
and may be characterized significantly by oxygen ions and by the pronounced
hydration and accumulation of hydroxyl ions (22). Pigments have air voids
trapped between particles and absorb moisture on their surface to reduce their
energy state (21).
Inorganic/Organic Surface Treatments

Surface treatments of micronized pigments are broadly classified as inorganic
and organic. Inorganic surface treatments are paramount to both the pigments
physical and chemical stability and heat stability, as was noted earlier by scien-
tists at Kemira. Alumina, silica, and zirconia are the widely used inorganic
surface treatments. Zirconia is not allowed in Europe. Inorganic treatments are
typically formulated by the manufacturers as part of the crystal, or they can
be added as a posttreatment. Calcination of the treatment results in the
bonding of the treatment to the pigment surface, but the high temperature
requirements cause the particle size to increase. Organic surface treatments
like alkoxy titanates, silanes, and methyl polysiloxanes react with and displace
the water of hydration absorbed on a pigment surface modifying it from hydro-
philic to hydrophobic or lipophilic. Organic surface treatments benefit the
particles’ physical and chemical stability and promote wetting and steric stabi-
lization in a carrier.
Popular Surface Treatments for Micronized Pigments

Tayca Corporation characterizes their surface-treated micronized titanium
dioxide as hydrophilic or hydrophobic (34). Tayca supplies micronized pigments
coated with inorganic and organic surface treatments, such as alumina, silica,
aluminum stearate, dimethicone, and methicone (35). The organic treatments
are applied by a wet process to minimize the aggregation of particles. Inorganic
treatments are either calcined or produced by a wet process. Aluminum hyd-
roxide and aluminum stearate have been the most popular combination for
surface treating micronized titanium dioxide. Treatments may be classified as a
lipophilic treatment, because it enhances the wetting of the pigment in an ester
(36). Researchers at Estee Lauder claimed a novel organic dispersion comprised
of this surface-treated micronized titanium dioxide and a suitable branched chain
ester without the use of a dispersing aid (37). In the ester isononyl isononanoate,
a dispersion consisting of 65% of Tayca’s MT-100T can be milled without a dis-
persant (38). Kemira utilizes wet milling to break down aggregates and treats the
surface with alumina to improve stability, and dimethicone to render the surface
property of its micronized titanium dioxide to hydrophobic (29).
Surface Treatments of Micronized Titanium Dioxide or Zinc Oxide

for Use with Avobenzone
Outside of the USA, combinations of inorganic UV filters and avobenzone are
allowed. It is necessary to have a uniform and densely coated pigment to maintain
the activity of the avobenzone, because it reacts with metal ions. Tayca’s MT-
100Z and Kemira’s M262 have both an inorganic and organic surface treatment,
which makes their pigments compatible with avobenzone. Showa Denka uses a
liquid phase deposition method to coat zinc oxide (and also titanium dioxide)
with a thin layer of silica (14). Sakai offers a grade coated with zinc silicate
and silica. These treated pigments have been found to be compatible with
avobenzone (39).
Hydrophilic Surface Treatments for Micronized Pigments

Alumina and silica are hydrophilic treatments that enhance the dispersability and
stability of the micronized pigment in an aqueous phase. Hydrophilic treatments
like polysaccharides, polyacrylates, and polyether silanes have been promoted
with limited success.
Selecting the Proper Surface Treatment

Popular surface treatments have distinct benefits and drawbacks. It is important
to consider the needs of the formula before deciding on the best treatment.
Schlossman and Shao measured the premix viscosities of hydrophobic and lipo-
philic treatments in esters, hydrocarbons and silicone fluids to determine their
dispersibility in multimedia (40). Popular surface treatments of micronized pig-

ments are detailed in Table 14.8.
Proper surface treatment is essential for:
. No aggregation
– Achieve transparency
. Homogeneous dispersion
– Ease of formulation
– Ability to disperse in formulation
– Stability
. Stable dispersion
– No dispersing agents required (22).
Popular surface treatments of micronized pigments are detailed in Table 14.8.
INFLUENCE OF PARTICLE SIZE ON UV ATTENUATION BY TiO2

AND ZnO
The theoretical calculations were reviewed in the section titled “Physical and
Chemical Properties of Titanium Dioxide and Zinc Oxide.” In the following
section, experimental data from practical applications of micronized pigments
will be reviewed and examined.
Particle Size
Many studies on the influence of the particle size on UV attenuation by inorganic
sunscreens have been reported in literature, but the term “particle size” was
seldom clearly defined. This often causes confusions when cosmetic chemists
try to apply the reported study result in real practice. Thus, it is necessary to
clarify the definition of particle size before undertaking the discussion about
the influence of the particle size on UV attenuation by inorganic sunscreens.
As shown in Fig. 14.6, both TiO2 and ZnO powders consist of primary
particles that are crystalline structures held together by atomic or molecular
bonding. The primary particle size is determined by process conditions when
TiO2 or ZnO crystals are forming and will not be affected by the subsequent pro-
cessing during their applications. The primary particles always aggregate to form
secondary particles due to their high surface energy such as van der Waals force,
electrostatic force, hydrogen bonding of surface hydroxyl groups, and water brid-
ging between the primary particles. These forces for the aggregation get stronger
as the primary size decreases and the specific surface area increases. The aggre-
gates in turn group to form agglomerates, the structure of which is often loose and
easy to break with mechanical force. Because the sizes of either agglomerate and
aggregate can vary depending on the dispersion status of the particles and are not
considered the intrinsic property of a particular grade of TiO2 or ZnO, the manu-
facturers often choose to report only the primary particle size, which is either
measured by using an electron microscope or calculated from the measured

specific surface area. Since the primary particles have a size much smaller
than the wavelength of UV light and always form aggregates, they do not interact
with light independently. As a result, the size of the aggregates rather than
primary particle size should be used to characterize TiO2 or ZnO in actual
application.
In practice, the particle size is often measured by using a light scattering
size analyzer. The powder or dispersion sample is diluted to a usually low con-
centration in an appropriate solvent. The scattering intensity of laser light by
the particles in the sample is recorded, calculated, and transformed into particle
size distribution from which mean particle size and standard deviation can be
derived. Although the dilution in the sample preparation may alter the particle
size in the actual product to some extent, the discrepancy has been generally
accepted until a better analytical method becomes available. In the following sec-
tions, the term of particle size will be used to represent the mean particle size.
Influence of Particle Size on UV Attenuation

Titanium Dioxide
Particle size and UV/visible transmittance: For sunscreen application,
attenuation grade titanium dioxide and zinc oxide with a primary particle size of
less than 100 nm are used to minimize the whitening. Although the primary par-
ticle size of these materials can be as small as 10 nm, the agglomeration is so
severe that an efficient milling of the pigment is always necessary to disperse
the particles. Otherwise, the advantage of a small size will not be displayed. A
common practice is to grind a predispersion of either TiO2 or ZnO. The
primary particle size becomes the key factor in deciding the highest possible
transparency when the dispersion is properly formulated and milled. In a study
by Schlossman, four types of titanium oxide with similar metal soap treatment
but different primary particle sizes were milled in fairly well controlled con-
ditions and the properties of all dispersions were compared. The particle sizes
are listed in Table 14.9 and the UV/visible transmittance curves are shown in
Fig. 14.7.
Table 14.9 Particle Size of TiO2 Dispersions
Sample PPS (nm) PS (nm)
1 15 125.3
2 35 154.1
3 100 251.1
4 180 263.4
Note: PPS, primary particle size; PS, particle size measured.

Figure 14.7 Transmittance curves of TiO2 dispersions in isononyl isononanoate;

primary particle sizes: 1 ¼ 15 nm; 2 ¼ 35 nm; 3 ¼ 100 nm; 4 ¼ 180 nm (TiO2 concen-
tration: 0.001% in CHCl3).
It is very clear from the transmittance curves in Fig. 14.7 that transmittance
of visible light (.400 nm) is much higher when the particle size is smaller. This
result was easily confirmed by comparing the drawdown of the dispersions on a
glass plate. When the particle size of TiO2 dispersion is .200 nm, like samples 3
and 4, the curves appears to be rather flat across both UV and visible regions.
These TiO2 samples cannot be used to make sunscreen lotions as they will be
too whitening and UV attenuation will be too weak (38).
Both samples 1 and 2 have high transmittance in visible range and are
suitable for sunscreen lotions. Sample 1 has smaller size and the transmittance
under 320 nm is also lower indicating that sample 1 will give a high SPF when
TiO2 use level is the same. However, sample 2 has a lower transmittance in
almost the entire UV-A range (335 – 400 nm). As a result, it is predicted that it
will give a better PFA (protection factor for UV-A) score.
Theoretical calculation by Stamatakis et al. (41) and experimental data
from Sakamoto et al. (42) showed that the attenuation of UV light with a wave-
length of 300 nm (UV-B) increases as the size decreases but that of UV light with
a wavelength of 350 nm (UV-A) decreases if the particle size is 100 nm or
smaller. Therefore, it became clear for TiO2 that:
1. UV-B attenuation is predominately due to its absorption, which
increases as the particle size decreases.
2. UV-A attenuation is predominately due to scattering by TiO2 . Particle
size needs to be controlled to maximize the attenuation without
causing whitening.
Particle size and sun protection factor: Scientists at Tayca and Tri-K
Industries, Inc. compared the sun protection factor (SPF) values of both o/w
(oil in water) and w/o (water in oil) sunscreen lotions using either straight
TiO2 powder or milled TiO2 dispersion (43). The TiO2 had a primary particle
size of 15 nm and was coated with aluminum hydroxide and stearic acid. The
particle size of TiO2 in dispersion was about 0.4 mm. The size of TiO2 powder
in emulsion was not reported but was probably over 1 mm. The in vitro
test results clearly demonstrated the advantages of using a preground TiO2 dis-
persion—up to 70% increase in SPF value (Fig. 14.8). Similar results have
been reported by other researchers in literature (44).
In vivo study on the relationship of the particle size of TiO2 and the SPF of
the corresponding sunscreen lotions was reported by Schlossman et al. (38). The
results are listed in Table 14.10. It is evident that SPF depends on the particle size
and the smaller size yields higher SPF.
Particle size and PFA: Table 14.11 lists the in vivo PFA test results for
sun lotions using different sized TiO2 (38). As mentioned above, TiO2 attenuates
UV-A mainly by scattering. As a rule of thumb, the maximum scattering at a par-
ticular wavelength occurs when the diameter of a particle is half of the wave-
length to be scattered (45). In addition, the scattering intensity by a bigger and
heavier particle is much stronger than by a smaller one. The particles in
formula A are too small to be effective in scattering UV-A. The particles in B
are bigger and are very effective in scattering UV-A. Therefore, when the size
of TiO2 is well controlled, it can be very effective in attenuating both UV-B
and UV-A, providing a broad-spectrum protection. This type of TiO2 can be
especially useful in formulating color cosmetics with sun protection claims.
Zinc Oxide
Particle size and UV/visible transmittance: In Schlossman’s study,
four types of ZnO were dispersed and milled under the same conditions. The par-
ticle sizes are listed in Table 14.12 and the transmittance curves are shown in
Fig. 14.9. Unlike TiO2, ZnO dispersions are rather transparent even when the
size is quite large. ZnO absorbs UV light more uniformly, and it has a sharp
cutoff that starts around 375 nm and shifts slightly to a shorter wavelength as
Figure 14.8 In vitro SPF of TiO2 in W/O and O/W emulsions: comparison of straight
TiO2 powder and ground TiO2 dispersion.
Table 14.10 In vivo SPF Test Results of TiO2-Containing Sunscreen Lotions
Formula PPS Dispersion PS Active SPF

type (nm) (nm) (%) (UV-B)
O/W 15 125.3 10.49 50.0

O/W 15 125.3 10.49 41.2
W/O 15 132.1 10.49 37.5
W/O 15 132.1 8.74 37.5
35 194.6 1.96
W/O 15 132.1 6.24 30.5
35 194.5 4.23
W/O 35 154.1 10.29 28.4
O/W 15 MT-100T powder 7.80 9.60
Note: 15 nm TiO2 is MT-100T; 35 nm TiO2 is MT-500B (from Tayca Corporation).

PPS, primary particle size; PS, particle size measured; SPF, sun protection factor.
the particle size gets smaller. The UV curves in Fig. 14.9 also show that the
smaller the primary particle size (PPS) the less UV light is transmitted across
the entire UV-B region and most of the UV-A region, indicating a better
broad-spectrum protection (38).
In in vitro PFA testing such as critical wavelength and UV-A/UV-B ratio,
the relative attenuation power in UV-B and UV-A is more heavily weighted than
the absolute attenuation power. As a result, sample 1 could give a lower PFA
score than sample 4 whose attenuation is more evenly distributed through
290 –400 nm. In in vivo SPF testing, the results can be opposite. Therefore, the
selection of a suitable grade of ZnO will depend on the test method chosen.
Particle size, SPF, and PFA: Table 14.13 lists the in vivo SPF and PFA
test scores for sunscreen lotions that contain ZnO of different particle sizes.
Obviously, as the particle size decreased the SPF increased dramatically.
The PFA scores also increased as the size decreased to 35 nm. However, the
UV-A/UV-B ratio obtained in vitro indicates that large particle size ZnO has a
better UV-A protection.
Because ZnO is not considered to be a potent UV-B attenuator, it is
often used in combination of other organic sunscreens. Therefore, the study on
Table 14.11 In vivo PFA Scores of TiO2-Containing Sunscreen Lotions
Formula PPS Dispersion PS Active PFA

type (nm) (nm) (%) (UVA)
A (O/W) 15 125.3 10.49 4.5

B (O/W) 15 154.1 10.29 6.75

Table 14.12 Particle Size of ZnO Dispersions
Sample PPS (nm) PS (nm)
1 20 228.3
2 60 246.0
3 100 263.6
4 200 292.2
sunscreen products containing only ZnO, especially by the in vivo method, is

limited. More investigations are needed to obtain a better understanding of
UV attenuation behavior of ZnO in cosmetic formulations and the optimum
particle size.
Characterization of TiO2 and ZnO Dispersions

Although the particle size is a useful parameter to predict the UV attenuation
power of TiO2 and ZnO, extinction ratio can be sometimes more informative
about their efficacy. In the measurement of UV/visible spectrum, sample of
TiO2 (or ZnO) powder or a dispersion is usually diluted to a level at which the
maximum absorbance is ,2. Figures 14.10 and 14.11 show the typical absorption
curves for TiO2 and ZnO, respectively. It should be noted that absorbance here
measures the total amount of UV attenuated by the sample through scattering
or absorption. The absorbance thus has a different physical meaning from that
of absorption discussed previously. Once an absorption curve is obtained, the
extinction coefficient can be calculated as in Fig. 14.12.
As a generally accepted industrial practice, the extinction coefficients
at the following wavelengths are selected to represent the UV/visible spectrum
Figure 14.9 Transmittance curves of ZnO dispersions in isononyl isononanoate;

primary particle sizes: 1 ¼ 20 nm; 2 ¼ 60 nm; 3 ¼ 100 nm; 4 ¼ ,200 nm (ZnO con-
centration: 0.005% in CHCl3).
Table 14.13 In vivo SPF and PFA Scores of ZnO-Containing Sunscreen Lotions
Formula PPS Dispersion PS Active SPF PFA UV-A/UV-B

type (nm) (nm) (%) (UV-B) (UV-A) Ratio
W/O 20 130.0 14.10 25.0 3.1

O/W 20 228.2 14.97 16.2 7.5 0.70
W/O 20 228.2 14.97 14.0 7.5 0.72
W/O 100 263.0 16.00 12.6 5.83 0.83
of TiO2 :
. 308 nm: maximum erythemal effectiveness
. 360 nm: middle of UV-A region
. 524 nm: blue end of visible light.
Therefore, the ratio of extinction coefficients at 308 and 524 nm is used to indi-
cate the UV-B protection and the transparency. Within the same spectrum,
the ratio of extinction coefficient is the same as the ratio of the absorbance at
the same wavelengths. The larger the ratio is, the higher the transparency
and the SPF are. On the other hand, the ratio of extinction coefficients at 308
and 360 nm is used to indicate that attenuation in UV-B vs. that in UV-A. A
lower ratio often indicates a broader-spectrum protection.
The extinction coefficient ratios and the absorption peak positions of TiO2
with various particle sizes are listed in Table 14.14. The ratios of both 308/360
and 308/524 increase substantially as the particle size reduces; a clear indication
that the TiO2 is getting more transparent and attenuation shifting further toward
UV-B. The ratio of 308/364 corresponding to a size of 110 nm or smaller is so
high that a very weak UV-A protection is predicated. It is worthy to be noted that
the maximum absorption shifts to UV-C region, which may negate its efficacy in
UV-B too. Since TiO2 dispersion with such a small size has been on the market
Figure 14.10 UV absorbance curve of TiO2.

Figure 14.11 UV absorbance curve of ZnO.
for only the past few years, a conclusive correlation of particle size and SPF/PFA
awaits more investigation. In general, TiO2 of such a particle size can be used in
combination with UV-A sunscreen agents to achieve a very transparent and yet a
broad-spectrum protection.
For ZnO, the absorbance below the cutoff wavelength is rather uniform
indicating an even attenuation of both UV-A and UV-B. Therefore, the selection
of wavelength to represent an UV/visible spectrum is:
. lmax: overall UV attenuation
. 524 nm: blue end of visible light.
The ratio of extinction coefficients at the maximum absorption and at 524 nm is
used to indicate the UV-A and UV-B protection and the transparency of a ZnO
product. Some experimental data are presented in Table 14.15.
It can be seen from the data that the extinction coefficient ratio of 308/360
is almost equal to 1.0 indicating that ZnO is a both UV-A and UV-B absorber. As
the size goes down to 130 nm or lower, the extinction ratio of lmax/524 nm can
be very high. As a matter of fact, when ZnO with a particle size of 110 nm was
used in a sunscreen lotion, almost two SPF units were achieved from each percent
of ZnO. The maximum absorption shifts downward as far as 360 nm when the
size decreases. In in vitro UV-A testing, the lower lmax would, as previously dis-
cussed, fare worse. In in vivo UV-A testing, the UV-A I (320 –360 nm) region is
more responsible for generating erythema, the outcome was also worse. There-
fore, it is very likely that a medium particle size is an optimum size for shielding
UV-A when it is measured in vivo. Again, both the particle size and the test
method have been considered when selecting a proper grade of ZnO.
Figure 14.12 Equation for extinction coefficient.

Table 14.14 Particle Size, Extinction Ratio, and Absorption Peak of TiO2
Particle size Ext. ratio Ext. ratio lmax

(nm) 308/360 308/524 (nm)
100 7.0 – 8.0 70 –90 275

110 4.5 – 5.5 50 –55 280 – 290
130 3.4 – 3.9 11 –26 290 – 305
150 2.0 9.0 300
150 2.0 17 313
250 1.1 2.6 318
DISPERSION OF INORGANIC ULTRAVIOLET FILTERS

Objectives of the Dispersion Process
Pigment Processing: Physico-chemical principles by J. M. Oyarzún, is an excel-
lent reference (46) on pigment dispersion. He defines pigment dispersion as a
stepwise process whose objective is to produce a stable and uniform dispersion
of finely divided pigment particles, that is, aggregates and primary particles, in
an application medium. The key elements of the process are further defined to
be mechanical breakdown, wetting, and stabilization. In order to achieve mech-
anical breakdown it is necessary to use energy to break down the cohesive forces,
the intermolecular forces of attraction that hold the solid particles together. The
cohesion forces acting between the structure units of pigment agglomerates are
essentially physical in nature and not accomplished by chemical bonding. The
surface forces of particles with microscopic dimensions are stronger than
coarse grain particles like sand.
Mechanical breakdown may be achieved with a high shear or a high-speed
disperser. The dispersion formulation typically consists of a micropigment,
surface treatment, dispersant, and a carrier medium. The surface treatment is
paramount for prewetting the pigment in the carrier and decreasing the absorption
of the dispersant by the pigment. The dispersant aids in the wetting and stabilizes
the particles in the carrier. Fig. 14.13 shows the role of the surface treatment and
dispersant in the premix of a 15 nm micronized titanium dioxide in
Table 14.15 Particle Size, Extinction Ratio, and Absorption Peak of ZnO
Particle size Ext. ratio Ext. ratio lmax

(nm) 308/360 308/524 (nm)
110 1.0 34 360

130 1.1 27 358
190 0.9 7.8 371
260 0.9 4.1 375
Figure 14.13 Surface treatment and prewetting of the pigment.
cyclopentasiloxane (36). The dispersion formulation must be well suited for the
mechanical process. The pigment solids and viscosity of the premix dispersion
dictate the choice of mill.
Index of Agglomeration
Dispersion processing becomes more problematic when the pigment is getting
finer (22). The index of agglomeration was proposed by Schlossman and Shao
as the ratio of the dispersion particle size over the primary particle size (47). It
can be observed from Table 14.16 that pigments having a smaller primary par-
ticle size contain larger indices of agglomeration. Modifying the components
of the dispersion formula will influence the pigment grind, meaning the dis-
persion particle size and the index of agglomeration. Table 14.17 lists the par-
ticles sizes for four distinct dispersion formulations containing UV-Titan
M170, a micronized titanium dioxide from Kemira.
Table 14.16 Influence of Primary Particle Size on

the Index of Agglomeration
PPS PS Index of
(nm) Type (nm) agglomeration
10 TiO2 110 11
15 TiO2 143 9.5
20 TiO2 143 7.2
20 – 30 ZnO 145 5.8
35 TiO2 179 5.1
120 ZnO 250 1.3

Table 14.17 Influence of Dispersion Formulation on the Index of Agglomeration

(Primary Particle Size is 14 nm for All Dispersions)
PS Index of
Dispersion formulation (nm) agglomeration
Iododecane and polyhydroxystearic acid (60% solids) 172 12.3

Iododecane and polyhydroxystearic acid (50% solids) 110 7.9
C12– 15 alkyl benzoate and polyhydroxystearic acid 165 11.8
Cyclopentasiloxane and PEG-10 dimethicone 165 11.8
Note: PS, particle size measured.
Advantages of Dispersions
The demand by formulators for dispersions instead of powders is increasing. The
desired particle size (and attenuation) can be more readily obtained with a dis-
persion of micronized pigments, because the concentration of particulates in an
oil or aqueous phase of a finished product formulation is likely to be too low
to provide enough particle to particle interaction to break apart agglomerates
and aggregates. The whitening effect can thus be minimized by formulating
with dispersions, because large particles that scatter visible light can be milled
finer. Producers of finished products are often poorly equipped with the proper
dust collection devices or mills to handle fine particle size pigments. Powerful
and specialized mixing equipment may be needed to wet these pigments,
because they are hard and dense, and possess a higher specific gravity.
Incorporating Micronized Pigments and Dispersions into Formulations

The process of dispersion takes place on the solid/liquid interface between the
pigment surface and the dispersion fluid (22). Suitable vehicles include oils/
esters, surfactants, glycols, silicone fluids, and water (48). A procedure often fol-
lowed by companies that make their own dispersions will be to make a predisper-
sion of the pigment in the carrier contained in the formulation. This predispersion
can be stored until it is needed to produce the finished formulation. An 80/20
mixture of titanium dioxide with barium sulfate coated with stearic acid dispersed
in isooctyl stearate is an example of a dispersion formula without a dispersing aid
(1). Dispersions are supplied to the personal care market either as thick pastes or
as low viscosity fluids. Pastes are more easily added to formulations by diluting
the pigment solids with more of the same carrier and dispersant. Low viscosity
fluids, for example, with viscosities under 30,000 cP, are typically added directly
to the oil or aqueous phase.
Producers of Dispersions
Uniqema began marketing their Tioveil dispersions during the late 1980s. Their
original product line featured aqueous and ester based 40% solids titanium
dioxide dispersions. They patented an oil dispersion comprising particles of
titanium dioxide having an average size of 10 – 150 nm surface treated with

alumina, silica, and an organic dispersing aid in an oil carrier. The organic dis-
persing aid claimed comprises monoesters of fatty acid alkanolamides and car-
boxylic acids wherein the fatty acids have from 6 to 22 carbon atoms, or is a
polyhydroxy carboxylic acid or an ethoxylated phosphate monoester (49).
In 1995, Kobo Products, Inc. entered the personal care market with High
Solidsw dispersions. The Kobo titanium dioxide dispersions were typically
thick pastes, as high as 65% solids, and were mainly ester based and incorporated
a polyglyceryl ester, Hexaglyn PR-15 from Nikko Chemicals, as a dispersing
aid. The micronized titanium was coated with aluminum hydroxide and stearic
acid. Their zinc oxide dispersions also contained Hexaglyn PR-15 and were
over 70% solids. It contained a titanate treated zinc oxide pigment to prewet
the particles in esters. The dispersion particle size was optimized by formulating
with a high pigment concentration (38). Collisions of pigment particles occur
inside the mill. Lower solids dispersions are not sufficiently viscous to grind
the particles in this type of mill.
New milling systems proposed initially for inks have been used to grind
low-viscosity dispersions. The viscosity of the milled dispersion formula, con-
taining pigment, surface treatment, dispersant (and possibly a resin) has to be
less than 10,000 cP. Kobo supplies these dispersions as High SpeedTM disper-
sions. Typically, the micropigment is hydrophobized with a silicone treatment,
and a silicone polyether copolymer can be used as a dispersant. Polyhydroxystea-
ric acid is a suitable dispersing aid that is effective to formulate dispersions with a
low viscosity. Kobo offers a 50% dispersion of Kemira M170 in isododecane that
has a viscosity of 20 cP. During 2003, Shao and Schlossman coauthored a paper
comparing micropigment dispersions made with silicone polyether copolymers,
silicone/acrylate copolymers, and polyhydroxystearic acid (50).
Uniqema and Degussa have recently introduced aqueous based dispersions
of hydrophobic micronized titanium dioxide. Aqueous-based dispersions of
hydrophobic titanium dioxide are purported to be sterically stable and tolerate
formulations over a wide range of pH (51,52). Tioxide patented an aqueous dis-
persion of particulate zinc oxide coated with amorphous silica, by mixing an
alkali metal silicate, an acid, and a stabilizing agent (53). They have also patented
a mixed oxide dispersion comprising an oil, particles of zinc oxide between 5 and
150 nm, particles of titanium dioxide between 5 and 150 nm, and an organic dis-
persing aid (54).
Suppliers of dispersions in water, esters, and silicone fluids are listed in
Table 14.18.
FORMULATIONS
Guidelines
Sunscreen compositions are formulated in the form of a cream, lotion, or oil. The
active agent when present on skin must be resistant to chemical or photodegradation
268
Table 14.18 Suppliers of Micropigment Dispersions
Supplier Dispersion Active Active (%) Surface treatment/dispersant Carrier
ANT Zinclear 40CCT ZnO 40 Stearic acid/polyhydroxystearic acid Caprylic/capric triglyceride

Elementis Nanoxw Gel 200 ZnO 55 Polyhydroxystearic acid C12 –15 alkyl benzoate
EMD Eusolexw T-Aqua TiO2 30 Alumina/sodium Metaphosphate Water
EMD Eusolexw T-45D TiO2 45 Alumina, dimethicone/polyglyceryl-6 Isononyl isononanoate
polyricinoleate
Ishihara TSK-5 TiO2 30 Silica Water
Sangyo
Kobo High SpeedTM CM3K50XZ4 ZnO 45 Methicone/PEG-10 Dimethicone Cyclopentasiloxane
Kobo High Solidsw IN60S4 TiO2 48 Aluminum hydroxide/stearic acid Isononyl isononanoate
Kobo High Solidsw INH73MZ ZnO 70 Isopropyl titanium triisostearate/ Isononyl isononanoate
polyglyceryl 6-polyricinoleate
Kobo High SpeedTM PM1P65M170 TiO2 48.75 Methicone/polyhydroxystearic acid Isohexadecane
Kobo High SpeedTM TNP50ZCL ZnO 50 Triethoxy caprylyl silane/ C12 –15 alkyl benzoate
polyhydroxystearic acid
Kobo High SpeedTM TNP55VTTS TiO2 41 ITT/TCS crosspolymer/ C12 –15 alkyl benzoate
polyhydroxystearic acid
Rhodia Mirasun w TiW60 TiO2 29 – 36 Silica (15%), alumina (5%) Water
Uniqema Tioveil AQ TiO2 ,40 Alumina, silica/Na polyacrylate Water
Uniqema Tioveil FIN TiO2 ,50 AS and alumina/polyhydroxystearic C12 –15 alkyl benzoate
aicd
Schlossman and Shao
to absorption through the skin, and to removal by perspiration, skin oil, or water. It
must be odorless and nonstaining to the skin or clothing (55). Consumer research
studies indicate that a sunscreen formulation should rub in easily, leave the skin
nonsticky, and above all should be invisible on the skin after application (1).
Emulsifiers and Additives

Novel emulsifiers, dispersants, thickeners, and film formers have enabled sun-
screen formulators to create more elegant formulators, improve emulsion stab-
ility, and boost SPF. Shin-Etsu, a leading supplier of silicone fluids in Japan,
has introduced new silicone compunds for surface treatments and new surfactants
that have contributed to the marketing of fluid water-in-silicone emulsions with
good spreading that may contain pigment loadings over 30% (56,57).
The SPF of sunscreen products containing micronized titanium dioxide can
be increased with the addition of beeswax (58). Nearn et al. described an O/W
sunscreen composition containing 0.5% to about 5% by weight of microfine tita-
nium dioxide having a particle size less than 100 nm and containing a dispersing
agent in an amount sufficient to stabilize the emulsion, comprising a long chain
saturated primary alcohol having an average of from about 25 to about 45 carbon
atoms in the long chain, ethoxylated or unethoxylated (59). L’Oreal described a
storage-stable, ultrafine O/W emulsion prepared by phase inversion containing
an inorganic nano pigment, the oily phase of said emulsion ranging from 100
to 1000 nm (60,61). Nicoll et al. patented a sunscreen emulsion containing a
mixture of hydrophilic and hydrophobic titanium dioxides with an average par-
ticle size ,100 nm and comprising a silicone surfactant (62). Dahms patented
O/W and W/O emulsions consisting of low levels of emulsifiers or low HLB
emulsifiers (,6), in combination with aqueous or oily dispersions of metallic
oxides with dispersing aids (63 –65).
According to E.M. Merck, the guidelines that should be observed in formu-
lating with Eusolexw grades of micronized titanium dioxide are as follows (66):
. Use nonionic (polymeric emulsifiers)
. Use nonpolar or polar solvents
. Use polar emollients in the presence of organic UV filters
. Use best pH.
Determining Suitable Levels of Actives

The active amount of inorganic sunscreens in a formula is close to 20% in Japan
(as reported in a market survey by Sakai during the late 1990s) and is estimated to
be 5% in the USA and in Europe. Climate, industry, consumer preferences, and
regulations are the major reasons for these differences. In Japan, the MHW only
recently limited the maximum SPF claim to 50þ, and restricts the amount of orga-
nic sunscreen at 20%. Asian consumers are more tolerant of skin whitening and, in
some instances, some whitening is preferred. In addition, Japanese formulations
may contain shaker balls in the package to help redisperse the particles before
application to the skin.
Foundations and Daily UV Lotions

The addition of micronized titanium dioxide to liquid foundations to obtain SPF
15 and higher is common. Typically, a 15 nm micronized titanium dioxide is
combined together with pigmentary titanium dioxide to balance coverage and
protection. Iron oxides, while not approved as an active inorganic sunscreen,
will boost the SPF of a make-up formula by approximately 0.5 SPF units per
weight. Broad-spectrum protection is more readily obtained in a foundation
where coverage and color are permitted than a skin care product, because pig-
mentary titanium dioxide and iron oxides both attenuate UV-A. Zinc oxide is
sometimes added to boost UV-A. Companies also formulate with a medium-
sized micronized titanium dioxide pigment between 20 and 35 nm, because
they will provide more UV-A and the amount of whitening is tolerable in their
formulation. Schlossman compared five marketed foundations labeled with
SPF 10 – 20 and found they all had critical wavelengths over 380 nm (67). It is
difficult to make foundations for all skin types that will not be ashy looking.
Kemira’s M262 and Tayca’s MT-500H and MT-500T are promoted for
their UV-A protection and have been found by the authors to have good light
stability and low reactivity. Kobo has formulated an SPF 44 water-in-silicone
foundation (with 13% active titanium dioxide) with a silicone based dispersion
of M262 (47). Both titanium dioxide and zinc oxide have been used by cosmetic
firms like Estee Lauder, P&G, and L’Oreal to offer daily UV protection in skin
care products.
Formulating with Zinc Oxide

The chemical property of zinc oxide needs to be taken into consideration
especially when an untreated zinc oxide is used in the aqueous phase. Even
when the zinc oxide is used in the nonaqueous phase, the zinc cation can bleed
into an aqueous phase over time and impair the long-term stability. A common
caution in formulating a ZnO-containing product is to avoid or to minimize the
use of anionic emulsifier or thickener such as carbomers. Combinations of zinc
oxide and titanium dioxide are more likely to be W/O formulations, because
of their different isoelectric points. Coating micronized titanium dioxide and
zinc oxide with silica or silicates may stabilize them sufficiently to be formulated
together in water. Showa Denka and Sakai manufacture such kinds of treatments
in Japan. Applications are limited outside of Japan, however, because the selling
prices of these ingredients are very high. SunSmart successfully patented and
marketed in the USA a sunblock with micronized zinc oxide said particles
having an average particle diameter ,0.2 mm and containing ,20 ppm lead,
,3 ppm arsenic, ,15 ppm cadmium, and ,1 ppm mercury (68).
Obtaining Broad-Spectrum Protection

Kemira has studied formulations with UV-Titan M262 combined with zinc oxide
or methoxy dibenzoyl methane. The UV-A protection provided by UV-Titan can
be improved to maximum protection, four stars ( ), by combining UV-Titan
M262 with zinc oxide or low levels of avobenzone (33), as shown in Table 14.19.
It is claimed in JP 60-231607 that an antisuntan cosmetic containing a
combination of 1 –30 wt% of ultrafine zinc oxide (average particle size of
10 –60 nm), a UV light absorber (a derivative of benzophenone, benzoic acid,
salicylic acid, or cinnamic acid, etc.) and a UV light scattering agent (titanium
dioxide, kaolin, or calcium carbonate) can be formulated to shield completely
the UV light (69).
Tanner et al. patented a novel sunscreen composition containing ,5% of
micronized titanium dioxide or zinc oxide in combination with avobenzone
and a stabilizing organic filter to achieve a broad spectrum protection with
good transparency (70).
SunSmart patented, in the USA, a physical sunscreen with micronized zinc
oxide having an average particle diameter ,0.2 mm and containing ,20 ppm
lead, ,3 ppm arsenic, ,5 ppm cadmium, and ,1 ppm mercury (68). They suc-
cessfully market in the USA their Z-Cotew(Z-Cote at the time of this writing is a
registered trademark of the BASF Corporation). A sunscreen with a UV-A/UV-B
ratio over 0.8 can be formulated using Z-Cote, because it is effective at scattering
long-wavelength UV-A light. Notwithstanding, there are scientists in the USA
who prefer to formulate with zinc oxides of smaller particle size because of
their superior transparency and higher UV absorption.
Cole et al. claimed a synergistic combination of titanium dioxide having a
particle size ,35 mm and zinc oxide having a particle size ,50 mm; the said
titanium dioxide and zinc oxide being present in a weight ratio of from about
1 : 25 to 10 : 1 and the total of said titanium dioxide and zinc oxide comprising
from about 4.0% to about 25% of the total composition to protect the skin
from the harmful effects of sunlight (71). Researchers at Boots described a
sunscreen composition containing a blend of 15 nm titanium dioxide between
Table 14.19 SPF Value and UV-A/UV-B Ratio Measured

for W/O Emulsions
SPF UV-A/UV-B
UV filter(s) in vitro ratio
5% M262 16 0.68
5% ZnO 4 0.85
5% M262 þ 5% ZnO 22 0.82
3% M262 8 0.67
0.5% BMDBM 1 UV-A only
3% M262 þ 0.5% BMDBM 8 0.80
10 –70% and 30– 90% of another grade of titanium dioxide with a primary
particle size of between 30 and 50 nm. It is substantially transparent on skin
and has a UV-A/UV-B ratio in the range of 0.25– 0.60 (72).
Approximately 3.5% Eusolexw T-2000 is claimed in formulation to be suf-
ficient to meet the Australian UV-A standard requirements (66).
Sample Formulations
W/O Waterproof Sunscreen Formula SPF 30þ
Phase A
Cetyl PEG/PPG-10/1 dimethicone (and) polyglyceryl-4-isostearate 5.00%
(and) hexyl laurate (Abil WE 09/Goldschmitd)
Isononyl isononanoate (Wickenol 151/Alzo) 6.00%
Cyclomethicone (DC 345 Fluid/Dow) 7.50%
Cetyl dimethicone (Abil Wax 9801/Goldschmitd) 3.00%
Methyl glucose sesqustearate (Glucate SS/Amerchol) 0.50%
Dioctyl malate (Ceraphyl 45/ISP Van Dyk) 2.00%
Phase B
Micronized titanium dioxide (and) stearic acid (and) aluminum 21.33%
hydroxide (and) isononyl isononanoate (IN60TS/Kobo)
Phase C
Deionized water 51.07%
Polycarbamyl polyglycol ester (Aculyn 44 C1/Rohm & Haas) 2.50%
Phase D
Sodium chloride 0.50%
Phenoxyethanol (and) methylparaben (and) ethylparaben (and) 0.60%
propylparaben (and) butylparaben (Uniphen P-23/Induchem)
Manufacturing procedure
Premix Aculyn 44 into water under propeller at ambient
temperate
When Aculyn 44 is fully dissolved, add premixed phase D to
phase C
Heat phase A to 758C and cool to 658c
Add phase B to phase A under homogenization
Return to propeller mixing and add premixed Phases C and D to
phases A and B.
O/W Sunscreen Lotion SPF 27
Phase A
Demineralized water 58.05%
Glyceryl methacrylate (Lubrajel MS/Barnet) 1.00%
Tetrasodium EDTA (Versen 220/Dow Chemicals) 0.10%
Phase B
Butyl octyl salicylate (Hallbright BHB/C.P. Hall) 6.00%
Monoglyceryl citrate (Dadex MGC/Eastman Kodak) 0.50%
Avobenzone (Parsol 1789/Givaudan-Roure) 1.50%
PVP hexadecane copolymer (AntaronV216/ISP) 2.00%
Cyclomethicone (SF1202/GE Silicones) 3.00%
Phenyl trimethicone (SF1550/GE Silicones) 1.00%
Shea butter (Cetiol SB-45/Henkel) 1.00%
Hydrogenated lecithin (Lecithin W/D/Henkel/CLR) 0.25%
Cetyl alcohol (and) glyceryl stearate (and) PEG-75 stearate
(and) ceteth 20 (and) steareth-12 (Emulsynth Delta/Gattefosse) 4.00%
Methyl glucose sesquistearate (Glucate SS/Amerchol) 1.00%
Homosalate and titanium dioxide (and) aluminum hydroxide 18.00%
(and) stearic acid (HS40S4/Kobo)
Phase C
Urethane/C1-20 Alkyl PEG Copolymer (Acculyn 44/Rohm & 2.00%
Haas)
Phase D
Diazolidinyl urea (and) iodopropynyl butyl carbamate (Germall 0.60%
Plus Liquid/ISP)
Mix Phase 1 in the order listed and heat to 758C
Heat items of phase B till 788C, mix till all dissolved
Then add HS40S4, homogenize till smooth and homogeneous
Heat to 75– 788C if need be after homogenization
Add phase B to phase A, continue mixing for 10 min,
then add phase C
Switch to homogenizer and homogenize for 15 min
Switch to sweep mixing and cool to 408C, then add phase D
Continue mixing while cooling to 308C.
Sunscreen Cream Gel
Phase A
Carbomer (Carbopol 980 2% solution/Noveon) 20.00%
Glycereth-26 (Liponic EG-1/Lipo) 3.00%
Butylene glycol 0.25%
Disodium EDTA 0.10%
Phase B
C12-15 alkyl benzoate (and) titanium dioxide (and) alumina 10.00%
(and) polyhydroxystearic acid (and) ITT/TCS crosspolymer
(TNP55VTTS/Kobo)
Caprylic/capric triglyceride (Liponate GC-K/Lipo) 5.00%

Benzophenone-3 (Uvinul M 40/BASF) 5.00%
Ethylhexyl salicylate (Escalol 587/ISP Van Dyk) 5.00%
Cetearyl alcohol (and) ceteareth-20 (Lipowax D/Lipo) 2.50%
Glyceryl stearate (and) PEG-100 stearate 1.75%
(Arlacel 165/Uniqema)
Stearyl alcohol 1.00%
Sillicone (DC 200-100/Dow Corning) 1.00%
Ethylhexyl methoxycinnamate (Uvinul MC 80/BASF) 7.50%
Phase C
Triethanolamine 99% (q.s. to pH 6.5 –7) 1.80%
Phase D
Ascorbyl glucoside (AA2G/Siberhegner) 2.00%
Phase E
Germaben II/ASP Sutton 1.00%
Mix phase A ingredients and heat to 658C
Mix phase B ingredients and heat to 658C until the titanium
dioxide is dispersed
Add phase B to phase A
Add phase C and cool to 458C
Add phases D and E, cool with mixing to room temperature.
Sprayable O/W Sunscreen SPF 15þ

Phase A
Butylene glycol 3.00%
Phenoxyethanol (and) methylparaben (and) ethylparaben (and) 1.00%
butylparaben (and) propylparaben (and) isobutylparaben
(Phenonip/NIPA Labs)
Phase B
C14 –22 alcohols (and) C12 –20 alkyl glucoside 4.50%
(Montanov L/SEPPIC)
C12 –15 alkyl benzoate (and) zinc oxide (and) 19.00%
polyhydroxystearic acid (and) triethoxy caprylsilane
(TNP50ZSI/Kobo)
Squalane (Phytolane LS/DD Chem Co) 1.00%
Tridecyl stearate (Liponate TDS/Lipo) 1.00%
Tocopheryl acetate (Vitamin E Acetate/BASF) 0.20%
Phase C
Acrylamides copolymer (and) mineral oil (and)
C13 –14 Isoparafin
(and) polysorbate 85 (Sepigel 501/SEPPIC) 0.50%
In main kettle, combine phase A ingredients and heat to 78 –808C with
moderate speed propeller mixing
Heat phase B to 808C and mix until uniform
Add phase B to phase A with medium speed propeller mixing; mix for
15 min or until emulsification is complete
Begin cooling batch
At 408C add phase C to batch and mix well
Cool to 258C.
REGULATIONS, CLAIMS, TOXICITY, AND TESTING

The landscape for new formulations containing micronized pigments has been
shaped as much by government regulations, testing, and labeling standards
(e.g., there are different specifications for purity between Japan and the USA),
and by toxicological and ecological concerns. As was mentioned earlier, the
FDA does not allow titanium dioxide or zinc oxide to be used with avobenzone.
Titanium dioxide labeled as attenuation grade for sunscreens must meet the
requirements of USP 24 for purity. The starting pigment is required to be
99.0% TiO2 calculated on the ignited basis. The specification for loss on ignition
is 13% after drying. Attenuation grade material may contain suitable coatings,
stabilizers, and treatments to assist formulators. All tests and assays are con-
ducted on uncoated, untreated material (73).
In Europe, the SCCNFP (Scientific Committee for Cosmetic Products and
Non-food Products) adopted a favorable opinion on the safety of micronized tita-
nium dioxide for use in cosmetic products at a maximum concentration of 25%.
Micronized titanium dioxide is required to pass the purity requirements of E171
laid down in the EEC directive concerning foodstuffs and coloring matters (74).
Acceptance of zinc oxide as an active sunscreen agent in the near future,
however, is uncertain, because of concerns with the mutagenicity and genotoxi-
city of zinc and its salts (6).
Recently, titanium dioxide has been selected for examination under
Proposition 65 in California as a potential carcinogen (see www.OESHA.ca.gov/
prop65/CRNR/notices/statelisting/proritizationnotice). There are other concerns
with zinc oxide manufacturers (ZOPA) over their waste streams causing aquatic
toxicity.
Inorganic UV filters are nonpenetrating making them suitable for use on
children and others with sensible skin. Lansdown and Taylor studied the percu-
taneous absorption of zinc oxide and titanium dioxide on rabbit skin (75).
SUMMARY
Inorganic UV filters have been marketed for over 25 years. The UV attenuation
performance of inorganic sunscreens in a finished product is influenced by their
particle size. Advancements in particle technology have enabled the production
of ultrafine particles and there are more specialty grades to choose from. Notwith-
standing, scientists continue to search for the optimum particle size that can com-
pletely shield all UV-A/UV-B and be transparent on all skin types. It is not as
simple as formulating with the smallest particle in all applications because,
while very fine particles offer unprecedented transparency, the maximum attenu-
ation by titanium dioxide shifts to UV-C, and UV-A attenuation by zinc oxide
becomes weaker (or we can say their UV-A/UV-B attenuation is likely to be
worse). The authors have recently tested in vivo a formulation containing
15 nm titanium dioxide and 60 nm zinc oxide. The SPF and PFA data showed
that this was a promising combination to obtain a high SPF/PFA score in formu-
lations containing solely inorganic UV filters.
Multiple surface treatments for particles are responsible for improving their
physical and chemical stability and promoting their wetting and stability in dis-
persions. New surfactants, dispersants and dispersions are all contributing to
improvements in efficacy.
The advances in surface treatment have enabled the development of par-
ticles with outstanding physical and chemical stabilty, and the restrictions on
their combination with avobenzone need to be eliminated. It would also make
sense to reexamine the USP specifications, because it is well known that the inor-
ganic coating gives the particle its physical stability. Conceptually, it makes
sense to decrease the purity requirements from 99% to a lower amount for attenu-
ation pigments. This would allow for a heavier alumina coating in the crystal, and
maybe there would be more grades of micronized titanium dixoide produced by
the chloride process.
The outlook for physical sunscreens remains promising, as evidenced by
the furious pace that new raw materials have become available to the personal
care industry. Competition between traditional suppliers and startup nanotechnol-
ogy companies will ensure a continuation of new and promising inorganic UV
filters for years to come.
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15
Inorganic Particulate Ultraviolet
Filters in Commerce
Nadim A. Shaath
Ismail I. Walele
Finetex, Elmwood Park, New Jersey, USA
Introduction 282
Inorganic Particulates: Background 282
Formulating with Zinc Oxide and Titanium Dioxide 283
Inorganic Particulate Suppliers in the USA 284
US Consumer Products with Inorganic Particulates 286
Children/Baby Product 286
Formulations with Combination of Organic/Inorganic UV Filters 286
Formulations with Inorganic Particulates “Only” 287
Daily Wear Long-Term Protective Products 287
Formulations with Inorganic Particulates “Only” 288
Recreational Products 288
Inorganic Particulates “Only” Products 289
Conclusions 289
References 290
281
282 Shaath and Walele
INTRODUCTION
Responding to the recent medical advances and expanded demands of both the
industry and the consumers ultimately using these products, the need for new
and improved sunscreen agents is well documented (1). The more than 1.5
million new cases of skin cancer reported each year in the USA alone, along
with the new emerging evidence of the damaging effects of UV-A rays and the
depletion of the ozone layer through the use of chlorofluorohydrocarbons, as
well as the demographic considerations and the popularity of modern leisure
outdoor lifestyles, are but a few of the reasons for the need for photoprotection
(2). The production of new, safe, more selective, specific, and effective ultraviolet
(UV) filters is paramount.
The heart of any sunscreen cosmetic formulation is the UV active ingredi-
ent. Formulations with organic UV absorbers and the new organic particulates are
dealt with in other chapters in this manuscript (3,4). Inorganic particulates
have witnessed a major boost in their use in cosmetic preparations especially
in sunscreen products for children, in products for sensitive areas of the body,
such as lips and eyes, and other products for both daily wear and recreational
protection.
INORGANIC PARTICULATES: BACKGROUND

Inorganic particulates, zinc oxide and titanium dioxide, have become an indis-
pensable tool in the UV protection of cosmetic and toiletry preparations (5).
Titanium dioxide has been on the FDA’s monograph since the introduction
of the Advance Notice of Proposed Rulemaking (ANPRM) in 1978 (6). The
approved level of use of 25% is still valid today, however, with major modifi-
cations in the physical and chemical properties of the particulates. No longer
are the pigment-like ingredients used, rather micronized particulates that are
coated with hydrophilic and/or hydrophobic ingredients and predispersed in a
variety of organic emulsions are available today.
Zinc oxide has only been recently approved for use as a Category I ingre-
dient (October 1998) despite the fact that millions of pounds have been used
in cosmetic applications annually. Microfine zinc oxide particulates (below
50 nm) that are coated and predispersed have also been introduced to the
cosmetic industry and have received wide acceptance as UV-A and broad-
spectrum UV protectors.
There are many reasons for this increase in the use of the inorganic parti-
culates, chief of which is their UV-A protection as well as their chemical and
photochemical stability in cosmetic applications. They absorb, scatter, and
repel a broad range of UV radiation. They have been perceived as being more
natural and benign than the organic UV filters despite the fact that they are not
used as the raw mineral itself, rather they now contain a wide array of coatings,
Inorganic Particulate Ultraviolet Filters in Commerce 283
additives, predispersants, and dispersion enhancers. Their attenuation of the sun

protection factor (SPF) of cosmetic formulations has been exceptional, covering
both the UV-A and the UV-B spectrum when used in combinations. The dis-
advantages of using the inorganic particulates include the higher cost when
compared to the current traditional organic UV absorbers approved in the USA
and more importantly, the difficulty in formulations. Due to the variations in
particle size, particle distribution, coatings, dispersants, and other additives in
the inorganic particulates, the cosmetic chemist must be a real expert to decipher
all these variations in form and activity. The inorganic particulates may be either
hydrophilic or hydrophobic and thus the appropriate phase, aqueous or oil, to add
to the particulates needs to be experimented with for optimal use. When the par-
ticle size of the particulates is not sufficiently small (.100 nm), the so-called
“whitening” phenomenon upon application is observed leading to undesirable
esthetic and efficacy considerations.
FORMULATING WITH ZINC OXIDE AND TITANIUM DIOXIDE

Hewitt, in a recent article (7), has listed three fundamental requirements for
achieving optimum efficacy when formulating with inorganic particulates,
namely:
1. Select material with the optimum particles size and particle size
distribution. As mentioned earlier, a particle size .100 nm or there-
abouts may cause skin whitening and render reemulsification after
application on the skin difficult. The supplier should provide this infor-
mation and the cosmetic chemist should run a UV/visible spectrum
and verify that no problem occurs in the formulation. It should also
be noted that in microfine titanium dioxide ingredients in particular,
a “graying” of the formulation when the particle size is well below
50 nm might be observed.
2. Insure that the particles are dispersed homogeneously throughout the
emulsion. This of course depends primarily on the type of predisper-
sion and coating of the inorganic particulate (hydrophilic or hydro-
phobic), the type of emulsion (o/w or w/o) and the many other
ingredients present in the formulation.
3. Insure an even distribution of the particles on the skin when the cos-
metic product is applied to the skin. The reader is referred to the excel-
lent discussions on rheology found in the chapters of Hewitt (8) and
also that of Dahms (9).
The cosmetic chemist should pay particular attention to the pH of the for-
mulation, especially for those involving zinc oxide. At pH values ,6, the solu-
bility of zinc oxide increases and migration from the oil phase to the water phase
is observed. Another consideration is the adequate dispersion of the inorganic
particulates into the formulation. If they are not predispersed with organic
emollients, the proper addition of sufficient quantities of emollients may be

required. Finally, care should be taken to insure that these high specific gravity
particulates remain in the suspension especially after storage and higher tempera-
tures are encountered. Note that carbomers in particular are incompatible with
zinc oxide and should be avoided.
Stability testing of the cosmetic formulation and quality control procedures
for both the inorganic particulates and the finished product should be imp-
lemented. The reader is referred to the many chapters dealing with these two
issues, in particular Klein and Palefski (10) for stability and the chapters
by Kalinoski (11), and Shaath and Flores for quality control and analytical
procedures (12).
Finally, the formulator of cosmetic products utilizing inorganic particu-
lates should be aware of the intellectual property and the many patents
issued that limit and restrict the use of a particular ingredient in their cosmetic
formulation. Also, regulatory issues should be monitored closely. For example,
the inorganic particulates are restricted in the USA when used in combination
with avobenzone. Also zinc oxide’s use in Europe is not yet approved. Both
issues are currently under review by the FDA and COLIPA, respectively.
INORGANIC PARTICULATE SUPPLIERS IN THE USA

The number of suppliers of inorganic particulates to the cosmetic industry has
quadrupled in the last 10 years. This is in response to the dramatic increase in
the use of inorganic filters in particular and the increase in the number of products
on the market that contain UV filters in general.
Micronized inorganic particulates (titanium dioxide and zinc oxide) are
commercially sold in several forms:
1. In powder form with or without surface treatments
2. In predispersions.
Each variety may be supplied in different particle sizes and particle size distri-
butions. A partial listing of current suppliers is as follows.
Suppliers of inorganic particulates in powder form with or without surface
treatments:
1. Advanced Nano Technologies (ZnO) 10. Rhodia (TiO2)

2. BASF Z-Cote (ZnO) 11. Sachtleben (TiO2)
3. Degussa (TiO2) 12. Sakai LP (ZnO)
4. Elementis (ZnO) 13. Showa Danka (TiO2)
5. EMD Eusolex (TiO2) 14. Sumitomo (ZnO)
6. Ishihara ISK TTO (TiO2) 15. Symrise (ZnO)
7. Kemira (TiO2) 16. Tayca MT/MZ (TiO2 and ZnO)
8. Nanophase (ZnO) 17. Titan Kogyo ST (TiO2)
9. Particle Sciences T-Cote (TiO2) 18. Uniquema (TiO2 and ZnO)
Suppliers of predispersions of inorganic particulates
1. BASF Z-Cote HP-1 9. Kemira (TiO2)

2. Collaborative Labs TioSperse 10. Kobo (ZnO and TiO2)
and Z-Sperse
3. Degussa Tego Sun (TiO2) 11. Rhodia Mirasun (TiO2)
4. EMD Eusolex (TiO2) 12. Sachtleben (TiO2)
5. Finetex (Natrlfine ZnO and TiO2) 13. Sakai (ZnO)
6. Granula (ZnO and TiO2) 14. Showa Denka (TiO2 and ZnO)
7. Ishihara (TiO2) 15. Tri-K Industries
8. ISP Escalol (ZnO and TiO2) 16. Uniquema Tioveil TiO2 and Solaveil ZnO
The coatings and surface treatments that have been used in TiO2 and ZnO
include:
1. Alginic acid 13. PEG-10

2. Alumina 14. Polyglyceryl-6-polyricinoleate
3. Aluminum hydroxide 15. Polyhydroxystearic acid
4. Aluminum laurate 16. Silica
5. Aluminum stearate 17. Silicone
6. Dimethicone 18. Simethicone
7. Ferric hydroxide 19. Sodium metaphosphate
8. Ferric stearate 20. Stearic acid
9. Glycerine 21. Triethoxy capryl silane
10. Isopropyl titanium triisostearate 22. Trimethoxy capryl silane
11. Methicone 23. Zirconia
12. Organopolysiloxane
The emollients that have been used as dispersants in the inorganic particu-
lates include:
1. Apricot kernel oil 15. Hexyl laurate

2. Behenyl benzoate 16. Hydrogenated decene oligomers
3. C12 – C15 alkyl benzoate 17. Isohexadecane
4. Caprylic capric diglyceride 18. Isononyl nonanoate
5. Caprylic capric monoglyceride 19. Isopropyl myristate
6. Caprylic capric triglyceride 20. Isopropyl palmitate
7. Cetearyl alcohol 21. Isostearyl benzoate
8. Cetearyl glucoside 22. Mineral oil
9. Cetyl dimethicone 23. Octinoxate
10. Copolyol 24. Octyl dodecanol
11. Cyclomethicone 25. PEG-40 esters
12. Cyclopenta siloxane 26. Polyglyceryl-4-isostearate
13. Ethyl hexyl hydroxy stearate 27. Stearyl benzoate
benzoate 28. Trioctyl dodecyl citrate
14. Ethyl hexyl palmitate 29. Water
It should be noted that in predispersions, the percentage of active may vary

from 25% to 60%. Request detailed information from your supplier on the par-
ticle size, the particle size distribution, the coatings, surface treatments, disper-
sants, predispersant enhancers, and above all, the percentage of active in their
formulation of the inorganic particulate.
US CONSUMER PRODUCTS WITH INORGANIC PARTICULATES

One of the first daily wear cosmetics with SPF that incorporated only inorganic par-
ticulates was Clinique’s Citiblock Oil Free Daily Face Protector launched in 1991
(13). It had an SPF of 13, claimed both UV-A and UV-B protection, and used only
micronized titanium dioxide. Unfortunately, they claimed that the product did not
contain any “chemical UV filters.” This misnomer had encouraged others to label
their product as having an “All Natural” claim that was unsupported. Titanium
dioxide is a chemical and the current commercial forms undergo a number of
chemical reactions and may include other synthetic chemical coatings or disper-
sants that render all current titanium dioxide UV ingredients not truly “natural.”
Inorganic particulates are incorporated mainly into two types of consumer
products, namely, children/baby sunscreen products and daily wear long-term
protective products, in particular, for individuals with sensitive skin. It should
be noted that both zinc oxide and titanium dioxide particulates are also being
rapidly incorporated into other general recreational sunscreen products.
Following is a review of the types of sunscreen products that include inor-
ganic particulates in their formulations. This review is not intended to serve as an
exhaustive review of all sunscreen products on the market rather it is presented to
illustrate the categories and type of products only. The listings are reported alpha-
betically, not in any order of importance or commercial rankings. The products
have not been analyzed and the information relies totally on the data available
on the internet and the product label.
Children/Baby Product
Formulations with Combination of Organic/Inorganic UV Filters
Schering-Plough’s new sunscreen line Spectra 3 highlights in their advertisement
campaign that their products have three modes of action, a clear reference to the
presence of the inorganic particulate ZnO with other organic UV absorbers,
namely that they scatter, absorb, and reflect the harmful rays of the sun. Products
that have both inorganic particulates and organic UV absorbers combined include:
. Banana Boat (Playtex) Baby Magic Block Spray SPF 48 has 2.14%
TiO2 plus four other organic UV filters.
. Banana Boat Kids (Playtex) SPF 30 has TiO2 plus three other organic
UV filters.
. Coppertone Kids Spectra 3 Block SPF 50 has ZnO and five organic UV
filters.
. Coppertone Water Babies Spectra 3 SPF 50 has ZnO as well.
. Hawaiian Tropic Baby Faces SPF 50 has TiO2 and two other organic
UV filters.
Formulations with Inorganic Particulates “Only”
A number of baby products have recently appeared on the market with only
inorganic particulates. These include:
. California Baby SPF 30þ with micronized TiO2 (fragrance free).
. Mustela Bebe High Protection Lotion SPF 50 with 14.4% TiO2 and 7% ZnO.
. Playschool Baby Blanket SPF 50þ with TiO2 .
. Playschool Baby Blanket SPF 45þ with ZnO.
It should be noted that most micronized forms contain about 50% load of
the inorganic particulate in a dispersant. Thus 5% ZnO or TiO2 reflects the
addition of about 10% of the inorganic particulate predispersion.
Daily Wear Long-Term Protective Products

Synergistic effects have been observed when combining inorganic and organic
UV filters. The reasons given include:
. Increased skin coverage
. Improved spectral coverage
. Increasing the optical path length of the UV light passing through the
sunscreen film (8).
Examples of products with the popular combination of octinoxate for
UV-B protection and ZnO/TiO2 for UV-A protection include:
. California North Titanium SPF 15 and 30 with TiO2 and octinoxate.
. M.D. Forte Total Daily Protector SPF 15 has 5% ZnO and 7.5%
octinoxate.
. Olay (P&G) Provital Day Lotion SPF 15.
. Olay (P&G) Complete All day SPF 15.
. Ti Silc Sheer Waterproof Sunblock SPF 45 contains octinoxate and ZnO.
. Vanicream SPF 35 has 8% Z-Cote HP1 and 7.5% octinoxate.
. Vaseline Removal Protection SPF 15 (Cheeseborough Ponds) has TiO2
and an organic UV absorber.
Examples of other products with multiple organic UV of absorbers and
ZnO/TiO2 include:
. Bristol Myers Squibb SPF 20 has two organic UV absorbers and ZnO.
. Celex-C Sunscreen SPF 30þ with 3% ZnO, 2%TiO2 , octinoxate, and
octisalate.
. Eucerin (Beiersdorf) SPF 30 has four organic UV absorbers and ZnO.
. Guthy-Renker Natural Advantage Moisturizer SPF 15 has TiO2 and
three organic UV absorbers.
. Neova Z-Silc Sunblock SPF 30 contains ZnO with octinoxate and

octisalate.
. Neutrogena Healthy Defense Moisturizer SPF 30 has three organic UV
absorbers and ZnO.
. Purpose One Treatment with SPF 15 has octinoxate, meradimate, and TiO2 .
Several lip balms contain titanium dioxide in combination with other
organic UV absorbers. Examples include Blistex Berry lip with TiO2 and two
other UV absorbers. Chapstick lip balm regular has TiO2 and Padimate-O and
NO-AD lip balm SPF 30 has TiO2 and three other organic UV absorbers.
Formulations with Inorganic Particulates “Only”
Recently, a number of consumer products with inorganic particulates only and
some with significantly high SPF labels have appeared on the US market.
They include:
. Celex-C Sunscreen SPF has 2% TiO2 and 2% ZnO.
. Neostrata Sun Block Lotion SPF 30 has only TiO2 .
. Neutrogena Sun Block Lotion for Sensitive Skin SPF 30 has only TiO2 .
. Peter Thomas Roth SPF 30 with TiO2 and ZnO.
. Skin Ceuticals Physical UV Defence SPF 30 contains 10% TiO2 and
5% ZnO.
Titanium dioxide has been an approved Category I ingredient long before
zinc oxide, hence there are currently many more formulations with it than those
with zinc oxide. This is likely to change in the future since zinc oxide offers better
UV-A protection.
Recreational Products
The use of titanium dioxide particulates in recreational products appeared on the US
market in the 1990s mostly in products with very high SPF products (SPF 30 and
above) due to the ability of these ingredients to substantially boost the SPF. Recently,
zinc oxide has been added to the regimen for SPF boosting and more importantly for
UV-A and broad-spectrum protection claims. Once the UV-A claims and testing
procedures by the FDA are finalized, a surge in the use of zinc oxide will be wit-
nessed. Also, if combinations of the particulates with avobenzone are approved in
the USA, an increase in their use will also be seen. Finally, if COLIPA in Europe
approves zinc oxide as an active ingredient, this will qualify that ingredient to be
used interchangeably in all formulations that are manufactured worldwide.
Examples of the many formulations of recreational products that have an inor-
ganic particulate in combination with an organic UV filter include:
. Coppertone Spectra 3 SPF 30 and 50 contains ZnO and four other
organic UV filters.
. Hawaiian Tropic Ozone SPF 70 has TiO2 and five other organic UV filters.
. Sea & Ski Faces Sensitive Skin Sun Block SPF 50 has ZnO and three
organic UV filters.
. Blue Wizard Australian Sunscreen SPF 30 has 5.7% ZnO plus three
organic UV filters.
. Banana Boat (Playtex) Ultra Sun Block Lotion SPF 15 has 1.2% TiO2
and three other organic UV filters.
Inorganic Particulates “Only” Products
Examples of the formulations that contain only inorganic particulates include:
. Cotz Total Block SPF 58 has both TiO2 and ZnO.
. Glyderm Super Sun Block SPF 25 has 2.5% TiO2 .
. OBAGI Nu-Derm Sun Block 24AM has 9% TiO2 and 6% ZnO.
. Vanicream SPF 15 with 3% T-Cote and 8% Z-Cote.
It should be noted that with few exceptions, the products on the market that
include the inorganic particulates are doing so to increase both the SPF and the
UV-A claims of their formulations. They are rarely added in recreational pro-
ducts only for their perceived safety, photostability, or inertness.
Finally, we have found no “sunless” tanning products that list inorganic par-
ticulates in their label. We have also noted that very few “generic” or drugstore
chain brands such as Eckerd, Rite Aid, Stop and Shop, Target and Wal-Mart
have products with only inorganic particulates in their formulations. This
obviously will rapidly change in the future since most of these brands generally
formulate products that follow the lead of the top-selling brands on the market.
CONCLUSIONS
Inorganic particulates have come of age. The micronized forms of titanium dioxide
and zinc oxide have made a significant contribution to the growth and credibility of
the sunscreen industry. Though they have been used primarily to formulate products
for children and for individuals with sensitive skin, they are rapidly finding their
way into daily wear sunscreen products and traditional recreational products.
With the finalization of all the pending regulatory issues concerning the
inorganic particulates, purveyors of these ingredients will enjoy a wave of unpre-
cedented growth as new and more innovative products appear in the market
place. These issues include the UV-A and broad-spectrum claims that may be
allowed pending the finalization of the standardized UV-A testing procedures.
They also include the adoption of zinc oxide in Europe and the permission by
the FDA to allow for the combinations of inorganic particulates and avobenzone.
The proliferation of the inorganic particulates in the sunscreen industry has
increased the burden on the cosmetic chemist to decipher between the hundreds
of variations of particulates in commerce today. Issues of photo-reactivity needs
to be resolved by the suppliers by providing more conclusive data on their safety
and improving the coatings, dispersants and additives to insure their lack of
photo-reactivity. New simplified and advanced analytical procedures to insure
quality and consistency have to be developed and adopted by the instrumentation,
research and quality control chemists. Standardization of the many variations of
inorganic particulates by the suppliers and by the United States Pharmacopoeia
will only make the task of the cosmetic chemist easier. All of the above consider-
ations bode extremely well in facilitating immensely their incorporation into
more preparations, thereby providing better products to protect the consumer
from the wrath of the harmful UV rays and allow for a major expansion of the
sunscreen industry in the future.
REFERENCES
1. Diffey BL. Dosimetry of ultraviolet radiation. In: Shaath NA, ed. Sunscreens:
2005:827 –841.
2. Nelson C. Photoprotection. In: Shaath NA, ed. Sunscreens: Regulations and Commer-
cial Development. 3rd ed. New York: Marcel Dekker, 2005:19 – 43.
3. Shaath NA. The chemistry of ultraviolet filters. In: Shaath NA, ed. Sunscreens: Regu-
lations and Commercial Development. 3rd ed. New York: Marcel Dekker, 2005:217–238.
4. Herzog B, Hueglin D, Osterwalder U. New sunscreen actives. In: Shaath NA, ed.
Sunscreens: Regulations and Commercial Development. 3rd ed. New York:
5. Schlossman D, Shao Y. Inorganic sunscreens. In: Shaath NA, ed. Sunscreens: Regula-
tions and Commercial Development. 3rd ed. New York: Marcel Dekker, 2005:239–279.
6. Holman MR, Shetty D. The role of FDA in sunscreen regulation. In: Shaath NA, ed.
Dekker, 2005:85 –94.
7. Hewitt JP. Formulating water-resistant TiO2 sunscreens. Cosmet Toilet 1999; 114(a):59–63.
8. Hewitt JP. SPF modulation: optimizing the efficacy of sunscreens. In: Shaath NA, ed.
Dekker, 2005:385 – 412.
9. Dahms, G. The role of surfactants in sunscreen formulations. In: Shaath NA, ed.
Dekker, 2005:413 – 448.
10. Klein K, Palefsky I. Formulating sunscreen products. In: Shaath NA, ed. Sunscreens:
2005:353 –383.
11. Kalinoski HT. Quality control of finished sunscreen products. In: Shaath NA, ed.
Dekker, 2005:719 – 733.
12. Shaath NA, Flores F. Modern analytical techniques in the sunscreen industry.
In: Shaath NA, ed. Sunscreens: Regulations and Commercial Development. 3rd ed.
New York: Marcel Dekker, 2005:751 – 766.
13. Lentini PJ. Daily use sunscreens. In: Shaath NA, ed. Sunscreens: Regulations and
16
New Sunscreen Actives
Bernd Herzog
Ciba Specialty Chemicals Inc., Grenzach-Wyhlen, Germany
Dietmar Hueglin and Uli Osterwalder

Ciba Specialty Chemicals Inc., Basel, Switzerland
Introduction 292
Trends in the Sunscreen Market 292
Objectives—Requirements 293
Efficacy 293
Safety 293
Registration 294
Patent Freedom 294
New Trends in the Development of UV Absorbers for Sunscreens 295
New Developments with Respect to Conventional UV Absorbers 296
New Product Forms 296
Case Study 1: Dispersions of Particulate Organic UV Absorbers 297
Photostability of MBBT 297
Synthesis of New Molecules 300
Case Study 2: BEMT—A New Filter Designed for
Application in Sunscreens 300
Overview of New Sunscreen Actives 302
The Most Important Properties of UV Absorbers for Sunscreens 302
UV-Spectroscopic Performance 302
Solubility 302
Photostability 303
291
292 Herzog, Hueglin, and Osterwalder
Discussion of the New UV Filters for Sunscreens 303

UV-B Filters 303
UV-A Filters 306
UV Broad-Spectrum Filters 309
Improved UV-A Protection with New UV-A and
Broad-Spectrum UV Absorbers 312
Safety of the New UV Absorbers 315
Conclusions 317
References 317
INTRODUCTION
Sunscreens should protect not only against sunburn, which is mainly caused by
UV-B radiation, but also against the damaging effects of the more deeply pene-
trating UV-A radiation (1). This new expectation from consumers and the
medical community has triggered the development of new UV absorbers and
led to the approval of seven new, organic UV absorbers in Europe over the
last decade (2). The US Food and Drug Administration has approved none of
them so far. In this chapter, the new development of UV filters will be presented
and the significant progress over the last few years, mainly in UV-A protection
will be discussed.
Trends in the Sunscreen Market

There are three major product categories that use UV absorbers for skin
protection. The classical sunscreen or so-called “beach product,” the daily skin
care formulation “with sun protection factor” designed to avoid photoaging
such as wrinkles, and the tanning prevention or whitening products that are
very popular in Asia. Besides these three major categories, there are differences
from country to country in terms of formulation, for example, Australians prefer
water-in-oil type formulation for the beach, whereas Europeans prefer oil-
in-water type emulsions in lotion or spray form. Depending on the country and
the region, there is also more or less cost pressure on the established mass
market brands due to tough competition from other brands and the low-cost
private label copies. These developments have to be taken into account in the
design of new sunscreen actives. In spite of the variations in the market, there
are many common factors that allow us to treat the requirements for UV absor-
bers very generally. From an economical point of view, UV absorber manufact-
urers would like to satisfy these criteria and categories with as few ingredients as
possible.
Since sun protection is a health issue, there are controversies regularly

brought up in the media about the safety of the sunscreens and particularly
their actives, the UV absorbers. A recent sunscreen issue is the compliance and
misuse to extend sun exposure excessively (3). The reasonable value of the
sun protection factor (SPF), and if there should be a cap, are also discussed in
this context. Most people do not realize that the actual SPF in use corresponds
only to about one-third of the value as declared on the product (4). In contrast
to the SPF value, which addresses mainly the UV-B radiation, there is still no
common standard for protection against UV-A. Other issues related to UV
absorbers are their skin penetration and sensitization potential (5), and also the
potential for endocrine disrupter activity (6).
Objectives—Requirements
Sunscreen manufacturers have four basic requirements on sunscreen actives,
which all must be fulfilled by the existing and new ingredients before they can
be incorporated in a final product.
Efficacy
Safety
Registration
Patent freedom
Efficacy
An efficient sunscreen active must, first of all, show good absorption at least in
parts in the relevant UV range between 290 and 400 nm. Efficacy also means
that the UV absorber must be easily incorporated in any kind of formulation. If
not, it may become difficult to achieve formulations that are also cosmetically
acceptable. This, in turn, would negatively influence the compliance of the sunsc-
reen user. The second requirement is thus the solubility of an UV absorber in
different emollients relevant to cosmetics. The third major characteristic influen-
cing efficacy is the photostability of the UV absorber, which can be determined
by irradiating a sunscreen sample in the laboratory (7). Unstable sunscreen
actives lose efficacy and may lead to safety concerns upon irradiation.
Furthermore, the UV absorber substance must be compatible with all other
ingredients in a formulation; there should be no discoloration of skin and hair, no
staining of textiles, and no odor. For claims of water resistance, the UV absorber
should be insoluble in water and, last but not least, the UV filter should be
economical in its use.
Safety
Sunscreen actives should have no adverse effect on humans and environment.
Although direct comparison with a new pharmaceutical drug is not appropriate,
the development of a new sunscreen active for global use is highly demanding.
Table 16.1 Typical International Safety Dossier

of a New Sunscreen
Acute oral and dermal toxicity

Dermal, ocular irritation, skin sensitization
Photo-irritation, photo-sensitization
Subchronic oral and topical toxicity
Chronic toxicity
Fertility, early embryonic development
Embryofetal toxicity and peri-/post-natal toxicity
In vitro and in vivo percutaneous absorption
Topical and oral pharmacokinetic and metabolism
In vitro and in vivo genetic toxicity
Carcinogenicity
Photo-carcinogenicity
Safety and efficacy in humans
Source: Ref. (8).
The toxicological studies required for a global registration are listed in

Table 16.1 (8).
Registration
In order to exploit the full economic potential of a UV filter, UV absorber
manufacturers are aiming for global registration. In Europe, South America,
Asia, and Africa, where sunscreens are considered as cosmetics, approval is poss-
ible within 1 –2 years of filing. In Australia, Japan, and the USA, it takes longer.
Only recently was a new procedure (TEA: material time and material extend
application) introduced in the USA. After a minimum of 5 years foreign market-
ing experience in five countries, a new sunscreen active can be registered in an
accelerated procedure (9). In a second step, data on efficacy and safety have to
be submitted. So far, three UV-B filters that are widely used outside the USA
have received the status of “eligibility to enter the Sunscreen Monograph” (10):
. Isoamyl p-methoxycinnamate (IMC), Amiloxate (US drug name)
. 4-Methylbenzylidene camphor (MBC), Enzacamene (US drug name)
. Ethylhexyl triazone (EHT), octyl triazone.
More recent filters as discussed here in this chapter will have to fulfill the 5-year
marketing experience first before they can apply for eligibility considerations.
Patent Freedom
Patenting of sunscreen actives and their applications deserve special attention in
this chapter. Patent freedom means the free use of sunscreen actives by any
sunscreen manufacturer, that is, without any uncertainty about whether any
third party patent rights are infringed by the use of a particular ingredient.
Until about 10 years ago, UV absorber manufacturers protected their inven-

tions by simple substance patents that included the basic applications, for
example, “invention of a novel UV absorber for the incorporation in personal
care formulations for the protection of skin and hair.” The innovative cosmetics
manufacturers would then file their own patents on specific applications and tech-
nologies that they had invented and were using in order to differentiate them-
selves from their competitors. This system allowed both the supplier and the
manufacturer of sunscreens to create new business by protecting their respective
inventions. In the mid-1990s, important cosmetics manufacturers started to patent
not only their specific technologies but also generic combinations of different
ingredients without the intention for use. This “blocking strategy” is aimed to
keep competitors from using new technology that emerged on the market (11).
But this strategy not only limits the potential of the competitors, which is part
of business, but is also detrimental for the suppliers who suddenly see the poten-
tial of their new sunscreen active shrinking due to patent restrictions.
As a consequence, the suppliers had to react and rethink their patenting strat-
egy and the whole innovation process, especially in the realization phase and the
market introduction. Patenting a substance together with its major applications
and sampling customers with new ingredients only under Confidential Disclosure
Agreement is not sufficient anymore. As soon as the identity of a new ingredient
becomes known, “all” applications have to be disclosed in detail and explicitly as
well, for example, combinations of the novel ingredient with other sunscreen
actives and other compounds such as emollients, emulsifiers, or thickeners, other-
wise such a new ingredient faces the threat of being blocked from major
applications.
A recent example is the combination of the two newly approved UV filters,
bis-ethylhexyloxyphenol methoxyphenyltriazine (BEMT) and disodium phenyl
dibenzimidazole tetrasulfonate (DPDT). The combination of these two UV
filters is mutually blocked by the two leading sunscreen manufacturers in
Europe and for everybody else in countries where the patent applications were
filed (12). A strategy to avoid such situations in the future is to publish all
sorts of combinations of ingredients and claims that may ever become relevant
before the identity of the new ingredient becomes publicly known. Institutions
to publish quickly, now exist on the Internet, for example, www.ip.com.
IP.com enables innovative companies to quickly and easily protect their inven-
tions by offering security services for many aspects of the invention process:
from the safeguarding of sensitive information such as R&D lab notebooks, to
the rapid publication and creation of prior art in the form of technical disclosures.
NEW TRENDS IN THE DEVELOPMENT OF UV ABSORBERS

FOR SUNSCREENS
During the last few years, the focus in R&D of several UV filter producers has
been in the development of new UV-A filters because of the necessity to cover
that part of the spectrum and because of the gap in the availability of such filters.
On the other hand, development of new UV-B filters is driven by need to replace
traditional filters mainly because of growing safety concerns, for example, skin
penetration of some of the lower molecular weight filters. Since higher efficacy
in terms of “less chemicals on the skin” is desirable, the class of UV broad-
spectrum filters is emerging, covering the UV-A and UV-B ranges with one
chemical entity.
To date, the two “workhorses” in UV-B and UV-A protection, ethylhexyl
methoxycinnamate (EHMC) and butyl methoxydibenzoylmethane (BMBM),
dominate the ranking of market shares in most countries. Exactly this combi-
nation is incompatible due to mutual amplification of photoinstability. Such
systems can also not be stabilized. As an alternative to organic UV filters, and
for better SPF and UV-A protection, the microfine inorganic pigments TiO2
and ZnO are gaining importance. They account for about 20% of the total
value of sunscreen actives, although a well-accepted cosmetic formulation is
still not easy to achieve.
Three trends to improve efficacy and/or safety of UV filters could be
observed in recent years:
. New developments with respect to conventional UV absorbers
– Stabilizing agents for BMBM
– SPF boosters (use of non-absorbing materials that increase SPF)
. New product forms
– Encapsulation of conventional UV absorbers
– Organic particles
. New Molecules
– Chromophore grafted onto polymer backbone
– Extending or multiplying the chromophore.
New Developments with Respect to Conventional UV Absorbers

As an example, the photostability problem of the widely used UV-A filter BMBM
can be overcome to a certain extent by stabilizing it with other UV filters such as
octocrylene or 4-methylbenzylidene camphor (MBC), or with non-UV-absorbing
compounds such as diethylhexyl-2,6-naphthalate (DEHN) (13).
A new way of boosting the efficacy of current filter systems was suggested
by incorporation of nonabsorbing particles that scatter the UV radiation and
thus lead to a longer pathway through the sunscreen film on the skin (e.g.
Sun-Spheresw) (14).
New Product Forms

The efficacy and safety aspect of UV absorbers has been addressed by reducing
skin penetration via encapsulation of UV absorbers, for example, EHMC in glass
particles (UV Pearlsw) (15). The UV filter is thus kept on the outermost layer of
the skin, reducing the dermal uptake as compared to free UV filters. The UV
Pearls prevent the chemical interaction of EHMC with BMBM, leading to a
significantly improved photostability of the combination.
Another new product form of UV filters is the use of insoluble organic UV
absorbers as pigment-like fine particles, which are held in a stable dispersion.
This concept will be pointed out in more detail in case study 1.
Case Study 1: Dispersions of Particulate Organic UV Absorbers
In their search for a new UV absorber, which has a good solubility in most
cosmetic solvents, researchers at Ciba got a bit frustrated, because the large
molecules they were looking at showed mostly low solubility. One day they
came up with a really creative idea. Making a virtue of necessity, molecules
with weakest solubility were identified in order to create organic UV absorbers
in microfine pigment form as already known from the inorganic filters. This
led to a new class of UV filters (16).
Methylene bis-benzotriazolyl tetramethylbutylphenol (MBBT) is the first
representative of this new class of UV absorber. The commercial form Tinosorbw
M is produced as a 50% aqueous dispersion of colorless organic microfine par-
ticles with a size ,200 nm (d0.5). These small particles are stabilized in their
size by a surfactant (17).
Composition of the dispersion of MBBT (Tinosorbw M):
Organic micropigment (MBBT) 50%
Surfactant (decyl glucoside) 7.5%
Thickener (xanthan gum) 0.2%
Propylene glycol 0.4%
Water to 100%
The structure of MBBT is shown in Fig. 16.1(a). Figure 16.1(b) shows the UV
spectra of MBBT dissolved in dioxane and in aqueous dispersion. Due to scatter-
ing and an intermolecular interaction of the UV chromophores, the spectrum of
the particles is changed in comparison to that in solution. The most striking
difference is that the extinction maximum in the UVA range is shifted from
about 350 to 360 nm (16).
Figure 16.1(c) shows the specific extinction E1,1 at 360 nm as function of
particle size. There is a strong dependence on particle size. It is obvious from
Fig. 16.1(c) that one has to create particles of sizes significantly below 1 mm
in order to obtain a satisfactory efficacy.
Photostability of MBBT
The absorption spectrum of MBBT shows a double band structure (Fig. 16.1b).
The longer wavelength band occurring between 340 and 350 nm in organic
solvents can be attributed to a pp charge transfer (CT) state. This is favored
by the planar orientation enforced by the intramolecular hydrogen bond, made
possible by the hydroxy group in the ortho position. The shorter wavelength
(a)
N OH OH N
N N
N N
(b) 500
400
300
E(1,1)
200 Solution of MBBT in dioxane
100 Dispersion of MBBT particles

with d(0.5) = 160 nm
0
290 310 330 350 370 390
Wavelength / nm
(c) 600
450
E(1,1) at 360 nm
300
150
0
0,01 0,10 1,00 10,00
d(0.5) / µm
Figure 16.1 (a) Structure of MBBT. (b) Spectra of MBBT in solution and dispersion.
(c) E1,1 of micronized MBBT at 360 nm in aqueous dispersion as function of particle
size (16).
band at about 305 nm arises from a local transition within the benzotriazole
moiety (18).
Excitation of the molecule by a photon increases the energy of the mol-
ecule, which switches from the electronic S0 ground state to the first electronic
excited state S1. After excitation different processes are possible (Fig. 16.2a)
(19). Fluorescence can occur, or, after intersystem crossing (ISC, a radiationless
pathway from S1 to T1) phosphorescence can also occur. There may be photo-
reactions ongoing from S1 or T1. Internal conversion (IC), another radiationless
pathway, is a redistribution of the absorbed energy from electronic excitation to
vibrational excitation. In contrast to the electronically excited molecule, the
vibrationally excited one can be deactivated by collisions with surrounding mol-
ecules, dissipating the energy into harmless heat. Therefore, the faster the rate of
internal conversion, the higher the photostability (20).
The energy gap law (19) states that the rate of IC becomes faster as the
energy gap between the ground state and the excited state decreases. This, for
instance, is the case with molecules where an excited state proton transfer
(also called phototautomerism) occurs, such as MBBT (Fig. 16.1a). The state
S01, which is reached after isomerization, has less energy than S1. After IC the
Figure 16.2 (a) Processes that may occur after photon absorption (Jablonski diagram).
(b) Reduction of the energy gap between ground and excited state after excited state intra-
molecular hydrogen transfer.
molecule relaxes from S0 0 0

0 ! S0. Since the ground state S0 of the isomer is ener-
getically higher than the ground state S0 , the deactivated isomer reacts back
immediately to the original ground state S0 (Fig. 16.2b). The whole proton trans-
fer cycle lasts less than 1 ps (10212 s). Since it is much faster than the other pro-
cesses, which may occur after excitation, it is a very efficient deactivation
mechanism.
Benzotriazole chemistry has been utilized for decades in technical appli-
cations. MBBT and drometrizole trisiloxane (DTS) are the first examples used
in sunscreens.
Synthesis of New Molecules

There is a comprehensive patent literature describing many new structures and
substances that can, in principle, be used as sunscreen actives. Most substances
that were once identified will, however, never make it to a commercial
product. A strategy for the development of UV filters, combining theoretical
aspects with practical synthesis within the quinoxaline chemistry has been pub-
lished recently (21), but there is no indication that this class of UV absorbers will
ever be used in sunscreens. In the following case study, the molecular design of
bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT), which is already in
use in Europe and South America, will be demonstrated.
Case Study 2: BEMT—A New Filter Designed for

Application in Sunscreens
In the year 2000, the first UV filter based on hydroxyphenyltriazine (HPT)
technology was added to the positive list of European cosmetic UV filters
(INCI: bis-ethylhexyloxyphenol methoxyphenyl triazine, BEMT; trade name:
TinosorbwS, Ciba Specialty Chemicals). BEMT is a new oil-soluble filter with
strong broad-spectrum protection in the UV-A and UV-B regions. Due to its
outstanding filter efficacy, combined with its inherent photostability and compat-
ibility with all types of cosmetic filters as well as other cosmetic ingredients,
BEMT represents a new generation of cosmetic UV filters. Its structure and
UV-spectrum are depicted in Fig. 16.3 (case D).
The strong absorption of tri-phenyl-triazines shown in the UV-B range (see
Fig. 16.3, case A) has pp character. An np transition may also contribute to
this band (22). As an ortho-hydroxy group is introduced (Fig. 16.3, case B), a
UV-A band emerges, which is due to an intramolecular charge transfer (pp -
CT). With two ortho-hydroxy groups at different phenyl moieties, this UV-A
absorption increases (Fig. 16.3, case D) and with three, even more so
(Fig. 16.3, case C). The optimized broad-spectrum structure was obtained with
case D (Fig. 16.3) referring to BEMT, which shows absorption maxima at 310
and 343 nm with 1max ¼ 46,800 and 51,900 M21 cm21, respectively, measured
in ethanol.
90000 OR2
(A)
75000 Ra
Rb
Rc
N N
(B) N
e/ l/(mol·cm)
60000 ( C) OR1 OR3
(A) Ra = H Rb = H Rc = H
45000 (D) (B) Ra = H Rb = OH Rc = H
(C) Ra = OH Rb = OH Rc = OH
(D) Ra = H Rb = OH Rc = OH
30000
15000
0
260 300 340 380 420
Wavelength / nm
Figure 16.3 HPT structure and spectral performance.
BEMT contains two intramolecular hydrogen bridges that enable an

excited-state intramolecular proton transfer (phototautomerism) after photoexci-
tation. This is followed by internal conversion and rapid energy dissipation,
resulting in inherent photostability. Thus, the presence of ortho-hydroxy
groups not only influences the shape of the absorption spectrum, but also the
photostability. The respective mechanism has been already discussed in detail
in case study 1 with MBBT. The photostabilizing effect of an ortho-hydroxy
group is also discussed by Shaath (23).
The molecular design was directed toward broad-spectrum characteristics
with high molecular extinction in the UV-A and the UV-B ranges, good solubility
in cosmetic solvents, and inherent photostability (Fig. 16.4) (24).
Figure 16.4 Molecular design for absorption efficacy, solubility, and water resistance.
OVERVIEW OF NEW SUNSCREEN ACTIVES

The Most Important Properties of UV Absorbers for Sunscreens
The most important properties of UV absorbers for use in sunscreens are
. the UV-spectroscopic performance
. the solubility in media used in sunscreen formulations
. the photostability.
UV-Spectroscopic Performance
There are two features which are important for the UV-spectroscopic perform-
ance:
1. The wavelength at which the extinction is at maximum, thus defining
whether the substance is a UV-A, a UV-B, or a UV-broad-spectrum
absorber.
2. The extinction efficiency, which is best expressed as the E1,1 value,
referring to the theoretical extinction of a 1% solution of the substance,
measured at an optical pathlength of 1 cm.
The E1,1 value can be calculated using Lambert – Beer’s law with the molar
decadic extinction coefficient 1 and the molar mass M via Eq. (16.1):
10½g=L
E1,1 ¼ 1½L=(mol cm) 1½cm (16:1)
M½g=mol
Thus, the E1,1 value has the meaning of extinction per mass of the UV absorber. A
further important quantity is the mean value of the specific extinction over the
spectral range from 290 to 400 nm, kE1,1lmean, characterizing the area under
the UV extinction curve.
Solubility
Most UV absorbers for use in sunscreens are more or less hydrophobic, which
means that the solubility in oils is better than that in water. In most cases it is
desirable to be able of achieving a concentration of an individual filter in the
order of 5%. Most formulations on the market are o/w emulsions with an oil
content of may be 30%. Thus the solubility of hydrophobic UV absorbers in
oils should be at least 15% in order to achieve the overall concentration of 5%.
With water-soluble filters the solubility should be in a comparable range.
Solubility of the oil-soluble filters is given for a limited number of typical
solvents (isopropylmyristate, caprylic/capric triglyceride, and dimethicone—see
Tables 16.3 –16.5). The solubility was measured by stirring an excess of
the active ingredient in the respective oil for 7 days at 258C. After this time
the nondissolved material was separated by centrifugation and filtration. The
concentration of the UV absorber in the clear saturated solution was determined
via UV spectroscopy.
Photostability
There are two advantages of photostable filter systems:
1. There is no loss of extinction upon irradiation and filter efficiency is
constant. Thus, the amount of filter used for a certain effect is less
compared to an unstable system.
2. There is no need to worry about the toxicology of possible photoproducts.
Photostability was tested according to the method suggested by Berset et al. (25)
and modified by Herzog and Sommer (26).
Discussion of the New UV Filters for Sunscreens

In Table 16.2, the new filters are listed using their names according to the Inter-
national Nomenclature for Cosmetic Ingredients (INCI) and the numbers of the
European Cosmetic and Toiletry and Perfumery Association (COLIPA). Supplier
and trademark are given as well as the maximum extinction coefficient, the wave-
length at the extinction maximum, an information whether the filter goes to the
oil or the aqueous phase, molecular mass, synthesis strategy, and status of
approval. Although photostability data are available, they will not be presented
in detail, since all new filters, with one exception, showed good photostability
Recovery of the parent substance [2% in formulation, applied on rough quartz
substrates as described in Refs. (25,26)] after irradiation with 10 minimal
erythemal doses (MED) was .90%.
UV-B Filters
Ethylhexyl triazone (EHT) (27): With EHT, the chromophore of para-
amino benzoic acid (PABA) was trebled by linking it to a triazine ring. Doubling
or trebling a chromophore is a strategy to optimize the specific extinction E1,1 and
to create filters with higher molecular mass (.500 Da). The chemical name of
EHT is 2,4,6-trinanilin-( p-carbo-20 -ethyl-10 -oxi)-1,3,5-triazine. The structure
and the UV spectrum (in ethanol) of this efficient UV-B absorber are shown in
Fig. 16.5.
The solubility of EHT is listed for three typical emollients in Table 16.3.
Although its solubility is limited, EHT can be incorporated in sunscreen formu-
lations in substantial amounts. The low solubility can be understood as a conse-
quence of the high symmetry of the molecule. In terms of synthetic feasibility the
symmetric structure is of advantage.
Dioctyl butamido triazone (DBT) (28): DBT can be regarded as an

improved version of EHT. The chromophore system is nearly the same, but con-
sidering the side groups the molecule is no longer symmetric and the solubility is
thus much increased in comparison to EHT (Table 16.3).
Table 16.2 Overview of New Actives for Sunscreens (Not Yet Approved in the USA) 304
Sunscreen Active COLIPA #, Trademark Ext. coeff. Spectrum max (nm) Mol. Mass (Da) Approval
Type INCI name (supplier) (mol21 cm21) (O/W soluble) (synthesis strategy) (status)
UV-B S69 EHT Ethylhexyl Triazone Uvinul T150 119,500 314 (oil) 823 Europe
(BASF) (triple chromophore) USA (TEAa)
S78 DBT Dioctyl Butamido Triazone Uvasorb HEB 111,700 312 (oil) 766 Europe
(3V Sigma) (triple chromophore)
S74 BMP Benzylidene Malonate Parsol SLX 108,000 312 (oil) 6000 Europe
Polysiloxane (Roche/DSM) (polymer backbone)
UV-A S71 TDSA Terephthalylidene Mexoryl SX 47,100 345 (water) 607 Europe, Japan,
Dicamphor Sulfonic Acid (L’OREAL) (extended chromophore) USA (NDAb)
S 80 DPDT Disodium Phenyl Neo Heliopan AP 52,400 334 (water) 675 Europe
Dibenz-imidazole Tetrasulfonate (Symrise) (extended chromophore)
DHHB Diethylamino Hydroxy- Uvinul A Plus 35,900 354 (oil) 398 Europe
benzoyl Hexyl Benzoate (BASF) (extended chromophore) (in progress)
BDHB (tentative) “Bis diethylamino None 66,200 354 (oil) 679 No application
hydroxybenzoyl benzoate” (Ciba SC) (double chromophore) so far
BBET (tentative) “Bis Uvasorb K2A 105,000 338 (oil) 760 No application
benzoxazoylphenyl (3V Sigma) (double chromophore) so far
ethylhexylimino triazine”
UV-B/ S73 DTS Drometrizole trisiloxane Mexoryl XL 15,900 and 303, 341 (oil) 501 Europe, Japan
UV-A (L’OREAL) 15,500 (extended molecule)
S79 MBBT Methylene bis- Tinosorb M 26,600 and 305, 360 659 Europe, Australia,
benzotriazolyl (Ciba SC) 33,000 (water (double chromophore; USA (TEAa)
tetramethylbutylphenol dispersible) microfine particles)
(Bisoctrizolec)
S81 BEMT Bis-ethylhexyloxyphenol Tinosorb S 46,800 and 310, 343 (oil) 629 Europe,
methoxyphenyltriazine (Ciba SC) 51,900 (extended chromophore) USA (TEAa)
(Bemotrizinolc)
a
TEA: Material Time and Extend Application with foreign marketing data.
b
NDA: New Drug Application.
Herzog, Hueglin, and Osterwalder
c
Generic drug name (United States Adopted Name).
1500
O O
1200
NH
900 N N
E(1 ,1 )
H
N N N
H
O O
600 O O
300
0
290 310 330 350 370 390
Wavelength / nm
Figure 16.5 UV spectrum and structure of ethylhexyl triazone E1,1(314) ¼ 1450,

kE1,1lmean ¼ 420.
The chemical name of DBT is benzoic acid, 4,40 -[[6-[[4-[[1,1-(dimethy-

lethyl)amino]carbonyl]phenyl]amino]1,3,5-triazine-2,4-diyl]diimino]bis-,bis(2-
ethylhexyl) ester. The structure and the UV spectrum (in ethanol) of this efficient
UV-B absorber are shown in Fig. 16.6.
Benzylidene malonate polysiloxane (BMP) (29): BMP is a polymeric

UV absorber with the chromophores in the side chains. The molecular weight
of the molecule is about 6000 Da. There is an improvement of safety since
skin penetration is practically excluded at this molecular size. The polymer
also shows some film-forming properties (30). However, since the fraction of
UV absorbing moieties in the overall mass of the molecule is small, the efficiency
in terms of E1,1 is quite low.
The chemical name of BMP is a-(trimethylsilyl)-v-(trimethyl-silyloxy)
poly[oxy(dimethyl)silylene]-co-[oxy(methyl)(2-{ p-[2,2-bis(ethoxycarbonyl)
vinyl]phenoxy}-1-methyleneethyl)silylene]-co-[oxy(methyl)(2-{ p-[2,2-bis(eth
oxycarbonyl)vinyl]phenoxy}prop-1-enyl)silylene]. The structure and the UV
Table 16.3 Solubility of New UV-B Absorbers in Few Selected Cosmetic Solvents
Isopropyl Caprylic/capric
UV-B absorber myristate triglyceride Dimethicone
Ethylhexyl triazone 2% 6% ,1%

Dioctyl butamido triazone .50% 47% ,1%
Benzylidene malonate polysiloxane .50% .50% 1%
1500
NH
O
1200 NH
N N
H
900 N
H
N N
E(1,1)
O O
O O
600
300
0
290 310 330 350 370 390
Wavelength / nm
Figure 16.6 UV spectrum and structure of diethylhexyl butamido triazine

E1,1(312) ¼ 1460, kE1,1lmean ¼ 380.
spectrum (in ethanol) of this polymeric UV-B absorber are shown in

Fig. 16.7.
The solubility of BMP in three typical emollients is listed in Table 16.3.
500
Si O Si O Si
400 R n
n = approx. 60
R=
92.1 - 92.5% CH3 O
300 O
E(1,1)
approx. 6% O O O
200 O
approx. 1.5% O O O
100
0
290 310 330 350 370 390
Wavelength / nm
Figure 16.7 UV spectrum and structure of benzylidene malonate polysiloxane

E1,1(312) ¼ 180, kE1,1lmean ¼ 67.
UV-A Filters
Terephthalylidene dicamphor sulfonic acid (TDSA) (31): TDSA was
the first development of an organic UV-A filter after BMBM. It is water
soluble, and therefore less efficient in terms of water resistance. The photostability
of TDSA, though still limited (60% recovery after 10 MED), is better than that of
BMBM.
The chemical name of TDSA is 3,30 -(1,4-phenylendimetylene)-bis-(7,7-
dimethyl-2-oxo-bicyclo-[2.2.1]heptane-1-methane sulfonic acid. The structure
and the UV spectrum (in water) are shown in Fig. 16.8. TDSA is captively
used by L’Oreal.
Disodium phenyl dibenzimidazole tetrasulfonate (DPDT)
(32 – 34): Another water-soluble UV-A filter, which in contrast to TDSA is
freely available, is DPDT.
The chemical name of DPDT is 1H-benzimidazole-4,6-disulfonic acid,
2,20 -(1,4-phenylene)bis-, disodium salt. The structure and the UV spectrum (in
water) are shown in Fig. 16.9.
Diethylamino hydroxybenzoyl hexyl benzoate (DHHB)
(35,36): DHHB was launched as a successor of BMBM. The UV-spectral prop-
erties are similar to BMBM, but the photostablility of DHHB, designed on classic
benzophenone chemistry, is superior.
The chemical name of DHHB is 2-(4-diethylamino-2-hydroxybenzoyl)-
benzoic acid hexylester. The structure and the UV spectrum (in ethanol) of this
UV-A absorber are shown in Fig. 16.10. The solubilities of DHHB in three
typical emollients are listed in Table 16.4.
Bis-diethylamino hydroxybenzoyl benzoate (BDHB, tentative INCI
name) (37): This UV-A absorber is made by doubling the chromophore of
DHHB, leading to a molecular weight .500 Da. The solubility of these types
of duplicated benzophenones depends on the characteristics of the bridge
between the chromophores.
1000
O
NaO3S
800 SO3 Na
O
600
E(1,1)
400
200
0
290 310 330 350 370 390
Wavelength / nm
Figure 16.8 UV spectrum and structure of terephthalylidene dicamphor sulfonic acid

E1,1(345) ¼ 775, kE1,1lmean ¼ 400.
1000
H O 3S N N SO 3H
N N
800 H
SO 3Na
H
SO 3Na
600
E (1 ,1 )
400
200
0
290 310 330 350 370 390
Wavelength / nm
Figure 16.9 UV spectrum and structure of disodium phenyl dibenzimidazole tetrasulfonate

E1,1(334) ¼ 775, kE1,1lmean ¼ 367.
The structure and the UV spectrum (in ethanol) of BDHB are shown in
Fig. 16.11.
Bis-benzoxazoylphenyl ethylhexylimino triazine (BBET, tentative

INCI name) (38): The chemical name of BBET is 2,4-bis-(5-1(dimethylpropyl)-
benzoxazo-2-yl-4-phenyl)-imino(-6-(2-ethylhexyl)-imino-1,3,5-triazine. The
structure and the UV spectrum of this UV-A absorber are shown in Fig. 16.12.
1000
O O
OH O
800
N
600
E (1 ,1 )
400
200
0
290 310 330 350 370 390
Wavelength / nm
Figure 16.10 UV spectrum and structure of diethylamino hydroxybenzoyl hexyl-

benzoate E1,1(354) ¼ 900, kE1,1lmean ¼ 359.
Table 16.4 Solubilities of New UV-A Absorbers
UV-A absorber myristate triglyceride Dimethicone
Terephthalylidene dicamphor Water soluble

sulfonic acid
Disodium phenyl dibenzimidazole Water soluble
tetrasulfonate
Diethylamino hydroxybenzoyl 12% 15% 1%
hexyl benzoate
Again, the strategy of doubling a chromophore was employed in this case,

and a high molecular weight has been achieved. Since the triazine ring is
substituted asymmetrically, several synthesis steps are necessary for preparing
this substance. Patents have been filed not only by the inventor 3V Sigma, but
also by the sunscreen manufacturer Beiersdorf, see application patents (39).
1000 O O
OH O O
O
O
N
800 HO
N
600
E (1 ,1 )
400
200
0
290 310 330 350 370 390
Wavelength / nm
Figure 16.11 UV spectrum and structure of bis diethylamino hydroxybenzoyl benzoate

(BDHB) E1,1(354) ¼ 975, kE1,1lmean ¼ 380.
UV Broad-Spectrum Filters
Drometrizole trisiloxane (DTS) (31): DTS is a pioneer in the category
of oil-soluble broad-spectrum filters. The siloxane rest gives rise to good oil solu-
bility and a high molecular weight (.500 Da), but at the cost of a lower specific
extinction (E1,1).
1500
1200
E(1,1)
900
600 O
O NH
300 N
N
N
N
N
N
H H
0
290 310 330 350 370 390
Wavelength / nm
Figure 16.12 Structure and UV spectrum of bis benzoxazolylphenyl ethylhexylamino

triazine (BBET) E1,1(338) ¼ 1405, kE1,1lmean ¼ 626.
The chemical name of DTS is 2-(2H-benzotriazol-2-yl)-4-methyl-6-[2-

methyl-3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]disiloxanyl]propyl]-phenol.
The structure and the UV spectrum (in ethanol) of this UV broad-spectrum
absorber are shown in Fig. 16.13.
The solubilities of DTS in three typical emollients are listed in Table 16.5.
DTS is captively used by L’Oreal.
500
Si
400 N OH O
N Si
N
O
300
E(1,1)
Si
200
100
0
290 310 330 350 370 390
Wavelength / nm
Figure 16.13 UV spectrum and structure of drometrizole trisiloxane E1,1(303) ¼ 309,

E1,1(341) ¼ 317, kE1,1lmean ¼ 200.
Table 16.5 Solubilities of New UV Broad-Spectrum Absorbers
UV broad-spectrum absorber myristate triglyceride Dimethicone
Drometrizole trisiloxane .50% .50% 6%

Methylene bis-benzotriazolyl Water dispersable
Bis-ethylhexyloxyphenol 6% 5% ,1%
methoxyphenyltriazine
Methylene bis-benzotriazolyl tetramethylbutylphenol (MBBT,

Bisoctrizole) (40 – 42): MBBT is the organic UV filter that comes as microfine
organic particles (see case study 1).
The chemical name of MBBT is 2,20 -methylen-bis-[6-(2H-benzotriazol-2-
yl)-4-(1,1,3,3-tetramethylbutyl)]-phenol. The structure and the UV spectrum
(dispersion in water) of this UV broad-spectrum absorber are shown in
Fig. 16.14.
Bis-ethylhexyloxyphenol methoxyphenyltriazine (BEMT, Bemotrizinol)

(40,41,43): BEMT was specially designed as a broad-spectrum UV filter and up
to now it is the most effective representative of this category.
The chemical name of BEMT is 2,4-bis-{[4-(2-ethyl-hexyloxy)-2-
hydroxy]-phenyl}-6-(4-methoxyphenyl)-1,3,5-triazine. The structure and the
500
400
300
E(1,1)
N OH OH N
200 N
N N
N
100
0
209 310 330 350 370 390
Wavelength / nm
Figure 16.14 UV spectrum and structure of methylene bis-benzotriazolyl tetramethyl-
butylphenol E1,1(305) ¼ 404, E1,1(360) ¼ 495, kE1,1lmean ¼ 373.
1000
800
600
E(1,1)
O CH3
400
OH N N OH
N
200 O O
0
290 310 330 350 370 390
Wavelength / nm
Figure 16.15 UV spectrum and structure of bis-ethylhexyloxyphenol methoxyphenyl-

triazine E1,1(310) ¼ 745, E1,1(343) ¼ 820, kE1,1lmean ¼ 529.
UV spectrum (in ethanol) of this UV broad-spectrum absorber are shown in

Fig. 16.15. The solubility of BEMT in three typical emollients is listed in
Table 16.5.
IMPROVED UV-A PROTECTION WITH NEW UV-A AND

BROAD-SPECTRUM UV ABSORBERS
In countries where the new UV filters are approved, there are more possibilities
than ever before to achieve good coverage of the UV-A region. The question as to
what this exactly means in terms of actual protection of the sunscreen user still
remains. There are several in vivo and in vitro methods to assess UV-A protec-
tion. Except for Japan where an in vivo method based on persistent pigment
darkening (PPD) is used (44,45) and Australia where an in vitro method based
on transmission measurement is applied (46), there are no official standards
yet. The chances for a harmonization as it has been achieved with the SPF
seem to be rather remote at the moment. To agree on a common UV-A assess-
ment method will be a substantial challenge in the future.
Figure 16.16 shows the results of PPD measurements according to the
Japanese standard. The meaning of the UV-A protection factor (PFA) is analo-
gous to the SPF, but referring to the UV-A range only and based on PPD measure-
ments. The formulations investigated contain various concentrations of the
photostable, broad-spectrum UV filter BEMT with and without the presence of
EHMC. All three Japanese categories of UVA protection PAþ (2 , PFA , 4),
PAþþ (4 , PFA , 8) and PAþþþ (PFA . 8) can easily be achieved with
this new system, whereas the reference sample of the Japanese Standard that
Figure 16.16 Concentration dependence of the UV-A protection in terms of PFA of

formulations containing BEMT with and without 5% of EHMC.
contains 5% BMBM and 3% EHMC does not get beyond a PFA of 4.5, since its
combination of filters is not photostable.
In Australia, a pragmatic approach was taken resulting in the UV-A
Standard 2604, since in this continent the rate of skin cancer is high and no
delay can be justified. Without waiting for all details of a scientific proof about
how damaging UV-A radiation may be, it was defined that a broad-spectrum
sunscreen has to reduce the UV-A radiation at least 10-fold between 320 and
360 nm (Australian Standard).
If we assess the available UV-A and broad-spectrum UV absorbers we can
determine the following ranking in terms of meeting the Australian Standard
(Table 16.6). This ranking is just one way to show the efficacy of these filters.
In real sunscreen formulations, they will of course be used in combination
with UV-B filters, which also contribute to fulfilling the Australian Standard.
Nonetheless, this comparison gives the formulator an upper limit about how
much UV-A filter is required to meet the Australian Standard. The performance
of these filters in commercial products also depends on the formulation.
There is a correlation between the Australian UV-A standard and the
Japanese in vivo standard. Achieving the Australian standard corresponds to an
in vivo PFA of about 4, that is, the minimum requirement to qualify for protection
class PAþþ (47).
From the new broad-spectrum UV absorbers we expect better UV-A coverage
when incorporated into a sunscreen or day cream (48). To illustrate and quantify
the improvement some calculations were carried out with different formulations
using the Cibaw Sunscreen Simulator (49) (www.cibasc.com/personalcare).
Table 16.6 Efficacy of Available UV-A and Broadband

Filters in Terms of Fulfilling the Australian Standard on Its
Own (Transmission ,10%, 320– 360 nm, Without Taking
into Account Photostability)
Amount
Efficacy Filter COLIPA # required (%)
1. S 81 BEMT 1.8
2. S 80 DPDT 2.1
3. S 71 TDSA 2.5
4. S 66 BMBM 2.9
5. S 79 MBBT 3.7
6. S 73 TDS 4.9
7. S 76 ZnO 7– 14a
a
Depends on size of microfine particles.
Figure 16.17 shows the UV transmission of three formulations with similar SPFs,
that is, UV-B protection, but different degree of UV-A protection. In spite of
great differences, all these formulations could make “UV-A” or “broad-spectrum”
claims.
Formula Composition SPF (calc.) UV-A transmission (%)

A1 8% EHMC, 2.5% BP-3 14.8 100
A2 5% EHMC, 3% BEMT 15.5 55
A3 1.5% EHT, 2.5% BEMT, 3% MBBT 15.1 25
Figure 16.17 Progress in UV-A protection.

The transmission spectrum was calculated using a two-step film model

(50). The area below the sunscreen with the highest UV-A transmission
(320 – 400 nm), A1 with benzophenone-3 has arbitrarily been set as 100%.
Formula A2 with BEMT reduces this UV-A exposure already to 55%. With
formula A3, using BEMT and another new UV-A filter such as MBBT, the
UV-A exposure is reduced down to 25% of the value achieved with the conven-
tional formulation.
SAFETY OF THE NEW UV ABSORBERS

The approval procedure in Europe is demonstrated in Table 16.7 with the first
broad-spectrum filter on the market, DTS. A margin of safety (MOS) is
calculated as the ratio between the no-observable adverse effect level (NOAEL)
and the systemic exposure determined via the percutaneous absorption data. The
European authorities require an MOS of .100-fold. Modern filters have
values .1000-fold. Table 16.7 lists the requirements for the assessment of
human safety (8).
What is the contribution of the new filters to the safety of sunscreens? A
major concern with the conventional UV absorbers has always been skin pen-
etration. Even if a substance is supposed to be “inert” it should not enter the
body. In order to penetrate the skin, a substance has to be lipophilic. In other
words, there should be practically no penetration of water-soluble substances.
Highly lipophilic substances tend to stay in the upper layer of stratum corneum
and are thus also useful for water-resistant formulations.
The skin penetration of filters can be influenced by the formulation, some
ingredients may act as enhancer (as desired in transdermal drug delivery) and
some do the opposite (51). Another very important factor is the molecular
weight (MW) of the UV absorber. Figure 16.18 shows the increase in the MW
Table 16.7 Assessment of Human Safety: EU 2001 (8)
Parameter Example Mexoryl XL (DTS, S73)
Amount of formulation applied (mg) 18,000

Concentration of UV filter (%) 10
Amount of filter applied (mg) 1,800
Percutaneous absorption (%) 0.5
Total absorbed amount (mg) 9
Typical human body weight (kg) 60
Systemic exposure dose (SED, mg/kg per day) 0.15
NOAEL ¼ no observable adverse effect level 1,000
(mg/kg per day, toxicology studies)
Margin of safety (MOS)a 6000-fold
a
MOS must be .100-fold, but modern sunscreens have MOS values .1000-fold.
Classic New
S1 PABA S69 Ethylhexyl triazone
S13 Ethylhexyl salicylate S73 Drometrizole trisiloxane
S28 Ethylhexyl methoxycinnamate S78 Diethylhexylbutamido triazone
S38 Benzophenone 3 S81 Bis-ethylhexyloxyphenol
S60 4-Methylbenzylidene camphor XA Diethylamino hydroxybenzoyl
hexyl benzoate
S66 Butyl methoxydibenzoylmethane XB Bis-diethylamino hydroxybenzoyl
benzoate
XC Bis-benzoxazoylphenyl ethylhexylimino
triazine
Figure 16.18 Molecular weight of classic and modern lipophilic sunscreen actives.
of the oil-soluble, lipophilic UV filters starting with PABA (COLIPA # S1)

at a MW of 137 Da and the other classic UV filters with MWs between 228
(benzophenone-3) and 310 Da (buthylmethoxydibenzoyl methane). The turning
point in the development of sunscreen actives came with the introduction of
ethylhexyl triazone (EHT, S69). EHT is the first filter based on chromophore
multiplication, and may thus be called the first modern UV filter. In EHT,
three moieties of PABA (ethylhexylester) are attached to a triazine core. Since
then all newly approved UV filters have had MW .500 Da.
The “500-Da rule for the skin penetration of chemical compounds and
drugs” has recently been proposed for the development of drugs to describe
the limit beyond which larger molecules cannot pass the corneal layer (52). Argu-
ments for the 500-Da rules are: (1) virtually all common contact allergens are
under 500 Da, larger molecules are not known as contact sensitizers. They cannot
penetrate and thus cannot act as allergens in man; (2) the most commonly used
pharmacological agents applied in topical dermatotherapy are all under
500 Da; and (3) all known topical drugs used in transdermal drug-delivery
systems are under 500 Da. As it seems logical to restrict the development of
new innovative compounds, to MW of ,500 Da, when topical dermatological
therapy or percutaneous systemic therapy or vaccination is the objective, we
may conclude that it makes sense to restrict the search for new sunscreen
actives to MW .500 Da. Figure 16.18 shows that this principle has been utilized
in the development of new sunscreen actives. In any case, all new sunscreen
actives have to undergo the scrutiny of safety testing as described in
Table 16.1 (8).
CONCLUSIONS
Triggered by new requirements towards better UV protection, seven new UV
absorbers have been developed and approved in Europe over the last few
years. These new filters give the formulators new possibilities to cover the
whole UV range from 290 to 400 nm, and also to use less filter due to the superior
efficacy of some of the new UV-A and broadband filters. With the considerably
higher molecular weight, leading to lower skin penetration, and the good photo-
stability of most of these new filters, additional safety of sun protection products
for adults and children can be gained.
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17
The Photostability of Organic
Sunscreen Actives:
A Review
Craig A. Bonda
CPH Innovations (an affiliate of the C.P. Hall Company),
Chicago, Illinois, USA
Introduction 322
Photostability as a Sunscreen Industry Concern 323
Photochemistry Review 323
Background 323
The Nature of Photon Absorption 324
Photochemical Reactions 324
Energy Transfer 325
Solvent Polarity and Electron Transfer Theory 327
Photostability of Individual Sunscreen Active Ingredients 328
Avobenzone (Butyl Methoxydibenzoylmethane) 329
Octinoxate (Octyl Methoxycinnamate) 334
Other UV Filters 335
UV Filter Combinations 338
Photostability of Sunscreen Formulations 339
Photostabilization Strategies 341
Formulation Strategies 341
Molecular Strategies 344
Conclusions 345
321
322 Bonda
Acknowledgments 346
References 346
INTRODUCTION
Organic ultraviolet (UV) filters, such as those used in sunscreens, convert the
energy in UV radiation into electronic excitation energy (1). At a molecular
level, the physical reality of this conversion is a sudden expansion of an area
of the electron cloud surrounding the molecule (2,3). This happens so rapidly
(on the order of 10215 s) (1: p.6) that the nuclei of the molecule at first remain
in their original positions. In effect, an electronic isomer of the original molecule
has been created. If we were to isolate and observe the molecule, we might in one
common scenario see the distorted electron cloud collapse almost immediately to
its original shape. Simultaneously, we might see a flash of light emerge from the
molecule. Close examination would reveal that the molecule is now indistin-
guishable from its preabsorbance condition. In another common scenario, we
might see that the distortion of the electron cloud persists and exerts a force
that causes bonds to stretch and nuclei to move to accommodate the new
shape. We might see that the bond stretching and nuclear motion dissipates the
electronic excitation energy until the electron cloud returns to its preabsorbance
shape and the nuclei return to their previous positions relative to each other.
Again, the molecule would be indistinguishable from its preabsorbance con-
dition. Therefore, it can repeat the cycle of absorbance, electronic isomerization,
and energy dissipation. It is, in effect, photostable.
If somewhere between absorbance and energy dissipation something
happens to the molecule that prevents it from returning to its preabsorbance
state, we say the molecule is photounstable or photolabile. We may apply
other terms such as “photodegraded,” “photoinactivated,” or “photodecayed.”
If enough of the UV filter molecules in a sunscreen undergo photodecay, the
sunscreen loses absorbance and its protective properties are reduced below
those expected from the level of active ingredients it contains. At the least,
this is wasteful and inefficient.
Which UV filters are prone to photodecay? Under what circumstances are
they most likely to decay? What can be done to improve photostability of those
chemicals and the sunscreens that contain them? Which UV filters are photo-
stable? And what steps can be taken to design new photostable UV filters? In
this chapter we will address these questions and others. To find the answers,
we will begin with a review of basic photochemistry. Following that, we will
draw on the published findings of numerous investigators around the world, as
well as data and commentary from research my colleagues and I conducted in
the laboratories of CPH Innovations.
The Photostability of Organic Sunscreen Actives 323
PHOTOSTABILITY AS A SUNSCREEN INDUSTRY CONCERN

Interest in sunscreen photostability has grown as use of the UV-A filter, avoben-
zone, in sunscreens has grown.† Spurred on by consumer demand for greater pro-
tection against solar UV-A radiation, which many believe causes a number of
damaging effects to skin including premature aging (4,5), avobenzone has
become the most widely used UV-A filter in the world. However, as discussed
below, under certain experimental conditions avobenzone is photolabile; that
is, under these conditions exposure to solar UV radiation causes its absorbance
of UV radiation to decline.
Several researchers have reported on avobenzone’s behavior in dilute sol-
utions, and in emulsions and commercial sunscreen products. Other researchers
have measured the photostability of other UV-B and UV-A filters. Photostability
of sunscreen preparations has become an important basis for predicting their per-
formance (6 – 9). Researchers have sought with some success to find or develop
ways to ameliorate avobenzone’s photolability (10 – 12).
Over the past 10 years or so, the effect of this research and development has
been a greater appreciation and understanding among major sunscreen manufac-
turers and their chemical suppliers of the photophysics and photochemistry
underlying these important consumer products. Many (though not all) sunscreen
products in the USA today reflect this new understanding with improved efficacy
against UV-A radiation. In Europe, new active ingredients are available that have
to some degree the advantage of avobenzone’s excellent UV-A absorbance,
without the disadvantage of its photolability.
PHOTOCHEMISTRY REVIEW
Background
As we shall see, a UV filter’s fate is best understood as a competition between the
many pathways the molecule can take between its elevation to an excited state
and its return to the ground state. All of the pathways result in the dissipation
of excited state energy. Some of the pathways are destructive to the molecule
(e.g., fragmentation, some types of isomerization, bimolecular reaction); others
are nondestructive (e.g., fluorescence, phosphorescence, some types of isomeri-
zation, energy transfer to another molecule). Each pathway is associated with
its own rate constant. If nondestructive pathways predominate, then, relatively

Throughout this chapter, the term “UV-A” is used to represent radiation from 320 to 400 nm, and
“UV-B” is used to represent the radiation from 290 to 320 nm. UV-C is the portion of the spectrum
between 200 and 290 nm.
†
Avobenzone is the USAN name for the chemical butyl methoxydibenzoylmethane (BMDM), and is
the name that appears in the United States Pharmacopoeia. The main body of the text will use nomen-
clature that I consider the most recognized for each of the chemicals discussed. In Fig. 17.5, alternative
nomenclature for each chemical is shown.
324 Bonda
speaking, the molecule will be photostable. Conversely, if destructive pathways

predominate, then the molecule will be unstable.
The Nature of Photon Absorption

To begin at the beginning: a photon is a quantum or “packet” of electromagnetic
energy with an energy equal to Planck’s constant (h) times its frequency (n). The
absorption of a photon by an organic molecule causes the excitation of one of a
pair of electrons in a low energy orbital to a higher energy unoccupied orbital (1)
(Fig. 17.1).
Before absorption, the orbital configuration of the electrons is the
“ground” state. Upon absorption, two electronic states are possible. In one,
the spins of the two electrons remain paired and, as in the ground state, the
net spin of the pair is zero. This is called the “singlet” excited state. In the
other, the spins of the two electrons are unpaired, and there is a net spin. This
is called a “triplet” excited state because three variations can be resolved in a
magnetic field (1: p. 23). The energy of both excited states is eventually dissi-
pated as heat (vibration, including both bond stretching and nuclear motion),
or heat and light (emission of a photon of lower energy/longer wavelength).
Emission of a photon from the singlet state is called “fluorescence.” Photon
emission from the triplet state is called “phosphorescence.” The singlet state
may return to the ground state directly, or it may decay to the triplet state (1:
pp. 4 –6) (Fig. 17.2).
Photochemical Reactions
The singlet state is often short-lived, typically 1029 – 1028 s. Therefore, reactions
that proceed from it must be quite rapid. Of more importance are reactions that
Singlet
Triplet
+ +
Figure 17.1 Schematic representation of photon absorption resulting in the excitation

of an electron to the singlet state, the decay to the triplet state, and the emission of a
photon before returning to the ground state.
S=½
S = -½
Figure 17.2 Vectoral model of an electron pair. Each electron may be viewed as spin-
ning about a vector that is precessing about an axis (Z). In the ground and singlet states, the
spins are paired, as indicated above. Net spin, therefore, is 0. In the triplet state, the spins
are unpaired and the net spin is 1.
proceed from the (usually) much longer-lived triplet state, which may last 1024 s
or longer (1: p. 90, 105, 352). During the triplet state lifetime, the
excited molecule looks and behaves as a diradical (1: p. 364– 365) from which
many chemical reactions are possible. In general, these reactions can be
grouped into four categories: photoaddition/substitution; cycloaddition; iso-
merization; and photofragmentation (1: Chaps. 10 –13). Of particular importance
to the sunscreen formulator are reactions between like or different UV filter
molecules, those between UV filter molecules and sunscreen excipients, and
isomerizations or fragmentations of the UV filter molecules, any one of which
may alter or destroy the UV absorption capacity of the sunscreen formulation
(Fig. 17.3).
Energy Transfer
The excited molecule may react (to produce isomers or new products), or return
to the ground state in its original form. Clearly, the latter is the preferred outcome
because the UV filter molecule is again available to absorb a photon. Many
factors determine the pathway an excited molecule will take including the
326 Bonda
O* O *
~ ~
n, * *
O O H
+ H X + X
(a)
O * O
+
(b)
(c) *
O O
R R
CH 2 + CH 2
(d)
Figure 17.3 Top: carbonyl and ethylene models show the diradical nature of the excited
triplet state. Bottom: (a) abstraction of a hydrogen; (b) 2þ2 cycloaddition; (c) cis – trans
isomerization; (d) photofragmentation.
triplet energy, the triplet lifetime, the identity and concentration of the reactants,
and the rates and activation energies of each competing reaction. Under certain
conditions, the excited molecule may return to the ground state (and its original
form) by transferring its energy to a nearby molecule. The excited molecule
becomes a “donor” (D ) and the nearby molecule becomes an “acceptor” (A).
Upon the transfer of energy, the donor returns to its ground state (D) and the
acceptor becomes elevated to its excited state (A ). Generally, triplet energy
transfer takes place when the triplet energy of the acceptor is equal to or lower
than the triplet energy of the donor (1: Chap. 9). The triplet energies of several
UV filters may be found in Table 17.1 (13).
Table 17.1 Triplet Energies of Some

Common Sunscreen Actives
PABA 75 kcal/mol
Oxybenzone 66 kcal/mol
Avobenzone 59.5 kcal/mol
Octocrylene 55– 60 kcal/mol
OMC 57 kcal/mol
MBC 55 kcal/mol
Optimizing sunscreen performance depends in part on encouraging a

photolabile UV filter such as avobenzone to dissipate its excited state energy
through nondestructive pathways. One strategy to accomplish this is to include
in the formulation an acceptor that will “quench” the excited state energy of avo-
benzone. Chemicals useful as acceptors for this purpose are diethylhexyl 2,6-
naphthalate, octocrylene, and methylbenzylidene camphor. Patent and regulatory
considerations sometimes affect the ability of formulators to use these chemicals
in their formulations. The uses of photostabilizers in formulation are discussed
later in the chapter.
Solvent Polarity and Electron Transfer Theory

Excited state quenching and its opposite phenomenon, sensitization, represent the
intermolecular transfer of excited state energy and, for organic chromophores, it
relies primarily on charge transfer; that is, the movement of an electron from one
molecule to another (1: p. 329).
The rapid expansion and contraction of a molecule’s electron cloud follow-
ing absorbance and relaxation cause dislocation and rearrangement of the solvent
molecules in the immediate vicinity. The energy required for the solvent mole-
cules to accommodate these changes in dimension and charge distribution has
a direct relationship to the rate at which electron transfer takes place (2,3). The
rules governing electron transfer processes were first elucidated by Rudolph
Marcus, now of the California Institute of Technology. In a series of papers pub-
lished between 1956 and 1965 and in numerous subsequent publications, Marcus
introduced simple equations that proved to be highly predictive of electron trans-
fer reactions in chemistry and biology. In part, his theory proposed that the
solvent mediates electron transfer reactions and the rate of electron transfer is
related to the driving force by a quadratic expression that is descriptive of a para-
bola (14 – 16). In 1992, Marcus was awarded the Nobel Prize in Chemistry for his
discovery.
Studies conducted at CPH Innovations documented a parabolic relationship
between the dielectric constant of the oil phase and the photostability of
several avobenzone-containing sunscreens that is reminiscent of the Marcus
theory (17). Briefly, we determined that in many sunscreens, the photodecay
rate, kpd, is related to the polarity of the sunscreen oil phase by the expression,
a12 þ b1 þ c, where 1 is the dielectric constant of the oil phase (comprising
the solvents, emollients, and UV filters), and a, b, and c are empirically
derived values for a given filter combination. The expression describes a para-
bola, the vertex of which identifies the dielectric constant at which photodecay
will be minimized and, therefore, sunscreen performance may be optimized.
The similarity of our findings to Marcus theory is perhaps not surprising given
the prominent role played by charge transfer in the causation and amelioration
of photodecay (Fig. 17.4).
328 Bonda
Dielectric Constant vs. Photodecay

0
-0.015
Photodecay Rate Constant
-0.03
-0.045
-0.06
-0.075
y = -.004215x2 + 0.072748x - 0.33701
-0.09
Vertex=8.63
-0.105
-0.12 R2 = 0.992
-0.135
-0.15
.4
.8
.2
.6
.4
.8
.2
4
8
2
6
4
8
2
6
4
8
2
6
10
12
4
8
4.
4.
5.
5.
6.
6.
7.
7.
8.
8.
9.
9.
10
10
11
11
12
12
13
Dielectric Constant
Figure 17.4 Data compiled on nine sunscreens prepared with identical UV filters (5%
octyl salicylate, 3% oxybenzone, and 2% avobenzone) but different solvents and emolli-
ents. Results show steady improvement in photostability as the dielectric constant of the
oil phase approaches the vertex, 8.63, then declining as the dielectric constant exceeds
the vertex value. The formulation represented by the large dot to the left achieved
SPF 17.14 in vivo. The formulation represented by the large dot at the vertex, or
peak, achieved SPF 25.0 in vivo, a 46% improvement.
PHOTOSTABILITY OF INDIVIDUAL SUNSCREEN

ACTIVE INGREDIENTS
Studies of individual UV filters are often carried out in dilute solutions of various
laboratory solvents. These studies are valuable for what they reveal about the
photochemistry of these chemicals, and instructive to the issue of what could
happen to them under actual conditions of use. However, a note of caution is

Photostability studies involve irradiating samples with UV radiation. People in the sunscreen indus-
try often express UV radiation in MED units. MED is an acronym for minimum erythemal dose.
Theoretically, 1 MED is the amount of solar UV radiation from 290 to 400 nm that, in the average
person with light skin, will result in a slight reddening (erythema). In 1987, McKinlay and Diffey pub-
lished an erythemal action spectrum that assigned to each wavelength of solar UV radiation an erythe-
mal effectiveness value or weight (see chapter titled “Dosimetry of UV Radiation” elsewhere in this
volume). This led to the development of radiometers that are filtered to “see” (and, therefore, measure)
erythemally effective radiation with greater sensitivity than other wavelengths. Sunscreen researchers
often employ these biologically weighted radiometers to measure the UV doses they deliver to their
sunscreen samples. When measured thusly, 1 MED is equivalent to 21 mJ/cm2. When all the UV radi-
ation is measured without giving special weight to some wavelengths over others, 1 MED is equival-
ent to 2.7 J/cm2.
in order. In the real world, UV filters are never used in isolation; they are always
combined with other UV filters and, indeed, with numerous excipients. Their
concentrations in sunscreen formulations are above those used in most photoche-
mical research by several orders of magnitude. Unquestionably, UV filters are
affected by the nature of the solvent. However, sunscreen formulations never
employ laboratory solvents (with the exception of ethanol, which is used specifi-
cally for its volatility). Importantly, sunscreens are designed to “set up” as films
on the skin (6), and therefore may behave more as solid state systems and less
as solutions. As any chemist will tell you, chemical behavior is very different
for solids, liquids, and gases. Consequently, the data generated by studies of indi-
vidual UV filters in dilute solutions may not be predictive of the behavior of the
same UV filters in sunscreen formulations and under actual conditions of use.
Please keep these “caveats” in mind as we review what is known about the photo-
stability of individual UV filters.
The molecular structures of the more common sunscreen UV filters and
schemes for the photoinduced isomerization of each are presented in Fig. 17.5.
Frequent reference to these graphic depictions may be helpful to the reader as
the findings of various researchers are discussed in the following text. Recall
earlier when discussing photochemical reactions, that isomerization was ident-
ified as one of the four photoinduced pathways a molecule can take following
photon absorption. Isomerization is an important pathway for dissipation of
excited state energy. Not all molecules can isomerize, and not all isomerizations
are nondestructive to the molecule. But in cases where the isomerization is
reversible, or where it has little effect on spectral attenuation, it often represents
an energy dissipation pathway that contributes to photostability.
Avobenzone (Butyl Methoxydibenzoylmethane)

Deflandre and Lang (18) incorporated avobenzone into an emulsion at 2% (w/w),
and then spread the emulsion in a very thin film (1.35 mm) between two finely
roughened quartz plates. Then they irradiated the sample with a solar simulator
filtered to deliver radiation between 290 and 400 nm, measuring UV absorbance
before and after irradiation. The researchers processed the data to produce an esti-
mate of photodegradation under standardized conditions: a 10-mm film exposed
to 1 h of sunlight. Based on their data, Deflandre and Lang projected that avoben-
zone will degrade by 36%. Deflandre and Lang also investigated the photostabil-
ity of other dibenzoylmethane derivatives including two that, unlike avobenzone,
featured hydroxyphenyl groups ortho to one of the carbonyls. Both of these
derivatives proved to be relatively photostable. In contrast to avobenzone’s
36% loss, one was projected to degrade by 5%, and the other by only 3.6%.
Andrae et al. (19) employed steady state irradiation using various UV-B and
UV-A radiation sources and flash laser photolysis (excitation at 355 nm) to induce
changes in avobenzone’s absorbance spectra. The solvent used was acetonitrile and
the avobenzone concentration was 1025 –10210 M. Before irradiation, avobenzone
330 Bonda
H
Avobenzoneu O O O O
Butyl
methoxydibenzoylmethanei
O O
Diketo tautomer Enol tautomer
O
Octyl
methoxycinnamate c O h O
(OMC)
Ethylhexyl O O
methoxycinnamatei O
Octinoxateu
trans isomer cis isomer
H H
Oxybenzoneu O O O O
Benzophenone-3i
2-Hydroxy-4- h
methoxybenzophenonee,r
O O
H
Octyl salicylatec O O H
O O
Ethylhexyl salicylatei
h
Octisalateu O
O
H H
Homosalateu O O O O
Homomenthyl salicylatec h
O O
CH3 O CH3
4-Methylbenzylidene h
camphori
(MBC)
Enacameneu
O
E-isomer Z-isomer
O
N O
Octocryleneu,i N
2-Ethylhexyl-2-cyano-3,3- O
diphenyl-2-propenoater O
Energy
H
Phenyl- N N
benzimidazole
sulfonic acidi + – N + – N
Ensulizoleu Na O3S Na O3S
H
O O
Octyl dimethyl O O
PABAi –e
Padimate Ou N N
Radical form of octyl dimethyl PABA
H
Methylene bis- N OH OH N O N
benzotriazolyl
tetramethyl- NN NN NN
butylphenoli
(MBBT)
uUSAN name (United States Adopted Name); iINCI name (International Nomenclature Cosmetic Ingredients); cCommon
name; rCAS Registry Name
Figure 17.5 Sunscreen UV filters and their isomerization or resonance schemes.

Na+ O 3S -
SO 3- Na+
O
Terephthalylidine E,E- isomer
dicamphor sulfonic
i
acid
(TDSA) hν
O SO 3- Na+
O
+ -
Na O 3S
E,Z- isomer
H
HO 3S SO 3H
N N
Disodium phenyl
dibenzimidazole N N
i
tetrasulfonate
(DPDT) SO 3Na H SO 3Na
hν
H H
HO 3S SO 3H
N N
N N
SO 3Na SO 3Na
O
Bis-
ethylhexyloxyphenol
i
methoxyphenyltriazine
((BEMT)
H
OH N N OH N N O
hν
N
N
O O
O O
O O
N N N
H H
N N
Octyl triazonei N H
hν
N N
N N
H
O O
Figure 17.5 Continued
exhibited its characteristically broad UV-A peak (lmax ¼ 350 nm). After
irradiation, the UV-A peak virtually disappeared and was replaced by a similarly
broad UV-C peak (lmax ¼ 260 nm). Flash laser photolysis, also done in aceto-
nitrile, revealed a short-lived peak in the UV-B region (lmax ¼ 300 nm). The
authors of this study attributed the broad UV-A peak to absorbance by the enol
tautomer of avobenzone, the UV-C peak to absorbance by the diketo tautomer
of avobenzone (see Fig. 17.6), and the UV-B peak to a transient species that
they speculated is an isomer, possibly a rotamer, of the enol tautomer.
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1.2
Before UV
0.8
332 min recovery
Absorbance
106 min. recovery

0.6
68 min. recovery
42 min. recovery
0.4
After 40 MED
0.2
0
240 260 280 300 320 340 360 380 400
Wavelength (nm)
Figure 17.6 Enol recovery. Graph shows absorbance measurements of a dilute solution
of avobenzone in cyclohexane taken before UV irradiation, immediately after, and over a
6.5-h span.
Schwack and Rudolph (20) irradiated dilute solutions of avobenzone with a

solar simulator in the polar solvents isopropanol and methanol, and in the non-
polar solvents cyclohexane and isooctane. They monitored the photodegradation
and isolated the resulting photoproducts by high performance liquid chromato-
graphy (HPLC), and characterized them using gas chromoatography– mass spec-
trometry (GC – MS). They conducted two sets of experiments: one with the light
source filtered to exclude radiation ,320 nm; the other filtered to exclude
radiation below ,260 nm. Surprisingly, they found that in the polar solvents,
avobenzone was photostable. In the nonpolar solvents, however, photodegrada-
tion grew exponentially with increasing time of irradiation. Irradiation with
shorter wavelengths (and therefore, higher frequencies and energies) (i.e.,
260 –320 nm) produced higher rates of photodegradation. They classified seven
groups of photoproducts, all originating from two radical precursors—a
benzoyl radical and a phenacyl radical, indicating that the avobenzone had frag-
mented on one side of the central methane. To find out why avobenzone was
photostable in the polar solvents, and photolabile in the nonpolar solvents, the
researchers took nuclear magnetic resonance (1H NMR) measurements on sol-
utions of avobenzone in deuterated solvents. They found that in the nonpolar
solvent cyclohexane-d12, both enol and diketo tautomers of avobenzone exist
in equilibrium, with the enol form predominating, 96.5% to 3.5%, over the
diketo form. In the polar solvent isopropanol-d8, NMR detected no diketo reson-
ances. They concluded that photodegradation probably proceeds through the
diketo tautomer and that in the absence of the specie avobenzone is photostable.
Shaath et al. (21) studied dilute solutions (200 ppm) of avobenzone in
mineral oil, isopropyl myristate, and a 70/30 mixture of ethanol and water.
Samples were placed in quartz cells and irradiated with a solar simulator
equipped with filters to eliminate radiation ,290 nm and .400 nm. Measure-
ments were made on a spectrophotometer before and after irradiation. After
5 MED, avobenzone absorbance declined 20.6% in mineral oil, 2.9% in isopropyl
myristate, and 4.8% in the ethanol and water mixture.
Roscher et al. (22) investigated photolysis reactions of avobenzone by irra-
diating a solution in cyclohexane for 70–140 h using a mercury vapor lamp. Pho-
tolysis products from avobenzone included tert-butylbenzene, p-tert-butylbenzoic
acid, and p-methoxybenzoic acid. Products obtained from the cyclohexane
included cyclohexanol, cyclohexanone, and dicyclohexyl ether. Also identified
were esters formed from the products of avobenzone and cyclohexane.
A 1997 study (23) also irradiated dilute solutions (10 ppm) of avobenzone in
isopropanol and cyclohexane, using optical filters to exclude radiation ,290 nm
and .400 nm. This study confirmed the Schwack and Rudolph finding that avo-
benzone is photostable in isopropanol and not in cyclohexane. As Andrae et al.
(19) had, the investigators observed a decline in absorbance attributed to the
enol tautomer, and a corresponding increase in absorbance attributed to the
diketo tautomer. However, continued observation revealed that within a few hours
following irradiation, in the nonpolar solutions, absorbance returned almost to pre-
irradiation levels, indicating that the enol–diketo tautomerization was reversible
and that there was virtually no permanent loss of avobenzone concentration.
This finding, shown in Fig. 17.6, was contrary to Schwack and Rudolph’s finding
of significant photodegradation by fragmentation that may have resulted from the
higher frequency, more energetic radiation and longer exposures used in the
Schwack and Rudolph study (.260 nm and 8 h) compared to the 1997 study
(.290 nm and ,30 min). It should be noted that the radiation used in the newer
study (24) more closely resembles the UV irradiance from sunlight, which does
not include radiation ,290 nm, and that the exposure times used were calculated
to approximate realistic exposure times of several hours on the beach.
The newer study also looked at the photostabilizing effects of protic
solvents of lower polarity such as longer chain alcohols and salicylates. The
purpose here was to test the hypothesis that it may be the protic nature of isopro-
panol and methanol that is responsible for the much higher photostability
observed in these solvents. The data appeared to support the hypothesis, demon-
strating that protic solvents have, to a point, a concentration-related effect on
avobenzone’s photostability.
Tarras-Wahlberg et al. (25) blended avobenzone in petrolatum in a concen-
tration intended to approximate commercial use levels (exact concentration not
reported). The group then applied the mixture to a quartz slide, placed another
334 Bonda
quartz slide on top, and squeezed the two slides to achieve a uniform thickness.
They irradiated the sample with two radiation sources: one for UV-A; another for
UV-B. The UV-A dose was 100 J/cm2. The UV-B dose was 20 MED. In addition
to monitoring changes in UV absorbance during and after irradiation, the Tarras-
Wahlberg group also employed GC – MS to isolate and identify the resulting
photoproducts, if any. They found avobenzone to be relatively photostable
upon irradiation with UV-B, and photounstable upon irradiation with UV-A.
They reported a well-defined photoproduct with absorbance in the UV-B, but
provide no further details.
Octinoxate (Octyl Methoxycinnamate)

Octinoxate, better known as octyl methoxycinnamate (OMC), is the most widely
used UV filter in sunscreens in the world and is well known for its low potential to
behave as a sensitizer or as a photoallergen (26). Therefore, its photostability is of
great interest to sunscreen formulators.
Deflandre and Lang (18) studied the photostability of OMC using the same
procedure they used for avobenzone, described above. Based on their data, they
projected that OMC would degrade by 4.5% after 1 h in sunlight. Deflandre and
Lang note that cinnamates isomerize when submitted to UV radiation, reaching
a photostationary equilibrium shortly after exposure begins. Before equilibrium
is reached, degradation occurs rapidly. After equilibrium is reached, degradation
occurs more slowly.
Shaath et al. (21) irradiated dilute solutions (200 ppm) of OMC in mineral
oil, isopropyl myristate, and a 70/30 mixture of ethanol and water, using the
same protocol as described for avobenzone previously. They reported declines in
OMC absorbance in the three solvents of 18.7%, 18.7%, and 39.1%, respectively.
Serpone et al. (27) irradiated dilute solutions (8 mg/L) of OMC in water,
methanol, acetonitrile, and n-hexane with UV radiation. Radiation was provided
by a 1000 W Hg/Xe lamp that was optically filtered to remove wavelengths
.400 nm and ,290 nm. Absorbance of the OMC was measured over time.
Irradiance was not given. Contrary to previous reports (28,29), the Serpone
study documented rapid and significant photodegradation of OMC. After
30 min of UV exposure, the amount of OMC lost was reported as 90% in
water, 40% in methanol, 45% in acetonitrile, and 40% in n-hexane.
At CPH Innovations, we qualitatively confirmed the Serpone study result
by irradiating a 10 ppm solution of OMC in isopropanol with 35 MED. OMC
absorbance declined by approximately 50% (unpublished results).
Tarras-Wahlberg et al. (25) also investigated the photostability of OMC,
employing the same protocol as described for their investigation of avobenzone.
They reported slight decomposition after 20 MED of UV-B irradiation, and
slightly greater decomposition following irradiation with UV-A. GC revealed
an additional peak; however, its mass spectrum was similar to the original sub-
stance assigned as the cis-isomer.
Schrader et al. (30) isolated and identified eight photoproducts following

irradiation of isoamyl methoxycinnamate, a close chemical cousin of OMC that
is used in European sunscreens. Schrader irradiated a 10% isopropanol solution
with 16.4 J/cm2 radiation from a xenon light source that was filtered to approximate
solar UV radiation. Schrader’s report does not indicate how much of the isoamyl
methoxycinnamate remained after irradiation, but seemed to indicate that the photo-
products appeared in low concentrations. The report proposed that the main reaction
products resulted from a cycloaddition between the trans double bond of one
molecule and the 3,4 double bond of the aromatic ring of a second molecule.
Another study prepared and tested a sunscreen emulsion containing 7.5%
OMC as the sole UV filter (unpublished data). A thin film of the sunscreen
was prepared on a substrate designed for in vitro sunscreen analysis, and this
was irradiated by a solar simulator† in increments of 5 MED doses to a total of
25 MED. The total exposure approximates the exposure during 5–6 h of direct
sunlight. As shown in Fig. 17.7, the OMC experienced rapid photodegradation
(approximately 10%) after the initial 5-MED exposure, then declined more gradu-
ally with subsequent 5-MED radiation doses. After 25 MED, the sample had lost
17% of its UV-B attenuation. This reinforces the earlier statement that UV
filters often behave very differently in formulation than they do in dilute solutions.
It also provides qualitative support for the finding and observation of Deflandre and
Lang (18) as mentioned earlier. An interesting result of this study was the increase
in absorbance at wavelengths .375 nm, possibly indicating the appearance of
photoproducts that absorb in the visible range, though none were visible to the
eye, and any result such as this could be unique to the particular formulation tested.
Other UV Filters
Deflandre and Lang (18) applied the protocol described above to photostability
studies of methylbenzylidene camphor, phenylbenzimidazole sulfonic acid
(as the sodium salt), octyl dimethyl PABA (Padimate-O), and oxybenzone.
They found all but Padimate-O to have good photostability. Their results are
summarized in Table 17.2.
Shaath et al. (21) used the same protocol as described in their study of
avobenzone and OMC to study dilute solutions of oxybenzone, octocrylene,
Padimate-O, homosalate, and octyl salicylate. Their results are summarized in
Table 17.3.
Serpone et al. (27) also determined the photostabilities of PABA,
Padimate-O, oxybenzone, and phenylbenzimidazole sulfonic acid in dilute sol-
utions using the same protocol they used for OMC outlined above. The results
are summarized in Table 17.4.

The thin film was prepared on the substrate, Vitro-skin, available from IMS Inc., Milford, CT.
†
Model 16S Solar UV Simulator equipped with PMA 2105 biologically weighted UV-B detector with
beam splitter adapter and controlled by a PMA2100 dose controller, Solar Light Company.
336 Bonda
Photostability of Sunscreen with 7.5% OMC
1.8
1.6
1.4
Before UV
1.2
5 MED
Ab so r b anc e
1 10 MED
15 MED
0.8
20 MED
0.6 25 MED
0.4
0.2
0
280 310 340 370 400
Wavelength (nm)
Figure 17.7 Absorbance of a sunscreen containing 7.5% OMC as the sole UV filter
before and after irradiation with 25 MED in 5 MED increments. This dose is approxi-
mately equivalent to 5 – 6 h of direct sunlight. Note the rapid decline after 5 MED
(about 10%), followed by the more gradual decline with repeated radiation doses.
A previously unpublished study tested the photostability of the organic

UV filters octocrylene, octyl salicylate, homosalate, and octyl triazone in dilute
solutions (approximately 10 –90 ppm) of isopropanol and cyclohexane. Results
are expressed as absorbance lost at the lmax. The results of these studies are
summarized in Table 17.5.
Table 17.2 Results of Study by Deflandre and Lang (18)
% (w/w) in %
UV filter formulation Loss
Methylbenzylidene camphor 4 ,1
Padimate-O 4 15.5
Oxybenzone 2 .1
Phenylbenzimidazole sulfonic acid 4 ,1
Table 17.3 Results of Study by Shaath et al. (21)
% of degradation by solvent
Concentration Radiation
UV filter (ppm) (MED) Mineral oil IPM Ethanol/water
Oxybenzone 200 5 0 1.8 Not soluble

Octocrylene 200 5 2.8 1.1 0
Padimate-O 200 5 31.2 52.8 3.9
Homosalate 200 5 4.0 4.7 1.6
Octyl salicylate 200 5 0 9.8 1.5
Tarras-Wahlberg et al. (25) tested the photostability of Padimate-O,

methylbenzylidene camphor (MBC), and oxybenzone. The study found
Padimate-O to be the least stable of the three. Analysis of the sample by gas
chromatography following irradiation revealed two peaks in addition to the
one for the parent compound. They tentatively identified these as octyl 4-methy-
laminobenzoate (representing the loss in the parent compound of a methyl group)
and octyl 4-(formylmethylamino) benzoate (presumed to represent oxidation of
the amine part). For MBC, they observed an initial decline in the absorbance
after 20 MED. They reported that the observed spectrum was indicative of a
cis –trans photoisomerization. In a finding similar to Deflandre and Lang’s for
OMC (see preceding text), the Tarras-Wahlberg group noted the establishment
of a photostable equilibrium that changed very little after irradiation with an
additional 100 J/cm2 of UV-A. Oxybenzone, in their study, declined in absor-
bance very slightly after 20 MED of UV-B, and no further after the additional
UV-A dose of 100 J/cm2.
Roscher et al. (22) irradiated oxybenzone in cyclohexane for 70 –140 h
using a mercury vapor lamp. The oxybenzone was recovered unchanged, and
no detectable products were produced. Irradiation of Padimate-O in cyclohexane
yielded the ethylhexyl esters of p-aminobenzoic acid, p-mono-methylaminoben-
zoic acid, and p-dimethylamino(o/m)-methylbenzoic acid.
Table 17.4 Results of the Serpone et al. Study (27)
Exposure % degradation by solvent

time
UV filter (min) Water Methanol Acetonitrile n-Hexane
PABA 60 65 60 45 87
Padimate-O 20 75 15 94 97
Oxybenzone 120 20 90 5 – 10 15
Phenyl benzimidazole 10 (20) 90 N/A (50) N/A
sulfonic acid
338 Bonda
Table 17.5 Results of a Previously Unpublished Study
Radiation % Loss in % Loss in

UV filter dose (MED) isopropanol cyclohexane
Octocrylene 35 11 0
Octyl salicylate 35 1 ,1
Homosalate 35 2 ,1
Octyl triazone 35 31 13
Terephthalylidine dicamphor sulfonic acid (TDSA) used as a salt is a

water-soluble UV filter that is proprietary to one company. It is photostable
(18,31). Its photostability is attributed to its ability to dissipate its excited state
energy through a nondestructive E– Z isomerization (see Fig. 17.5).
Three relatively new European UV filters are also reported to be photo-
stable, as noted in the following text.
The sodium salt of disodium phenyl dibenzimidazole tetrasulfonate
(DPDT) is soluble in water at 12% (w/w). Johncock and Schuricht (32) prepared
1% and 3% solutions of DPDT, which they irradiated with 13.5, 27, 40.5,
and 54 J/cm2, (equivalent to 5, 10, 15, and 20 MED, respectively). As deter-
mined by HPLC, the 1% DPDT solution showed loss of 1%, 4%, 4%, and 8%,
respectively, and the 3% DPDT solution showed losses of 1%, 2%, 3%, and
3%, respectively. Johncock and Schuricht reported similar results when DPDT
was incorporated into an oil in water emulsion, of which 2 mg/cm2 was
applied to quartz plates. They observed 2%, 5%, 7%, and 8% loss after irradiating
the 1% DPDT emulsion with 5, 10, 15, and 20 MED, and 1%, 1%, 3%, and 3%
loss, respectively, for the emulsion with 3% DPDT.
Methylene bis-benzotriazolyl tetramethylbutylphenol (MBBT) is an
organic microparticle that is employed in sunscreen formulations much as
microfine metal oxides are. The photostability of MBBT was tested according
to the method of Berset et al. (33). Herzog et al. (34,35) report that 99% of
MBBT was recovered after irradiation with 10 MED, and 98% was recovered
after irradiation with 50 MED.
Bis-ethylhexyloxyphenol methoxyphenyltriazine (BEMT) is an oil-soluble
crystalline solid. In a study comparing the photostability of BEMT with OMC,
avobenzone, and MBBT, BEMT was reported to be photostable; recovery of
BEMT was higher than 95% after irradiation with 50 MED (36,37).
UV Filter Combinations
Serpone et al. (27) combined the two organic UV filters, OMC and oxybenzone,
at 8 mg/L in air-equilibrated aqueous media and irradiated the solution with
UV-A/UV-B radiation. They reported significant photodegradation of the
OMC after only 15 min. Oxybenzone degraded by 60% after 260 min.
The Serpone group (27) also irradiated oxybenzone and titanium dioxide at
8 and 300 mg/L, respectively, in aerobic aqueous media, using what they call an
“ultrafine sunscreen-grade TiO2.” They report that about 70% of the oxybenzone
degraded after 20 min of UV exposure. This was much faster degradation than
observed in the solution containing oxybenzone alone, where it took 260 min
of UV irradiation to achieve 50% degradation. The Serpone report concluded
that oxybenzone degradation was photocatalyzed by the titanium dioxide. As
the mechanism, they note that “UV illumination of TiO2 yields conduction
band electrons and valence band holes, which interact with surface-adsorbed
molecular oxygen to yield superoxide radical anions, O2 2 , and with water to
produce the highly reactive OH radicals,” which then may react destructively
with oxybenzone.
The photostability of a sunscreen emulsion (oil in water, O/W) that
contained OMC and oxybenzone at 5% and 3%, respectively was tested (unpub-
lished data). The emulsion contained no other UV filters. The investigator pre-
pared a thin film of the emulsion and allowed it to dry before irradiating
it with 20 MED from a solar simulator. Scans of the thin film performed on
a Labsphere UV-1000 Ultraviolet Transmittance Analyzer before and after
irradiation showed a 13.5% reduction in UV-B attenuation and no loss of
UV-A attenuation.
PHOTOSTABILITY OF SUNSCREEN FORMULATIONS

Diffey et al. (7) tested nine commercial sunscreens available on the market in
Europe during 1997. Briefly, the researchers dispensed each sunscreen on a
quartz plate such that the sunscreen coated the quartz to 1 mg/cm2. The quartz
plates were dried in an oven set at 308C for 15 min, then exposed to radiation pro-
vided by a Xe lamp that was filtered to remove wavelengths ,290 nm and
.400 nm. The UV transmittance of the quartz plates was measured at intervals
of continuous irradiation of 60, 120, and 180 min. The cumulative dose of UV
radiation received by each slide at each time interval corresponded to 18, 36,
and 54 J/cm2, respectively. A theoretical sun protection factor (SPF ) was calcu-
lated from the transmission data.
Of the nine products tested, five were photostable, one showed minor
photodegradation, and three exhibited marked increases in transmittance and
were therefore judged to be photounstable. The photostable products lost no
more than 10% of their calculated SPF after 3 h of irradiation. The UV filter
systems in four of the five photostable products included the combination of avo-
benzone and methylbenzylidene camphor (MBC) (see section on photostabili-
zers). Three of the five photostable products also contained terephthalylidine
dicamphor sulfonic acid (TDSA) and TiO2. A fourth photostable sunscreen, in
addition to the avobenzone and MBC, also contained octyl triazone, octyl sali-
cylate, homosalate, and TiO2. The fifth contained no avobenzone, containing
instead OMC, octyl salicylate, and oxybenzone.
340 Bonda
The three photounstable products in the Diffey study all combined

avobenzone with either OMC or isoamyl methoxycinnamate. Cinnamate deriva-
tives and avobenzone have been widely reported to be photounstable in combi-
nation (6,32). The sunscreen that showed minor degradation contained OMC
and TiO2. It lost about 33% of its calculated SPF after 3 h.
Stokes and Diffey (6) also tested the photostability of four commercial
sunscreen products by applying them to roughened quartz plates and to ex vivo
human skin excised during breast reduction surgery. The study tested the effect
of application thickness (1 vs. 2 mg/cm2) and radiation source (Xe lamp vs. sun-
light) on photostability assessment. Of the four sunscreens tested, one combined
avobenzone and octocrylene in its UV filter system and also contained TDSA and
TiO2. Octocrylene is widely known to photostabilize avobenzone (see section
on photostabilizers). Not surprisingly, this product proved to be photostable on
both the roughened quartz and ex vivo human skin substrates, and under all
test conditions. The other three sunscreens combined OMC and avobenzone, a
combination known to be unstable. In addition to OMC/avobenzone, one also
contained oxybenzone, another contained methylbenzylidene camphor and
TiO2, and the third contained only TiO2. All three sunscreens proved to be photo-
unstable when tested on roughened quartz. Surprisingly, however, the sunscreen
that combined OMC, avobenzone, and oxybenzone proved to be photostable
when tested on ex vivo human skin. By way of explanation, Stokes and Diffey
speculated that an epidermal substrate may provide the excited sunscreen mol-
ecules with alternative pathways to dissipate their energy than they would have
on a roughened quartz plate, adding that these alternative pathways may affect
sunscreen efficiency in a beneficial way.
In 2001, Maier et al. (38) tested the photostability of 16 sunscreens com-
mercially available in Europe. They spread measured amounts of each sunscreen
to a quartz slide to make a uniform film. The slides were dried for 30 min, then
irradiated with a solar simulator at a rate of 12.75 SED (standard erythemal dose)
per hour. Spectral absorbance of each slide was measured in both the UV-A range
(320 – 400 nm) and UV-B range (280 – 320 nm) using a spectrophotometer.
In reporting their results, the Maier group distinguished between UV-B and
UV-A photostability. Basically, they found all 16 products to be photostable in
the UV-B range; one product showed inactivation of 5.1% after a 25 SED
exposure; all others showed inactivation of less than 1% in the UV-B range.
In contrast, Maier et al. found seven of the 16 products to be photounstable in
the UV-A range. Photoinactivation in these products after 25 SED ranged from a
low of 12.3% to a high of 48.4%. All seven of the photounstable products contained
avobenzone as one of the filters, as did most of the photostable products. All seven
of the unstable products combined OMC (and/or isoamyl methoxycinnamate) with
avobenzone in their filter systems. Surprisingly, three of the photostable products
also combined OMC with avobenzone. Methylbenzylidene camphor was used in
six of the seven photounstable products, and in the three photostable products
that also contained OMC and avobenzone. In apparent frustration, the Maier
report concluded “that the behavior of suncare products was not predictable from
its individual ingredients.” It continued, “The inclusion of a single photounstable
filter did not mean photoinstability of the complete suncare product.”
Research at CPH Innovations into the relationship between solvent polarity
and sunscreen photostability may offer a partial answer to the Maier group’s
dilemma. The CPH Innovations study (17) included an experiment in which a
matched pair of sunscreens was tested in vivo for SPF. Both sunscreens contained
5% octyl salicylate, 3% oxybenzone, and 2% avobenzone. One sunscreen was
made with the relatively nonpolar solvents, C12 –15 alkyl benzoates and octyldo-
decyl neopentanoate, while the other was made with the relatively polar solvents,
diisoamyl malate, dibutyloctyl malate, and dimethyl capramide. The measured
dielectric constants of the sunscreen oil phases were 5.48 and 8.71, respectively.
The sunscreen with the nonpolar solvents achieved SPF 17.1; the sunscreen with
the relatively polar solvents achieved SPF 25, a 46% improvement.
The photostability of an SPF 30 sunscreen, commercially available in the
USA in 2003, was tested (unpublished data; test peformed on Coppertone SPF
30 Sunblock Lotion). The sunscreen’s filter system included octyl salicylate,
homosalate, oxybenzone, avobenzone, and octocrylene determined by GC to
be present at 2% (w/w) in the formulation. A measured amount of the sunscreen
was spread on an artificial skin-like substrate, allowed to dry, and then irradiated
with 35 MED. Absorbance across the solar UV spectrum was measured before
and after irradiation. The sunscreen proved to be quite photostable, losing none
of its UV-B attenuation, and only about 4% of its UV-A attenuation. The
results of this test can be seen in Fig. 17.8.
Sayre and Dowdy (39) tested six commercial sunscreen preparations avail-
able in the USA in 1999. They used an apparatus that simultaneously irradiated a
film and monitored the UV transmittance of the film in real time. Of the products
tested, four contained OMC and avobenzone, one contained Padimate-O and avo-
benzone, and one contained OMC, homosalate, and oxybenzone (and not avoben-
zone). Results were reported in terms of “monochromatic protection factor”
(MPF), which was calculated as the reciprocal of transmittance. Sayre and
Dowdy reported that only the sunscreen that contained no avobenzone was
photostable; it lost none of its MPF after irradiation with 10 MED. The sunscreen
with Padimate-O and avobenzone was the most unstable, retaining only 20% of its
MPF after 2 MED, and ,10% after 10 MED. The other avobenzone-containing
sunscreens showed various degrees of instability, retaining from about 60% MPF
to 30% MPF after 10 MED.
PHOTOSTABILIZATION STRATEGIES
Formulation Strategies
By one count, 126 US patents were granted between 1984 and 2003 that are con-
cerned in some way with photostabilizing avobenzone, the latest being granted
342 Bonda
Photostability of Commercial SPF 30

Sunscreen Sold in U.S., 2003
1.8
1.6
1.4
Absorbance
1.2
1 Before
irradiation
0.8 After 35 MED
0.6
0.4
0.2
0
280 310 340 370 400
Wavelength (nm)
Figure 17.8 The good photostability of an SPF 30 sunscreen sold in the USA in 2003
after a 35-MED exposure. The filter system of this sunscreen includes octyl salicylate,
homosalate, oxybenzone, avobenzone, and octocrylene at 2% (w/w) by GC.
two days before this search was undertaken. Clearly, the task of photostabilizing
avobenzone has been, and remains, a primary focus of sunscreen formulators and
chemical suppliers worldwide.
The ideal formulation strategy removes ingredients known to be deleter-
ious to avobenzone photostability, and includes ingredients that are known to
improve photostability. A survey of the sunscreen products tested by investi-
gators whose work has been cited in the chapter reveals that few appear to
meet this ideal. Many, for example, combine avobenzone with OMC. Excep-
tions notwithstanding (see the Maier study referenced earlier), the OMC/
avobenzone combination is well known to be photounstable and not amenable

Search by author of United States Patent and Trademark Office website (www.USPTO.gov) con-
ducted August 21, 2003. Search terms used were (avobenzone AND photostability) OR (dibenzoyl-
methane AND photostability) OR (dibenzoylmethane AND photostable).
to photostabilization unless segregated by some means such as encapsulation

(40,41).
Certain UV filters and chemical additives are known to exert a photostabi-
lizing effect on avobenzone. These chemicals share two things in common: they
“quench” the triplet state of the avobenzone by an energy transfer mechanism,
and they dissipate the excited state energy harmlessly.
One of these photostabilizers is methylbenzylidene camphor (MBC), a UV
filter permitted in Europe, though not in the USA. Berset et al. (42) reported that
even low concentrations of MBC (0.5 – 3%) in formulation are sufficient to
preserve 80– 90% of the avobenzone from photodegradation.
Octocrylene, a UV-B filter used worldwide, is well known to be an effective
photostabilizer for avobenzone. Patents exclude most formulators from using octo-
crylene for this purpose when the mole ratio of octocrylene to avobenzone is 0.8
(12). Translated, this means, for example, that when the avobenzone concentration
is 3%, the octocrylene concentration cannot exceed about 2.5%. Berset et al. (42)
reported that low levels of octocrylene (0.5–2.5%) in formulation will preserve
80–90% of the avobenzone from photodegradation. Use of these low levels of
octocrylene to photostabilize avobenzone is also the subject of a patent from one
of the manufacturers of avobenzone and is, therefore, available to license (43).
A relatively new addition to the list of photostabilizers is diethylhexyl
2,6-naphthalate (DEHN). According to Bonda and Steinberg, use of DEHN at
4% can preserve over 90% of avobenzone’s UV-A and UV-B attenuation after
irradiation with 10 MED of UV radiation from 290 to 400 nm (10). In another
example, a formulation containing 5% octisalate, 4% oxybenzone, 3% avoben-
zone, and 5% DEHN, lost virtually none of its absorbance across the UV spec-
trum after irradiation with 25 MED. The same formulation was tested in vivo
and achieved an average SPF of 32. Figure 17.9 shows the high photostability
of a formulation stabilized by diethylhexyl 2,6-naphthalate that contains in its
filter system 8% homosalate, 5% octyl salicylate, 5% oxybenzone, and 3%
avobenzone. After 35 MED, this sunscreen lost none of its UV-B attenuation,
and only 3.5% of its UV-A attenuation (unpublished data).
Derivatives of benzophenone such as oxybenzone and others that share the
basic 2-hydroxybenzophenone structure help to photostabilize avobenzone.
According to one patent, adding a 2-hydroxybenzophenone moiety can increase
avobenzone photostability by a factor of 10, though the avobenzone still loses
.60% of its absorbance (44).
A study by Chatelain and Gabard (37) showed that bis-ethylhexyloxyphe-
nol methoxyphenyl triazine (BEMT) improves the photostability of avoben-
zone, and the combination of avobenzone and OMC. The researchers
employed the method of Diffey et al. (7) and Sayre to compare UV filter recovery
as measured by HPLC on irradiated quartz slides and nonirradiated quartz slides.
They used a standard dose of 30 MED of UV radiation, 290 – 400 nm. They report
that formulations containing avobenzone alone lost between 56% and 70% of the
starting material after irradiation. With BEMT added, only 5% to 15% of the
344 Bonda
Photostability of Sunscreen stabilized by

Diethylhexyl 2,6-naphthalate
2
1.8
1.6
1.4
Absorbance
1.2
1 Before
irradiation
0.8 After 35 MED
0.6
0.4
0.2
0
280 310 340 370 400
Wavelength (nm)
Figure 17.9 After irradiation with 35 MED, this SPF 30 sunscreen lost no UVB absor-
bance and only 3.5% UVA absorbance. Its filter system is comprised of 8% homosalate,
5% octyl salicylate, 5% oxybenzone, and 3% avobenzone. It is stabilized with 5% diethyl-
hexyl 2,6-naphthalate.
original avobenzone was lost. In a formulation containing 5% avobenzone and

5% OMC and no BEMT, 65% of the OMC and 45% of the avobenzone were
lost. With BEMT, the comparative loss was 35% of the OMC and 17% of the avo-
benzone. Chatelain and Gabard report that the optimal photoprotective amount of
BEMT for OMC and avobenzone is 5%.
Methylene bis-benzotriazolyl tetramethylbutylphenol (MBBT) is reported
to improve the photostability of OMC (45). Without MBBT, 27% of OMC
was lost after irradiation with 10 MED. In the presence of MBBT, the loss was
only 8%.
Molecular Strategies
Earlier, we discussed some of the many pathways a molecule may take between
absorbance of a photon and dissipation of its excited state energy. Each pathway
is associated with a rate constant, and each is associated with its own timescale.
To illustrate, laser flash photolysis studies of terephthalylidine dicamphor
sulfonic acid (TDSA) revealed that, following UV-A excitation, ,10% of the
initially excited molecules decay to the triplet state, and that they remain in
the triplet excited state about 100 ns (100 1029 s) (33). This information
tells us that, at most, 10% of the TDSA can engage in reactions that proceed
from the triplet state, and further, that TDSA is likely to engage in reactions
that take place in 100 ns or faster. We know that even fast chemical reactions
between two molecules require timescales more on the order of 1000 ns
(1: p. 7). So we can conclude that TDSA is not likely to undergo much photo-
degradation as a result of bimolecular reactions, though photodegradation by
other pathways is still theoretically possible.
The process by which an excited molecule shifts from one spin-paired state
to another (e.g., from the singlet excited state to the ground state) is called
internal conversion. The transition from a spin-paired state to an unpaired state
(e.g., a singlet excited state to a triplet excited state) is called intersystem cross-
ing. Since intersystem crossing leads to the triplet excited state, and since most
chemical reactions proceed from the triplet state, a sound molecular strategy
to encourage photostability will promote internal conversion to the exclusion
of intersystem crossing. Isomerization and intramolecular hydrogen transfer
can facilitate rapid internal conversion (46). We have seen that some isomeriza-
tions such as those presumed for MBC and octocrylene, are associated with rela-
tively high photostability, and with the ability to photostabilize avobenzone. We
have also seen that molecules that contain a hydroxyphenyl group ortho to a car-
bonyl or a ring-bound nitrogen, such as octyl salicylate, homosalate, oxybenzone,
MBBT, and BEMT are all very photostable. This structural feature permits a very
rapid excited-state intramolecular proton transfer (ESIPT) that, in turn, promotes
rapid internal conversion. Residual energy can then be dissipated harmlessly in
collisions with surrounding molecules (47).
CONCLUSIONS
The organic UV filters used in sunscreens are powerful photochemicals whose
behavior is closely related to their molecular structure and their immediate
environment. Individually, they exhibit varying degrees of photoinstability
depending in part on the experimental model used to measure them. In
general, they can be divided into a relatively photostable group and a relatively
photounstable group. Into the first group may be placed octyl salicylate, homosa-
late, oxybenzone, methylbenzylidene camphor, TDSA, octocrylene, DPDT,
MBBT, and BEMT. Into the second group may be placed octyl dimethyl
PABA, octyl methoxycinnamate, octyl triazone, and avobenzone. Of the photo-
unstable UV filters, avobenzone has attracted the greatest attention because of its
preeminent role as the UV-A absorber of choice, and therefore, its greater poten-
tial impact on overall sunscreen performance.
346 Bonda
For reasons that are not always clear, UV filters often behave differently
in sunscreen formulations and under conditions of use than they do in some lab-
oratory experiments. Some of their behavior in formulation may be explained
by solvent considerations. In particular, the photostability of avobenzone may
be influenced by the protic and polar natures of other chemicals in the formu-
lation. As a practical matter, avobenzone may be rendered photostable in for-
mulation by using photostabilizers such as octocrylene, methylbenzylidene
camphor, diethylhexyl 2,6-naphthalate, and BEMT, and by avoiding chemicals
that are destabilizing such as octyl methoxycinnamate and octyl dimethyl
PABA.
Photostability bears a direct relationship to molecular structure. Mol-
ecules with vinylic moieties (octyl methoxycinnamate) or amine substituents
(octyl dimethyl PABA) exhibit lower photostability, though it must be empha-
sized that formulations containing OMC without avobenzone generally exhibit
high photostability. Molecules that undergo rapid isomerization upon excitation
(octocrylene, methylbenzylidene camphor, TDSA) dissipate their excited state
energy efficiently and show good photostability. Molecules that are capable of
extremely fast intramolecular proton transfer (octyl salicylate, homosalate,
oxybenzone, MBBT, and BEMT) are all very photostable. At first glance, it
may appear that avobenzone should be one of these since in its enol form it
appears equipped to undergo rapid intramolecular proton transfer. However,
photodegradation takes place through the diketo form and the drive to maintain
the enol – diketo equilibrium likely paves the way for further degradation.
Designers of new UV filters would be wise to heed these lessons in their
efforts to develop the next generation of sunscreen active ingredients.
ACKNOWLEDGMENTS
I gratefully acknowledge the invaluable contributions of Gary Wentworth, PhD,
and Anna Pavlovic, PhD of CPH Innovations, Gary Neudahl of RTD Hallstar,
and Tom Meyer, PhD, of Schering-Plough Healthcare, to the preparation of
this chapter.
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18
Formulating Sunscreen Products
Kenneth Klein and Irwin Palefsky

Cosmetech Laboratories, Inc., Fairfield, New Jersey, USA
Introduction 354
Formula Types 356
Emulsions 356
Oils 358
Gels 359
Sticks 361
Mousses 361
Aerosols 362
Ointments 362
Formulating Basics 362
Principles of Emulsification 362
Selecting Key Ingredients 365
Emulsifiers 365
Emollients 367
Film Formers 368
Stabilizers/Protectants 369
Organic Sunscreens 370
Inorganic/Particulate Sunscreens 372
Fragrances 373
Achieving Formula Goals 373
To Achieve High SPFs 373
To Achieve Water Resistance 374
353
354 Klein and Palefsky
To Obtain Mild Formulations 374

Patent Issues 375
Stability Evaluation 375
Organoleptic Considerations 376
The Use of Antioxidants in Sunscreen Formulations 376
Formulations 376
References 382
INTRODUCTION
With the publication of the Final Sunscreen Monograph on May 21, 1999, the
“playing field” for marketers of finish goods became more complex and now
offered some new opportunities for “marketing handles.” Although some
claims could no longer be made, such as those relating to aging and wrinkling,
we now see the appearance of strong claims dealing with ultraviolet-A (UV-A)
radiation. In fact, the US Food and Drug Administration (FDA) has even pub-
lished a list of those sunscreens for which usage permits UV-A reference.
Some additional claims have begun to appear deal with protection against infra-
red (IR) radiation. The FDA Tentative Final Monograph (TFM) does not deal with
IR in any way. Thus, IR claims are cosmetic and not drug claims. They must
be substantiated for the Federal Trade Commission (FTC), but not the FDA.
Marketersalso have made claims for “all-day” waterproof protection. The FDA
no longer allows a waterproof claim. They feel that the term suggests an
absolute—waterproof—which is not borne out by the currently available test
methods. The sweat proof claim can now be made, if the product meets the
requirements for a very water-resistant claim. Additionally, extended claims
such as “all day” are not permitted.
The last several years have seen the appearance of products on the shelf that
make the claim “chemical-free” sunscreens. Marketers are trying to take advan-
tage of the public’s general erroneous belief that “chemicals” are “bad.” This
claim is silly and has no basis in reality. All sunscreen actives whether they
are organic or inorganic are “chemicals.” Products that make this claim generally
are formulated with particulate sunscreens (zinc oxide or titanium dioxide). In the
minds of some consumers “chemicals” are bad things to put on their skin, so mar-
keters try to take advantage of this. This is a questionable approach, at best, and
quite misleading. The FDA has not looked kindly at this “claim.”
The cosmetic chemist has at his or her disposal many vehicles from which
to choose; these include, but are not limited to, emulsions, oils, gels, sticks,
mousses, aerosols, and ointments. There are many factors, some technical and
some not, that determine which will be the vehicle of choice. Each of the vehicles
has strengths and weaknesses that can have a significant influence on the
Formulating Sunscreen Products 355
cosmetic chemist’s choice. To make a wise choice, relevant factors and questions
must be addressed:
What is the target sun protection factor (SPF)? This is a market- and
marketing-driven question. The trend toward higher SPFs seen from the
mid-1980s through the 1990s has not yet leveled off. Although there have been
products introduced with an SPF as high as 70 by major marketers, almost all
sunscreen products have SPFs of 45 or less. One should question the real need
for a product with this degree of protection. If the average minimum erythemal
dose (MED) is taken as 20 min (for a person with type II skin in New Jersey
exposed to noonday sun), then a SPF 50 product would permit exposure to
noonday sun for 1000 min (16.67 h). Where can one get this type of exposure?
Certainly not in New Jersey! Although it is true that other latitudes do indeed
yield much shorter MED times, an SPF of 50 would seldom, if ever, be required
by most of the population at large. With this in mind, the FDA has limited the
maximum that can be claimed to “30þ.” It is likely that when the monograph
becomes the “law of the land” products making SPF claims beyond “30þ”
will be seized and forced off the market by the FDA.
Who is the target group? If it is persons with very sensitive skin then maybe
“aminobenzoic acid (PABA) free” should be the approach of choice. The FDA
feels that a PABA-free statement should not appear on the label. First, the drug
name for PABA is aminobenzoic acid. Second, by making the statement that
this product is PABA free you are implying that PABA is either unsafe, or is inef-
fective. Because it has been judged safe and effective by the FDA, they feel that
such a statement should not be made. Although it is true that more people are sen-
sitive to PABA than some of the other approved materials, the PABA-free state-
ment implies a degree of safety that may not be present. With this in mind, the
FDA will permit marketers to say “aminobenzoic acid (PABA) free.” Certainly,
there have been ample questions raised concerning the safety profile of several
sunscreens including oxybenzone, yet in this country; there has been no major
push to market products that are “oxybenzone free.” From this situation one
could conclude that marketers and raw material suppliers, at least occasionally,
put economic considerations before technical and safety ones.
What is the cost of materials limitations? The sunscreen business, as with
all mass merchandise efforts, is extremely sensitive to pricing. While the cost of
the popular approved organic sunscreen active agents has dramatically dropped
throughout the 1990s into 2003, their cost contribution to the overall formulation
is still quite high compared with other typically employed cosmetic raw
materials. This reflected in the high selling price of finished goods in this cat-
egory. It is most notable because of the increasing popularity of high SPF
products.
How important are water-resistant or very water-resistant claims? This
claim is most important for those sunscreen products designed for use at the
“beach.” Consumers now expect the products they purchase, that have an SPF
of 15 or higher to be very water resistant.
How will the formula be packaged? Because sunscreens are very good sol-
vents, particular care must be paid to this factor. Use of low-density polyethylene
should be avoided since the sunscreen will possibly collapse the package.
Additionally, do not forget that often the sunscreens will be stored in a very
warm environment such as the glove compartment of your car where the temp-
erature may, for short time periods, exceed 508C! With this in mind, be sure
your package (and product) can stand up to this temperature extreme.
How important are esthetic considerations? Although sunscreens are
drugs, the consumers who purchase them have become accustomed to elegant
vehicles, such as those that deliver their cosmetics. If the sunscreen gives a
greasy, occlusive feel, or leaves an opaque residue, then the purchaser will
probably look elsewhere. In recent years, formulators have become more
sophisticated, and successful, in developing products that are quite elegant and
yet deliver a very high level of sunscreen protection. As dermatologists have
found, the more the patient (or consumer) wants to use the product the greater
the likelihood of “patient compliance.”
FORMULA TYPES
Emulsions
By far the most popular of all vehicles used for sunscreens, the emulsion offers
almost unlimited versatility. Lotions are more popular than creams owing to their
easier spreadability on the skin and dispensability from bottles. An emulsion is
termed a cream or lotion on the basis of its viscosity (resistance to flow). It is dif-
ficult to determine the exact point at which a lotion becomes a cream and, some-
times, the designation may be quite arbitrary. Lotions typically have viscosities
,50,000 centipoise (cP) and will flow when the container is tilted or squeezed.
The viscosity of creams can run into the millions of centipoises, but usually is in
the 150,000 – 500,000 cP range. Although emulsions are the most popular
vehicle, they are also the most difficult to stabilize. We will discuss methods
of stabilizing emulsions later in this chapter. If the highest SPF possible, at the
lowest possible cost, is the goal, then the emulsion vehicle must be strongly con-
sidered. To appreciate why emulsions are so effective one must understand the
factors (1) that lead to consistently high SPFs:
Uniform sunscreen film
Thick sunscreen film
Nontransparent sunscreen film
Minimum ingredient interaction with the sunscreen’s active agent.
In each of these important areas, emulsions exhibit good performance.
Emulsions allow easy incorporation of sunscreen active agents, which are typi-
cally oils that can be readily emulsified. Emulsions can be prepared that contain
a large percentage of water; thus, they can be, and are, a most cost-effective
vehicle. From an esthetic viewpoint, emulsions are an elegant medium that can
give the skin a smooth silky feel without being greasy. They can accommodate
an almost infinite variety of raw materials; thus, you can tailor the formulation
to suit your needs. On the negative side, emulsions are quite difficult to stabilize,
particularly at elevated temperatures. Cosmetic emulsions are thermodynami-
cally unstable (with the exception of spontaneously forming microemulsions).
Thus, they will always eventually separate. Hopefully, the sunscreen emulsion
will be purchased and used before the separation occurs! Additionally, emulsions
present a perfect medium for microbial contamination and eventual product
breakdown. As more and more consumers seek the protection of very high
SPF products (30 and higher) that are water resistant or very water resistant,
the cosmetic chemist finds it increasingly difficult to achieve these goals
with an emulsion vehicle. Emulsions can be broadly placed into two categories:
oil-in-water (O/W) and water-in-oil (W/O). By far, the O/W emulsions are more
popular vehicles. This is, at first glance, a bit surprising since W/O emulsions
are inherently better sunscreen vehicles. W/O emulsions are by their very
nature very water resistant and they will consistently yield a higher SPF for
the same concentration of sunscreen actives when compared to O/W emulsions.
One explanation for this better sunscreen performance rests with the notion that
since (most) sunscreens are soluble in the oil phase, in W/O emulsions the oil
phase is continuous and thus when they are applied to the skin there is no need
for agglomeration to occur (as there is with O/W emulsions) and so a very
uniform sunscreen film results along with a high SPF. Additionally, W/O
emulsifiers (low hydrophilic – lipophilic balance) do not have a “large head
group” and thus they will not upset the lipid bilayer between the skin cells.
Thus, they do not promote the penetration of sunscreens or other materials in
the emulsion which may have a negative effect on the skin.
Another formula approach to consider is the use of emulsifiers that
promote the formation of liquid crystals as emulsifiers. It has been known for
many years that emulsions are often stabilized by liquid crystals. Generally,
these liquid crystals are lamellar in structure and either form a gel network in
the external phase or surround the oil droplets as layers (onion skin effect). In
both cases the liquid crystals act as a barrier to coalescence (due to the high vis-
cosity of the lamellar structure) and thus promote emulsion stability. This emul-
sion approach is a very good one for sunscreen formulators to consider for
several reasons:
1. Emulsifiers that form liquid crystals are not very hydrophilic and thus
do not promote sunscreen wash-off. Thus, they are excellent in formu-
lations where water resistance is an important factor. It has been
suggested that the lipophilic sunscreen migrates to a place between
the fatty tails of the liquid crystal emulsifiers and thus can be delivered
in a most uniform film to the skin surface. This insures a most efficient
sunscreen system!
2. Liquid crystal emulsions are nonirritating. Since the skin lipids and
skin cell membranes are of liquid crystalline structure, it is not sur-
prising that emulsions that utilize these structures as a stabilization
mechanism are less likely to upset the cell membranes or mobilize
the interstitial lipids. With this in mind, emulsions based on liquid
crystal emulsifiers will not upset the lipid bilayer and will not
increase the trans epidermal water loss (TEWL). Additionally,
they will not promote penetration of emulsion ingredients such as
sunscreens (2).
As can be readily seen, emulsions present great opportunities for
the creative, experienced formulators and great difficulties for the novice.
Without doubt they will remain the vehicle of choice for the foreseeable
future.
Oils
Oils are one of the oldest and most easily formulated sunscreen vehicles. There is
only one phase, so excellent product stability is readily achievable. Because most
sunscreen active agents are lipophilic, they are soluble in sunscreen oils; thus,
manufacturing processes are greatly simplified (most can even be prepared at
room temperature); certainly when compared with the manufacture of emulsions.
Oils are easily applied to the skin, spreading rapidly to cover a wide surface area.
Unfortunately, there are numerous negatives associated with sunscreen oils.
Their excellent spreadability results in a very thin, transparent sunscreen film,
and thus lowered SPF. Sunscreen oils exhibit the poorest SPF performance of
any vehicle. This poor performance is further explained by the interaction
between the most popular sunscreen (nonpolar esters) and the very nonpolar
oils vehicles. Nonpolar oils, such as mineral oil, cause the position of the UV
curves to shift to shorter wavelengths (3). Thus, part of the curve is moved
into the area of wavelength ,290 nm where it is wasted (from an erythemal
perspective). The result is a poorer-performing sunscreen; that is, a lowered
SPF rating (4). This shift to the shorter wavelengths is due to stabilization of
the ground state by the nonpolar vehicle. Another factor to consider is the
spreading ability of the emollients, which can play a major role in determining
the SPF of the finished formula (5). Lastly, the solubility parameter (a measure
of molecular stickiness/cohesiveness) will influence how the sunscreen is
oriented within the oil (or oil phase of an emulsion) (6). An additional negative
for oils relates to packaging. Sunscreen esters are excellent solvents. When they
are combined with other esters in sunscreen oils, the resulting product can attack
the plastic packaging typically used. Certainly, low-density polyethylene is a
poor choice, unless expensive internal coatings are employed. Another obstacle
to their use relates to cost of goods. Since this in an anhydrous system, there is no
water to lower the cost of expensive raw materials. Sunscreen oils are one of the
most expensive systems found.
Gels
The crystal clarity of cosmetic sunscreen gels projects an aura of purity and
elegance. On initial consideration, they would seem to present, from an esthetic
perspective, the ideal sunscreen vehicle. Unfortunately, this perception is quiet
premature. There are four major formula categories of sunscreen gels: (1)
aqueous, (2) hydro-alcoholic, (3) microemulsion, and (4) gelled oleaginous
(oily anhydrous). All of these present the cosmetic formulator with an abundant
supply of formulating difficulties.
The aqueous gel must use water-soluble sunscreens or employ solubilizers
(usually nonionic surfactants), which may be ethoxylated fatty moieties or
phosphate esters at sufficiently high levels to ensure that the gel will remain
clear at all temperature extremes. Neither of these approaches provides good
answers, for the resultant product is very prone to wash-off when exposed to
water or perspiration. The high level of surfactant can often make the finished
formula both expensive, and more importantly, quite irritating. Add to all of
this the great batch-to-batch variation these gels exhibit, owing to the very
delicate raw material balance required to achieve clarity. Manufacturing these
gels presents a rather unique problem in itself. Aeration must be avoided,
because deaeration can be time-consuming, expensive, and sometimes impos-
sible. The gel formation is often accomplished through the incorporation of an
appropriate “gum.” Although cellulose-based materials can be used, they must
be incorporated at very high levels (2 – 3%) to obtain the desired gel structure.
At these use levels, they can be quite sticky on application. The carbomers, syn-
thetic carboxyvinyl polymers, first introduced by the B. F. Goodrich Company
(now Noveon), are by far the most popular thickeners used in this category,
allowing the cosmetic formulator to achieve crystal clarity at reasonable use
levels (0.5 –1.0%). Unfortunately, the carbomers have compatibility, esthetic,
and performance problems. Because they are anionic when neutralized, care
must be taken not to include any cationic ingredients, as gel breakdown will
probably result. The carbomers can impart a transient tackiness that is most
evident during rubout. This is very apparent in gels for which use of emollient
esters must be minimized or eliminated to ensure optimum clarity. In addition
to these difficulties, the carbomers are quite sensitive to electrolytes found on
the skin. Thus, when applied, the carbomer gel “breaks,” and the product exhibits
very poor application characteristics. This effect is exacerbated by swimming in
salty water or by heavy sweating. Lastly, it is very difficult to obtain high SPFs
in this vehicle because the clarity issue rules out the use of high levels of the
best sunscreen active molecules, such as octinoxate, oxybenzone, or octocrylene.
Many of the comments concerning the aqueous gel also apply to the hydro-
alcoholic gel. A real benefit that is afforded by this vehicle is the desirable
cooling effect as it is applied to the skin. This is particularly refreshing on a
hot summer day. As its name implies, this gel employs the use of alcohol
(usually ethanol) in conjunction with water (which frequently comes from the
alcohol being used), as the main carrier components. The use of alcohol
greatly reduces the need for additional solubilizers because most of the lipophilic
sunscreens are readily miscible in ethanol. Some of the problems associated with
the hydro-alcoholic gels are the following:
1. Water resistance: By incorporating resins and other film formers, water
resistance can be improved, but the inherent nature of this vehicle
limits its effectiveness.
2. Facial or eye sting: The high levels of alcohol tend to cause facial and
eye stinging on certain individuals. Use of humectants can ameliorate
this but not eliminate it entirely.
3. Packaging: The high volatility of alcohol gives it a great tendency to
evaporate. This is most evident at high temperatures, such as those
encountered at the beach in the summer. Packaging must use barrier
coatings to retard this, which further increases costs. Closures should
be tight-fitting and easily resealable.
4. Efficacy: It is in this key area that hydro-alcoholic gels exhibit
their poorest performance. As mentioned earlier, to realize high
SPFs, one must lay down a uniform sunscreen film on the skin. On
exposure to heat and sunlight, the alcohol flashes off rapidly, leaving
a porous or discontinuous film. Thus, there are areas where there is
no coverage, and a lowered SPF is the result. Use of film formers
can help, but in the end the level of sunscreen must be increased to
overcome this effect; in reality, it is never completely conquered.
In microemulsion gels, the particle size is so small (,0.25 mm) that light
seems to pass right through the emulsion and a clear gel is the result. These
gels can have an elegant skin feel and can lay down a smooth, thick, and
uniform film on the skin, thus optimizing the SPF. Unfortunately, as with the
previous gels, there are numerous negative factors to contend with:
1. Cost: To achieve clear microemulsions, it is necessary to employ very
high levels of emulsifiers. Levels as high as 15 –25% are not uncom-
mon. This results in a very costly product.
2. Safety: In many emulsion systems the emulsifier is often one of the
most irritating ingredients in the formula. At use these levels one
must indeed be aware of this factor.
3. Water resistancy: The high emulsifier levels make the sunscreen easily
removed by swimming or perspiring.
4. Manufacturing problems: Slight variations in raw materials can, and
often do, lead to hazy or cloudy products. A slight change in the ethox-
ylation distribution may be all that is needed for disaster.
The microemulsion route is certainly a precarious one at best.
The oleaginous gels share many attributes with the ointments (addressed
later), but they are clear, whereas the ointments are translucent or opaque.
There are no popular products of this type on the market, as they are difficult
to manufacture and are quite expensive. They are generally produced
by gelling a combination of mineral oil and sunscreen with fumed silica or
other gellants.
Sticks
A relatively new form of sunscreen vehicle, the stick, brings with it a real
convenience of usage. Sticks are mostly used on the lip or nose. Because they
cover very small surface area on each application it is not practical to use
them on large areas of the body. The vast majority of sticks are composed of
oils and oil-soluble sunscreens, which in turn are thickened through the incorpor-
ation of waxes and petrolatum. They tend to have an oily or greasy skin feel and
are probably the most water resistant of any product form. With the addition of a
particulate sunscreen, such as titanium dioxide or zinc oxide, the resultant
product is often seen on the noses of lifeguards—not very esthetic, but quite
functional. Clear sticks can be made (using organic sunscreens), with the use
of alkanolamides as gellants, but stability and cost considerations have not
allowed marketing of these products. Recent work, modeled on the technology
of antiperspirant sticks (W/O microemulsions), has led to some niche clear gel
sunscreens, but the high cost of goods and difficult formulation issues will
keep this a very minor entry.
Mousses
The sunscreen mousse was first introduced several years ago. It has not attained
much consumer acceptance, and remains a niche product at best. A mousse is
typically an emulsion lotion to which some propellant has been added. When
the product is exposed to the lower pressure of the atmosphere (as compared
with the inside of the container), the propellant flashes off and a foam is
formed. These foams have more in common with shave creams than with other
product types. Most use anionic (triethanolamine stearate) emulsifier systems,
often coupled with a lesser amount of nonionic (ethoxylates). The sunscreen
active agents can be readily incorporated into the internal phase of these O/W
emulsions. They mimic most of the functional and esthetic characteristics of
the non aerosol emulsions. Their primary functional reason for being lies in
their ease of use. Great care must be taken to ensure that the cans are able to
withstand the temperature extremes encountered at the beach that give rise to
a significant increase in internal pressure and could potentially present a safety
hazard. Nonaerosol mousses have begun to appear on the market. They
employ a foaming surfactant and use high pressure (mechanical) to force the
product through a mesh to produce the form. The highly hydrophilic surfactant
will make it very difficult to keep this sunscreen from washing off.
Aerosols
The sunscreen aerosols have not enjoyed the same popularity as have the other
sunscreen vehicles for several reasons. Typically, they are oil-based, which
makes them rather expensive and often reduces their effectiveness (see foregoing
discussion). Additionally, it is difficult to see where you have applied the
sunscreen, and unless you are careful the sunscreen could be sprayed accidentally
into the eyes. Aerosols also put down a discontinuous film onto the skin; this
to, reduces their effectiveness. They can be either mechanical (pump spray) or
propellant-base, at this time neither has made any significant market penetration.
Ointments
These oily products closely mirror the composition and function of the stick pro-
ducts. They are generally based on mineral oil and esters that have been
thickened by the addition of petrolatum and some waxes. Their main benefit is
that they are very difficult to remove with water; thus, they are used by people
who must have a sunscreen that stays on the skin no matter how much swimming
or physical activity is done. They are, however, not very esthetic to use because
they are oily and greasy.
FORMULATING BASICS
Because the vast majority of all sunscreen products are creams or lotions, it is
important to understand the intricacies of formulating this most challenging
product category.
Principles of Emulsification
Although it is clear that it is extraordinarily difficult to produce emulsions that
meet the primary market objectives of efficacy, esthetics, and cost parameters.
An ever-present, but underlying, requirement is product integrity; or stated
another way: emulsion stability. At times it may seem that obtaining emulsion
stability is quite an elusive goal, in fact, perhaps unattainable. But by understand-
ing underlying principles of emulsification, coupled with a healthy mix of experi-
ence gained through many failures, we can make real inroads in this quest.
Even though emulsions come in two basic varieties, O/W and W/O, and
two basic “styles,” creams and lotions, the ideas presented in this chapter are
quite universal; thus, they can be successfully applied to all.
It is good to start with a healthy appreciation for the problem at hand;
improving emulsion stability. That which you are trying to do (make a stable
emulsion) is quite impossible (from a thermodynamic viewpoint) (7). An emul-
sion is a dispersion (the internal phase) of one immiscible liquid in another (the
external phase) in the form of tiny droplets. These droplets are constantly trying
to come back together, coalesce, to form a single large droplet phase. This is the
continuing battle of the cosmetic formulator against the laws of thermodynamics.

Can the battle ever be won, or is the only hope to put off the inevitable for a long
enough period to successfully market the product? Sometimes this emulsion
breakdown can be put off for several years. Some very viscous creams have
remained “stable” for more than 10 years through rather harsh temperature fluc-
tuations. The basic goal of all cosmetic chemists who formulate emulsions must
be to prevent, or more realistically, minimize particle interaction. If this can be
accomplished, the formulator is well along the road to success. There is an
equation that describes this interaction: Stokes law (8)
½d 2 ( p1 p2 )g
V¼
18h
where V is the velocity of sedimentation (interaction) of spherical particles, d is the

diameter of the particles of the dispersed phase, p1 is the specific gravity of the dis-
persed (internal) phase, p2 is the specific gravity of the continuous (external) phase,
g is the acceleration due to gravity, and h is the viscosity of the external phase.
After studying this simple equation it becomes apparent that our goal is to
minimize the value of V, the velocity of sedimentation (coalescence). This can be
done in only two ways.
1. Reduce the value of the numerator
2. Increase the value of the denominator.
Let us first deal with the numerator, d: reducing the size of the dispersed
droplets is indeed a very good approach that may be accomplished in several
ways. Choice and level of emulsifier (see discussion later) is certainly of
primary importance. Choice of optimum manufacturing procedure is also most
important. Generally, it is advisable to add the external phase to the internal
phase. In this way, the emulsion can go through a definite phase inversion.
This occurs because of the predominance of the internal phase relative to the
external phase. The phase volume ratio does not permit the formation of the
expected emulsion type. As more of the external phase is added, the phase
volume ratio permits the formation of the predicted emulsion type and, thus,
a phase inversion is seen. The result will be a reduced particle size and, just as
important, a narrow distribution of particle sizes. Unfortunately, this type of
phasing is seldom available during production, as usually the phase volume
ratio between the internal and external phases is such that there is not enough
internal phase to reach the mixing blade; thus, one cannot use this method.
The particle size can also be reduced by employing the method of Lin (9).
An emulsion concentrate is formed, composed of all of the internal phase (oil,
emulsifier, sunscreen, and other components) and a part (approximately 30%)
of the external phase (water, emulsifier, or such). The water phase can be
added to the oil phase to go through a phase inversion. The percentage of
emulsifier is higher in the concentrate than it will be after all of the water is
added; thus, you have effectively increased the level of emulsifier, without adding
more emulsifier. Very often a smaller particle size will be the result. The remain-
der of the water (at room temperature) can be added to the emulsion concentrate.
It will cool the emulsion and dilute the external phase. This addition of water will
not have a detrimental effect on the particle size. Lin’s technique can dramati-
cally reduce production cost and produce better emulsions.
The particle size can also be reduced through mechanical means. If the
finished emulsion is subjected to high shearing forces, the large particles will
be reduced in size. Numerous devices have been designed to accomplish this
feat, which are categorized broadly as homogenizers or (colloid) mills. Although
they often do an excellent job in reducing the particle size, great care must
be taken with their use, as they can degrade certain emulsion components,
such as gums, with their high shear. Another benefit of using homogenizers is
that they give a more uniform particle size distribution. Very often this is even
more important than reducing the average particle size. If the range of particle
size is quite narrow, there will be lower probability of coalescence when two
particles of similar masses collide, as the collisions tend to be more elastic
(less transfer of energy) under these conditions. Thus, the emulsion will
exhibit better stability. Another way to decrease the numerator is to make the
factor (p1 2 p2) as small as possible. In other words, make the specific gravities
of the internal and external phases as close as possible to each other. Since
the external phase primarily composed of water (O/W emulsion) the specific
gravity (SG) (ratio of the density of a substance relative to the density of
water) (10) is approximately 1. The internal phase is mostly composed of oil,
which has an SG of 0.80 – 0.95. Therefore, to make these two phases close to
each other in density we must either lower the SG of the water phase. The
obvious way to accomplish this is by adding alcohol to the water phase. At
first glance this seems to work quite well. But the emulsion rapidly breaks
down because of the alcohol’s excellent solvency with various emulsifiers;
hence, because of partition coefficient considerations, it extracts the emulsifier
from the oil –water interface and the emulsion breaks. Adding alcohol to the
water phase is thus not a worthwhile approach.
The last factor in the numerator is g, the acceleration due to gravity. This
cannot be altered by even the most creative cosmetic chemist.
The denominator has only one factor that we can work with, h (the
viscosity of the external phase). If we could increase this, it would decrease (vel-
ocity of sedimentation coalescence), and a more stable emulsion would be the
result. Here, we have the most often used technique (successfully) by cosmetic
chemists. There are many ways to increase the viscosity of the external phase.
1. Add more internal phase: This can effectively be used in both O/W
and W/O emulsions. It will certainly increase the viscosity of the
emulsion at room temperature, but at elevated temperatures, the emul-
sion will thin out and instability may very well result.
2. Reduce the particle size, so that the same amount of internal phase will
seem to occupy a greater volume, and the viscosity will increase.
3. Add a fatty moiety to form liquid crystals in the external phase. The
following phenomenon has been observed by many cosmetic chemists:
When a small amount of fatty alcohol is added to an O/W emulsion the
viscosity is seen to dramatically increase. According to Suzuki et al.
(11) “The self-bodying action of fatty alcohols was caused by the for-
mation of a network structure of liquid crystalline phase in the emul-
sion system.” In addition, the fatty alcohol will complex with
emulsifiers at the O/W interface to strengthen it and improve emulsion
stability.
4. Add a thickener (“gum”) to the external phase. Indeed this is a simple
and very effective approach. There are a bewildering number of gums
available to serve this purpose. Cellulosics are often used and can
be very successful. Unfortunately, they do not improve the high-
temperature stability to any great extent. There are several gums that
can do this: the carbomers and xanthan are the most popular. Both
of these allow the emulsion to retain a real measure of viscosity at
elevated temperatures. Consequently, the emulsion is much less
likely to show signs of instability. One must, however, be careful to
only use these last two thickeners in nonionic (the emulsifiers are
unchanged) systems because they are anionic in character themselves.
Selecting Key Ingredients

To formulate successfully you must have a thorough understanding of the prin-
ciples and rules by which we choose the appropriate ingredients for each
formula. Nowhere is this truer than in the formulation of sunscreen emulsions,
which are drug vehicles. One must appreciate the potential for ingredient inter-
action and keep in mind the formula requirements laid down by the various inter-
ested internal groups: marketing, R&D, packaging, claim substantiation, and
safety. Certainly, all ingredients selected must be cosmetically acceptable
(color, odor, skin feel, have good safety parameters, be stable to chemical and
UV exposure, and must not interfere with the efficacy of the sunscreen active
agent in any way. The following are some comments on how to select ingredients
with these thoughts in mind.
Emulsifiers
The oldest and most widely used method of selecting emulsifiers is the hydrophilic–
lipophilic balance (HLB) system. This system, invented by Griffin (12) in 1949,
was the first attempt to put a scientific basis behind the choosing of emulsifiers.
The HLB was determined for each emulsifier: that is, the relative percentage by
weight of the molecule that is water-loving vs. the oil-loving part. If a greater
weight percentage was water-loving, the emulsifier would be assigned a high
HLB number and this would be judged to be an O/W emulsifier. The oil phase
components are assigned a required HLB; thus, by choosing emulsifiers that
match the HLB requirements of our oil phase, a fairly good emulsion can be
formed. Experience has shown that this system works better for nonionic than
for ionic emulsifiers. Although the HLB system has great usefulness for choosing
a starting point for emulsions, there are several major concerns about the use of
this system that must be addressed.
Temperature effect on nonionics (ethoxylates): As the temperature
increases, the apparent HLB of emulsifiers decreases. Because ethoxylates (emul-
sifiers that employ ethylene oxide to increase their polarity and, hence, water
solubility) are soluble as a consequence of hydrogen bonding to water, they
become less soluble as increased kinetic energy (heat) causes a breakage in the
hydrogen bonds. This is often referred to as the inverse solubility of nonionics.
As the temperature increases they become less soluble. This is not what we typi-
cally see dealing with chemicals. Thus, an emulsifier that orients toward O/W
emulsions at one temperature may indeed orient toward W/O at some higher
temperature. The temperature at manufacture will play a significant role in the
quality (type and particle size) of the emulsion. This is one of the reasons that
many nonionic emulsions are not so easily scaled-up from the bench top to the
5000 gal kettle.
Ingredient interaction: Anionic and cationic emulsifiers will interact to
produce a precipitate and break the emulsion, but the HLB system does not take
this into account.
Fatty alcohol: According to the HLB system fatty alcohols are oils that
have a required HLB. However, experience has shown us that indeed fatty
alcohols are effective emulsion stabilizers and can be considered to be secondary
emulsifiers.
Phase/volume relations: The HLB system ignores the relative sizes of
the internal and external phases. As we know, this factor can and does have a pro-
found effect on the emulsion. Yet, while all of these drawbacks to the HLB
system exist, it should not be abandoned by cosmetic chemists. Rather, it
should be used in conjunction with sound experience and other systems to
choose emulsifiers.
The phase inversion method of choosing emulsifiers was proposed by
Shinoda (13). This system takes into account many of the drawbacks of the
HLB system, yet its underlying principles are closely linked to it. The inverse
solubility phenomenon can be used to choose emulsifiers. After the oil and
water phases have been combined, the cooling process begins. During this
cooling, the effective HLB of the emulsifiers becomes higher. There is a
temperature, the phase inversion temperature (PIT), at which the hydrophilic
and lipophilic tendencies of the emulsifiers balance. At this temperature, a phase
inversion can be observed as a dramatic change in viscosity. Additionally, one
can notice a stable pH below the PIT. If the PIT is at least 208C above the highest
storage temperature, you can be fairly confident that the emulsion will be a stable
one. You thus choose the level and type of emulsifier to achieve this PIT
temperature.
Lin et al. (14) have proposed a rather unique method of selecting emulsi-
fiers. All of the oil phase components are combined (esters, waxes, emulsifiers,
sunscreens) and heated until liquid. Then water is slowly added (titrated in)
while stirring. As the first drop of water hits the oil mixture, turbidity is
formed that slowly disappears. According to Lin et al. the more water that can
be solubilized into the oil phase, the smaller the emulsion droplets; hence, the
better the emulsion will be. You can modify the emulsifier types and concen-
trations to increase the water solubilization capacity of the oil phase. There is
ample experience to show that this method does indeed work. There is an
inverse correlation between the amount of water soluble in the oil phase and
the particle size of the final emulsion.
Up to this point, I have addressed mainly nonionic emulsifiers. Perhaps the
most widely used emulsifier is, however, anionic: soap; to be specific, triethano-
lamine (TEA) stearate. This emulsifier, prepared in situ, is one of the most power-
ful and inexpensive of the O/W emulsifiers known. This accounts for its
unmatched popularity. Other monovalent soaps can be used (sodium and potass-
ium), but the interfacial film they form is not as flexible as that of TEA stearate.
Emulsion stability will be further enhanced if combinations of emulsifiers are
employed. Thus, use of several types of emulsifiers (anionic and nonionic) is rec-
ommended. The variety of emulsifiers is almost unlimited; by using one or more
of the foregoing systems you can minimize the trial-and-error approach, and
maximize your chances for success.
Emollients
Emollients represent one of the most important classes of emulsion components.
Although there are both oil-soluble and water-soluble emollients, by far the oily
materials predominate. They provide a silky skin feel on application, while acting
as the vehicle in which the oil-soluble sunscreen is delivered. There are several
categories of fatty emollients: esters (liquid and solid), waxes, fatty alcohols,
mineral oils, and silicone materials.
Esters are a very widely used class of compounds in sunscreen emulsions.
Quite simply, they are the condensation product of an alcohol and an acid. By
varying the fatty moiety of each, an almost endless variety of esters can be pro-
duced, each with slightly different properties from the next. Some general rules
can be made that should provide guidance in choosing the best ester for your
requirements.
1. Chain length increase: As the chain length increases, the ester becomes
more viscous, eventually becoming solid; it becomes more difficult to
emulsify; it becomes less irritating to the skin; it acquires an oilier skin
feel and becomes less polar (this has an effect on the position of the UV
curve that may influence the effectiveness of the sunscreen actives).
2. Branching: As the ester becomes more branched it produces a drier
skin feel; it becomes less polar.
3. Unsaturation: As the ester becomes more unsaturated it becomes less
polar; it becomes harder to emulsify; and it seems to disappear into
the skin during rubout.
4. One area that should be considered when choosing an emollient for use
in formulating a sunscreen product is the solubility of one or more of
the sunscreens (i.e., oxybenzone, avobenzone) in the particular emol-
lient system. Poor solubility will have an adverse affect on sunscreen
performance and possibly product stability.
Waxes are not used to any great extent in sunscreen emulsions. Certainly,
carnauba, ceresin, beeswax, and many others are available to us, but they tend to
give a rather “draggy” feel to the skin and, thus, their use is held to a minimum.
Fatty alcohols provide a skin-smoothing during rubout, a matte, nongreasy
feel that is quite desirable. They can, however, if used at too high a level (2%
maximum), become “draggy” on the skin, certainly not a desirable feature. As
would be expected, as the chain length increases the melting point increases.
Thus, stearyl alcohol (18 carbon atoms) has a higher melting point than cetyl
alcohol (16 carbon atoms) and has a slightly heavier feel on the skin.
Mineral oil is one of the main constituents of many emulsions. Its wide-
spread use can be easily understood when one considers its low cost, broad
chemical compatibility, and safety. There are several grades of viscosity to con-
sider, depending on the skin feel and emulsion viscosity desired (minor effect).
One must remember that mineral oil can have a rather oily skin feel, which
can be reduced by combining it with esters. Because it is so nonpolar, it
usually has a detrimental effect on the sunscreen efficacy.
Silicone-based “oils” have enjoyed an almost explosive increase in popu-
larity in recent years. Dimethicone (polydimethylsiloxane) is the most widely
used material of this type. It provides a smooth initial skin feel, reduces skin
whitening (soaping), and minimizes tacky afterfeel. The cyclomethicones, also
called volatile silicone, greatly improve initial skin feel without contributing to
final greasiness. Questions have been raised regarding the safety of cyclomethi-
cones in recent years and thus their popularity is diminishing. Additionally, use of
volatile low molecular weight hydrocarbons and poly-alpha-olefins can effec-
tively reduce sticky afterfeel.
Film Formers
In recent years, there has been a noticeable trend toward increased efficacy in
sunscreen products. This could be manifested in a higher SPF or a product that
maintains its SPF after exposure to water. Film formers play a key role in both
of these endeavors. One of the primary factors that influence the ability of a
sunscreen product to achieve a high SPF is the uniformity of the sunscreen film
on the skin. It is absolutely crucial that this film be thick and uniform. Several
materials have been used to develop this type of film. Cellulosic gums lay
down a rather even film and can be readily incorporated into almost any emul-
sion. Polyvinylpyrrolidone (PVP) also serves this purpose. Unfortunately, none
of these ingredients imparts any measure of water resistancy to the formulation.
There are, fortunately, materials that can function as film formers that impart
wash-off resistance. The two that are used most are based on acrylic – acrylate
copolymer or PVP-hexadecene copolymer. Recently, polyethylene has also
been used. This material can act to increase the film thickness and additionally
can improve both the SPF and the water resistancy.
Stabilizers/Protectants
Emulsions are very delicate and are subject to attack from many directions. If
any of these attacks are successful, the emulsion will exhibit instability and
will not be sellable. We have previously discussed the thickeners (gums) as
stabilizers and will not do so again. Antioxidants represent a most useful and
functional class of materials. When oil-phase components are used that are
unsaturated (contain one or more double bonds), it is advisable to employ an
antioxidant to prevent oxidation of the double bond, with its associated rancidity
and discoloration. BHA, BHT, propyl gallate, and tocopheryl (acetate) are
frequently used. Antioxidants can also act as free radical scavengers and,
thereby, reduce chances of skin damage by these highly reactive moieties. It
has been suggested that use of antioxidants can actually increase the SPF. It is
likely that this effect is due to a reduction in erythema, rather than any increase
in UV absorbance. Chelating agents find use in many cosmetic formulations,
ranging from emulsions to hair products (shampoos). They can improve the
preservative efficacy of conventional preservatives and can tie up unwanted
metal ions that can cause discoloration and viscosity of the emulsion.
Preservatives must be considered one of the most important parts of the emulsion.
No emulsion is complete or safe without them. As with emulsifiers, they seem to
work best when several are combined at the same time. The subject of
preservation is so important and complex that the reader is urged to study it in
some depth using the many excellent texts available. This is no area for the
novice. Some suggestions that should be kept in mind when formulating
emulsions include:
When using gums or proteins, enhance the preservative system. When
using ethoxylated nonionic emulsifiers, paraben use levels should be
increased (the para-hydroxyl group of the parabens can hydrogen bond
to the ethylene oxide chains and thus effectively inhibit it from acting
as a preservative).
Always place the preservative in the water phase (this is the phase that must
be protected).
Organic Sunscreens
We are now ready to choose the primary functional ingredient in the sunscreen
formulation—the sunscreen. At the present time (in the USA) our choice is
limited to 16 sunscreen chemicals (15). Although the list of chemicals may
seem to be extensive, in reality only very few are seen in finished products.
Most of the materials have serious drawbacks associated with them.
Aminobenzoic acid: One of the oldest sunscreens, p-aminobenzoic acid,
commonly known as PABA has many drawbacks. Its UV curve peaks at the low
end of the UVB spectrum; it is too water-soluble (owing to high polarity at both
ends of the molecule); a segment of the population exhibits some sensitivity to it;
and it can stain clothing and skin.
Avobenzone (butylmethoxy dibenzoylmethane): A UVA absorber, this
sunscreen has enjoyed wide usage in the European Union (EU), Australia, and
Japan for a number of years. When approved by the FDA in its final monograph
it began to see acceptance in the USA. Issues exist regarding its photostability
and compatibility with commonly used cosmetic ingredients (formaldehyde
donating preservatives and transition metals). It cannot be used (at the time of
this writing) with either titanium dioxide or zinc oxide in sunscreen products
in the USA. Additionally, there are several sunscreen combinations that are not
permitted when using avobenzone (see Final Sunscreen Monograph) such as
ensulizole. Avobenzone is sold as an off-white crystalline powder that must be
solubilized into the oil phase of emulsion. Care must be taken to insure its
complete solubility. A number of materials have been proposed for use with
avobenzone to reduce the photo instability seen when used in many formulations.
The reader is urged to fully explore this area since there are several patents issued
(L’Oreal, P&G, C.P. Hall).
Oxybenzone and dioxybenzone: The best known of the UV-A absorbers
(they are actually primarily UV-B absorbers with a slight peak in the short
UV-A); they are seldom if ever used alone, but are combined with UV-B
screens to give high SPFs. They have poor solubility and moderate extinction
coefficients. The benzophenones are all ketones and thus can show discoloration
when used in the presence of primary or secondary amines (Schiff base
formation). Since they are ortho (and para) they do not exhibit a solvent shift
often seen with the para disubstituted sunscreens.
Cinoxate: A UVB absorber that is no longer in use.
Octocrylene (2-ethylhexyl-2-cyano-3, 3 diphenylacrylate): This had
not seen wide acceptance owing to its high cost, stickiness, off-yellow color,
and moderate extinction coefficient. In recent years, however, its usage has
dramatically increased. This is probably due to its ability to boost the SPF and
also improve the water-resistancy of many formulations. It also has the ability
to help stabilize avobenzone through triplet –triplet quenching (16).
Octisalate (octyl salicylate) and homosalate (homomenthyl

salicylate): Both of these compounds have a long history of use. Both were
supplanted by the more efficient PABA and cinnamate derivatives. With the
trend toward high SPFs, a significant increase in the use of octyl salicylate
has been observed. This has been accelerated by another marketing trend:
PABA-free. Octyl salicylate, like all salicylates, is ortho-disubstituted and,
thus, exhibits a rather low extinction coefficient. It has the ability to solubilize
oxybenzone.
Octinoxate (octyl methoxycinnamate): This para-disubstituted sunsc-
reen is, by far, the most popular sunscreen in the world. It is principally a
UV-B absorber. Since it contains a conjugated double bond, its UV curve is
broader than one would typically expect. Another consequence of the conjugated
double bond is that this sunscreen can (and does) exist in two isomeric forms (cis
and trans). As would be expected the trans form has a higher extinction coeffi-
cient and is the primary form. When used alone, SPFs of 6– 8 can be achieved.
It exhibits very strong absorbance in the middle of the UV-B range (310 nm)
and has the attributes most sought after in a sunscreen chemical. It is not water
soluble (will not wash off easily); will not stain the skin or clothing; are very
safe, chemically inert, and UV stable; stay on the skin (minimal percutaneous
absorption); have minimal odor; will not color the emulsion; and are relatively
inexpensive. It seems like the ideal sunscreen and, in fact, it comes very close
to that goal.
Padimate-O (octyldimethyl PABA): Padimate-O was for many years
the most widely used sunscreen agent throughout the world. It has the highest
extinction of any UV-B organic sunscreen filter permitted in the USA. Companies
have moved away from it since “PABA free” has become a marketing approach,
and thus it is now very rarely used.
Ensulizole (phenylbenzimidazole sulfonic acid): This material
becomes water soluble when neutralized by an appropriate base (triethanolamine,
NaOH, AMP, trisamino, or others). It has found use in clear gels owing to its
water solubility. It also exhibits a very high efficiency. This is probably due to
its ability to partition into the upper layers of the stratum corneum; thereby pro-
viding a very uniform film on the skin. Additionally, its high polarity does not
allow it to be adversely affected by the nonpolar skin lipids. Some formulators
have neutralized it with fatty amines and thus (to some extent) made it useful
in water-resistant products. It has also been used in W/O emulsions where it
resides in the internal phase and thus is somewhat resistant to wash-off.
Trolamine salicylate: A weak UV-B absorber, it has poor oil solubility
(good water solubility).
Sulisobenzone: This sulfonated version of oxybenzone is water soluble
and thus, is not used in water-resistant formulations. As with oxybenzone, it is
a rather reactive molecule; thus, care must be taken when formulating with these
materials from a stability and safety viewpoint.
Meradimate (menthyl anthranilate): This UV-A screen is not widely

used because of its low absorptivity (ortho-disubstituted). This screen may see
increased acceptance as the trend toward higher SPFs and UV-A claims con-
tinues. It should be combined with other screens to achieve this end.
Inorganic/Particulate Sunscreens
We should discuss how solid opaque (high index of refraction) particles like tita-
nium dioxide and zinc oxide can be used in sunscreen formulations and still
appear transparent on the skin. If a particle is one-fourth or less of the wavelength
of light then it will be invisible. Let us assume the average wavelength of light is
600 nm. This means those particles 150 nm or less will be invisible. The average
wavelength of UV radiation is 300 nm, thus particles between 75 nm (1/4 of
300 nm) and 150 nm will be invisible to visible light but scatter/block UV
radiation. In reality, both titanium dioxide and zinc oxide are sold as microfine
particles with an average primary particle size of less than 40 nm! This is
because there is always some agglomeration and the size of the agglomerates
must be less than 75 nm as discussed. When smaller particles are present in
significant quantities we will often see the “blue/white” appearance seen on
the skin during application of these products. Formulators sometimes incorporate
colorants (iron oxide) or natural antioxidants (melanin) to mask this effect.
When incorporating these sunscreens into a formulation great care must be
taken to insure that good dispersion has been achieved. Formulators are urged to
predisperse the particulate into a portion of the oil phase (if the particulate has
been treated with a hydrophobic coating, as they typically are) using high
shear agitation. The dispersion should be checked for dispersion quality by
using a Hegman gauge to check for large particles (agglomerates) and then by
examining the dispersion under a light microscope at 200– 400 magnification.
There has been a movement away from the usage of particulate powders given
the difficulty of adequately dispersing them and towards predispersed systems.
Several companies now offer predispersed titanium dioxide and zinc oxide in
various “oils” such as C12 – 15 alkyl benzoate, caprylic/capric triglygerides,
ethylhexyl palmitate, cyclomethicone, poly-alpha-olefins, etc. Often a dispersing
agent is employed to minimize dispersion and reagglomeration. Phosphate esters
have been widely used for this purpose.
Another factor to consider when using particulates is suspension! The rela-
tively high SG of these materials will cause them to fall out of suspension. This is
most evident at elevated temperature conditions (408C and higher) when most
emulsions thin out. With this in mind it is strongly suggested that the formulator
employ a suspension aid. When using titanium dioxide the choice is quite wide
since it is very compatible with practically all thickeners/suspension aids. Use
of carbomer, xanthan gum, sodium polyacrylates, and many other materials is
commonly seen. However, when using zinc oxide the choice is much narrower
due to the solubility (even though small) of zinc ion in water. The polyvalent
zinc will react with the acrylic acid in carbomer and all suspension will be
lost! A similar thing is seen when using zinc oxide with fatty acids. Polyvalent
soaps are W/O emulsifiers and thus zinc stearate (or laurate) will destabilize
O/W emulsions. It is suggested that the reader consider using W/O emulsions
when employing particulate sunscreens. When the consumer applies a W/O
sunscreen and goes swimming (or perspires) no rewhitening is observed. Quite
the opposite is seen with particulate based O/W emulsions. Another consider-
ation using particulates is to combine them with organics into what is referred
to as a hybrid system. In this case the consumer gets the best of all worlds!
The organics provide excellent UV absorbance and the SPF is dramatically
boosted through the UV absorption and increase in optical path length afforded
by the particulates.
Titanium dioxide: This physical blocker had not gained acceptance for
many years owing to its poor esthetics (skin whitening). Usage has skyrocketed
with the appearance of microfine grades of this material that substantially address
this problem. Additionally, titanium dioxide comes in two crystalline varieties
(anatase and rutile). While both have UV blocking/absorption abilities, the use
of rutile is preferred since it is far more photostable. If too much anatase titanium
dioxide is present, then a graying will be noticed upon exposure to UV radiation.
Zinc oxide: This material has been used for many years in both cosmetic
and toiletry products. It was not on the original list of 21 sunscreens approved by
the FDA. With the publication of the TFM it was placed into category III (needs
more data). Data submitted to the FDA illustrating its efficacy caused the agency
to move it into Category I status with the publication of the final monograph. It
now enjoys wide usage. The reader is urged to review the patent literature when
using this material for sunscreen applications, since patents have been issued
dealing with particle size and surface coatings.
Fragrances
The choice of a proper fragrance can enhance the esthetics of any sunscreen
product. Because these materials can be quite irritating, their use level must be
kept as low as possible. A typical use level is 0.2–0.4%. Additionally, their break-
down products can be photosensitizers; hence, great care must be taken in choosing
them (the reader is referred to the chapter on fragrancing of sunscreens).
ACHIEVING FORMULA GOALS

To Achieve High SPFs
a. Avoid “bad” ingredients. Use of ethanol at high levels can reduce the
SPF of the finished formulation. It is likely that ethanol (very volatile)
flashes off and leaves a porous film on the skin. This discontinuous
(17) film is not conducive to high SPFs. The use of very nonpolar
materials, such as mineral oil, petrolatum, and highly branched
esters, results in a shift of the lmax (wavelength of maximum absorption),
of nonpolar sunscreens, to a shorter wavelength. This is very detri-
mental to the efficiency of these sunscreens.
b. Use the correct vehicle. Emulsions in general, and creams in particular,
can achieve the highest SPFs attainable. They put down a very uniform
film on the skin. This is most true with W/O emulsions.
c. Combine sunscreens. Use sunscreens that absorb into the short UVB
area (320 – 340 nm), as well as sunscreens that show good absorbance
in the erythemal range (290 –320 nm). Although these wavelengths are
much less effective at producing erythema than the 290– 320 nm
wavelengths, they must be blocked if very high SPFs are to be realized.
d. Obtain uniform film on skin: use of film formers (see foregoing) can
optimize the SPF.
To Achieve Water Resistance

a. Use water-resistant sunscreens (18).
b. Use high-level oil phases in O/W emulsions.
c. Use water-resistant resins.
d. Use minimum levels of hydrophilic emulsifiers. This will minimize the
reemulsification of films left on the skin when exposed to water.
e. Have the O/W emulsion break on the skin during rubout. This
leaves an oily (water-resistant) film on the skin. This can be accom-
plished by making an O/W emulsion using weak O/W emulsifiers
and add in low levels of W/O emulsifiers. As the emulsion is
rubbed onto the skin and water begins to evaporate, the phase
volume ratio now favors a W/O emulsion. Given the presence of
W/O emulsifiers, the emulsion now inverts. The sunscreens are
now in the continuous external phase and a high SPF results with
excellent water resistancy!
f. Use W/O emulsions.
g. Use liquid crystal based emulsions.
To Obtain Mild Formulations

a. Use minimum emulsifier levels, particularly soaps.
b. Minimize use of fragrances.
c. Minimize use of preservatives, making sure, however, to use adequate
levels.
d. Use the minimum level of sunscreen to achieve the target SPF.
e. Use long-chain esters, which are less irritating than their short-chain
analogs.
Patent Issues
Before selecting the sunscreens to be used it would be advisable to understand
the patent environment. As of this writing there are several patents that have
been issued that involve the use of combinations of sunscreens in particular
the use of avobenzone with octocrylene for the purposes of stabilizing
avobenzone/octinoxate combinations (19,20).
Stability Evaluation
The stability evaluation of sunscreen products is not unlike that required for
other cosmetic or toiletry products. The finished formulation, in the production
package, must be subjected to both high- and low-temperature extremes. A
typical minimal program should include the following:
258C for 6 months
378C for 3 months
458C for 2 months
508C for 1 month
48C for 6 months
2208C for 6 months
Freeze –thaw (458– 258C) for five cycles
UV exposure
High-humidity exposure.
The following parameters must be monitored:
Particle size and distribution (for emulsions)
Color
Odor
Preservative efficacy
Weight loss
Viscosity
pH
UV profile (curve)
Closure torque.
While it is generally believed that storage at 458C for 90 days will
predict room temperature storage for 2 years, many times this is not the case.
This is most often seen with W/O emulsions where, typically we observe
better high-temperature stability than that seen at room temperature! When
using particulates (titanium dioxide and zinc oxide) it is suggested that the
formulator subject the formula to centrifuge testing (3000 rpm and 608C for
15 min) to insure that adequate suspension has been achieved.
Organoleptic Considerations
Although consumers purchase sunscreen products for protection from the dama-
ging rays of the sun, they will not buy them a second time if they do not possess
the cosmetic attributes they have come to expect from all toiletries. Use of
fragrance to provide a pleasant note on application and hide the unpleasant
odor of some needed ingredient is a must. Use of silicones or other emollients
will reduce the dragginess on rub out often found in high glyceryl monostearate
(GMS), stearic acid, or fatty alcohol-containing emulsions. The formulation
should exhibit easy spreadability on the skin, without any dragginess. When par-
ticulate materials (TiO2 and zinc oxide) are used, great care must be taken to
ensure that minimum skin whitening is seen. Additionally, these formulations
have a tendency to rewhiten when one goes into the water or sweats profusely.
The cosmetic chemist’s assignment is not complete until the formula for efficacy,
safety, stability, and last, but not least, organoleptic considerations is optimized.
A successful formula has all of these areas addressed.
The Use of Antioxidants in Sunscreen Formulations

As was mentioned previously, antioxidants are frequently used in formulations to
help protect product integrity and can help reduce skin damage. In addition to
these erythemal effects of excessive, unprotected UV exposure there is also evi-
dence that there is oxidative damage that may result in DNA damage, immuno-
logical responses and the possibility of potentiating UV carcinogenesis (21). As a
result there is much interest in using antioxidants in sunscreen formulations.
These antioxidants can be vitamins, botanicals, or synthetic materials and there
has been much published information about the use of antioxidants in topical for-
mulations (22,23) and there have been patents issued that cover the use of anti-
oxidant ingredients, that is, green tea (24).
The use of antioxidants in combination with sunscreens is not currently
regulated any more than the use of any other non-OTC regulated ingredient by
the FDA. It is, however, an area of interest to regulatory agencies in the USA
and other major markets. Their use currently falls under the area of “cosmetic”
claims.
FORMULATIONS
Following is a compilation of formulations that serves to illustrate the diversity of
formula types currently available in the marketplace. By no means, is this collec-
tion of formulations complete; but it is representative of the state of art and
science (as of this moment).
Formula type: Cream

Comments: Emollient skin feel
Expected SPF: 45
Ingredients %w/w
Phase A
Octocrylene 8.0
Oxybenzone 4.0
Octinoxate 7.5
Cyclomethicone 10.0
Glyceryl stearate SE 5.0
Phenyldimethicone 2.0
Cetearyl alcohol (and) ceteareth-20 2.0
Cetyl alcohol 1.0
Ethylhexyl palmitate 10.0
Phase B
Water qs
Preservative qs
Glycerin 5.0
Titanium dioxide (water dispersible, hydrophilic coating) 5.0
Xanthan gum 0.2
Hydroxyethylcellulose 0.1
Phase C
Fragrance 0.3
Comments: This O/W emulsion uses three organic sunscreens in combination with
titanium dioxide to achieve a very high SPF. Xanthan gum is used to suspend the
titanium dioxide. Note the use of ethylhexyl palmitate to assist in solubilizing
the oxybenzone. This formula would not be water resistant due to the inclusion
of the rather hydrophilic emulsifiers (glyceryl stearate SE, cetearyl alcohol, and
ceteareth-20). If we wanted to make this more water resistant we might consider
incorporating a good film forming resin as well as reducing the concentration of
the emulsifiers.
Formula type: Daily use lotion

Comments: Inexpensive lotion with outstanding high-temperature stability
Expected SPF: 8
Ingredients %w/w
Phase A
Octinoxate 6.0
Oxybenzone 2.0
Stearic acid XXX (triple pressed) 4.0
Isopropyl Palmitate 7.5
Myreth-3 myristate 4.0
Glyceryl dilaurate 1.5
Ingredients %w/w
Phase B
Water qs
Preservative qs
Carbomer 1342 0.2
Phase C
Triethanolamine 99% 0.7
Phase D
Fragrance 0.3
Comments: This light lotion is designed to be used under make up
without being greasy/oily. Note the use of glyceryl dilaurate to
make this inexpensive lotion feel much richer with more cushion.
Formula type: Cationic lotion

Comments: Cationic lotion offers excellent skin feel
Expected SPF: 4 –6
Ingredients %w/w
Phase A
Glycol stearate 5.0
C12 –15 alcohol benzoate 3.5
Octinoxate 5.0
PEG-40 stearate 1.5
Phase B
Water
Preservative qs
Stearamidopropyl PG-dimonium chloride qs
Phosphate 3.5
Glycerin 4.0
Phase C
Fragrance 0.3
Comments: Cationic lotions are substantive to the skin and provide
wonderful skin feel! The cationic emulsifier used here is stearamidopropyl
PG-dimonium chloride. We have added an nonionic emulsifier (PEG-40
stearate) to insure good stability with a small uniform particle size.
Formula type: Water-resistant lotion

Expected SPF: 15
Ingredients %w/w
Phase A
Mineral oil 5.0
Sorbitan sesquioleate 1.0
Octinoxate 7.5
Ingredients %w/w
Oxybenzone 4.0
Octyl salicylate 3.0
Laureth-23 1.0
Stearic acid XXX (triple pressed) 2.0
PVP/eicosene copolymer 2.5
Phase B
Water qs
Sorbitol 70% 5.0
Acrylates C10 – 30 alkyl acrylates cross polymer 0.2
Preservative qs
Phase C
Triethanolamine 99% 0.3
Phase D
Fragrance 0.5
Comments: This lotion uses very low emulsifier level to insure that this sunscreen
will be very water resistant. Additionally, we have added a low HLB emulsifier (sor-
bitan sesquioleate) to counteract any high HLB emulsifier left behind on the skin
further inhibit washoff. Lastly, note the inclusion of a film former (PVP/Eicosene
copolymer) to thicken the sunscreen film on the skin and improve water resistancy.
Formula type: Sunscreen oil

Expected SPF: 4 –6
Ingredients %w/w
Octisalate 5.0
Meradimate 3.5
Jojoba oil 2.0
Cocoa butter solid 2.0
Isocetyl alcohol 15.0
Fragrance 1.0
Octyl palmitate qs
Vitamin E acetate 0.1
Mineral oil 40.0
Comments: Meradimate provides absorbance into the short
UVA in this simple sunscreen oil. Isocetyl alcohol acts as
an emollient and as a coupling agent to insure excellent
compatibility of the materials with varying polarities.
Formula type: Sunscreen cream (very water resistant)

Expected SPF: 30þ
Ingredients %w/w
Phase A
Water 27.65
Ingredients %w/w
Xanthan gum 0.3
Phase B
Octinoxate 7.50
Dihydroxycetyl phosphate 1.50
Cyclomethicone 1.00
Tridecyl neopentanoate 7.50
Octisalate 5.00
Cetearyl alcohol 2.00
Octocrylene 10.00
Tocopheryl acetate 0.25
Ceteareth-20 0.50
Tricontanyl PVP 3.00
Phase C
Zinc oxide (microfine) 7.00
Phase D
Preservative 1.00
Comments: A sunscreen cream that provides a very high level of
SPF protection! The combination of the particulate zinc oxide
with the organics (octinoxate, octisalate, and octocrylene) gives
broad spectrum UV absorbance. Tricontanyl PVP improves
water resistancy. The emulsifier level is quite low and this too
improves water resistancy. During manufacture the zinc oxide
should be added to the oil phase (phase B) using high shear to
insure good dispersion and reduce agglomeration.
Formula Type: W/O cream

Expected SPF: 25þ
Ingredient %w/w
Water (aqua), deionized qs
Preservative qs
Disodium EDTA 0.05
NaCl 1.00
PEG-30 dipolyhydroxystearate 3.00
Cyclomethicone (pentamer) 10.00
Zinc oxide (microfine) 7.00
Titanium dioxide (microfine) 7.00
Ethylhexyl palmitate 5.00
Octyldodecanol 4.00
Hydrogenated castor oil 0.75
Polyethylene 2.00
Comments: This W/O cream uses PEG-30 dipolyhy-
droxystearate as the W/O emulsifier. We use NaCl to
enhance the stability of this cream. Hydrogenated castor oil

and polyethylene act as external phase thickeners to further
improve high temperature stability. This cream would
exhibit excellent broad spectrum absorbance!
Formula Type: Lip balm

Expected SPF: 25þ
Ingredient %w/w
Octinoxate 7.50
Oxybenzone 5.00
Octisalate 4.00
Zinc oxide (micronized) 7.50
Castor (Ricinus communis) oil qs
Octyldodecanol 10.00
Beeswax (cera alba) 6.00
Ozokerite 4.00
Candililla (euphorbia cerifera) wax 6.00
Myristyl lactate 4.00
Petrolatum 5.00
Comments: This lip balm provides excellent protection.
Octyldodecanol improves spreadability and dispersion of
the zinc oxide. Thus we do not get the white residue often
seen with products of this type.
Formula Type: Lotion with UV-B/UV-A absorbers

Expected SPF: 20
Ingredient %w/w
Water (aqua), deionized qs 100.00
Disodium EDTA 0.05
Methylpropanediol 2.00
Carbomer 0.20
Ethylhexyl naphthalate 8.00
Dihydroxycetyl phosphate 1.25
Octinoxate 7.50
Oxybenzone 5.00
Avobenzone 3.00
Cetearyl alcohol (and) ceteareth-20 0.50
PVP/eicosene copolymer 2.00
NaOH, 10% soln 2.50
Phenoxyethanol (and) methylparaben (and) propylparaben 1.00
Comments: This O/W lotion provides excellent broad spectrum performance. The oxybenzone
helps to stabilize the avobenzone in the presence of octinoxate. Ethylhexyl naphthalate also
improves the photostability of this lotion. We have taken care not to employ a preservative
that may liberate formaldehyde which would play havoc with the avobenzone. Additionally,
we use disodium EDTA to insure that no excess metals are available to react with avobenzone.
Formula type: Water-resistant spray

Expected SPF: 15þ
Ingredient %w/w
Water (aqua), deionized qs 100.00
Disodium EDTA 0.1
Methylpropanediol 2.50
Acrylates C10 – 30 alkyl acrylates crosspolymer 0.25
Octinoxate 7.5
Octisalate 5.0
Oxybenzone 2.0
Castor isostearate succinate (and) PEG-8 ricinoleate 1.5
Castor isostearate beeswax succinate 2.5
Triethanolamine (99%) 0.20
Phenoxyethanol (and) methylparaben (and) propylparaben 1.00
Comments: This O/W spray is very water resistant and has elegant skin feel. The primary
emulsion stabilizer is acrylates C10– 30 alkyl acrylates crosspolymer neutralized by the
triethanolamine. Castor isostearate succinate (and) PEG-8 ricinoleate improve film
spreadability and reduce oiliness.
REFERENCES
1. Stockdale M. Sun protection factor. Int J Cosmet Sci 1985; 7:235 – 246.
2. Gao T, Tien J, Choi Y. Sunscreen formulas with multilayer lamella structure 2003;
118(October):41– 52.
3. Agrapidis-Paloympis L, Nash RA, Shaath N. The effects of solvents on the ultraviolet
absorbance of sunscreens. J Soc Cosmet Chem 1987; 38(July/Aug):209 –221.
4. Klein K, Doshi I. Sunscreen solvent interactions: an in-vitro evaluation. 14th IFSCC
Congress, Barcelona, Spain, Sep 1986.
5. Dahms G. Choosing emollients and emulsifiers for sunscreen products. Cosmet Toilet
1994; 109(11):45– 52.
6. Vaughan CD. Using solubility parameters in cosmetic formulation. J Soc Cosmet
Chem 1985; 36(5):319– 333.
7. Klein K. Improving emulsion stability. J Cosmet Toilet 1984; 99(March):121– 126.
8. Stokes GG. Philos Mag 1851; 1:337.
9. Lin TJ. Low energy emulsification, principles and applications. J Cosmet Chem 1978;
29(March):117– 125.
10. Martin A, et al. Phys Pharm 1969; 2:4 – 5.
11. Suzuki T, Tsumi H, Ishida A. Secondary droplet emulsion: Mechanism and effects of
liquid crystal formation in o/w emulsions. Dispers Sci Technol 1984; 5(2):119 – 141.
12. Griffin WC. Classification of surface active agents by “HLB.” J Soc Cosmet Chem
1940; 1:311 –326.
13. Shinoda K. Comparison between phase inversion system and the hydrophilic lipophi-
lic balance value system for emulsifier selection. Nippon Kagaku Zashi 1968; 89:1– 8.
14. Lin TJ, et al. Prediction of optimum o/w emulsification via solubilization measure-
ments. J Soc Cosmet Chem 1977; 28(August):457– 479.
15. Docket No. 78N-0038, Sunscreen Drug Products for over the counter human use; final
monograph, 21CFR Parts 310, 352, 700 and 740, May 21, 1999; 64:98.
16. Bonda C. Avobenzone Photostability in Simple Polar and Non-Polar Solvent Systems.
C.P Hall Publication.
17. Eierman H. US Patent 3,342,419, 1967.
18. Formulating vehicles for sunscreens. Norda Shimmel Briefs, 935, Feb. 1966.
19. Tanner, et al. US Patent 5,935,556, August 10, 1999.
20. Kaplan. US Patent 6,048,517, August 11, 2000
21. Ichihashi M, et al. UV-induced skin damage. Toxicology 2003; 189(1 – 2):21– 39
22. Vayalil PK, Elmets CA, Katiyar SK. Treatment of green tea polyphenols in hydrophi-
lic cream prevents UVB-induced oxidation of lipids and proteins. Carcinogenesis
2003; 24(5):927– 936.
23. Afaq F, Adhami VM, Ahmad N. Prevention of short-term ultraviolet B radiation-
mediated damage by resveratrol in SKH-1 hairless mouse. Toxicol Appl Pharmacol
2003; 186(1):28– 37.
24. McCook, et al. US Patent 5,306,486, April 26, 1994.
19
SPF Modulation: Optimizing the
Efficacy of Sunscreens
Julian P. Hewitt
Uniqema Health & Personal Care, Wilton, Redcar, UK
Outline 386
Introduction 386
Fundamental Requirements 387
Rheology 388
Emulsion Rheology 389
De-Emulsification Behavior 391
Formulating with Organic Sunscreens 391
Oil-Soluble Organic UV Filters 392
Effect of Emulsion Type 392
Effect of Added Emollients 393
Water-Soluble Organic UV Filters 394
Effect of Emulsion Type 394
Effect of Emulsifiers 394
Formulating with Inorganic Sunscreens 394
Basic Principles 394
Formulating with Water-Dispersed TiO2 401
Formulating with Oil-Dispersed TiO2 403
Formulating with Zinc Oxide 404
Combining Sunscreens 404
Combining Organic Sunscreens 405
385
386 Hewitt
Combining Inorganic Sunscreens 406

Combining Organic and Inorganic Sunscreens 406
SPF Modulation by External Factors: Water Resistance 406
Fundamental Requirements for Water Resistance 407
Strategies for Water Resistance 408
W/O Emulsions 408
Silicones 408
Specialized Emulsifiers 408
Liquid Crystal Gel Networks 409
Film-Forming Polymers 409
The “Dual-Strategy” Approach 409
Summary 409
References 410
OUTLINE
Formulators of modern sunscreen products are required to meet ever-increasing
demands in terms of product efficacy, both for SPF claims and for broad-spectrum
(UV-A) protection. While it is well known (and intuitively understood) that SPF is
dependent on the type and concentration of UV filters incorporated in a formu-
lation, what is sometimes overlooked is the vital role played by the formulation
itself. This chapter discusses the influence of various aspects of the formulation
on product efficacy, and aims to provide the formulator with the some guiding
principles to optimize the effectiveness of UV filters in finished products.
The topics covered include
. Fundamental requirements for achieving high SPF
. Formulating with organic sunscreens
. Formulating with inorganic sunscreens
. Combining sunscreens
. Modulation of SPF by external factors—water resistance
INTRODUCTION
In recent years, SPF claims for sunscreen products have increased rapidly. Less
than 20 years ago, the vast majority of sunscreen creams and lotions provided
SPFs of less than 10, and SPF 15 was considered very high. Nowadays, most
experts would regard SPF 15 as the minimum required to provide effective pro-
tection, while SPF 30 has become the norm and claims of SPF 50 and above are
not uncommon. Whether it is meaningful or useful for such high claims to be
used is still a subject of debate (1,2), and indeed in some countries such claims
SPF Modulation 387
are not permitted [at the time of writing, the US FDA’s Final Monograph on
Sunscreens (3) proposes a maximum SPF claim of 30þ]. Nevertheless, the sun-
screen formulator is often presented with the task of creating formulations which
will achieve these high SPF values.
Increasing SPF values is not simply a matter of adding more and more
active ingredients (UV filters) into the formulation; many other factors influence
the efficacy of products, and the formulator must be aware of these factors and
how to optimize them in order to achieve high SPF in a cost-effective, elegant
formulation. This chapter discusses the various parameters which affect SPF
and aims to provide some practical guidance on how to optimize the SPF efficacy
of both organic and inorganic UV filters.
FUNDAMENTAL REQUIREMENTS
Ideally, for maximum efficacy of actives, what is required is for the product to
deposit a film on skin which is of even thickness, following the contours of the
skin and containing a homogenous distribution of the UV filter(s) (dissolved mole-
cules of organic sunscreen or dispersed particles of physical sunscreen). This is
illustrated in Fig. 19.1. However, this is never achieved in the real world [Sottery
(4) showed that if this could be achieved, then at an application rate of 2 mg/cm2,
a concentration of only 2.8% octyl dimethyl PABA would be sufficient to achieve
a monochromatic protection factor of 1,000,000 at 310 nm]. The true situation is
probably more like that depicted in Fig. 19.2, with the product film partially
“pooled” in the wrinkles of the skin, while the peaks have only thin coverage
or even no coverage at all. O’Neill’s “Step Film Model” (5) showed how
uneven distribution of sunscreen could account for the discrepancy between
the measured SPF results and theoretical expectations based on simple spectro-
graphic data. Other workers (4,6 – 8) have expanded upon this model, demonstrat-
ing that it is the areas where film is either very thin or nonexistent which have the
biggest influence on SPF. A simple example will serve to illustrate this.
Suppose we have a sunscreen product which deposits an incomplete film on
skin, such that 5% of the skin area has no coverage. In this situation, no matter
how much active is incorporated into the product, at least 5% of the incident
SKIN
Figure 19.1 Idealized distribution of sunscreen on skin.

388 Hewitt
SKIN
Figure 19.2 Uneven distribution of sunscreen on skin; arrows indicate where film is thin
or broken and UV light is most likely to penetrate through to skin.
UV radiation will reach the skin. Therefore, it will be impossible for the product
to achieve an SPF of greater than 20. However, if the formulation is modified
such that film-forming is improved and only 2% of the skin is left uncovered,
then the absolute maximum achievable SPF increases to 50.
So we see that good film-forming is a fundamental requirement for achiev-
ing high SPF efficacy. The second fundamental requirement is a homogenous
distribution of the sunscreen active(s) throughout the film. The factors which
influence the latter are dependent on the type of sunscreen active used, and are
dealt with in the next two sections. However, the factors influencing film-
forming are applicable generally, whatever type of active is used. These can be
discussed under the general headings of rheology and de-emulsification behavior.
Rheology
In order to achieve even coverage of the skin, the product must initially spread well
over the skin surface to form a film, but this film must have a degree of structure in
order to maintain coverage over the peaks and valleys of the skin. Therefore, the
rheological behavior of the product critically influences the SPF efficacy (9).
Spreading of a personal care product on skin is a high-shear process, with
shear rates typically of the order of 103 –104 s21. Therefore, it is the behavior of
the product under such high-shear conditions, and then immediately after the
shear is removed, which affects film-forming and hence SPF. It has been demon-
strated (10,11) that the main requirements for high SPF efficacy, in terms of
rheological behavior, are
. Low viscosity under high-shear conditions
. Short recovery time after spreading, that is, rapid recovery of structure
and viscosity once shear is removed
. Low but finite thixotropy
These can be intuitively understood. To start with, the product must spread easily
to achieve good coverage of the skin. Note that this does not mean that the
SPF Modulation 389
viscosity of the product at rest must be low; for example, a high-viscosity cream
can still achieve good spreading if it is very shear-thinning. Once even coverage
has been achieved, however, it is not desirable for viscosity to remain low
because this would result in the product continuing to flow and pooling in the
skin wrinkles, hence the requirement for rapid recovery. Thixotropy is more
complex because it in turn depends on other rheological parameters: viscosity
at rest (the so-called “zero-shear” or residual viscosity), viscosity under shear,
and recovery time. Measured values of thixotropy are dependent on the con-
ditions under which the rheological measurement is carried out and hence such
values cannot be compared unless they are measured under identical conditions.
Sunscreen products can take a variety of different physical forms (12).
Sunscreen oils usually resemble Newtonian fluids in their rheological behavior,
that is, viscosity does not vary with shear. They also usually are of low viscosity.
As a result, while initial spreading is very efficient with such products, film-
forming tends to be poor because the product has no structure; therefore, sun-
screen oils tend to be limited to low SPFs only. Most other product forms (gels,
sticks, foams/mousses, emulsions) exhibit—to varying degrees—viscoelastic
behavior. In other words, their flow behavior includes elements of both viscous
(liquid-like) and elastic (solid-like) behavior. Therefore, it is possible to design
such products so that they exhibit the required rheology outlined here, that is, pre-
dominantly liquid-like at high shear (to facilitate spreading) and predominantly
solid-like at very low shear (to maintain film structure).
Emulsion Rheology
The vast majority of sunscreen products are emulsions, so the remainder of this
discussion concentrates on these. As well as the traditional creams and lotions, a
strong recent trend has been the growth in sunscreen sprays based on emulsions,
and wipes impregnated with sunscreen emulsions. Both these approaches usually
require a very low-viscosity emulsion, and one might intuitively expect that such
emulsions would suffer from similar drawbacks as the sunscreen oils (plus the
inherent difficulty of stabilizing such low-viscosity emulsions). However, tech-
nology is now available which allows formulation of emulsions which are thin
enough to be sprayable (at least when subjected to the shear of a spray nozzle)
but have sufficient structure to be stable and give good film-forming on skin (13).
Obviously, the strategies to be adopted in order to optimize rheology
depend on whether the emulsion is of the oil-in-water (o/w) or the water-in-oil
(w/o) type. W/O emulsions are the simpler case to discuss and to study,
because the evaporation of water from the emulsion is relatively slow. This
means that rheological measurements on the emulsion itself represent a close
approximation to the behavior of the product in actual use.
Waxes and other rheological additives have been found to boost SPF in W/O
sunscreen formulations (11,14–16) and this has been correlated with shorter
recovery times after shear (11). The rheology of W/O emulsions can also be modi-
fied by altering the phase volume fraction; because cosmetic W/O emulsions
390 Hewitt
typically have a high internal phase (usually .50% water), the water droplets are
crowded close together. In this situation an increase in the proportion of internal
water phase results in an even more crowded system, causing viscosity to increase.
The combined effects of wax concentration and phase volume fraction have
been investigated in the following frame formula:
%w/w
PEG-30 dipolyhydroxystearate 2.5
Mineral oil 4.0 – 8.0
Hybrid sunflower oil 2.0 – 4.0
Isopropyl myristate 4.0 – 8.0
Beeswax 0 – 3.0
TiO2 dispersion 5.0
Demineralized water To 100%
Magnesium sulfate 0.7
Preservative qs
Note: The TiO2 dispersion was a 50% solids dispersion
of coated TiO2 in a 50:50 blend of mineral oil and
caprylic/capric triglyceride.
The content of beeswax was varied from zero to 3%, and the total content
of added oils was varied from 10% to 20%, with the relative proportions of the
three oils kept constant. The SPF data obtained from these formulations are
shown in Fig. 19.3.
13
12
11
In-vitro SPF
10
9
8
7
6
5
4
0 1 2 3
% Beeswax
Figure 19.3 Effect of waxes on SPF in W/O emulsions at different phase volume
fractions (V: 10% oil; A: 20% oil).
SPF Modulation 391
As can be seen from this data, the optimum level of wax (in terms of SPF)
depends on the phase volume fraction. At 5% dispersion (2.5% solids), with only
10% of added oils, the phase volume fraction is such that the formulation is already
quite viscous with no addition of wax. Therefore, while adding 1% wax increases
the SPF, any further addition means that the formulation becomes too viscous to
spread easily (i.e., high-shear viscosity is now too high), and SPF decreases.
When we increase the amount of oil phase, the viscosity of the base emulsion is
lower, and the beneficial effect of the wax (shorter recovery time) continues to out-
weigh the negative effect (increase in high-shear viscosity) even at higher wax
loadings. At 20% added oils, we see that the SPF continues to increase up to 3%
wax, where the SPF is over 12 (from the same level of active).
O/W emulsions represent a more complex case, because evaporation of water
is more rapid and occurs already to a significant extent during rub-in of the product.
Therefore, the composition of the emulsion (and hence its rheology) is constantly
changing while the product is being applied. Laboratory measurements of rheology
are conducted on the complete emulsion, without any evaporation taking place, and
hence do not replicate the real situation. Nevertheless, some correlations between
SPF and rheological parameters have been observed (17).
The rheological behavior of O/W systems is influenced by many formu-
lation components, including emulsifiers, hydrocolloids, and “lipid thickeners”
such as fatty alcohols or fatty acids. Many O/W cosmetic emulsions incorporate
liquid crystalline structures (18 – 21), and these also have a significant influence
on rheology.
De-Emulsification Behavior
With O/W emulsions, film-forming is also affected by the breakdown of the
emulsion during application. As the water phase evaporates, the oil droplets
coalesce to form a film. In a sunscreen product, for optimum efficacy, this film
needs to be as homogenous as possible, with the active(s) dispersed evenly
within it. Dahms (22) discussed how the coalescence and spreading of the oil
phase is affected by the properties of the oil/air and oil/skin interfaces, and
derived a relationship between SPF, the surface tension of the oil phase, and
the interfacial tension between oil phase and water phase. In a separate
paper, the same author showed how efficient and rapid de-emulsification is
aided by the small droplet size in the emulsion (23).
FORMULATING WITH ORGANIC SUNSCREENS

Most organic UV filters are oil-soluble; however, a few are designed to be incor-
porated into the water phase. The latter are usually molecules with an acid group
and are only rendered soluble in water when this group is neutralized by addition of
a base. Another recent innovation is the development of an organic UV filter which
is an insoluble particulate, and is incorporated into the finished formulation as a
392 Hewitt
water-based dispersion (24). Organic UV filters are usually also classified as either
UV-B or UV-A filters, since most only absorb over a relatively narrow wavelength
range (although there are examples with broader absorption spectra). This means
that in the vast majority of formulations, more than one filter is used, as it is neces-
sary to protect against both UV-B and UV-A in order to achieve high SPF values.
Detailed practical advice on formulating with organic sunscreens is given
elsewhere in this book. The following discussion concentrates on how to achieve
a homogenous distribution of the active in the product film that is deposited on
skin; as indicated in the previous section, this is key to achieving high SPF effi-
cacy. With organic sunscreens, how this is done depends on whether the active is
oil-soluble or water-soluble.
Oil-Soluble Organic UV Filters

Effect of Emulsion Type
Oil-soluble organic sunscreens generally exhibit greater efficacy in W/O than in
O/W emulsions, as evidenced by the data shown in Fig. 19.4 (25). In this work,
various UV filters were individually incorporated into W/O and O/W emulsions,
with different carrier emollients. Each data bar in Fig. 19.4 therefore represents
an average over 12 formulations. In most cases, it is apparent that the W/O
system gives higher SPF efficacy than the O/W one. This is to be expected
since the active is in the external phase in a W/O system and achievement of
an even distribution of sunscreen is not dependent on the de-emulsification of
the emulsion on skin.
12
10
In-vitro SPF
0
EHMC EHS Oct EHT Bz-3 BMDM
Figure 19.4 Effect of emulsion type on efficacy of organic UV filters. (B: W/O emulsions;
A: O/W emulsions. EHMC ¼ ethylhexyl methoxycinnamate; EHS ¼ ethylhexyl salicy-
late; Oct ¼ octocrylene; EHT ¼ ethylhexyl triazone; Bz-3 ¼ benzophenone-3; BMDM ¼
butyl methoxydibenzoylmethane.)
SPF Modulation 393
Effect of Added Emollients

Some oil-soluble organics [e.g., octocrylene, ethylhexyl methoxycinnamate
(EHMC)] are liquids and are readily mixed with the oil phase of the formulations.
One might think, therefore, that a homogenous distribution of the active is
virtually automatic and good efficacy is assured. However, even in these cases,
one must ensure that the actives are compatible with the oil phase; the materials
may be visibly miscible but, on a molecular level, flocculation can occur which
will have an adverse effect on SPF (4). Also, as is well known (26,27), the
solvents within which the actives are dispersed can affect the absorption spec-
trum, either by shifting the peak of absorption to a different wavelength or by
affecting the amplitude of the peak.
Many organic UV filters are crystalline solids, and for these materials the
solubility of the active in the oil phase is a critical factor. The oils or esters used
must be capable of dissolving the UV filters and maintaining them in solution
over the lifetime of the product; if the active crystallizes to any degree, it’s
efficacy can be significantly reduced. Polar oils tend to be the best solvents;
suppliers of organic UV filters typically include in their literature data on the
solubility of their products in various cosmetic emollients. Use of liquid UV
filters (e.g., ethylhexyl methoxycinnamate) in combination with the solid filters
can be a useful tactic, as the liquid UV filters are themselves good solvents for
the solid actives.
Figure 19.5 [data from Ref. (25)] shows in vitro SPF data for various solid
actives, in different carrier emollients, in W/O systems. There is a clear corre-
lation between SPF and solubility in the carrier emollient.
18
16
14
In-vitro SPF
12
10
8
6
4
2
0
0 5 10 15 20
Solubility (% w/w)
Figure 19.5 SPF vs. solubility for solid organic UV filters in various solvents (V: ethyl-
hexyl triazone; A: benzophenone-3; D: butyl methoxydibenzoylmethane).
394 Hewitt
The nature of the emollients can also, of course, affect the rheology of the
emulsion or the de-emulsification behavior, as discussed in the previous section.
Water-Soluble Organic UV Filters

Effect of Emulsion Type
While it is intuitive that oil-soluble organics should be more effective in W/O
than in O/W emulsions, what is perhaps more surprising is that the same
applies to water-soluble sunscreens. Experiments with phenylbenzimidazole
sulfonic acid (S. Housley, personal communication, 1998) show that this active
gave a higher SPF in a W/O emulsion than in an O/W system.
This can be understood by once again considering what happens to the
emulsion during and after application on skin. In an O/W emulsion, as the
water evaporates, a water-soluble active may partially crystallize on the skin
surface if it cannot disperse into the oil film deposited on skin, whereas in a
W/O emulsion, the water phase is encapsulated within the product film, so the
active can remain dissolved. Provided that the droplets are small and homo-
geneously dispersed (which, for a stable W/O emulsion, would normally be
the case), a good dispersion of the active within the product film can be achieved.
Effect of Emulsifiers
In truth, with most O/W emulsions, the product film on skin is not entirely homo-
genous, since in addition to oils it may contain liquid crystalline phases, sili-
cones, etc. The nature and type of liquid crystalline phases formed depends on
the emulsifiers used (18,19), and will often include both lipophilic and hydrophi-
lic parts, including entrapped water. In such cases, the efficacy of water-soluble
organic UV filters can be maintained if the hydrophilic structures are sufficiently
well dispersed. This requires therefore that the structures be delocalised, for
example of a lamellar gel network type (21).
FORMULATING WITH INORGANIC SUNSCREENS

Basic Principles
By far the most commonly used inorganic (or “physical”) sunscreens are titanium
dioxide (TiO2) and zinc oxide (ZnO). TiO2 provides mainly UV-B protection but
is also effective in the UV-A, while ZnO is principally used for UV-A protection,
its efficacy in the UV-B being relatively low. A list of the principal suppliers of
inorganic sunscreens and their products is given in Tables 19.1 and 19.2 (note that
this is not intended to be an exhaustive list).
It is well known that the efficacy of inorganic sunscreens depends on par-
ticle size and size distribution (15,28 –30). Ultimately, if we think again about the
general principles discussed in the second section, what is required is a homo-
genous dispersion of the particles on skin after the product has been applied.
SPF Modulation 395
Table 19.1 Inorganic Sunscreens Supplied in Powder Form
Supplier Type Product name Surface treatment
Tayca TiO2 MT-100S Aluminum laurate/aluminum hydroxide

MT-100T Aluminum stearate/aluminum hydroxide
MT-100Z Aluminum stearate/aluminum hydroxide
MT-100F Ferric stearate/ferric hydroxide
MT-150W None
MT-100AQ Alumina/silica/alginic acid
MT-100SA Alumina/silica
MT-100HD Alumina/zirconia
MT-100SAS Alumina/silica/silicone
ZnO MZ-300 None
MZ-300S Methicone
MZ-300M Dimethicone
Ishihara TiO2 TTO-S-3 Alumina
TTO-S-4 Alumina/stearic acid
TTO-V-3 Alumina
TTO-V-4 Alumina/stearic acid
Kemira TiO2 M160 Stearic acid/alumina
M170 Alumina/dimethicone
M212 Glycerin/alumina
M262 Alumina/dimethicone
Degussa TiO2 T805 Trimethoxycaprylylsilane
BASF TiO2 Uvinul TiO2 Trimethoxycaprylylsilane
ZnO Z-Cote None
Z-Cote HP1 Dimethicone
Titan Kogyo TiO2 ST-452 Alumina/stearic acid
ST-455 Alumina/stearic acid
ST-485SA15 Alumina/stearic acid
ST-485DS Alumina/silicone
Merck TiO2 Eusolex T-2000 Alumina/simethicone
Particle Sciences TiO2 T-Cote 031 Dimethicone
Elementis ZnO Nanox 200 None
Symrise ZnO Zinc oxide None
neutral H&R
Sakai ZnO 50LP Organopolysiloxane
Therefore, there are three fundamental requirements for achieving optimum

efficacy with inorganic sunscreens (31):
1. Select material with the optimum particle size and particle size distribution
2. Ensure that the particles are dispersed homogeneously throughout the
emulsion
3. Ensure an even distribution of the particles on skin when the product is
applied
Table 19.2 Inorganic Sunscreen Predispersions
396
Supplier Type Product name Surface treatment Carrier medium %Solids
Uniqema TiO2 Tioveil FIN Alumina/silica C12 – 15 alkyl benzoate 40

Tioveil IPM Alumina/silica Isopropyl myristate 40
Tioveil MOTG Alumina/silica Mineral oil/caprylic-capric 40
triglyceride
Tioveil OP Alumina/silica Ethylhexyl palmitate 40
Tioveil TG Alumina/silica Caprylic-capric triglyceride 40
Tioveil AQ-G Alumina/silica Water 40
Tioveil AQ-N Alumina/silica Water 40
Tioveil 50 FCM Aluminum stearate/alumina C12 – 15 alkyl benzoate/ 50
cyclomethicone
Tioveil 50 FIN Aluminum stearate/alumina C12 – 15 alkyl benzoate 50
Tioveil 50 GCM Aluminum stearate/alumina Octyldodecanol/cyclomethicone 50
Tioveil 50 IPM Aluminum stearate/alumina Isopropyl myristate 50
Tioveil 50 MOTG Aluminum stearate/alumina Mineral oil/caprylic-capric 50
triglyceride
Tioveil 50 OP Aluminum stearate/alumina Ethylhexyl palmitate 50
Tioveil 50 TG Aluminum stearate/alumina Caprylic-capric triglyceride 50
Tioveil CM Aluminum stearate/alumina Cyclomethicone 40
Solaveil CT-100 Aluminum stearate/alumina C12 – 15 alkyl benzoate 45
Solaveil CT-10W Aluminum stearate/alumina Water 40
ZnO Spectraveil FIN None C12 – 15 alkyl benzoate 60
Spectraveil IPM None Isopropyl myristate 60
Spectraveil MOTG None Mineral oil/caprylic-capric 60
triglyceride
Spectraveil OP None Ethylhexyl palmitate 60
Spectraveil TG None Caprylic-capric triglyceride 60
Hewitt
Kobo TiO2 GC40VS Aluminum hydroxide/stearic acid Caprylic-capric triglyceride 40
IN60S4 Aluminum hydroxide/stearic acid Isononyl isononanoate 60
TNP055S4 Aluminum hydroxide/stearic acid C12 – 15 alkyl benzoate 55
CM3K25VM Alumina/methicone Cyclopentasiloxane 25
CM3K40T4 Alumina/methicone Cyclopentasiloxane 40
SPF Modulation
CMKP25VM Alumina/methicone Cyclopentasiloxane 25

CMKP60M262 Alumina/silica/methicone Cyclopentasiloxane 60
INP45M170 Alumina/dimethicone Isononyl isononanoate 45
TNP40VTTS Alumina/Isopropyl C12 – 15 alkyl benzoate 40
titanium triisostearate/
Triethoxycaprylylsilane
cross-polymer
ZnO GC55XZ4 Methicone Caprylic-capric triglyceride 55
INH73MZ Isopropyl titanium triisostearate Isononyl isononanoate 73
CE50ZCI Triethoxy caprylylsilane Trioctyldodecyl citrate 50
CM3K50XZ4 Methicone Cyclopentasiloxane 50
CM3K50HP1 Dimethicone Cyclomethicone 50
CMKP50XZ4 Methicone Cyclopentasiloxane 50
TNP50ZSI Triethoxycaprylylsilane C12 – 15 alkyl benzoate 50
Granula TiO2 Granlux CCT-40 DNAa Caprylic-capric mono/ 40
diglycerides
Granlux MSN-50 DNA Apricot kernel oil PEG-40 50
esters/cetearyl glucoside/
cetearyl alcohol/hydrogenated
decene oligomers
Granlux EM-50 DNA Cetearyl glucoside/cetearyl 50
alcohol
(continued )
397
398
Supplier Type Product name Surface treatment Carrier medium %Solids
Granlux TEM-45 DNA Caprylic-capric triglyceride/ 45

cetearyl glucoside/cetearyl
alcohol
Granlux AB-50 DNA C12 – 15 alkyl benzoate 50
Granlux TG-50 DNA Caprylic-capric triglyceride 50
Granlux TG2-50M1 DNA Caprylic-capric triglyceride 50
Granlux GAW-45 Alumina/dimethicone Polyglyceryl-4-isostearate/cetyl 45
dimethicone copolyol/
hexyl laurate
Granlux GAI-45 Alumina/stearic acid Polyglyceryl-4-isostearate/cetyl 45
dimethicone copolyol/hexyl
laurate/isononyl isononanoate
Granlux NA-50M1 Alumina/dimethicone Hydrogenated decene 50
oligomers/cetyl dimethicone
copolyol
ZnO Granlux EM-45Z DNA Cetearyl glucoside/cetearyl 45
alcohol
Granlux TEM-45Z DNA Caprylic-capric triglyceride/ 45
cetearyl glucoside/cetearyl
alcohol
Granlux AB-55Z DNA C12 – 15 alkyl benzoate 55
TiO2/ZnO Granlux EM-45TZ DNA Cetearyl glucoside/cetearyl 45
alcohol
Granlux TEM-45TZ DNA Caprylic-capric triglyceride/ 45
cetearyl glucoside/
cetearyl alcohol
Hewitt
Granlux GAW-45TZ Alumina/dimethicone Polyglyceryl-4-isostearate/cetyl 45
dimethicone copolyol/
hexyl laurate
Granlux GAI-45TZ Alumina/stearic acid Polyglyceryl-4-isostearate/cetyl 45
SPF Modulation
laurate/isononyl isononanoate
Granlux GAC-45TZ Alumina/dimethicone Polyglyceryl-4-isostearate/cetyl 45
laurate/cyclopentasiloxane
Granlux NA-50TZ Alumina/dimethicone Hydrogenated decene 50
oligomers/cetyl dimethicone
copolyol
Collaborative TiO2 TioSperse Ultra Stearic acid/dimethicone/ Ethylhexylhydroxystearate 50
Labs aluminum hydroxide benzoate/cyclopentasiloxane
ZnO Z-Sperse Ultra Dimethicone/ Ethylhexylhydroxystearate 60
triethoxycaprylylsilane benzoate/cyclopentasiloxane
TiO2/ZnO TZ-Sperse Ultra Stearic acid/dimethicone/ Ethylhexylhydroxystearate DNA
aluminum hydroxide/dimethicone/ benzoate/cyclopentasiloxane
triethoxycaprylylsilane
Degussa TiO2 Tego Sun TAQ40 Trimethoxycaprylylsilane Water 40
Rhodia TiO2 Mirasun TiW60 Silica/alumina Water 40
Merck TiO2 Eusolex T-Aqua Alumina Water 30
ISP TiO2 Escalol T-100 Alumina/dimethicone Ethylhexyl methoxycinnamate 50
ZnO Escalol Z-100 Methicone Ethylhexyl methoxycinnamate DNA
a
DNA ¼ data not available.
399
400 Hewitt
The first requirement is primarily the responsibility of the raw material

supplier. Most suppliers of inorganic sunscreens will provide particle size data
for their products; unfortunately, it is difficult or impossible to compare data pro-
vided by different suppliers in any meaningful way, because measured particle
size data vary enormously depending on the technique used for the measurement
and how the samples are prepared. (It is for this reason that particle size data are
omitted from Tables 19.1 and 19.2.) In selecting a particular product, it is more
meaningful and informative to look at the UV/visible absorption spectra of the
materials being considered, as this bears a closer relationship to the properties
of the active in the final formulation.
The tasks for the formulator, then, are to fulfill requirements 2 and 3.
Keeping a homogenous dispersion of the particles within the emulsion requires
that there must be sufficient repulsive force between the particles to prevent them
from agglomerating if they approach each other. This is achieved by means of
either electrostatic or steric repulsion (29). Within the formulation, these repul-
sive forces need to be maintained in order to keep the particles well dispersed.
Physical sunscreen particles used in sunscreens are almost always coated
(surface-treated); these coatings can be either hydrophilic or hydrophobic. Hydrophilic
coatings typically consist of other inorganic oxides, such as silica or alumina. Elec-
trostatic repulsion is normally used to maintain dispersion of such particles in
water, either by making use of the inherent surface charge on the particles or by
including a dispersing agent which itself carries a charge. In either case, a key para-
meter in maintaining the dispersion is the point of net zero charge, or isoelectric point.
All inorganic particles carry charges on their surface. When such particles
are dispersed in water, the surface charges can play a major role in the interpar-
ticle forces. Both positive and negative charges are present; at high pH there is a
net negative charge, while at low pH the net charge is positive. In between, there
is a certain pH at which the positive and negative charges exactly balance each
other and there is no net charge; this is the isoelectric point (see Fig. 19.6).
The isoelectric point is characteristic of the surface of the particles, and therefore
depends on the coatings applied and also on the dispersing agent used.
In formulation, the isoelectric point must be avoided, since the lack of elec-
trostatic repulsion at this point means that the particles can agglomerate. These
agglomerates are difficult to break up again once formed. Therefore, control of
emulsion pH is an important aspect of formulating with hydrophilic particles
in the aqueous phase.
One might intuitively expect that hydrophilic coating is a prerequisite for
dispersion of TiO2 particles in water; however, recently, there have been two
aqueous dispersions launched on the market (32,33) which are based on hydro-
phobically coated particles. In these cases, surfactants or polymers are used to
provide steric repulsion between the particles and hence maintain the dispersion.
The molecular architecture of these dispersing agents is critical; the molecule
must have an anchor group, which associates or binds with the particle surface,
and a stabilizer part which extends out into, and is solvated by, the carrier
SPF Modulation 401
+
Net
Charge pH
+ + + + + -+ - - - - -
+ - + - - +- + + - + -
+ + + + + -+ - - - - -
- + - + - +- + - + - +
+ + + + + -+ - - - - -
pH < IEP pH = IEP pH > IEP
Net positive charge No net charge Net negative charge
High repulsive force No repulsive force High repulsive force
Figure 19.6 Effect of pH on the net charge on particle surfaces.
medium. In the case of hydrophobic particles in a water dispersion, the anchor

should be hydrophobic and the stabilizer hydrophilic, so that it is effectively sol-
vated by water in order to provide the steric repulsion. An advantage with such
dispersions is that the repulsive forces are not pH dependent; therefore, they
do not exhibit an isoelectric point, and so can be used over a wide range of pH.
When physical sunscreens are incorporated into the oil phase, the surface
charges are insulated and electrostatic repulsive forces are small; in this case,
steric repulsion once again plays the major role in keeping the particles dispersed.
This is achieved either by coating the particles with organic or silicone species, or
by use of a suitable dispersing agent which associates with the particle surfaces.
In either case—oil-dispersed or water-dispersed particles—the best results
are normally achieved by use of a stabilized predispersion of the physical sun-
screen, formed by milling the particles in the carrier medium in the presence of
a suitable dispersing agent. Fine powders tend to agglomerate in the dry state, and
these agglomerates cannot be broken down by the mixing energies normally
found in the production of cosmetic emulsions. As a result, the dispersion of
the particles is not ideal, and SPF is adversely affected. Published data indicate
that predispersions give higher SPF efficacy than dry powders (34).
Assuming that an optimized predispersion is used, the factors further
affecting SPF with physical sunscreens depend on whether the particles are
dispersed in the water phase or the oil phase.
Formulating with Water-Dispersed TiO2

As discussed earlier in this chapter, optimum SPF efficacy requires that the
active(s) be well dispersed throughout the film that is deposited on skin. In the
402 Hewitt
case of an O/W emulsion (Fig. 19.7), this film consists predominantly of lipophi-
lic materials (the oil phase of the emulsion), so one might logically expect that
water-dispersed TiO2 would have poor efficacy in such systems, as it would be
excluded from the oil film (Fig. 19.7b). And yet there are numerous examples
of formulations containing aqueous TiO2 dispersions which display good efficacy
(both in the literature and on the market). This suggests that there must be a
mechanism by which the TiO2 particles are incorporated into the oil film
(Fig. 19.7c).
With hydrophilic TiO2 particles, the most likely explanation for this is
liquid crystals. Liquid crystalline structures are present in many cosmetic O/W
emulsions (18 –21), and studies using freeze – fracture electron microscopy
have shown that, with a suitable dispersing agent, TiO2 particles from an
aqueous dispersion tend to locate within these structures (35). Previous formu-
lation studies (36) have indicated that gel networks formed from lamellar
liquid crystalline structures are advantageous for achieving optimum efficacy
with such dispersions. A logical explanation for this is that the TiO2 is preferen-
tially located within the lamellar structures, which are in turn incorporated into
the oil film during de-emulsification. In other words the liquid crystalline
(a) Water evaporates
SKIN
(b)
SKIN
(c)
SKIN
Figure 19.7 (a) Schematic representation of O/W emulsion, containing TiO2 particles
in the water phase, on skin immediately after spreading. (b) Emulsion after dry-down; if
TiO2 is hydrophilic and cannot migrate into oil film, coverage is discontinuous leading
to low SPF. (c) If TiO2 can migrate into the oil film, much better coverage is achieved
(see text).
SPF Modulation 403
structures provide a vehicle to ensure the transfer of the TiO2 into the oil film.
A variety of different types of surfactants can form these structures, including
glyceryl stearate, sorbitan esters, sucrose esters, and polyglyceryl esters. As a
result, many familiar and commonly used emulsifier systems can be used to for-
mulate effective products with these aqueous TiO2 dispersions. However, recog-
nition of the potential of lamellar gel networks (in other applications as well as
this one) has led to the development of emulsifier systems designed specifically
for this purpose. An additional advantage of such emulsifiers is that they can be
used with a wide range of different oils, including silicone oils (20,21).
With hydrophobic TiO2, the mechanism is simpler. In this case it is unli-
kely that the particles will be located within the lamellar structures, but the hydro-
phobic coating means that, as the water evaporates, the particles have a natural
tendency to migrate into the oil phase. So lamellar structures are not required
to ensure homogenous distribution of the particles in the oil film.
In the subsection on the effect of emulsion type, we discussed how water-
soluble organic UV filters have often been found to be more effective in W/O
emulsions than in O/W systems. And yet the same has not been found to be
the case with water-dispersed TiO2 (15). This is because, historically, all
aqueous dispersions used hydrophilic TiO2; as discussed in the subsection on
basic principles, such dispersions rely principally on electrostatic repulsion to
keep the particles well dispersed. It is common practice in W/O emulsions to
incorporate an electrolyte, which aids stability by preventing dissolution of the
emulsifier in the water phase. This electrolyte content is sufficient to destabilize
an aqueous TiO2 dispersion based on hydrophilic particles, resulting in poor effi-
cacy. However, the advent of aqueous dispersions containing hydrophobic TiO2
opens up new possibilities, since such dispersions are not expected to be sensitive
to electrolytes.
Formulating with Oil-Dispersed TiO2

By using appropriate dispersing agents, either hydrophilic or hydrophobic TiO2
can be used to make a stable oil-based dispersion, and either can be used effec-
tively in both O/W and W/O emulsions. Evidence indicates that hydrophobic
TiO2 is more versatile in formulation (16) and that such a coating, together
with optimized particle size distribution, gives improved cosmetic elegance as
well as high efficacy (30).
Other ingredients included in the formulation can affect the SPF provided
by physical sunscreens via two principal mechanisms:
1. Altering the degree of dispersion of the particles
2. Altering the extent to which the product effectively covers the skin
Each of these mechanisms can be subdivided into different effects. For example,
consider the use of oil-dispersed TiO2 in an O/W emulsion. In this case, the
degree of dispersion can be improved by optimizing the dispersion of the
404 Hewitt
particles within the oil phase by selection of suitable emollients (16), or by alter-
ing the droplet size of the oil phase. Effective coverage of skin can be achieved by
optimizing the rheology of the emulsion (as discussed in the subsection on emul-
sion rheology), altering droplet size (23), and using film-forming polymers (37),
for example.
Formulating with Zinc Oxide

The primary purpose of ZnO in sunscreen formulations is UV-A protection,
rather than SPF; nevertheless, UV-A filters do make a significant contribution
to SPF, and the same principles apply to optimization of UV-A efficacy.
Many of the principles of formulating with TiO2 also apply with ZnO,
because they are based on the characteristics of inorganic particulates rather
than of TiO2 specifically. However, there are additional challenges presented
by ZnO (15,38 – 40). ZnO tends to form alkaline complexes when dispersed in
water, causing pH values which are too high for products which are to be left
on the skin. For this reason, ZnO is usually incorporated into the oil phase of
the formulation. However, ZnO is highly hydrophilic, and tends to migrate
from the oil phase to the water phase. This process is promoted if the pH of
the water phase is less than 6, as the solubility of ZnO in water increases signifi-
cantly below this pH (39). This migration/solubilization causes pH to drift
upward, and can also decrease the efficacy of the ZnO, if measures are not
taken to maintain a good dispersion of the particles in the aqueous phase.
These problems can be minimized or eliminated by various means. Use of
an optimized predispersion maintains the ZnO in a finely dispersed form in the oil
phase. In W/O emulsions, such dispersion techniques are sufficient to eliminate
migration and maintain the efficacy of ZnO. ZnO can also be coated with hydro-
phobic materials in order to reduce migration. However, in either case further for-
mulation measures are necessary in order to completely eliminate migration, or to
mitigate its effects, in O/W systems (15).
COMBINING SUNSCREENS
Of course, it is unusual nowadays for sunscreen products to contain only a single
UV filter, the possible exception being products formulated with only an inor-
ganic filter and targeted at young children or individuals with sensitive skin.
This is because it is virtually impossible to achieve the high SPFs demanded
by today’s market by using a single organic filter, and while such high SPFs
are achievable by use of TiO2 alone, it is often necessary to use a high concen-
tration of the active, resulting in poor aesthetic properties (whitening on skin).
The difficulty in achieving high SPF with a single organic filter is due to
two main reasons: the narrow spectrum of most organics and the fact that
product films deposited on skin rarely are completely homogenous oil films.
SPF Modulation 405
Consideration of the erythemal action spectrum and the solar spectrum (41)
shows that SPF is dependent primarily on UV-B protection, but that UV-A also
plays a part, in particular the short-wavelength UVA region sometimes referred
to as “UV-A-II” (320 –340 nm). Products must provide effective protection at
these wavelengths in order to reach a high SPF, and most UV-B filters fail to
do this, while UV-A filters tend to have poor efficacy in the UV-B. Also, since
product films often contain both hydrophilic and lipophilic regions, a product
which contains, say, only an oil-soluble filter will not adequately protect the
whole surface and this also limits efficacy. Combination of these two factors
leads to a “Law of Diminishing Returns”, illustrated in Fig. 19.8 for EHMC.
This shows SPF values for a series of formulations containing increasing
levels of EHMC as the sole active. As the active level is increased, SPF increases,
but the overall efficacy (in terms of SPF per %active) decreases.
Combining Organic Sunscreens

It is common practice, then, to combine UV filters. In designing a filter system,
the formulator should take account of the principles discussed in this chapter
and elsewhere in this book, and choose filters which complement one another
in some way. This usually means combining UV-B filters with UV-A filters
to achieve better spectral coverage, or combining oil-soluble and water-
soluble filters to achieve better skin coverage. The formulator must also be
mindful of intellectual property, however, as there are numerous patents
covering such combinations.
Certain combinations have other advantages, for example, ethylhexyl
methoxycinnamate is a very good solvent for solid organic UV filters, and
16
14
12
In-vitro SPF
10
8
6
4
2
0
0 2 4 6 8 10 12
% EHMC
Figure 19.8 SPF vs. %active for a series of formulations containing ethylhexyl
methoxycinnamate.
406 Hewitt
therefore can help to optimize the efficacy of such filters. Another consideration
might be photostability; it is well known that certain organics, for example, avo-
benzone, decay on exposure to UV (42,43), but it is also well known that this
decay is automatically taken into account by in vivo SPF testing since this is a
time-resolved measurement. However, the in vivo efficacy of such materials
can be improved by combining them with other filters which photostabilize
them; it has been established that, for example, octocrylene achieves this with
avobenzone (44).
Combining Inorganic Sunscreens

TiO2 alone is effective enough in both UV-B and UV-A to generate high SPF
values when used as a sole active. However “broad-spectrum” coverage can
still be improved by combining it with ZnO (39). Another “combination” strategy
is to use oil-dispersed and water-dispersed TiO2 in the same formulation, thereby
achieving more efficient overall skin coverage (45).
Combining Organic and Inorganic Sunscreens

A very common strategy is to combine both organic and inorganic filters, not the
least because substantial “synergistic effects” have been observed when organic
and inorganic sunscreens are combined; the SPF data measured on the combi-
nations are substantially higher than would be expected from adding together
the SPFs from the individual actives (46 –51). There are three reasons for these
synergistic effects:
. Improved skin coverage—incorporation of one active in the oil phase
and one in the water phase of an emulsion results in improved
overall coverage of the skin, as explained earlier.
. Improved spectral coverage—for example, addition of ZnO to a
formula containing an organic UV-B sunscreen can dramatically
improve the SPF, in the same way as can be achieved with a UV-A
organic.
. Increased path length—the scattering of UV light by the inorganic
sunscreen means that light does not pass through the sunscreen film
in a straight line (see Fig. 19.9); therefore, the optical path length is
increased. As a result, the efficacy of the organic is improved.
SPF MODULATION BY EXTERNAL FACTORS: WATER RESISTANCE

The bulk of this chapter has discussed how different aspects of the formulation
affect SPF. However, the true SPF in use is also affected by external factors, relat-
ing to the type of activity in which the user is engaged. Most commonly, sun-
screen products are used during leisure time, since this is when most people
receive the majority of their sun exposure. For example, the average British
SPF Modulation 407
UV UV TiO2
PARTICLES
Sunscreen
Skin
Figure 19.9 Increase of optical path length due to scattering by TiO2 particles.
consumer receives 70% of his annual UV dose during summer vacations and
summer weekends (2). Typical activities during these times would include
outdoor sports, sunbathing, and swimming. As a result of these activities, SPF
can be affected by sweating, water immersion, towelling, and other external
agents such as sand. Claims for “sand resistance” or “rub resistance” are some-
what unusual, probably because there are no universally recognized methods
for substantiating such claims, although methods have been proposed (52). On
the other hand, tests for water resistance are well established (3,53), and water-
resistant claims are now the norm for “beach” suncare products. So how can
the formulator make his product water resistant? To answer this we need to
once again go back to first principles.
Fundamental Requirements for Water Resistance

Once a product has been applied and has dried down on skin, there are three
processes by which UV filters may be removed on contact with water:
1. Re-emulsification of the product film
2. Removal of the product film by mechanical action of water moving
over the skin surface
3. Removal of active UV filters which are excluded from the product film
The first of these occurs where a significant concentration of hydrophilic emulsi-
fiers is present in the product film. This facilitates easy re-emulsification of the
oils, etc., by the water moving over the skin.
Mechanical removal can occur where the product film is discontinuous or
has poor adhesion to the skin. This allows water to penetrate under the product
film and “lift” it from the skin surface. This can be observed in a simple
in vitro experiment. A film of an emulsion is applied onto a glass slide, left to
dry, and then placed in a beaker of water which is gently agitated. If the
408 Hewitt
product re-emulsifies, the water becomes turbid or cloudy; such products are
unlikely to be water resistant. However, some products do not re-emulsify but
peel away from the slide in one piece.
An example of exclusion of active from the film was illustrated earlier in
Fig. 19.7b. If hydrophilic TiO2 is incorporated into an O/W emulsion, and has
no means of migrating into the oil film on dry-down, then even if the film
itself is water resistant, the TiO2 is readily redispersed and removed by water.
The fundamental requirements for water resistance are therefore
1. A low concentration of hydrophilic emulsifiers, to avoid
re-emulsification
2. A continuous, coherent product film after application and dry-down
3. Actives effectively dispersed within the product film
Strategies for Water Resistance

Several different formulating strategies have been employed to provide water
resistance. Each of these approaches addresses one or more of the fundamental
requirements mentioned earlier.
W/O Emulsions
The film deposited on skin by a W/O emulsion can be expected to be resistant to
re-emulsification, since oil is the external phase of the emulsion, and such emul-
sions employ predominantly hydrophobic emulsifiers. There are guide formu-
lations available in the literature (54,55) demonstrating the use of this strategy
for water resistance.
Silicones
Silicone oils aid water resistance in two ways: the oils themselves are inherently
hydrophobic and they also have very good spreading properties, which assist in
formation of a coherent, continuous film. Certain specialty silicone ingredients
have also been shown to give improvements in water resistance (14,56).
Specialized Emulsifiers
Several specialized emulsifiers are now available which use different technologies
to impart water resistance. For example, phosphate-based emulsifiers such as pot-
assium cetyl phosphate, have a similar chemical structure as that of skin lipids,
and it is claimed that this facilitates increased water resistance. Phosphate emulsi-
fiers have been developed which are targeted specifically at this application (57).
Another material, acrylates/C10 – 30 alkyl acrylate cross-polymer, stabil-
izes emulsions by electrostatic means, forming an aqueous gel structure within
which the oil droplets are suspended. By use of such technology, surfactant-
free (so-called “emulsifier-free”) emulsions can be made. With no surfactant
present, re-emulsification is prevented. Sunscreen formulations based on this
material have been published (54,55).
SPF Modulation 409
Liquid Crystal Gel Networks

Lamellar gel network systems are based on hydrophobic, lipid emulsifiers,
making them difficult to re-emulsify after dry-down. Additionally, as far as
physical sunscreens are concerned, such liquid crystalline systems have been
found to be especially suitable for use with aqueous TiO2 dispersions (36),
providing a means of incorporating the water-dispersed TiO2 in the oil film, as
illustrated earlier in Fig. 19.7c.
Film-Forming Polymers
Perhaps the most common approach is to incorporate a “waterproofing agent”.
These materials are typically film-forming polymers, which can be used to
make the product film more coherent and hence more substantive. The efficacy
of these polymers in promoting water resistance has been demonstrated (58,59)
and specific example formulations can be found in the literature (54,55).
The “Dual-Strategy” Approach

While all of the above strategies have been used successfully, none provides a guar-
antee of success. With each strategy, examples can be found in which the strategy
failed to yield a water-resistant formula. For example, Angelinetta and Barzaghi
(37) observed significant increases in SPF when film-forming polymers were incor-
porated into TiO2 formulations. However, the formulations used by were based on
high-HLB (hydrophile–lipophile balance), hydrophilic emulsifier systems, which
are readily re-emulsified. Despite the improvement in static SPF, subsequent in
vivo SPF tests demonstrated that the formulations were not water resistant.
In order to build a more reliable approach for creating water-resistant pro-
ducts, we must consider all of the fundamental requirements. This means invok-
ing at least two of the basic strategies in the same formula. The two chosen
strategies should complement each other, that is, one should address the
re-emulsification issue, while the other should take care of forming a hom-
ogenous film. This “dual-strategy” approach (60) can be applied in different
ways, for example:
. W/O emulsions with high silicone content
. Film-forming polymers in a liquid crystal gel network system
. Phosphate emulsifiers formulated to give a multilayer lamellar struc-
ture (61)
Test data indicate that considering the fundamental requirements in this way sig-
nificantly increases the chances of achieving a water-resistant formulation.
SUMMARY
The demands of the modern sun care market mean that the formulator must
be able to achieve high efficacy from the actives used in order to meet
410 Hewitt
ever-increasing SPF targets. However, by a judicious choice of filters, and by

considering how other aspects of the formulation influence SPF, the need for
numerous and time-consuming “trial-and-error” experiments can be substantially
reduced.
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20
The Role of Surfactants in Sunscreen
Formulations
Gerd Dahms
Institüt für Angewandte Colloidtechnologie, Duisberg, Germany
The Role of Emulsifiers in General 414

Film Formation 415
O/W Sunscreen Formulations 422
Quick-Breaking O/W Sunscreen Emulsions 433
Sprayable O/W Emulsions 437
W/O Emulsions 440
Autoxidation of Emulsifiers 446
References 448
Although the formulation of emulsions is not all that easy, they are the most
frequently used vehicle for UV filters. Here, as in all emulsions, the most import-
ant structural element is the emulsifier system used; this system is primarily
responsible for the stability of the sunscreen emulsion. In addition to ensuring
emulsion stability across a broad temperature range, the emulsifier system used
contributes to many other quality characteristics of a sunscreen product, for
example, easy spreadability on the skin, the waterproofness of the formulation,
413
414 Dahms
the film formation during and after application, the stability of the degree of
dispersion of micropigments, and product safety—to name only a few examples.
Even today a suitable emulsifier system is selected for sun protection
products on a purely empirical basis in most cases. However, this approach
results in an optimum selection of emulsifiers in only a few cases—and even
less frequently when the formulating chemist has to choose from among an over-
whelming assortment of emulsifiers.
For this reason, this chapter intends to explore the role of the emulsifier in
sunscreen products more closely and thus facilitate a targeted and product-
specific selection of emulsifiers for sun protection products.
THE ROLE OF EMULSIFIERS IN GENERAL

The relationships between the chemical structure of surfactants and their emulsi-
fying effect are quite complicated because, in general, the oil and the aqueous
phase are of variable composition. It is not possible, therefore, to classify individ-
ual surfactants as general emulsifiers. Nevertheless, we can set down several
general guidelines which can be useful for selecting surfactants as emulsifiers.
To be effective, an emulsifier must possess the following qualities:
1. It must generate a sufficiently low interfacial tension at the oil –water
interface to make the emulsification process possible at all. It must be
possible, therefore, for the emulsifier to migrate to the oil – water inter-
face and be firmly fixed there instead of remaining in the bulk phase.
Hence, there must be a balance between the hydrophilic and lipophilic
groups in the emulsifier.
2. At the oil –water interface, the emulsifier, acting on its own or together
with other molecules, must form a resilient, elastic, and condensed
film. On the basis of our present knowledge, such films occurring in
cosmetic products such as sunscreen emulsions consist of liquid crys-
talline surfactant structures.
3. It must be available at the oil –water interface quickly enough to ensure
that the interfacial tension is reduced to a sufficient degree during the
emulsification process.
4. It must be adapted to the polarity of the oil phase. Very polar oils
require emulsifiers that are more hydrophilic than do oils with low
polarity.
The reduction of the interfacial tension between oil and water is only one
criterion for the dispersion of droplets during the emulsification process proper;
however, it is of secondary importance for the stability of the emulsion.
Whether an oil-in-water (o/w) or a water-in-oil (w/o) emulsion will be
formed depends primarily on the selection of the emulsifier. Which of the two
emulsion types is formed depends on the solubility of the emulsifier in the
phases. According to Bancroft’s rule, the phase in which the emulsifier is most
The Role of Surfactants in Sunscreen Formulations 415
soluble will constitute the external continuous phase. However, this maxim should
be viewed with caution. In particular, solid lipophilic coemulsifiers, which are by
nature soluble in oil, can migrate at temperatures above their melting point to the
water phase, thereby forming with small amounts of a hydrophilic surfactant
mixed micelles. As a result, such systems form oil-in-water emulsions. Since
the interfacial film has two surfaces, we can apply the Windsor principle which
says that a film will bend on the side with the higher interfacial tension. In
other words, the curvature will enclose the dispersed phase (1 –4).
In addition to Bancroft’s rule and the Windsor principle, the “oriented
wedge theory” can also be used to derive the type of emulsion. According to
this theory, the part of the surfactant with the larger cross-section will also
always project into the continuous phase. Thus, a typical W/O emulsifier
always has a hydrophobic part exhibiting a larger cross-section than its hydro-
philic part.
In addition to the criteria stated above, which depend on the solubility, the
interfacial tension behavior, or the molecular geometry of the emulsifier, there is
also the phase – volume theory, which states that above the densest sphere
packing, a breakdown of the emulsion or phase inversion will occur.
Depending on the structure and concentration of the emulsifier, however,
this limit can be exceeded without the emulsion breaking down or inverting. In
such cases, the emulsion structure will change and be converted into a single-
phase microemulsion after the critical phase – volume ratio has been exceeded.
Such systems are used in sunscreens only very rarely even though they have a
high potential for incorporation in highly efficient sunscreen products, especially
with regard to film formation.
FILM FORMATION
We do not know what actually happens to an emulsion on the skin during and
after application. The analytical methods at our disposal determining film-
forming properties are either unsatisfactory or too complicated. In a first approxi-
mation, however, we can look at the spreading equilibrium of liquids on solids in
combination with the rheological properties of the emulsion and its oil phase in
order to achieve a better understanding of film formation.
When a droplet of liquid or, in our case, a droplet of emulsion is placed on
the surface of a solid body, it can either spread over the solid body or remain there
in the form of a droplet with a defined contact angle u. Figure 20.1 shows various
contact angles.
Assuming that various surface forces are represented by interfacial
tensions, we see that they can act in the direction of the surfaces. For the three
phases, that is, air (A), liquid (L) and solid surface (S), that are found at one
point, we obtain Young’s equation by vector addition (Fig. 20.2):
gSA ¼ gSL þ gLA cos u (20:1)
416 Dahms
θ θ = 80°°
θ θ = 40°
θ θ = 10°
Figure 20.1 Contact angles between liquids and solids.
where gSA is the solid–air interfacial tension, gSL is the solid–liquid interfacial
tension, gLA is the liquid–air interfacial tension, u is the liquid–solid contact angle.
Generally, u 908 is correlated with wetting and u . 908 with nonwetting.
By combining Eq. (20.1) with Dupré’s equation,
WSL ¼ gSA gSL þ gLA (20:2)
we obtain the Young– Dupré equation:
WSL ¼ gLA (1 þ cos u) (20:3)
According to this equation, a reduction of gLA by means of a wetting agent
always causes a reduction of the contact angle u and thus improved spreading
(Fig. 20.3). This has been proven by in vivo testing on the human forearm (5).
However, the wetting process taking place on a nonsmooth surface contain-
ing capillaries, that is, a surface similar to the skin, is even more complex than
that described here since the penetration of the liquid into the capillaries, that
is, the folds of the skin, also has to be taken into account. The following
applies to penetration by a liquid (Fig. 20.4)
2gLA cos u
P¼ (20:4)
r
where P is the capillary pressure and r is the capillary radius.
γ
LA
γ
SA θ
γ
SL
Figure 20.2 Spreading equilibrium according to Young.

25
Spreading on skin [mm2]
20
15
10
0
20 22 24 26 28 30 32 34 36
Surface tension [ mN/m ]
Figure 20.3 Impact of surface tension gLA of oils on spreading on skin according to
Kaymer (5).
According to Washburn, the wetting of a rough surface containing capil-

laries over time can be described by the following equation:
dl r gLA cos u
¼ (20:5)
dt 4 h l
where l is the depth of penetration, t is the time of wetting, and h is the viscosity
of the liquid.
It is important for the wetting process that the contact angle u is ,908 and
that the rate of penetration into the capillaries is relatively high.
According to the Washburn equation, quick penetration occurs at a high
value of gLA cos u, a small contact angle u, a low viscosity h, and a large diameter
of the folds of the skin. A high value for gLA and a low contact angle u are
mutually exclusive.
According to Young’s equation, however, the following applies:
gSA
gLA cos u ¼ 1 (20:6)
gSL
Thus, as soon as the interfacial tension between the solid body and the liquid
approaches zero, gLA cos u takes on high values. The interfacial tension
between a solid body and a liquid cannot be determined with sufficient accuracy.
Moreover, it is difficult to find reliable values in the literature. Nevertheless, the
r q
Figure 20.4 Penetration of a liquid into a capillary.

418 Dahms
old rule that polar solids are wetted well by polar liquids is very useful here.
In other words, the higher the affinity of a liquid to the surface of a solid body,
the better the liquid will spread.
The spreading of liquids on the skin can be simulated quite well on
filter paper because both skin and filter paper represent porous and absorbing
surfaces. In this context, however, we must point out that it is not possible to
use filter paper as a general skin model. It is suitable, however, for performing
the first investigations, using the technique of approximation, on the spread-
ability of oils on the skin. For comparative spreading studies a defined quan-
tity of oil dispersion is trickled onto filter paper and the spreading radius
determined in defined time intervals. The spreading speed of the pure oils
and of the oil– pigment dispersions can be determined quite easily in this
manner.
The independent spreading of pigment-in-oil dispersions, which was
measured without additional rubbing, is indeed an important indicator of spread-
ing on the skin. However, it cannot completely reflect the spreading process
taking place during rubbing-in under the effect of shear forces since, under
the influence of shear forces, the viscosity h of structured dispersions can be
reduced or, alternately, flocculation of the pigments on the skin can be
induced. The risk of migropigments flocculating on the skin when rubbed in
increases with pigment concentration. In most cases, flocculation of the micro-
pigments manifests itself as a whitening of the micropigments during rubbing.
In the area of the hair follicles, in particular, this is a constant danger. If
there are good spreading conditions for the oil in which the pigments have
been dispersed and the average particle diameter is larger than the pores on
the hair follicles, only the pure oil will penetrate the pores. As a result, the con-
centration of the pigment will increase in the oil phase above the pores. If,
during this process, the pigment in the oil phase is enriched up to concentrations
close to the critical phase –volume range, during application irreversible floccu-
lation will occur in insufficiently stabilized pigment dispersions, that is, the
aggregates generated cannot be redispersed by further rubbing. As flocculation
increases, and the average diameter of the particles becomes larger, wetting
decreases.
In order to form the required uniform film, micropigments must be dis-
persed in a manner resistant to the effect of shear forces. The dispersing agent
must, on the one hand, be well anchored in the pigment surface and, on the
other hand, display a good skin affinity in order to form, by means of an
anchoring mechanism, a homogenous layer on the skin which almost
completely absorbs and reflects the UV light hitting the skin. PVP and their
alkyl-substituted derivatives are good dispersing agents satisfying these
requirements.
Although the spreading of the oil phase is the basic prerequisite for film for-
mation, the rheology of the oil phase plays a decisive role in the creation of a film
with a sufficient layer thickness on the skin (6). The rule of thumb for a high
photoprotection effect is that the film must have a corresponding thickness. It is

obvious that a film can only achieve a high layer thickness when the viscosity of
the film-forming substance is high. High viscosity, however, is in conflict with
spreadability. Viscoelastic behavior represents a compromise here.
In a resting state, substances with viscoelastic behavior display very high
viscosities. Under the effect of shear forces, however, such as those that occur
when an emulsion is rubbed into the skin, the viscosity can take on a low
value in comparison with the value in the resting state. The viscosity values
for a viscoelastic oil phase under the effect of shear forces are usually 10 times
higher than that of an oil phase with Newtonian flow. In accordance with the
Washburn equation, the spreading of such viscoelastic systems depends primarily
on the value of gLA cos u, which is directly connected to the interfacial tension
gSL existing between the viscoelastic liquid and the solid surface of the skin.
As discussed above, this value can be sufficiently reduced only by the affinity
of the emulsifier and coemulsifier to the skin during film formation by sunscreen
lotions. Thus, for achieving the required viscoelasticity of the photoprotection
film, gSL is the only variable available to guarantee sufficient spreading.
Hence, the selection of the emulsifier system to be used plays a key role.
After having discussed the fundamental principles of spreading and the
penetration of the skin by emulsions and oils so far, we will now explore the prac-
tical application of these principles to show the role played by the emulsifiers
used in sunscreen formulations.
Films are formed on the skin by sunscreen emulsions in two steps. In the first
step the emulsion is spread over the skin; a pure emulsion film is formed. In the
second step, during which the emulsion is rubbed further into the skin, the aqueous
phase is caused to evaporate and the oil film is massaged into the skin. However, the
underlying mechanism is quite different for W/O and O/W emulsions.
When a W/O emulsion is applied, it is the continuous external oil phase
which first comes into contact with the skin. Consequently, for this type of emul-
sion, it is primarily the spreading and penetration capability of the oil phase
which is decisive for film formation. With the exception of silicone emulsifiers,
W/O emulsifiers are not capable of significantly reducing the interfacial tension
gLA. Accordingly, spreading and penetration by the oil phase can only take place
to a significant extent as a result of the interfacial tension between the oil phase
and the skin. According to the rule that the high affinity of the liquid phase to a
solid body leads to high spreadability, only emulsifiers exhibiting a high affinity
to the skin can be employed to reduce gSL to a sufficient degree. For this purpose,
all emulsifiers with hydrophilic amino-functional head groups can naturally be
used. Especially, alkyl modified PVP derivatives and hydrophobic amino-
functional silicones seem to work best. By bridging these groups with the skin,
the interfacial tension gSL can then be reduced to a sufficient degree, resulting
in spreading of the film.
The required viscoelastic behavior of the oil phase is achieved by adding
waxes. In order to obtain a favorable viscoelasticity achieving sufficiently low
420 Dahms
values during shearing and permitting extremely high viscosity values in the
resting state, a favorable wax structure and an optimum concentration must be
found for the selected oil phase. Figure 20.5 demonstrates the influence of wax
structure and concentration in a simple W/O sunscreen formulation.
The process of film formation by an O/W emulsion is much more complex
in comparison with the same process for a W/O emulsion. It is true that during
application, in this case as well, the pure emulsion is spread over the skin during
the first step. In the case of an O/W emulsion, however, there is no film formation
by the oily photoprotection phase at this stage. Spreading of the emulsion pro-
vides only the basis for such formation. Only in the second step, when the
aqueous phase evaporates and the critical phase volume is exceeded, does film
formation start after the emulsion has been rubbed in further. After the critical
phase – volume ratio has been exceeded, there are two possible scenarios.
Either the emulsion breaks and the oil droplets quickly coalesce to create a homo-
genous film when rubbed in further or the emulsion is converted into a single-
phase microemulsion in which the remaining amount of water is present in
stored form. If the microemulsion is distributed further, it will display a behavior
similar to that of a W/O emulsion.
When an O/W emulsion comes into contact with the skin, the spreading
that occurs during the primary distribution initially depends on the interfacial
tension gSA of the aqueous phase to the skin and the viscosity of the emulsion
when the emulsion is rubbed in. It is doubtful, however, whether these conditions
suffice to cover all inner folds of the skin and pores with the emulsion. Distri-
bution of the emulsion is important mainly as preparation for the eventual spread-
ing of the oil film. During distribution, only the rheological properties of the
emulsion appear to be important. If these have been favorably designed, it
creates a good basis for the decisive film formation phase.
During distribution of the O/W emulsion, the water phase, in particular, is
distributed. Depending on the interfacial tension gLA and the viscosity hExt of the
Candellila Wax
25
Bees Wax
20 Castor Wax
SPF Value
Ozokerite
15
10
0
0.0 0.5 1.0 2.0
Wax Concentration [ %wt ]
Figure 20.5 Impact of wax concentration and structure on SPF value.

external aqueous phase, the water also reaches the pores and the folds of the skin.
The more the pores and folds of skin that get into contact with the aqueous phase,
the more the skin is hydrated. Sufficient hydration of the skin leads often to a
higher SPF efficiency (7).
Actual spreading of the sunscreen film starts only when most of the water
has evaporated and the concentration of the oil phase has exceeded the critical
phase – volume fraction. At this point, it depends on the emulsifier system used
whether a coherent microemulsion film is formed or the emulsion breaks down
and only the pure oil phase is spread.
If a microemulsion is formed during dry-down of the emulsion on skin,
during this transition state the system takes on a slightly higher viscosity
which, however, breaks down upon being rubbed in further and thus achieves
the required lower values. From the point of view of the Washburn equation,
this means that independent spreading without further rubbing is nearly excluded
due to the high viscosity. As the water is more strongly bound in the microemul-
sion than in a normal emulsion, the evaporation process is delayed. At this stage,
spreading of the emulsion is determined by the liquid crystalline structure. We
can proceed on the assumption that the interfacial tension gSL of the microemul-
sion to the skin drops to nearly zero and good spreading and penetration are guar-
anteed at this stage. We do not know how long this intermediate condition of the
microemulsion is maintained. In many cases, however, we can expect that
the microemulsion will survive the period of normal rubbing in and that film
formation will start relatively late. This process probably plays a decisive role
in the delayed occurrence of the maximum SPF value which is described in
the literature (8).
Proceeding on the assumption that the microemulsion changes over time by
losing the stored water into a pure oil phase, we see that at this point spreading
and penetration display the behavior already described for the W/O emulsion.
The emulsifier mixture, which has to generate the low interfacial tension gSL
required for spreading, is now responsible for this phenomenon.
If the stage of microemulsion formation is not attained during the rubbing-
in of an emulsion, de-emulsification will occur when the critical phase – volume
ratio wc is exceeded in the emulsion. Subsequently, rubbing will only lead to
spreading of the oil phase.
Whereas in W/O emulsions the required viscoelasticity of the oil phase is
controlled by waxes, in most O/W sunscreen emulsions the viscosity is regulated
by means of the mixed emulsifier system used. As a result, modifications of the
viscoelastic behavior can only be achieved in such cases via the emulsifier com-
position and its concentration ratio compared with the oil phase. Achieving this
type of optimization is not all that simple, however, because both changes in
emulsifier concentration and variations in emulsifier composition can exert a
detrimental effect on emulsion stability.
It should be noted, moreover, that, in contrast to an oil – wax film, the
emulsifier –oil film can absorb water from the skin and store it. When the
422 Dahms
storage space for the bound water is larger than one photon, light can pass through
it without being filtered. The possibility of such gaps in the photoprotection film
occurring for O/W emulsions is demonstrated by the fact that the addition of
water-soluble UV filters often creates synergistic effects with regard to the photo-
protection effect. On the basis of the small amount of data available, we are at the
moment not in a position to make a useful prediction as to which emulsifier
system can store larger amounts of water in which oil phase. Further investi-
gations need to be conducted on this subject.
O/W SUNSCREEN FORMULATIONS

The majority of sun protection formulations are based on complex mixed
emulsifier systems. Mixed emulsifiers of this kind are built up from micelle-
forming hydrophilic emulsifiers and lipophilic coemulsifiers. Depending on
their composition, mixed emulsifiers may be capable of creating membrane-
like multilamellar liquid-crystalline structures in aqueous phases; in emulsions
these structures can envelop the dispersed phase in a multilamellar membrane
as well as create gel networks in the continuous water phase.
Mixed emulsifiers exhibit a multifunctional behavior in emulsion struc-
tures. The lamellar gel network structure running, in the form of a gel structure,
through the continuous water phase is responsible for the flow behavior of an
emulsion and its stability against creaming (Fig. 20.6). The viscosity h of an
emulsion with a lamellar gel network running through the water phase rises
Figure 20.6 TEM of an O/W emulsion containing gel network structures.

exponentially as the liquid-crystalline gel structure increases:
h ¼ Ae(BCG ) (20:7)
where h is the emulsion viscosity, CG is the gel network concentration, and A and
B are constants. If the concentration of the gel network phase in an O/W
emulsion is low, flowable liquid emulsions will be formed. At higher concen-
trations, the viscosity increases and emulsions with a creamy to solid consistency
are created.
According to Stoke’s Law, the creaming behavior or sedimentation of the
dispersed phase is described by the following equation:
2R2 Drg
V¼ (20:8)
9h
where V is the creaming/sedimentation velocity, R is the particle radius, Dr is the
density difference between the oil and water phases, h is the emulsion viscosity,
and g is the gravity constant.
It is evident, from the Eq. (20.8), that the rate of creaming and sedimen-
tation drops sharply at increasing gel network concentrations, that is, as the vis-
cosity h rises. It is thus possible to stabilize an O/W emulsion by boosting the
concentration of the mixed emulsifier. If micropigments are worked into the
emulsion as sunscreen filters, the difference in density Dr will quite naturally
rise appreciably. Here again this tendency can be counteracted by raising the con-
centration of mixed emulsifier.
The gel network structure only exists, however, within a certain tempera-
ture range. Above a critical temperature, the gel network phase will collapse
and the viscosity of the emulsion will consequently decrease to the same
extent. In the temperature range in which the gel network is completely dissolved,
the viscosity of the emulsion will conform to the expanded Einstein equation:

1 þ (1 þ 2:5hdk )w
h ¼ hk (20:9)
1 þ hdk
where hdk ¼ hd/hk, hd is the viscosity of the dispersed phase, hk is the viscosity
of the continuous phase, and w is the phase volume fraction.
The critical temperature range in which the structure-forming gel network
is broken down depends primarily on the melting point of the mixed emulsifier.
The lower the melting point, the lower the critical temperature at which the gel
network breaks down. This process is reversible, that is, when the temperature
falls below this critical temperature, the gel network will be built up again.
The critical temperature range can be determined relatively easily analytically
by rheological measurements or conductivity determination.
The critical temperature spectrum can be reliably identified by determining
the complex shear modulus G by rheological oscillation measurements
(Fig. 20.7). If we plot ln G vs. temperature, we see that G remains relatively
424 Dahms
three phase emulsion transition two phase emulsion

based on gel network temperature without gel network
G*
Temperature
Figure 20.7 Determination of temperature-dependent states in three-phase O/W emul-
sions by complex shear modulus G .
constant in the temperature range in which the gel network is stable. In the temp-
erature range in which the gel network breaks down, however, G drops sharply; it
does not take on constant values again until the gel network has dissolved
completely.
With the commonly used mixed emulsifiers, we can achieve a critical
temperature range of about 40 – 458C in sunscreen formulations. Since sunscreen
emulsions are often exposed to temperatures above this critical range, however,
hydrocolloids have to be added to ensure that the emulsion will have sufficient
stability even in higher temperature ranges. Taking film formation and the com-
patibility of the emulsion with micropigments into account, we see that only a
limited number of hydrocolloids are suitable for this purpose. To promote film
formation, the selected hydrocolloids, which first come into contact with the
skin when an emulsion is rubbed in, must form a compatible intermediate
layer between the skin and the sunscreen film. Hydrocolloids with amino-
functional groups appear to be advantageous in this context. Quite frequently,
the commonly used cross-polymers of the carbomer or Permulenw type display
very poor compatibility with micropigments. If cross-polymers are mixed with
linear polymers such as xanthan gum or PVP, however, incompatibility with
micropigments can no longer be detected.
As already mentioned, mixed emulsifiers are not only responsible for the
creation of gel networks in O/W emulsions, but they also cover the interface
of the dispersed oil phase with multilamellar liquid-crystalline layers. Below
the critical gel network temperature, these layers form a solid mechanical
barrier which prevents the droplets from coalescing when they come too close
to each other. Above the critical temperature, the viscosity of this barrier declines
markedly. If two droplets collide in this state, the lamellar layers may merge. A
fusion process of this kind may lead to coalescence, depending on the size of the
droplets and the thickness of the lamellar layer. Large droplets with a thin lamel-
lar layer coalesce more readily than small droplets with a relatively thick lamellar
layer. If the outer shell of the droplets is covered by linear polymers, fusion and
coalescence can be prevented by steric repulsion. At the very most, aggregation
caused by the entanglement of polymer layers will then occur.
The lamellar layer built up by the mixed emulsifiers displays favorable
properties with respect to the emulsification process as well. It is known that
liquid-crystalline lamellar structures reduce the interfacial tension between oil
and water to extremely low values. Nature also makes use of this phenomenon
in the production of milk. During the milk production process, oil droplets
come into contact with a liquid-crystalline membrane; the droplets are stably
emulsified by this membrane with practically no input of energy. The emulsifica-
tion process for O/W emulsions can proceed in a similar low-energy fashion on
the basis of mixed emulsifiers. If new emulsification techniques (9) are employed
in a laminar and viscous flow field, even nanoemulsions may result. If the emul-
sification process is carried out with conventional methods, care should be taken
that a turbulent flow field prevails during the mixing process.
It is advantageous in any case to place the mixed emulsifier in the oil phase;
care should be taken, however, to always add the oil phase to the water phase.
Placing the emulsifier in the oil phase during the emulsification process leads
to the “stranding” phenomenon. When the mixed emulsifiers diffuse out of the
oil phase into the water phase during mixing, they tear oil droplets from the
phase interface of the bulk oil phase. These oil droplets then strand finely dis-
persed in the water phase. The “stranding” process is thus very close to the
process found in self-emulsifying systems.
The most favorable emulsification temperature lies in the range just above
the melting point of the mixed emulsifiers (Fig. 20.8). If a homogenization
Optimum homogenization
temperature
G*
Temperature
Figure 20.8 Determination of optimum emulsification temperature of O/W emulsions
by complex shear modulus G .
426 Dahms
process is necessary, it should always be carried out slightly below the melting
point of the mixed emulsifiers since the interfacial tension reaches its minimum
value here.
The favorable dermatological characteristics of the mixed emulsifiers are
among their multifunctional properties. Multilamellar gel networks have a posi-
tive effect on transepidermal water loss (TEWL). This effect appears to be of
interest for the formulation of sun protection products since it is general knowl-
edge that longer exposure to UV radiation dries out the skin. In predamaged skin
as well, however, the addition of an aqueous gel network dispersion results in
much quicker regulation of the TEWL value than can be achieved by the
skin’s natural healing process (Fig. 20.9).
In addition to the properties discussed so far, gel networks can also incor-
porate amphiphilic sunscreen filters into their membrane structure. All molecules
with a structure including a free hydrophilic group can be classified as amphiphi-
lic sunscreen filters. Two examples are octyl salicylate and avobenzone.
The admittance of amphiphilic sunscreen filters into the gel network struc-
ture can have both positive and negative repercussions. The process leading to
these inclusions will be discussed later in this chapter on emulsifier optimization.
Among the positive qualities of the gel networks is the protective effect
they exert against changes in the structure of the sunscreen filters. Inside the
gel networks the molecules placed firmly in the lamella are protected for the
most part against attack from the outside. A good example of how sensitive
sunscreen filters can be protected by being incorporated into the gel network
lamella is provided by avobenzone. In oily media avobenzone forms crystalline
complexes together with microcrystalline titanium dioxide, for example; the
nature of these complexes remains largely unexplored. After only a few days,
300
250
200
TEWL [%]
Control
150 Gel Network
100
50
0
0 1 3 5
Days
Figure 20.9 Impact of gel networks on TEWL.

submarine-shaped crystal structures are formed in oily titanium dioxide

dispersions containing dissolved avobenzone; the concentration of these crystal
structures rises quickly with storage time. In O/W emulsions in which avoben-
zone has been firmly incorporated in the liquid-crystalline lamella of the gel
network, incompatibility with microcrystalline titanium dioxide is not created.
If avobenzone is incorporated in gel network lamella, it can be assumed,
moreover, that the undesirable keto-enol tautomerism does not take place or at
least occurs with a noticeable time delay.
The changed rheological behavior of the emulsion testifies to the fact that avo-
benzone has actually been taken up by the mixed micelles since any change in the
viscosity behavior of an O/W emulsion built up from gel networks must be attribu-
table solely to changes within the gel network structure. Increasing the avobenzone
concentration in a defined emulsion causes the viscosity of the emulsion to rise
exponentially along with the avobenzone concentration, that is, as the avobenzone
concentration rises, the gel network concentration will go up as well (Fig. 20.10).
Like avobenzone, octyl salicylate is incorporated at least partially into gel
networks. As a liquid component, octyl salicylate, when incorporated into the
lamella of a gel network, exerts an effect on the critical gel network temperature
and thus on the thermal stability of the emulsion. The critical gel network temp-
erature drops steadily as the concentration of octyl salicylate rises.
If sunscreen filters are built into gel network lamella, disturbances may
occur in the film formation process. If the gel network is not completely
broken down during the drying phase on the skin so that all of its components
are fused homogenously with the oil phase, homogenous spreading of the amphi-
philic sunscreen filters will not be possible either. As a result, the efficiency of
this UV filter as a sunscreen will be reduced. Care should be taken during emul-
sion formation, therefore, to ensure that the emulsion goes through a critical
phase during drying in which the existence of the gel network comes to an end.
So far we have discussed only the multifunctional properties of mixed
emulsifiers in O/W emulsions. In the following we will be looking into the
120000.00
Viscosity [mPas]
90000.00
60000.00
30000.00
0.00
0.00 1.00 2.00 3.00 4.00 5.00
Concentration Avobenzone [%wt]
Figure 20.10 Impact of avobenzone concentration on three-phase O/W emulsion

viscosity.
428 Dahms
question of how to find the right combination of single emulsifiers for a mixed
emulsifier composition.
A basic observation to be made about an O/W emulsion consisting of an
oily phase, an aqueous phase, and an emulsifier is that it will always be unstable
when the emulsifier system consists solely of either hydrophilic micelle-forming
emulsifiers or lipophilic coemulsifiers. Only a combination of hydrophilic emul-
sifiers and lipophilic coemulsifiers results in stable systems. Emulsifier combi-
nations of this kind are referred to as mixed emulsifiers.
Before going into the details of the actual combination technique used to
manufacture mixed emulsifiers, we will first discuss the mechanism by which
liquid-crystalline lamellar structures are formed from mixed emulsifiers. The
formation of micelles, which are present in the aqueous phase in spherical or
disk form, constitutes the basis for the formation of liquid-crystalline lamellar
structures. If the number of micelles in an aqueous system exceeds the critical
concentration, the micelles will be converted to the rod form. A further increase
in the rod micelle concentration causes the formation of lamellar liquid-
crystalline structures superimposed on the micelles (10). Accordingly, a sufficient
concentration of emulsifier micelles serves as the basis for the formation of
lamellar structures. If the lamellar structures are cooled below the melting
point of the emulsifiers they contain, solid gel networks may be formed.
The role played by the hydrophilic emulsifier becomes clear at this point. A
useful rule of thumb when drawing up the definition of a hydrophilic emulsifier is
that such emulsifiers have an hydrophilic lipophilic balance (HLB) value .6.
Emulsifiers with an HLB value ,5 can be defined as coemulsifiers. Coemulsifiers
can be taken up by the micelles of a hydrophilic emulsifier, thereby creating
mixed micelles.
The concentration of a coemulsifier in a mixed micelle may be several
times the concentration of the hydrophilic emulsifier present at that location.
The ratio between the concentration of the hydrophilic emulsifier and the concen-
tration of the lipophilic coemulsifier depends, in the first approximation, on the
HLB value of the latter. The higher the HLB value of the coemulsifier, the
higher is the proportion of the mixed micelle it accounts for.
During the formation of mixed micelles, the geometric properties of the
participating emulsifier molecules naturally also play a role. Thus, not every
micelle is capable of taking up every coemulsifier in sufficient amounts to
create the critical concentration of mixed micelles leading to the formation of
liquid-crystalline lamellar structures.
It is fairly easy to select hydrophilic emulsifiers. Regardless of their struc-
ture, nearly all emulsifiers or surfactants which form micelles in aqueous systems
can serve as building blocks for mixed emulsifiers. Selecting a suitable coemul-
sifier is admittedly somewhat more difficult.
Initially, only emulsifiers that exist in solid form at room temperature are
potential coemulsifiers since only solid emulsifiers can give the gel network
the necessary mechanical strength.
Microscopic examination is the best method of determining whether a

selected coemulsifier builds up the necessary lamellar structure with a hydrophi-
lic emulsifier. To perform this examination, first coat part of a microscopic slide
with the selected solid coemulsifier. Then, using a dropper, deposit an 10 wt.%
of aqueous solution of the hydrophilic emulsifier at the interface with the
coemulsifier.
Next, heat the slide slowly to the melting temperature of the coemulsifier.
Using polarized light, observe the interface. If the formation of lamellar liquid-
crystalline structures can be observed at the phase interface after a certain
time, you can assume that the emulsifier and the coemulsifier will form the
desired lamellar structure if they are mixed in the correct proportions
(Fig. 20.11). Table 20.1 provides an overview of several classes of hydrophilic
emulsifiers and the matching coemulsifiers.
From the discussion so far, it is very evident that, in addition to the coemul-
sifiers, there are other molecules which also have an amphiphilic structure and
can thus be easily incorporated into mixed micelles which can be inserted into
liquid-crystalline lamellar structures. The substances which can be included in
sunscreen formulations for this purpose include, in particular, sunscreen filters,
film-forming agents, and certain active agents.
The process of optimizing a mixed emulsifier system is based on the fol-
lowing assumption. Lamellar gel networks are always formed from mixed
micelles containing a maximum concentration of coemulsifier; geometrical con-
siderations are also taken into account here. Below the maximum coemulsifier
concentration, the curvature displayed by the lamellar sandwich structure of
the gel network increases, owing to the growing number of voluminous head
groups in the hydrophilic emulsifier. Since not all of the micelles in a mixed
micelle system have the same composition and number of aggregates, an
mixed
emulsifier
water
Figure 20.11 Lamellar liquid crystalline myelin structures formed at the mixed
emulsifier – water interface.
430 Dahms
Table 20.1 Examples of Hydrophilic Surfactants and Coemulsifiers That Form in

Combination Gel Networks
Hydrophilic surfactants Coemulsifiers
Lecithin Solid fatty acids (myristic, palmitic, stearic, etc.)

Acyl lactylates Solid fatty alcohols (myristyl, cetyl, stearyl, etc.)
Cetyl sulfates and phosphates Glycerol monostearates
Alkyl polyglucosides Solid sorbitane esters
PEG surfactants (HLB .7) Solid polyglycerine esters
Sugar ester Solid methyl glucoside esters
Cationic surfactants Cholesterol, ceramides, etc.
equilibrium is established between the lamellar sandwich structure and the

spherical vesicular structure (Fig 20.12).
Whereas the micelles saturated with coemulsifier form the gel network
structure, the micelles with surplus hydrophilic emulsifier form vesicles. As
the concentration of coemulsifier drops further, the equilibrium between the ves-
icular and the sandwich structures will increasingly shift toward the vesicular
structure. If the coemulsifier concentration falls below a critical concentration,
there will now be only a micelle structure and micelle concentration which do
not permit the formation of liquid-crystalline structures.
If there is a high surplus concentration of coemulsifier, mixed micelles will
be formed with the maximum coemulsifier concentration until the hydrophilic
Surfactant
Structure
Critical Packing
1 1 1 ~
V < 1 1 =1
3 3 2 2
lCa0
a0
Packing
Geometry V lC
Favored
Structure
Rod Vesicle Sandwich

Micelle Micelle Bilayer Bilayer
Figure 20.12 Impact of surfactant structure on micelle and bilayer formation.

emulsifier is consumed. The mixed micelles with maximum coemulsifier concen-

tration are converted to a lamellar gel network structure, whereas the surplus
coemulsifier remains behind in the water phase in the form of incompletely
swelled crystals. If the concentration of coemulsifier continues to rise, the con-
centration of incompletely swelled crystals will also increase and the gel
network concentration will decrease to the same degree.
Since the lamellar gel network structure, the vesicles, and the incompletely
swelled coemulsifier crystals take on different viscosities in an aqueous medium,
the optimal mixed emulsifier composition can be determined by viscosity
measurements. The lamellar gel network sandwich structure is the structure
that determines the viscosity. The mathematical relationship between the concen-
tration of gel network structure (CG) and the viscosity behavior in aqueous media
is described by the following equation:
h ¼ AeBCG (20:10)
where h is the emulsion viscosity, CG is the gel network concentration, and A and
B are constants.
Since both vesicular structures and incompletely swelled coemulsifier
crystals display nearly Newtonian flow behavior at a correspondingly low con-
centration in aqueous media, a viscosity maximum is attained once the gel
network structure has been established on the basis of optimal proportions of co-
emulsifier and hydrophilic emulsifier (Fig. 20.13). Below this maximum we find
either incompletely swelled crystals or mixtures of gel networks with vesicles.
Mixtures of this kind display a lower viscosity than a pure gel network.
Just how pronounced the viscosity maximum is depends on the structure
of the hydrophilic emulsifier used. Extremely hydrophilic emulsifiers with
60000
50000 preferred region preferred region

for sandwich structure for vesicle structure
Viscosity [mPas]
40000
30000
20000
10000
0
0 10 20 30 40 50
Concentration of Ceteareth-20 in Cetearyl Alcohol [ %wt ]
Figure 20.13 Impact of ceteareth-20 – cetearyl alcohol ratio on the formation of lamellar
sandwich and vesicle structures.
432 Dahms
voluminous head groups bring about curvatures in the sandwich structure of the
gel network and thus display a lower viscosity at the gel network point than do
emulsifiers with a lower HLB value. The lower the critical micelle concentration
of a hydrophilic emulsifier, the earlier the viscosity maximum is achieved, that is,
the concentration of the hydrophilic emulsifier in the mixed emulsifier system is
relatively low. In keeping with the rule that the maximum concentration of the
coemulsifiers in mixed emulsifiers increases as the HLB of the coemulsifier
rises, the required concentration of hydrophilic emulsifier will, of course,
decrease (Fig. 20.14). The following mathematical relationship has been
derived from the results of numerous experiments carried out to determine the
optimal proportion of the hydrophilic emulsifier CS:
CS ¼ 87e0:54HLBco (20:11)
where CS is the required concentration of hydrophilic surfactant and HLBCO is

the HLB value of the coemulsifier.
It is now relatively simple to determine the optimal concentration ratio for
the hydrophilic emulsifiers and the coemulsifiers. In actual practice the following
procedure can be followed. The first step is to select the individual emulsifiers
which will later be used to make up the mixed emulsifier, that is, a hydrophilic
emulsifier and a coemulsifier system. The selected coemulsifier system usually
consists of several single coemulsifiers. In cosmetic emulsions mixtures of
cetyl alcohol and glyceryl stearate are frequently employed for this purpose.
The second step is to calculate the correct proportions of the coemulsifiers to
be missed and their respective HLB values. On the basis of Eq. (20.11), we
can now calculate the approximate composition of the mixed emulsifier. To be
sure that the calculated composition is optimal for the mixed emulsifier as
well, we can perform practical tests to check this ratio. For this purpose, 10
parts of the emulsifier mixture determined by calculation are heated to 758C
60
50
Surfactant in mixed
emulsifier [%wt]
40
30
20
10
0
0 1 2 3 4 5 6
HLB Co-Emulsifier
Figure 20.14 Impact of HLB value of coemulsifier on required hydrophilic surfactant

concentration in mixed emulsifiers.
and then emulsified into 90 parts of the water phase foreseen for the sunscreen
formulation, whereby the water phase has also been heated to 758C. After
the emulsifier mixture has been added, the entire mixture is homogenized for
1 min and subsequently cooled. Afterward, two experiments with a similar
configuration are carried out in which the calculated composition of the mixed
emulsifier is shifted slightly in the direction of the hydrophilic emulsifier in
one experiment and slightly in the direction of the coemulsifier in another. The
emulsifier mixture which has exhibited the highest viscosity in the water phase
during the three experiments represents the optimum.
Optimal mixed emulsifiers are relatively resistant to variations in oil phase
polarity: both nonpolar oils, for example, isoparaffins and silicone oils, and polar
oils such as sunscreen filters can be emulsified without any difficulty to form a
stable emulsion with a fine droplet distribution.
O/W sunscreen formulations based on mixed emulsifiers may react sensi-
tively to the addition of micropigments. Owing to their enormous polar surface,
micropigments are able to adsorb substantial amounts of hydrophilic emulsifiers
and thus disturb the equilibrium of the mixed emulsifier. The concentration of
hydrophilic mixed emulsifiers adsorbed by micropigments is strongly dependent
on the surface modification and degree of dispersion of the micropigment used in
the particular case. For this reason, it is not possible to carry out exact calcu-
lations showing the percentage by which the concentration of the hydrophilic
emulsifier is to be raised by a given micropigment dispersion.
It is always beneficial, however, to predisperse the micropigments to be
employed. Alkyl-substituted PVP derivatives, silicone polyoils, and mixtures
of these are suitable dispersants for this purpose. Dispersants of this kind are
able to cover large parts of the pigment surface, thereby reducing the free inter-
face on which the hydrophilic emulsifiers can be adsorbed.
Pigment dispersions are ideally added to an emulsion below the critical gel
network temperature. The reason for this is that the hydrophilic emulsifier is
already firmly bound into the gel network matrix in this temperature range and
is thus still available to only a limited degree for adsorption onto free pigment
surfaces. Since gel networks are relatively resistant to the impact of shear
forces, the homogenization energy required to finely distribute the pigment
dispersion can be introduced without any difficulty and without any notable dis-
turbance of the gel network occurring as a result. If micropigments are employed,
care should always be taken, when determining the composition of the mixed
emulsifier, to select a concentration of hydrophilic emulsifier above the
optimal gel network concentration.
QUICK-BREAKING O/W SUNSCREEN EMULSIONS

Most sunscreen emulsions in cream or lotion form are stabilized by the use of
mixed emulsifiers, which results in the buildup of a liquid-crystalline gel
network and the formation of a multilamellar interfacial membrane.
434 Dahms
Nevertheless, we would like to discuss the quick-breaking type of O/W emul-

sion here since this type of emulsion exhibits a film-forming mechanism quite
different from that displayed by conventional emulsions. When these emul-
sions are rubbed into the skin, and the water phase allowed to evaporate,
they break when the critical phase –volume ratio is exceeded. Continuing to
rub these products into the skin after this point results in further distribution
of the coalesced oil film. The literature does not shed any light on the question
of whether the films formed by these emulsions are superior, with respect to
SPF efficiency, to the films formed by emulsions based on mixed emulsifier
systems.
The task of stabilizing a quick-breaking emulsion and thus preventing pos-
sible sedimentation or creaming is carried out by hydrocolloids. These build up a
gel structure in the aqueous phase which counteracts the movement of particles
due to the effect of gravity. Much like the gel networks formed from mixed emul-
sifiers, organic hydrocolloids, for example, carbomers, sodium alginate, and cel-
lulose, display a certain skin protection effect (11).
The role played by the emulsifier in a quick-breaking O/W emulsion
system is fairly simple to describe. The emulsifier is responsible for creating
droplets of sufficient size and for protecting the droplets created during the emul-
sification process against coalescence.
The maximum input of mechanical energy during an emulsification process
can be varied to only a small degree. On the basis of the emulsification tools
available, it can be viewed as practically constant. If we study the mathematical
relationship described by La Place’s equation, namely,
2s
DP ¼ (20:12)
r
where DP is the pressure difference, s is the interfacial tension, and r is the
droplet radius. It becomes evident that the only way to actually produce an emul-
sion with a sufficiently fine droplet distribution is to lower the interfacial tension
by adding an appropriate amount of a suitable emulsifier. The most favorable
characteristics in this context are displayed by nonionic emulsifiers with an
HLB of 7 – 14. However, a number of anion-active emulsifiers, for example,
sodium cetearyl sulfate, sodium lauroyl lactylate, and potassium cetearyl phos-
phate, also display good values to lower the interfacial tension here. The selected
emulsion should be soluble in the oil phase in any case; otherwise, disturbances
may occur during film formation which impair the SPF efficiency. In the event
that the chosen emulsifier is insoluble in the selected oil phase, it must be
mixed with an emulsifier displaying a lower HLB value in proportions ensuring
sufficient solubility.
The necessary concentration of emulsifier is based primarily on the selected
phase – volume ratio. The higher the concentration of the selected oil phase, the
higher the concentration of the chosen emulsifier. Since the thickness of the
emulsifier layer at the water –oil interface is not known, it is impossible to set
down an equation that calculates the correct emulsifier concentration for the
particular oil phases to be emulsified. The correct emulsifier concentration can
thus only be determined empirically. After conducting numerous studies of our
own on this subject, however, we have found that the necessary emulsifier
concentration is located in the range between 0.2 and 0.6 wt.% (of the total
formulation), depending on the selected phase – volume ratio.
La Place’s equation does not provide sufficient information, however, on
the optimal droplet size to be achieved in emulsions. Favorable flow conditions
must be present before droplets pull out of the bulk oil phase. The Weber number
is an important parameter in this context (12). It is defined as follows:
t
We ¼ (20:13)
p
where We is the Weber number, t is the emulsion yield stress, and p is the emul-
sification pressure.
t ¼ gh (20:14)
where g is the shear rate and h is the viscosity.
2s
DP ¼ (20:15)
r
where DP is the pressure difference, s is the interfacial tension, and r is the
droplet radius.
Inserting the parameters t and p, we obtain
ghr
We ¼ (20:16)
2s
Solving Eq. (20.16) for the droplet radius r, we see that we can expect to obtain
very small droplets in the presence of the prevailing high values for viscosity h
and low values for interfacial tension s:
2Wes
r¼ (20:17)
gh
The high viscosity required during the emulsification process for a quick-
breaking O/W emulsion cannot be generated solely by the polymer used since
a polymer solution usually takes on low viscosity values under the effect of the
shear forces occurring during emulsification.
To attain the viscosity needed to produce the required droplet size, it is
necessary to resort to a small trick (6), namely, to simply divide the emulsifica-
tion process into two phases. During the first phase a concentrated emulsion is
produced in which the dispersed phase accounts for a large volume fraction;
436 Dahms
this is because the viscosity h increases exponentially as the phase – volume

ratio rises:
h ¼ AeBwi (20:18)
The decrease in viscosity h observed under the effect of shear forces is lower in
emulsions with a high phase –volume fraction than in polymer solutions.
From Eq. (20.17) we see that the droplets become smaller and smaller as
the phase – volume ratio rises. It is not necessary to increase the input of mechan-
ical energy in this context. In the range shortly before the critical phase – volume
ratio, nanoemulsions will be produced.
After a concentrated O/W emulsion has been produced, it is diluted by
means of the remaining water phase down to the stipulated phase –volume
ratio, a process accompanied by mild agitation.
The two-stage process can be simplified into a continuous process via con-
tinuous process guidance. Continuous processes carried out in a microreactor
with a suitable mixing unit result in time, space, and energy savings. The
droplet sizes which can be achieved here lie in the nanometer range, that is,
they are considerably smaller than the droplet size found in conventional
emulsions.
As has been mentioned at the beginning of this chapter, the emulsifier suit-
able for use in a quick-breaking O/W emulsion determines droplet size in several
ways and not just by reducing the interfacial tension. In addition, this emulsifier
should envelop the emulsified droplets so well that they are protected against
coalescence during storage. As discussed above, emulsifiers which are able to
build up liquid-crystalline interfaces provide the best protection here. Several
anionic emulsifiers, as well as several nonionic polyglycerine esters, satisfy
this requirement without the addition of coemulsifiers. Prominent examples
include polyglycerine-10 dicaprylate, sodium lauroyl lactylate, and sodium
cetearyl sulfate.
If film-forming agents from the class of solid alkyl-substituted PVP
derivatives are used in the formulation, they can act as coemulsifiers and, in
combination with the selected hydrophilic emulsifier, also build up lamellar
liquid-crystalline structures at the oil –water interface. The concentration of
solid alkyl-substituted PVP derivatives must be determined with extreme
caution. If high concentrations are used, lamellar liquid-crystalline gel networks
will be formed automatically. In such cases, we are no longer working in the
range of quick-breaking emulsions since the film-forming mechanism now at
work is similar to that observed in emulsions based on mixed emulsifiers.
Here again it is important to note, when adding micropigments, that they
can bind nondefined amounts of the particular emulsifier system used. This can
result in a critical disturbance of the emulsifier concentration equilibrium,
which is already on a shaky footing in quick-breaking emulsions. When adding
micropigments, the only course of action available is to determine the required
emulsifier concentration empirically. As we have already discussed in the section

on mixed emulsifiers, predispersed micropigment dispersions, in which hydro-
phobic dispersants are used to cover the pigment surface, are the most suitable
dispersants for this purpose.
At the end of this discussion on quick-breaking O/W emulsions, it should
be pointed out that—in contrast to O/W emulsions based on mixed emulsifiers—
the former type of emulsion does not build up an oil film possessing the required
viscoelasticity on the basis of the particular emulsifiers used. For this reason, it is
advisable to compensate for this deficit in quick-breaking O/W sunscreen emul-
sions by adding wax-like emollients. The group of wax-like emollients that can
be used here include, in particular, hydrogenated cocotriglyceride, bethenyl tri-
glyceride, cetyl palmitate, or myristyl myristate. The concentration of solid emol-
lient should be about 5 –10 wt.% of the oil phase used.
SPRAYABLE O/W EMULSIONS

The sprayability of an emulsion depends primarily on its rheological behavior.
Emulsion viscosity plays an especially important role in this context as can be
demonstrated by the example of sprayable Newtonian liquids. The spray cone
generated by a given pump spray head decreases exponentially as the viscosity
increases. This can be illustrated by using silicone oils of different viscosities:
a ¼ AeBh (20:19)
where a is the spray cone and h is the viscosity.
It is easy to see from Fig. 20.15 that only an emulsion with a fairly low vis-
cosity will be able to generate a decent spray cone. According to Stoke’s Law,
emulsions with a low viscosity are only stable against creaming if the droplets
80
70
60
Spray angle [°]
50
40
30
20
10
0
0 20 40 60 80 100 120
Silicone oil viscosity [mPas]
Figure 20.15 Impact of oil viscosity on spray angle by the use of a hair spray nozzle.
438 Dahms
are correspondingly small. As already discussed in the foregoing chapter on

quick-breaking emulsions, small droplets can only be generated if the interfacial
tension is low and the rheological conditions are favorable for the droplet
break up.
The phase inversion temperature (PIT) method, which uses ethoxylated
niosurfactants, is frequently employed to manufacture emulsions (13). The mech-
anism of action of the PIT method can be explained quite well by describing the
cloud point phenomenon observed in conjunction with alkoxylated surfactants.
Below a critical temperature, ethoxylates with an HLB .10 usually form a
clear solution when dissolved in water. If aqueous emulsifier solutions of this
kind are heated to a critical temperature, however, they become turbid instan-
taneously. This turbidity is caused by a sudden enlargement of the micelles. In
this temperature range, the micelles attain a mean diameter above the critical
wavelength of light. Above the cloud point the emulsifier experiences an
almost complete loss of its previous solubility in water. If we repeat the exper-
iment, and this time oil is placed on the water phase and then interfacial
tension is measured as a function of temperature, we see that the interfacial
tension approaches zero at the cloud point. Above the cloud point, however, it
increases markedly again. What has happened here? Below the cloud point temp-
erature, the emulsifier is present in the water phase in micellar form. As we
approach the cloud point, the micelles grow. At the cloud point, also known as
the demicellation point, the micelles fuse to form liquid-crystalline lamella.
Above the cloud point the liquid-crystalline structures collapse again and the
emulsifier migrates into the oil phase, where it forms inverse micelles.
In the field of emulsion technology, the cloud point phenomenon is also
known as the PIT. The observations made with emulsions at the PIT suggest
that it might be possible to produce emulsions with nanofine droplets in this
temperature range, owing to the low interfacial tension produced by the liquid
crystalline phases. This is in fact possible. Unfortunately, however, there are
still numerous obstacles to the technical production of such emulsions on a
large scale. First, it is very difficult to stay within the stipulated narrow tempera-
ture window, especially when energy is constantly introduced into the emulsion
structure by vigorous homogenizing. Second, the cloud point of the emulsifiers
used quite naturally fluctuates from batch to batch, causing the PIT to change
as well, of course. Third, detailed investigations have not yet been carried out
to determine how stable the liquid-crystalline phases are once the entire
mixture has cooled down after emulsification. For all of the above reasons,
colloid chemists currently resort to the addition of hydrophobic solid coemulsi-
fiers, which are known to stabilize liquid-crystalline lamellar structures, to
stabilize such emulsions.
Despite the use of such stabilization techniques, it has been our experience
that nanoemulsions produced via the PIT often display a very strong tendency
toward coalescence; this tendency is especially pronounced in the temperature
range containing the melting point of the coemulsifier.
To illustrate this statement, we performed somewhat more extensive tests

on a commercially available low-viscosity spray emulsion formulated according
to the PIT method. Applying laser light scattering analysis to investigate the
droplet size distribution, we did, in fact, detect a very fine droplet distribution
which should actually suffice to trigger Brownian motion (Fig. 20.16)
However, if we then – parallel to this test – analyze the creaming behavior of
the same emulsion with the very sensitive method of conductivity analysis,
during which the conductivity is measured simultaneously at the bottom of the
vessel and at the fill height, we observe that the conductivity at the bottom of
the vessel has already increased after about 2 h. This process can be speeded
up by heating the sample. During these measurements, a sudden difference in
conductivity can be clearly observed at 328C (Fig. 20.17).
After a longer storage period at room temperature, there is an increase in
both particle size and the critical time within which the first detectable instability
occurs.
A second method that can be employed to manufacture sprayable O/W
emulsions is the three-phase emulsification method already described in the
chapter on quick-breaking emulsions. When selecting emulsifiers which will
result in an extremely low viscosity, particular care should be taken to select
substances which (a) lower the interfacial tension sufficiently to ensure the
production of extremely small droplets during the emulsification process and
(b) permit the formation of a robust interfacial layer to protect the droplets
against coalescence despite the high-energy Brownian motion.
As explained above, lamellar liquid-crystalline mixed emulsifiers are best
suited for this task since they lower interfacial tension to an extreme degree (14)
and, at the same time, build up a sturdy interfacial layer. In the case of low-
viscosity emulsions, however, mixed emulsifiers of this kind should presumably
not build up any gel networks. To prevent the formation of sandwich-type gel
16 Spray RT storage
14 Spray 40°C storage
12
10
%
8
6
4
2
0
0 0.5 1 1.5 2
Particle size [mm]
Figure 20.16 Impact of 4 weeks’ storage of PIT emulsion on particle size.

440 Dahms
3 critical temperature
2.5
rel. Conductivity
2
1.5
1
Top
0.5
Bottom
0
0 20 40 60
Temperature [°C ]
Figure 20.17 Determination of critical temperature stability by relative conductivity

measurement.
network structures the composition of the mixed emulsifier must provide for a
surplus of hydrophilic emulsifier. This surplus of hydrophilic emulsifier sup-
presses the formation of the sandwich structure for geometric reasons and
leads to the formation of spherical multilamellar protective layers instead. The
approach taken to formulate a mixed emulsifier is similar to that followed
during the selection, described above, of an O/W mixed emulsifier. In this
case, however, the descending viscosity curve is selected.
To prevent a possible superimposition of the liquid-crystalline structures
which envelop the dispersed droplets, polymer hydrocolloids are employed.
These have the characteristic of attaching themselves to the outer boundary
layer of the membranes (15), thus creating a steric barrier which prevents the
membranes from coming too close to each other and merging. Highly branched
polymers, for example, gum arabic, are most suitable for this purpose. When they
are in equilibrium with the external water phase, polymers of this kind preserve
the sprayability of the emulsion since they do not create any viscosity in this
phase. However, highly thixotropic polymers such as microcrystalline cellulose
can also be used successfully for this purpose.
To permit optimal film formation, a wax-like emollient should be added to
the oil phase at an optimal concentration in any case.
W/O EMULSIONS
In the original sense of the word, W/O emulsions are pure two-phase systems.
In these emulsions the emulsifiers serve the sole function of protecting the dis-
persed water phase against coalescence. The viscosity required to counteract
the force of gravity is attained by regulating the phase – volume ratio or raising
the viscosity of the external phase by the addition of waxes.
In cosmetic W/O emulsions, the selected concentration is usually above
50 vol.%. In concentrated emulsions of this kind, the droplets lie close together
and are subject to different forces (Fig. 20.18).
Ft + Fg Ft + Fg
W/O W/O
Ft Ft
Ft + Fg Ft + Fg
O/W O/W
Ft = Fh + Fs + Fvw
Fh = hydrodynamic force causing the flow of the continuous oil

phase between the water droplets.
Fs = the steric repulsion
Fvw = van der Waal's attraction forces
Fg = gravity force
Figure 20.18 Forces which have an impact on droplets in concentrated emulsions.
To successfully counteract forces of this kind and thus avert the threat of
coalescence, the water – oil interface formed via the emulsifiers must possess a
high mechanical strength. In the case of W/O emulsions, this strength is achieved
via the inverse liquid-crystalline hexagonal phase formed by means of the emul-
sifiers. Moreover, part of the oil phase is embedded in these phases. The oil struc-
ture in the external phase plays a decisive role in the creation of these inverse
hexagonal phases. The anchoring with the dispersed water phase is carried out
by means of the hydrophilic groups of the emulsifier system.
Because of the necessity for the oil phase to be compatible with the inverse
hexagonal structure created via the emulsifier, the emulsifier is selected accord-
ing to the polarity of the oil phase.
To find the right emulsifier for the oil phase selected, the droplet retention
method (16) can be used. This method is based on the development of highly
viscoelastic interfacial films between the oil and water phases. With this
method, an oil phase containing a selected emulsifier system at a concentration
of about 10 wt.% is layered over a given water phase. A highly viscous film
will invariably form at the interface if the emulsifier is capable of forming
inverse liquid-crystalline structures together with the water and oil phases.
442 Dahms
The viscosity of the interfacial film drops drastically if inverse liquid-crystalline

structures are not formed.
If we place a water droplet on the oil side of the oil– water phase interface,
the retention of the droplet at this location will be depend on the interfacial vis-
cosity hInt, the film thickness b, and the film elasticity G:

3C 1
t¼h 2
wt (20:20)
Ab G
where t is the droplet retention time, h the interface viscosity, C is the critical
deformation factor of droplet, G is the droplet elasticity, b is the thickness of
the interface, and w(t) is the elastic deformation per unit stress.
If the interfacial viscosity h is high, and the film thickness b and film elas-
ticity G assume high values as well, the retention time for a droplet placed on the
interface may be several days. If no high-viscosity inverse liquid-crystalline layer
is formed at the phase interface, however, the maximum droplet retention time
will be several minutes. After the selected oil phase has been layered over the
water phase, and before the water droplet is placed on the interface, an equili-
brium time of about 30 min should be maintained. This amount of time is
required for the necessary liquid-crystalline interfacial film to be completely
formed.
The method described above is relatively simple to carry out and yields
excellent values for predicting whether a selected W/O emulsifier system will
be suitable for the intended oil and water phases. At retention times longer
than 8 h, we can assume that sufficiently stable interfacial films will be
formed; in this case the selected emulsifier can be considered suitable.
The usefulness of the droplet retention method for making predictions con-
cerning the suitability of a W/O emulsifier for a stipulated oil– water system can
be tested impressively by the following experiments.
Sorbitan monooleate is very suitable as a W/O emulsifier in paraffin-
based systems; however, it is completely unsuited for the task of stabilizing
water droplets in a polar oil medium, for example, capric/caprylic triglyceride.
It is also known that silicone copolyoils exhibit excellent emulsification prop-
erties in cyclomethicone. The droplet retention times found in this case verify
this quite clearly. If we employ silicone copolyoils in polar oil phases, for
example, isopropyl myristate or capric/caprylic triglyceride, we can observe
that films of sufficient viscosity are still formed at the phase interface;
however, much higher concentrations of silicone copolyoils are needed to
accomplish this.
As in all liquid-crystalline phases, the formation of the inverse hexagonal
structure is a function of the temperature. If, for example, we measure the inter-
facial tension of an isoparaffin – water interface stabilized by sorbitane oleate as a
function of temperature, we observe that the interfacial tension rises steadily at
Capric/Caprylic
Concentration Sorbitan
Triglyceride
10
Mineral Oil
oleate [%wt]
1 10 100 1000 10000 100000

Log Retention time [sec]
Figure 20.19 Impact of oil structure on droplet retention time.
temperatures above 608C. Below this temperature range, the interfacial tension
remains nearly constant. It does not matter at all in this context whether we
measure the interfacial tension from the lower temperature range into the
higher or the other way round. We can proceed on the assumption, therefore,
that the inverse hexagonal layer required for the formation of stable W/O
emulsions is formed within a temperature range below 608C.
Since this temperature range is similar for most W/O emulsifiers, we can
assume that the stability of W/O emulsions is guaranteed up to this temperature
range—provided that the right emulsifier system has been chosen. The infor-
mation that inverse hexagonal structures are only formed at temperatures
below 608C is also important for the conduct of the emulsification process.
The homogenization of a W/O emulsion at temperatures above 608C is very inef-
ficient, therefore, since the relatively high interfacial tension at high temperatures
permits only a coarse droplet distribution. It should thus be taken into account,
during the manufacture of W/O emulsions, that the actual homogenization
process should take place distinctly below this temperature. Just how far we
have to go below the critical temperature of 608C depends on the energy perform-
ance of the particular emulsifier used. The higher the energy input, the larger the
energy portion dissipated as heat and the more the emulsion is heated up during
homogenization. By carrying out homogenization at temperatures around 458C,
we can be confident of being on the safe side in most cases.
The simplest way to manufacture a W/O emulsion is the hot – cold method.
When this method is used, the cold water phase is added to the oil phase during
vigorous homogenization. With this approach, any waxes present in the oil phase
will not crystallize.
Since most W/O emulsifiers are mixtures of polymer homologs, they also
generally contain hydrophilic portions. The hydrophilic molecules can migrate
out of the oil phase into the aqueous phase. At this location they are able to
444 Dahms
extract large fractions of hydrophobic emulsifier molecules out of the oil phase
during the formation of mixed micelles. Consequently, the emulsifier concen-
tration can rise steadily in the water phase and be simultaneously depleted in
the oil phase. If the concentration of the emulsifier fraction in the water phase
exceeds the concentration of the fraction remaining in the oil phase, phase inver-
sion will occur according to Bancroft’s rule. Depletion of the emulsifier in the oil
phase can also result in not enough emulsifier molecules being still available to
build up a sufficiently thick layer of the required inverse hexagonal structure at
the phase interface. This phenomenon can be counteracted by adding an electro-
lyte to the aqueous phase.
By means of a “salting out” effect, the electrolyte added to the water phase
causes the suppression of micelle formation by the hydrophilic polymer homo-
logs in the water phase. The type of electrolyte added is irrelevant in this
context. The only thing that matters is the correct concentration. This concen-
tration can be determined empirically and is different for every formulation.
A concentration that is “too high” is impossible. The results of numerous
experiments have shown, however, that a concentration of 0.5– 1.0 wt.% of
sodium chloride is sufficient.
Classic W/O emulsions are stable only up to the critical phase – volume
ratio. If the water phase is increased above this ratio, the surplus water will sep-
arate out during storage or sometimes even during manufacturing. The critical
phase – volume ratio depends on droplet size and on the layer thickness of the
inverse hexagonal structure present at the interface. The explanation for this
phenomenon is that part of the oil phase is incorporated firmly into the phase
interface of the inverse hexagonal structure. For a given emulsifier system, the
layer thickness can be viewed as constant. If the dispersed water phase is
broken down further to form smaller and smaller droplets, new interfaces are con-
tinually created which are covered by the inverse liquid-crystalline hexagonal
structure consisting of emulsifier, water, and oil phase. Since the water droplets
and the hexagonal structure bound to them constitute a single unit, the inverse
hexagonal structure must also be considered part of the dispersed phase.
It is easy to understand, therefore, that, as the degree of dispersion rises, the
critical phase –volume ratio must decline. Since the layer thickness of the inverse
hexagonal phase depends on the concentration of the incorporated oil phase as
well as on the emulsifier system, no precise prediction can be made with
respect to the critical phase – volume ratio in the particular case.
The breakdown of an emulsion due to overhomogenization is a frequently
observed phenomenon caused by the exceeding of the critical phase – volume
ratio when a critical small-droplet diameter is reached. Overhomogenization
can be easily brought under control, however, by adding oil phase to the col-
lapsed emulsion again. In such a case, a small amount of emulsifier must often
be added as well.
Not all W/O emulsions secrete water when the critical phase –volume ratio
is exceeded. If the size of the droplets in the water phase lies in the nanometer
range, W/O microemulsions can also be formed if the emulsifier composition is

favorable. A transition of this kind is thoroughly plausible in connection with the
formation of bicontinuous structures (17). The concept of a microemulsion struc-
ture containing bicontinuous phases was developed on the basis of photographs
made with an electron microscope. According to this theoretical model, a
mixture containing both a spongy structure and a pure droplet structure is
present at the critical phase –volume ratio. If the critical phase – volume ratio is
exceeded, the emulsion structure will shift increasingly toward the spongy micro-
structure. This process has been observed, in particular, when silicone polymers
are used.
At a critical concentration of polyols in the water phase, clear microemul-
sions can also be formed when the critical phase –volume ratio is exceeded.
Several experiments performed to explore this question have shown clearly
that the transparency of the emulsion is not attributable to an equalization of
the index of refraction of the two phases. If we assume that the transparent
mixed emulsions are also formed from bicontinuous phases with a spongy
structure, we see that the continuous bilayer structures are probably cubic in
nature.
In W/O sunscreen formulations, the critical phase –volume ratio is also
affected by the addition of micropigments. In W/O emulsions, micropigments
are considered part of the dispersed phase, as are the emulsified water droplets.
Consequently, as the micropigment concentration rises, the emulsion moves
closer and closer to the critical phase – volume ratio. If the critical phase –
volume ratio is exceeded, owing to the addition of micropigments, the result –
depending on the type of emulsion structure created– is either the breakdown
of the emulsion accompanied by separation of water or the formation of micro-
emulsions. Adding micropigments to the emulsion in nonpredispersed form
results, in most cases, in adsorption of the emulsifier onto the surface of the
micropigments. Since substantial amounts of the W/O emulsifier are adsorbed
on the pigment surface at higher pigment concentrations, emulsifier will be
depleted in the actual W/O emulsion. If the emulsifier concentration falls
below the critical concentration required to stabilize the W/O emulsion, the equi-
librium of the W/O emulsion will become instable. In many W/O sunscreen for-
mulations, it has proven advantageous to raise the emulsifier concentration when
micropigments are added. The micropigments should be predispersed before
being added in any case.
In W/O sunscreen formulations micropigments can also be predispersed in
the water phase in the first step. Since the water phase usually constitutes the
largest fraction by volume in a W/O emulsion, an undesired crowding effect
can be avoided via a higher pigment concentration. Ideally, pigments that are
readily dispersed in water should be used for this purpose. After the pigments
have been ground in the water phase, they should be emulsified in the oil
phase. During the emulsification process the micropigments undergo a “flushing
process” during which they are transported from the water phase into the inverse
446 Dahms
liquid-crystalline hexagonal structure consisting of the emulsifier and the oil

phase.
As a result of being embedded in the hydrophobic hexagonal structure, the
pigment surface takes on a lipophilic character. This guarantees that the final for-
mulation will be sufficiently waterproof even though a hydrophilic micropigment
has been used. The degree of dispersion of the micropigments dispersed via a
“flushing process” is usually considerably higher than that achieved in W/O
emulsions with conventional dispersing techniques. Using a “flushing process”
of this kind, it is possible to produce waterproof W/O sunscreen formulations
containing micropigments as the sole UV filter with in vivo sun protection
effects equal to an SPF .40. Owing to the extremely good pigment dispersion,
only a slight whitening effect is noticeable even at high micropigment
concentrations.
In W/O emulsions undesirable interactions have been observed in numer-
ous cases between the preservatives used and the liquid-crystalline protective
layer protecting the dispersed water droplets against coalescence. Preservatives,
like emulsifiers, are amphiphilic molecules. The same amphiphilic molecular
configuration which allows the preservative to attack microbial cells via a mem-
brane-active mechanism also allows them to penetrate the liquid-crystalline
emulsifier membrane. As lipophilic amphiphilic substances, preservatives are
able to penetrate—and eventually break down—the inverse hexagonal structure.
The kinetics governing the penetration of preservatives into the hexagonal
structure are very slow; for this reason, the incompatibility and destabilization of
the interface are not evident immediately after emulsion manufacture. Analytical
methods suitable for detecting instabilities attributable to the preservative used
include both droplet size analysis and rheological studies. Owing to the low-
grade kinetics, however, only small changes can be detected over a short
period of time. For particle size analysis, therefore, we have to resort to measur-
ing the change in specific surface over the storage time instead of the usual par-
ticle size determination. Since the kinetics for the migration of the preserving
agent increase at rising temperatures, samples stored at around 508C are best
suited for these tests. Tests performed at 2-day intervals reveal constant
changes in the specific surface if the preserving agent used causes instabilities
in the W/O system.
Any change in droplet size occurring during storage also causes changes in
the rheological parameters of the emulsion (18). The larger the droplets become
during storage, the lower is the resulting viscosity of the emulsion.
AUTOXIDATION OF EMULSIFIERS
“Mallorca acne”, or acne aestevalis, is a special form of sun allergy which occurs
frequently during summer vacations in southern countries. Typical dermatologi-
cal symptoms are red keratinous papules on the upper arms, back, and face.
Mallorca acne is presumably caused by the application of especially greasy
and oily sunscreen products in combination with intensive exposure to solar radi-
ation. In persons with a predisposition to Mallorca acne, moreover, the eruptions
can be triggered by the application of peroxide simultaneously with exposure to
UV radiation (phototoxic – chemotoxic skin reaction). In 90% of individuals
with this predisposition, cutaneous manifestations can be prevented by using
sunscreens and after-sun products containing no peroxide-forming ingredients.
One of the main causes for the formation of radicals is the autoxidation of
emulsifiers. In particular, emulsifiers with a molecular structure containing ether
bonds oxidize very readily when exposed to light and oxygen. The nonionic poly-
ethylene glycol (PEG) emulsifiers are a classic example of this phenomenon. The
degradation of the PEG chain takes place via the following mechanism:
[ H2C CH2 O C2 H 4 ] n h*• [ H 2C CH O C 2 H4 ] n
+O2
[ H2C CH O C2H4 ]n [ H2C CH O C2H4 ]n
OO
[ H2C CH O C2H4 ]n [ H2C C O CH4 ]n

OO OOH
[ H2C C O CH4 ]n [CH2 CH O O CH2 CH2]n

OOH
[CH2 CH O O CH2 CH2]n R COOR > R CHO +
R C R >> R OOH
O
A number of secondary products, for example, aldehydes, ketones, and car-

bonic acids, are formed in addition to the radicals. The oxidative degradation of
nonionogenic PEG emulsifiers can be detected via IR analysis or wet analytical
methods such as the determination of the acid or saponification number.
The oxidative degradation of a PEG emulsifier starts at the end of the PEG
chain. The results of recent studies indicate that closed PEG chains are degraded
via oxidation to a far lesser extent than are open chains.
However, the oxidative degradation of emulsifiers containing ether bonds
does not take place only on the skin following exposure to light. Progressive
oxidative degradation can also be observed during the storage of emulsions.
The oxidative degradation occurring during the storage of O/W emulsions can
be demonstrated analytically, for example, by measuring the change in pH.
During the storage of O/W emulsions containing PEG emulsifiers, an increasing
number of water-soluble short-chain carboxyl acids are formed by the process
described above. This process is naturally accompanied by a steady drop in pH.
448 Dahms
Antioxidants cannot stop the autoxidative process either on the skin or in

emulsions; at best they can slow it down. Furthermore, antioxidants can ensure
optimal protection against oxidative reactions only if the starting materials for
these reactions are protected against light, heat, and oxygen (19). In the presence
of excess oxygen—like that observed on the skin after the application of a sun
protection emulsion—the process of resonance stabilization will not be sufficient
to bind all the radicals which are formed.
This kind of situation is totally beyond the ability of antioxidants to cope
since even suberythematogenic doses of UV radiation induce the formation of
free radicals—in addition to the radicals created by other processes, for
example, the autoxidation of PEG emulsifiers. If antioxidants are to have any
effect at all in sunscreen emulsions, the use of emulsifiers or other substances
susceptible to oxidation should be avoided when formulating sun protection
products.
Since the process of autoxidation induced by PEG emulsifiers takes place
during the storage of sunscreen emulsions—and not just after the application of
sunscreen products to the skin in combination with direct exposure to solar radi-
ation—we must assume that other ingredients of sunscreen emulsions, such as the
sensitive sunscreen filters, are also vulnerable to oxidative attack.
REFERENCES
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Dekker, 1993:403.
12. Asche, Essig, Schmidt. Technologie von Salben, Suspensionen und Emulsionen.
Stuttgart: Wissenschaftliche Vertriebsgesellschaft, 1984:71.
13. Shinoda KJ. Colloid Interface Sci 1969; 24:4.
14. Benton I, Miller C, Fort T. J Dispersion Sci Techol 1982; 3:1.
15. Ringsdorf H, Schlarb B, Venzmer I. Angew Chem 1988; 100:117.
16. Biswas B, Haydon DA. Proc Royal Soc 1963; 271:296.
17. Strey R. Chem Tech Lab 1992; 40:213.
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21
Role of Emollients and Emulsifiers
in Sunscreen Formulations
Utilizing Synergies in the Formulation of
Cosmetic Sunscreen Products
Stefan Bruening and Mark Leonard

Cognis Corporation, Ambler, Pennsylvania, USA
Rolf Kawa and Ulrich Issberner

Cognis Deutschland GmbH & Co. KG, Duesseldorf, Germany
Andrea Tomlinson
Cognis UK, Waltham Cross, UK
Introduction 450
What Are the Functions of Cosmetic Emollients
in Sunscreen Emulsions? 450
Solvent Properties 450
Pigment-Dispersing Properties 451
Increased UV Absorption 453
Spreading Properties 454
What Are the Functions of Emulsifiers in Sunscreen Emulsions? 455
O/W Emulsifiers 456
W/O Emulsifiers 457
Technology for New Sunscreen Applications: Phase Inversion
Temperature Emulsions 457
449
450 Bruening et al.
Conclusions 459
Acknowledgments 460
References 460
INTRODUCTION
In recent years innovative products with high sun protection factors (SPFs) have
shaped the global sun care market.
Consumer education has resulted in the growing use of higher SPF pro-
ducts. In 2002, 41% of sun protection products purchased in Germany and
28% of those in the UK had SPFs higher than 15 (1). Consumers are also becom-
ing increasingly educated on the need for UV-A protection with many products
claiming to protect them from high levels of UV-A and UV-B radiation or to offer
“broad-spectrum” cover. Mass market products with SPFs of up to 60 are widely
available across the USA, Europe, and Asia.
Application properties and skin feel are becoming ever more important
with many sun care brands matching the aesthetics of everyday face and body
care products and offering a range of physical forms from creams and lotions
to sprays and gels. Markets are increasingly fragmented with products targeted
at those with sensitive skin, children, babies and different activities such as
sports or swimming.
It is not only dermatological and sensory factors that are responsible for
influencing the efficiency of the formulation matrix of sunscreen products. Syner-
gies between cosmetic raw materials and UV filters must be utilized to create
cost-efficient products with high SPFs.
The authors describe modern formulation technologies, technical perform-
ance profiles, and synergistic effects of innovative cosmetic emollients and emul-
sifiers for formulating contemporary cosmetic sunscreen products.
WHAT ARE THE FUNCTIONS OF COSMETIC EMOLLIENTS

IN SUNSCREEN EMULSIONS?
The cosmetic emollients used to formulate sunscreen products must contri-
bute more than just sun care properties. They must also be good solvents and
dispersants for UV filters and pigments and they must significantly boost the
SPF. In addition, they must exert a positive influence on the overall sensory
properties of the formulation.
Solvent Properties
If sunscreen products are to be stable and effective, it is essential that crystalline
UV filters dissolve fully and remain dissolved in the cosmetic emollients of
Emollients and Emulsifiers in Sunscreen Formulations 451
Avobenzone (Butyl Methoxydibenzoylmethane)
Dicaprylyl Carbonate
Dibutyl Adipate
Cocoglycerides
Dicaprylyl Ether
C12-15 Alkyl Benzoate
Cyclomethicone
0 5 10 15 20
Solubility [%]
Assessment criterion: 1 week at 15°C
Figure 21.1 Solubility of Avobenzone.
the oil phase. The performance of various emollients as solvents for three
common crystalline UV filters was tested. It was found that the UV-A filter
Butyl Methoxydibenzoylmethane, the UV-B/UV-A filter Benzophenone-3, and
the UV-B filter 4-Methylbenzylidene Camphor can be dissolved especially in
Dibutyl Adipate1 in high concentrations. There is, therefore, no danger that the
filters will crystallize over time, causing the formulation to become unstable
and the SPF to decrease (Figs. 21.1 –21.3).
Pigment-Dispersing Properties
Inorganic micropigments, for example, microfine Titanium Dioxide and Zinc
Oxide, are gaining in importance in the field of cosmetic sun protection. The par-
ticles of these materials usually measure between 10 and 100 nm, so they reflect
almost no visible light. Formulations containing these substances appear almost
transparent when applied to the skin and do not tend to whiten. The correct blend-
ing of micropigments, however, makes considerable demands on developers’
skills. The micropigments must not agglomerate during preparation or storage,
otherwise the product will provide less protection against UV, the pigment
particles will tend to separate, and an undesirable whitening will occur on appli-
cation. Detailed knowledge of the dispersing properties of the emollients is,
1
Dibutyl Adipate—Cetiolw B (Cognis Corporation, Care Chemicals).
452 Bruening et al.
Benzophenone-3
Dibutyl Adipate
Cocoglycerides
Cyclomethicone
0 5 10 15 20 25 30
Solubility (%)
Assessment criterion: clear aspect 1 week at 15 °C
Figure 21.2 Solubility of Benzophenone-3.
therefore, essential if uniform distribution of the pigment particles is to be

achieved and their agglomeration prevented.
Comparisons of the ability of emollients with different structures
and polarity to disperse microfine Titanium Dioxide showed that polar
4 - Methylbenzylidene Camphor
Dibutyl Adipate
Cocoglycerides
Dicaprylyl Ether
Cyclomethicone
0 5 10 15 20 25 30
Solubility (%)
Assessment criterion: clear aspect 1 week at 15 °C
Figure 21.3 Solubility of 4-Methylbenzylidene Camphor.

120
115
% increase vs control
110
105
100
95
90
Mineral Oil Dibutyl Dicaprylyl Coco- C12-15 Alkyl
Adipate Carbonate glycerides Benzoate
UV absorption of 50 ppm Ethylhexyl Methoxycinnamate in

selected emollients at 308 nm wavelength
Figure 21.4 Influence of emollients for UV absorption.
Cocoglycerides2 and emollients with medium polarity, for example, Dibutyl

Adipate and Dicaprylyl Carbonate3 influence pigment distribution very favorably
and also have a positive effect on the viscosity of the dispersion. They can there-
fore contribute considerably to the stability of the emulsion whereas nonpolar
emollients influence the homogeneity of pigments unfavorably. Therefore,
their use should be avoided in pigment containing sunscreen formulations.
Increased UV Absorption
In addition, it has been found that the efficiency with which organic UV protec-
tion filters absorb UV light increases significantly as a function of the polarity of
the emollients. Figure 21.4 shows a comparison of the increases in absorption
associated with emollients of different polarity.
The absolute absorption in mineral oil was used as a reference value. The
results were subsequently checked in vivo and in vitro with a model formulation
(Fig. 21.5).
It was shown that an increase in UV absorption results in a considerable
increase in the SPF if, for example, the polar Cocoglycerides or Dicaprylyl
Carbonate are used instead of the nonpolar Paraffin Oil (Table 21.1).
2
Cocoglycerides—Myritolw 331 (Cognis Corporation, Care Chemicals).
3
Dicaprylyl Carbonate—Cetiolw CC (Cognis Corporation, Care Chemicals).
454 Bruening et al.
INCI / CTFA weight %
Emollient 16.0
Isoamyl Methoxycinnamate 6.4
Benzophenone-3 1.6
Tocopherol 1.0
Carbomer 0.3
Lauryl Glucoside, Polyglyceryl-2
Dipolyhydroxystearate, Glycerin5 3.5
Glycerin 3.0
Aqua 67.5
KOH (20% ) 0.7
Perfume, Preservatives qs
Figure 21.5 In vivo/in vitro SPF evaluation/test formulation.
Spreading Properties
The spreading ability of an oil component is an important and objective criterion
for the sensory properties of a sunscreen emulsion (2). The emulsion must spread
evenly if the UV filters are to be distributed uniformly and homogenously on the
skin. Only in this way reproducible sun protection can be guaranteed.
As described by Zeidler (2), cosmetic emollients were classified as slow-,
medium-, and fast-spreading emollients. If a cosmetic emulsion is formulated
solely on the basis of fast-spreading emollients, the desired smooth sensation is
imparted to the skin very quickly. However, it does not last long and the original
situation is soon restored (3). At the same time there is a wax-like sensation on the
skin, that is, a higher frictional resistance, which is related to the amount of
nonspreading substances, for example, consistency factors or emulsifiers, that
are present. In contrast, slow-spreading oil-soluble UV filters, for example, Ethyl-
hexyl Methoxycinnamate, give a less marked sensation of smoothness, which
Table 21.1 In Vivo/In Vitro SPF Evaluation for Various Emollients
SPF in vivo, SPF in vitro,

Emollients COLIPA Labsphere UV 1000 S
Cocoglycerides 11 15
Dicaprylyl Carbonate — 15
Paraffinum liquidum 8 6
Smoothness
Cocoglycerides
Ethylhexyl Methoxycinnamate
Penetration time
Figure 21.6 Spreading cascade of emollients.
remains virtually unchanged over a very long period of time. Ideally, slow-
spreading UV filters are now brought together with fast and medium-spreading
emollients, for example, a combination of Dicaprylyl Carbonate or Dibutyl
Adipate with Cocoglycerides, to give a spreading cascade, avoiding any gaps
in the imparted sensation of smoothness (Fig. 21.6).
Figure 21.7 describes a sun milk formulated in this way, which can be
prepared by cold processing.
Knowledge of the spreading properties are especially useful if the sensory
properties of a range of sun protection products with increasing SPFs are to be
harmonized. To compensate for the negative sensory properties of the UV
filters as the SPF increases, it is necessary to increase the proportion of fast-
spreading emollients, for example, Dicaprylyl Carbonate or Dibutyl Adipate,
and to combine them in a balanced relationship with medium-spreading emolli-
ents, for example, Cocoglycerides or Hexyldecanol and Hexyldecyl Laurate.4 In
this way it is possible to obtain a constant sensory profile across a complete
product range despite the variation in the SPF.
WHAT ARE THE FUNCTIONS OF EMULSIFIERS IN

SUNSCREEN EMULSIONS?
In normal use, sunscreen emulsions are often exposed to high temperatures. They
therefore need emulsifiers with excellent interfacial stabilizing characteristics,
4
Hexyldecanol and Hexyldecyl Laurate—Cetiolw PGL (Cognis Corporation, Care Chemicals).
456 Bruening et al.
INCI Name (DE02/096/77) weight %
Lauryl Glucoside (and) Polyglyceryl-2 0.5

Dipolyhydroxystearate (and) Glycerin5
Cocoglycerides2 10.0
Dicaprylyl Carbonate3 6.0
Tocopherol 1.0
Ethylhexyl Methoxycinnamate 7.5
Butyl Methoxydibenzoylmethane 2.0
Sodium Polyacrylate 0.3
Glycerin 5.0
Aqua 67.7
Preservative q.s.
Figure 21.7 O/W sun fluid cold processed, with harmonized spreading properties—SPF
16 acc. COLIPA.
even at high temperatures, irrespective of the polarity of the components used

in the formulation.
O/W Emulsifiers
In the light of these considerations, tests were carried out on a new vegetable-
based O/W emulsifier compound. It is a mixture of a hydrophilic part and a
hydrophobic, stabilizing synergist with the nomenclature Lauryl Glucoside,
Polyglyceryl-2 Dipolyhydroxystearate, Glycerin.5 This synergistic blend exhibits
good dermatological compatibility, and the fact that it is pumpable makes it suit-
able for the production of emulsions by either an energy saving cold process or
(in combination with hydrophilic waxes, e.g., glycerides) by a conventional hot
processing method. Its emulsification performance in a test formulation based on
4.5% emulsifier and 16% emollient was systematically studied in relationship to
the structure of cosmetic emollients. The emollients were emulsified by cold
processing, in the way that the water phase was blended into the oil phase at
room temperature. No additional homogenization was carried out. The viscosity
was adjusted with a polymer, as is usual in cold processes. The size of the
droplets, evaluated under the microscope, was used as the assessment criterion,
5
Lauryl Glucoside, Polyglyceryl-2 Dipolyhydroxystearate, Glycerin—Eumulginw VL 75 (Cognis
Corporation, Care Chemicals).
because this parameter is a significant indicator of the stability of an emulsion and

can also influence the magnitude of the SPF.
The results show that the tested emulsifier exhibits very good emulsifica-
tion potential for different emollient structures. Emulsions with Cocoglycerides
in particular were very finely distributed. This is important as Cocoglycerides
are of considerable importance for sun protection, due to their good solubilizing,
dispersing, and booster properties. It was also clearly demonstrated that polar UV
filters, such as Ethylhexyl Methoxycinnamate, and medium and nonpolar emol-
lients are emulsified very finely. Only Cyclomethicone showed unacceptable
particle distributions.
The new emulsifier enables sunscreen emulsions to be produced by the
ecologically and economically superior cold emulsification concept, as shown
with an example in Fig. 21.7. In this context the authors wish to point out that
emulsions based on the new vegetable emulsifier exhibit especially favorable
stabilization properties if polymers like Sodium Polyacrylate or the Carbomer
types are dispersed in the oil phase.
W/O Emulsifiers
Alongside their good protection and care properties, W/O emulsions have the
advantage of being water resistant. Moreover, the use of Polyglyceryl-2 Dipoly-
hydroxystearate6 – 8 as a W/O emulsifier enables lighter emulsion concepts with
superior sensory properties to be achieved, irrespective of the polarity of the
formulation components (4). Figure 21.8 shows the formulation of an elegant
W/O baby sunscreen cream.
TECHNOLOGY FOR NEW SUNSCREEN APPLICATIONS:

PHASE INVERSION TEMPERATURE EMULSIONS
One of the trends in the sun protection market are O/W emulsions with the
viscosity of water, which can be sprayed. These emulsions can be formulated
with the help of phase inversion temperature (P.I.T.) technology. This technology
is based on the knowledge that O/W emulsions with nonionic ethoxylated
emulsifiers exhibit different phase behavior, depending on the composition,
structure, and concentration of the emulsifiers (Fig. 21.9). The temperature
level determines the phase in which the emulsifier accumulates (water or oil).
In the transition range, at the P.I.T., the interfacial tension is at a minimum. As a
consequence, microemulsions form spontaneously and without any special
input of mechanical energy (5). O/W emulsions produced in this way contain
6
Polyglyceryl-2 Dipolyhydroxystearate—Dehymulsw PGPH (Cognis Corporation, Care Chemicals).
7
Polyglyceryl-3 Diisostearate—Emerestw 2452 (Cognis Corporation, Care Chemicals).
8
Titanium Dioxide, Alumina, and Simethicone—Eusolexw T 2000 (EMD Chemicals Inc.—Rona
Business Unit).
458 Bruening et al.
INCI Names (DE99/095/14) weight %
Polyglyceryl-2 Dipolyhydroxystearate 6 4.0

Polyglyceryl-3 Diisostearate7 2.0
Zinc Stearate 1.0
Beeswax 3.0
Dicaprylyl Carbonate3 11.0
Cocoglycerides2 10.0
Titanium Dioxide, Alumina, 15.0
Simethicone8
Isostearic Acid 1.0
Tocopherol 2.0
Glycerin 5.0
Magnesium Sulfate 1.0
Aqua 44.5
Bisabolol 0.5
Perfume, Preservative q.s.
Figure 21.8 Elegant W/O baby sunscreen cream—SPF 30 acc. COLIPA.
very fine droplets in the range of, on average, 100 – 300 nm even after cooling to
room temperature; they have the viscosity of water and exhibit excellent phase
stability due to their very small-sized inner phase.
A clear understanding of the structure-based relationships between
nonionic ethoxylated emulsifiers and cosmetic emollients allows the optimal
Temperature (°C)
W/O
80 - 85 °C microemulsion / phase inversion O/W
W/O O/W
80:20 50:50 20:80

Ratio: oil phase/water phase
Figure 21.9 Phase behavior of O/W emulsions.

INCI/CTFA (DE99/240/2) weight %

Glyceryl Stearate, Ceteareth-20, Ceteareth-12,
7.8
Cetearyl Alcohol, Cetyl Palmitate9
Ceteareth-30 5.2
Dicaprylyl Ether 2.0
Cetearyl Isononanoate 2.0
Benzophenone-3 4.0
Ethylhexyl Methoxycinnamate 7.5
Homomenthyl Salicylate 7.0
Octyl Salicylate 5.0
Glycerin 5.0
Aqua 54.5
Perfume, Preservatives qs
Figure 21.10 Sprayable O/W sun fluid—SPF 30 acc. FDA.
composition of a P.I.T. emulsion to be calculated. It is then not necessary to carry

out a time-consuming empirical test series. Fine-particle O/W emulsions can
therefore be produced by a time and money saving method that requires no
homogenization or special equipment. As a result of applied research studies a
tailor-made compound based on a balanced composition9 of hydrophilic and
hydrophobic ingredients has been proven to be the best material for phase inver-
sion formulations. The only technical production steps needed are heating, simple
stirring, and cooling. Figure 21.10 describes a sprayable sunscreen emulsion as
an example of this marketing concept.
CONCLUSIONS
New emulsion technologies as well as innovative emulsifiers and emollients with
polyfunctional and synergetic performance profiles are described. The authors
demonstrate that balanced sensory effects in sun care formulations require accu-
rate knowledge of the spreading behavior of the emollients used and can best be
formulated on the basis of the concept of cascading spreading values. Further-
more, it is shown that the emulsifying and pigment dispersal properties, the
suitability as solvents for UV filters, and the dermatological compatibility
govern the choice of emulsifiers and emollients. Ways of increasing the SPF
by targeted use of raw materials are explained.
9
Glyceryl Stearate, Ceteareth-20, Ceteareth-12, Cetearyl Alcohol, and Cetyl Palmitate—Emulgadew
SE (Cognis Corporation, Care Chemicals).
460 Bruening et al.
ACKNOWLEDGMENTS
The authors wish to thank Helga Gondek and Susan Lang for the care taken in
carrying out the experiments.
REFERENCES
1. The market report, sun care: summer loving. ECM April 2003; 125 – 142.
2. Zeidler U. Fette Seifen Anstrichmittel 1984; 87:403.
3. Ansmann A, Kawa R, Prat E, Wadle A. Seifen Öle Fette Wachse J 1994; 120:160.
4. Ansmann A, Kawa R, von Kries R, Strauß G. Seifen Öle Fette Wachse J 1996; 122:653.
5. Förster Th, Schambil F, von Rybinski W. J Dispersion Sci Technol 1992; 13(2):183.
22
Surfactant-Free Sun Care
James M. Wilmott
Ridgefield Drive, Shoreham, New York, USA
Introduction 462
Background 462
Issues with the Current Sunscreen Products 462
Issues with Emulsions 465
Use of Surfactant-Free Dispersions in Sun Care 468
Properties of Lamellar Phase Dispersions 469
La Dispersions of Ultraviolet Absorbers 474
Dispersions of Organic UV Absorbers 474
Physical Sunscreen Suspensions 475
Formulating with Dispersions 475
Defining a Semiquantitiative Aesthetic Scale 475
Preparing the Final Formulation 479
The Advantages of Surfactant-Free Sunscreens 480
Beyond Conventional Sunscreens 485
Conclusion 488
References 488
Appendix 1 489
Sunscreen Formulations 489
461
462 Wilmott
INTRODUCTION
The sun may be considered one of life’s ultimate enigmas. On the one hand, it is
critical for the support of life on earth. From photosynthesis in plants to vitamin
D production in mammals, the sun plays an integral role in sustaining our existence.
On the other hand, studies during the past half-century have clearly demonstrated
that too much sun can give rise to physiological complications that can lead to the pre-
mature appearance of aging, the development of uneven pigmentation, the formation
of cancer, and even death in some cases. In fact, incidents of skin cancer are one of the
fastest growing problems in the field of dermatology. Why is this trend occurring
when the knowledge of the damage done by the sun is so well recognized?
Ironically, the rise in skin pathologies associated with sun exposure exists at
the same time that the use of sunscreens is increasing dramatically. The Skin
Cancer Foundation, the American Academy of Dermatology, and other medical
organizations have done a very effective job in promoting the use of sunscreens
with higher sun protection factors (SPFs) to counter the detrimental physiological
effects of ultraviolet (UV) light. They have recruited celebrities and have published
extensively in professional journals and in the popular press. However, their effort
is countered by society’s desire to be outdoors more often. More people want to
have a tanned appearance, which represents an image of health and success.
To some extent the use of sunscreens has encouraged people to be in the sun
for a longer duration, but, unfortunately, with a false sense of security. Recent
studies have determined that most people apply far less sunscreen than is necessary
to achieve the claimed SPF value. Why is this the case? The cosmetic and over-
the-counter (OTC) drug industries have developed a seemingly infinite variety of
creams, lotions, gels, sticks, and sprays to appeal to the user’s every need and aes-
thetic preference. Further, the Food and Drug Administration (FDA) has identified
in its final OTC Sunscreen monograph the ultraviolet A (UV-A) and ultraviolet B
(UV-B) absorbers that are considered “safe and effective” for use in successful
sunscreen products. With all this available, one might think that everything that
can be done with sunscreens has been done already. But this is not the case!
Most current sunscreens are prepared by combining a hydrophobic phase
with a hydrophilic phase in the presence of a surface-active agent called an emul-
sifier. This approach to formulating sunscreen products has many deficiencies,
which will be outlined later. There is clearly a need for an alternative approach
to the formulation of sunscreens. This chapter will present a new method of com-
pounding sunscreen products that does not utilize traditional emulsifying agents.
This approach offers many advantages over the current art.
BACKGROUND
Issues with the Current Sunscreen Products
Perhaps the single greatest reason that sunscreens are applied inadequately by
the user is the typically poor aesthetic characteristics of most products. Many
Surfactant-Free Sun Care 463
forms of sunscreens leave a heavy, greasy residue on the skin due to the physical
properties of the chemical UV absorbers employed and the high concentrations
required to achieve maximal SPF values. Sunscreens containing physical UV
absorbers, such as titanium dioxide (TiO2) or zinc oxide (ZnO), can be sticky
because of the dispersing fluids used to homogenously suspend the particles of
physical absorber. Further, these products can leave an undesirable white cast
to the skin especially as the particle size gets larger. The use of alcohol or
other volatile solvents to prepare spray sunscreens can pose a respiratory
concern and may leave the skin looking and feeling dry and damaged.
Another potential issue with current sunscreens is the effect that sunlight
has on the chemical and physical UV absorbers. Chemical filters can absorb a
photon of light. Typically, they will dissipate this energy by exchanging it
with another molecule in the vicinity, by releasing the energy at much lower
dosages, or by re-emitting it as quanta of much lower, less damaging energy
such as heat. However, occasionally conditions occur whereby the UV filter
absorbs UV light and then goes through an irreversible molecular rearrangement
or a reaction with a neighboring compound to produce a new entity that has
different properties from the original UV absorber. These by-products may
provoke unwanted irritation, sensitization, or other physiologically damaging
reactions. Similarly, it has been shown that certain physical UV absorbers,
such as TiO2 , can induce the generation of physiologically damaging free radicals
in response to UV exposure if they are not surface treated properly and used in
well-conceived sunscreen formulations.
The trend to market products with extremely high SPFs and the desire of
marketing departments in many companies to produce even higher values has
led to the incorporation of large quantities of multiple UV absorbers. As
indicated earlier, this trend creates aesthetic problems. Ironically, some of these
problems may be unnecessary. The latest version of the FDA monograph has
focused more extensively on the generation of a sunburn rather than on total
UV damage. The sunburn process concentrates exclusively on the development
of erythema from the exposure of skin to UV-B radiation and, to a lesser extent,
UV-A radiation. Historically, this has been evaluated by measuring the
minimum dosage of incident UV light that can produce an erythemal effect
or minimal erythemal dose (MED). SPF values are calculated from the multiple
MEDs that the UV protected skin can withstand vs. unprotected skin. From a
realistic point of view, a product containing SPFs approaching 30 should effec-
tively prevent up to 99.9% of the erythemal response to UV radiation if applied
correctly. Products with SPF values much higher than 30 really have no appr-
eciably greater value in preventing the onset of the sunburn response than those
with an SPF of 30. That is not to say that products with very high concentrations
of UV absorbers do not have any value. They are just not as relevant for the
reduction of erythema. Since sunburn development appears to be the main
focus of the FDA’s final OTC Sunscreen monograph, a cap may be put on
the maximum SPF value that a product can claim. This would reduce the
464 Wilmott
amount of UV absorbers used and improve the aesthetic properties of the

marketed sunscreens.
Products with high concentrations of UV filters may still be critically
important to reduce or eliminate UV radiation that can lead to other deleterious
physiological effects such as cancer and uneven pigment development, which
were alluded to earlier. However, high UV absorber levels generally maximize
the aesthetic concerns of the product.
Another issue with the current approach to sun care formulation is that the
SPF value can change enormously from composition to composition even with
the same level of UV absorbers added. One reason for this effect is that the
change in the solvent character of the oils used for aesthetic purposes can
modify the absorbance properties of the UV filters, thus making them less effec-
tive. Another, perhaps more compelling, reason for this effect is that the nature of
the film that is deposited on the skin is changed by the addition or substitution of
formula components. Generally, new marketing concepts will necessitate a
change in composition from the prior art. Also, different aesthetic properties
are frequently requested by Marketing in order to generate new products with
compelling claims. This is particularly true for cream and lotion products that
presently constitute the vast majority of product forms on the market. Clearly,
the preferred cosmetic and personal care vehicle for topical application contains
both aqueous and anhydrous phases. Such products have a variety of aesthetic
properties and can be applied in many forms such as serums, lotions, and
creams. However, these components are generally incompatible with one
another unless an agent is added that more significantly reduces the interfacial
tension between the oil and the water phases. This phenomenon allows the
formation of a two-phase system in which one of the phases (e.g., the oil) is
suspended in the other (e.g., the water). Such ingredients are called surface-
active agents (surfactants). A special subcategory of surfactants is called an emulsifier.
These materials not only lower the interfacial tension at the oil/water interface
but, with the input of shearing energy, they enable the formation of droplets of
one phase within the other. Such emulsifiers have a wide range of surface-
active properties. When carefully selected, they can stabilize the incorporation
of oil into a water phase or water into an oil phase. The resulting product is
called an emulsion. In many cases such emulsions are prepared by heating the
oil and water phases to a temperature of 708C or greater before combining the
two phases. The purpose of heating the phases is to insure that all waxes used
are melted, and that the two phases have a low enough viscosity so the two
phases can mix freely. The oil and water phases are typically mixed together
until they achieve a homogenous appearance. Thereafter, they are slowly
cooled to insure the formation of appropriately small-sized droplets. It is essential
that the droplets be very small in order to insure the stability of the emulsion
since, in these cases, Brownian motion will retard sedimentation. Such emulsions
typically have a homogenous, opaque, white appearance. They provide a smooth,
pleasant feel upon application to the skin, hair, or other epithelial surfaces.
Issues with Emulsions

The introduction of surfactants in the cosmetic industry has provided a “double-
edged sword” for formulators. Although the many different types of surfactants
have yielded a vast array of cosmetics with very desirable aesthetic properties,
they have also generated undesirable issues associated with their use. These
issues can produce thermodynamically unstable, nonreproducible, and difficult-
to-scale emulsion systems that have limited aesthetic properties. Further, the
development of emulsion-based sunscreens is a time-consuming event because
of the complexity of the process used to prepare them.
When changes to either the aqueous or the oil phase are made, the emulsifer
blend, which was effective in previous systems, generally must be altered. The
stability of the sunscreen composition is often compromised as a result, and
the SPF performance may be radically altered. This behavior may indicate a
potential problem with the long-term shelf life of the product, and it is insidious
since it requires either rebalancing of the emulsifier ratios or a change in the
emulsifiers selected. Such modifications may result in a change in one or
more aesthetic, safety, or performance properties. Often the SPF value of the
product will vary significantly with seemingly minor changes to the oils, emulsi-
fiers, or other formula components. This is typically due to the change in the
thickness and uniformity of the sunscreen film on the surface of the skin. If
the emulsifier blend permits greater and nonuniform penetration of the sunscreen
into the skin, then either gaps in the film occur or the concentration of the sun-
screen is decreased. Since by the Beer – Lambert law the absorbance of the UV
filter is proportional to its concentration, the absorbance will decrease and the
SPF value will be reduced.
Compounding this issue is the effect that processing can have on the
outcome of a batch. Emulsion stability is dependent on a variety of parameters
such as the zeta potential, particle size, crystal formation, and water binding
activity of the ingredients employed to achieve the desired rheological properties
of the product. These parameters are dependent on the temperature to which the
oil and water phases are heated, the rate of heating, the method and rate of mixing
of the phases when combined at elevated temperatures, and the rate of cooling.
Most emulsions require heating to insure that all higher melting point materials,
such as waxes and butters, are completely melted, dissolved, or dispersed in the
appropriate phase. Further, if the rate of mixing is high, there is a chance that air
can be entrapped in the emulsion. This phenomenon causes an undesirable
decrease in the specific gravity of the product and an increase in product vis-
cosity. Any variability in processing can lead to a range of undesirable rheologi-
cal and textural properties. This issue can occur even if the formulation is not
modified! Often, if two or more formulators prepare the same product, the result-
ing compositions may vary considerably. This surprising variation can occur
even though each person utilizes the same lots of raw ingredients. This unsettling
phenomenon occurs because it may be very difficult to exactly reproduce all of
466 Wilmott
the processing parameters used to make an emulsion. If any of the processing

variables is modified, unexpected particle size variations may occur or the
crystalline properties of the emulsion can be compromised.
Since there is so much uncertainty at the “bench” level in the laboratory,
there is often concern that a typical 500 to 2000 g laboratory preparation of a
sunscreen will not translate directly to a manufacturing environment. This
concern is often well founded. Compounding this scale-up problem is the fact
that the equipment used in the laboratory generally does not correlate with that
used in the plant. There is usually a need for an intermediate phase during
scale-up that facilitates this transition. Some equipment is engineered to mimic
plant conditions but at a fraction of the size. Even so, scale-up issues abound.
To deal with the vagaries of scale-up, the product may be subjected to a wide
range of processing variations in order to optimize the conditions of manufacture.
Since sunscreens are OTC drugs, the reproducibility of the properties of the
product and the concentrations of the active ingredients must be validated
every time a new piece of equipment is used. Products made at each level of
scale-up must be subjected to accelerated stability testing in order to insure the
integrity of the product for its anticipated shelf life. When one adds the proces-
sing variability and the need for scale-up to the uncertainty of the selection of the
emulsifier system, it is almost a wonder that any product ever makes it to the
market on time!
Beyond the problems already cited, there are other issues with sunscreen
emulsions. The presence of a surface-active agent, coupled with the need for
high-temperature water or steam to heat the phases, can damage many of the
unique delivery systems that are being used to enhance the SPF. Wax-based
particles will melt. Vessicular delivery systems, such as liposomes, will be
destroyed. The contents of polymeric encapsulates will partition into the
aqueous phase. They can also damage the properties of adjuvants, such as anti-
oxidants and anti-inflammatories, which are being added to sunscreens to boost
their performance properties. Finally, prolonged heating of certain sunscreens,
such as avobenzone (butyl methoxydibenzoylmethane), can accelerate the
reaction of the UV absorber with other components in the emulsion. This is
particularly noticeable if iron, copper, or some other metals are present since
an undesirable color change may result.
Traditional emulsion systems also create difficulties in manufacturing. The
need for heating and cooling systems, specialized high- and low-shear mixing,
and assorted additional processing devices makes the manufacture of emulsion
systems very capital intensive. Further, equipment specifications and energy
requirements will vary from country to country. This situation will cause a modi-
fication in the processing variables, thereby making it almost impossible to have a
truly “global” manufacturing protocol. The energy needed to process such pro-
ducts can be significant and undoubtedly will add to the final cost of the finished
unit. This is especially true in Europe and Asia where the cost of energy is very
high. Similarly, there is the long duration of time required to prepare a batch.
It can take from 5 to 24 h, or more, to complete the processing of emulsions

depending on the batch size and number of subphases required. This reality
makes the production of sunscreens labor intensive, adds to the cost, and
reduces the gross margin of the final product.
As indicated above, the complexity of the manufacturing procedure for per-
sonal care emulsions, and its dependence on many processing variables, leads to
frequent quality issues. This is especially true with respect to the product’s final
textural and rheological properties. If any factors such as the heating, cooling, or
mixing rates are not carefully duplicated, the material prepared may have differ-
ent properties from the preceding batches of the same product! As a result, the
stability of the emulsion may vary from batch to batch.
Often, the difference of a single parameter is significant enough to cause the
product to be outside the established optimum specifications. Inevitably, batches
have to be either discarded or reworked. The lack of reproducibility is especially
problematic for a sunscreen product, which is a drug and contains an “active”
ingredient. Lack of reproducibility, due to manufacturing variations, can affect
the SPF performance and decrease consumer satisfaction. It also results in
products having undesirable aesthetic properties that the user may perceive as
a lack of quality. This will ultimately lead to consumer dissatisfaction or
reduced compliance in product use. This may result in a lower SPF protection
than that which is claimed for the product.
Perhaps most importantly, the presence of a significant amount of surfac-
tant in an emulsion can strip the lipid barrier of the skin. It can also disrupt the
lipid bilayer of epithelial cell membranes, thereby leaving the tissue vulnerable.
The surfactants themselves may evoke an irritation. Furthermore, the resulting
damaged skin barrier then can permit the passage of other materials that can
cause irritation, or increase skin sensitivity.
Figure 22.1 illustrates the migration of auxiliary emulsion components into
the skin. These components include the preservative, chelating agent, fragrance,
buffers, and other actives. Migration of these components is sufficient to allow
penetration deep enough into the lower layers of the skin and evoke an irritation
reaction. The literature is replete with clinical evidence of the damaging conse-
quences that can occur with the use, or overuse, of such surfactants. Effendy and
Maibach (1) state that “many surfactants elicit irritant reactions when applied to
the skin, partially due to their relative ability to solubilize lipid membranes”
Barany et al. (2) claim that “the majority of adverse skin reactions to personal
care products are presumed to be caused by substances like surfactants”. In
view of their surface-active nature, surfactants and emulsifiers can alter mem-
brane fluidity, disorganize lipid structure, denature both proteins and nucleic
acids, disrupt barrier function, and release inflammatory mediators. The results
of these actions on the skin can lead to a variety of undesirable conditions.
These include redness, dryness, scaliness, swelling, and tightness. Other con-
ditions that can occur include itching, fissuring, stinging, roughness, and even
clinical conditions such as contact dermatitis (3 –9).
468 Wilmott
Figure 22.1 Penetration of emulsion content into the skin.
As discussed earlier in the chapter, the presence of surface-active agents in

sunscreen emulsions can reduce the SPF efficacy of the product due to the uneven
penetration of the UV absorbers into the skin. Further, the surfactants remain in
the film once the aqueous phase is absorbed or evaporated. However, because of
their amphiphilic nature, surfactants will try to recreate micelles of the hydro-
phobic UV absorbers when they again come in contact with water. This property
reduces the interfacial tension between the hydrophobic sunscreen and the sur-
rounding water and promotes the transfer of the UV absorber from the skin
into the water. This water can come from swimming in a pool, a lake, or the
ocean. It can also be produced internally due to increased perspiration. Thus,
surfactants facilitate the removal of the sunscreen from the surface of the skin
when it comes in contact with water. Therefore, emulsion-based sunscreen for-
mulations often include waterproofing agents, such as high-molecular weight
polymers or high-molecular weight silicone derivatives, to improve the water-
resistant properties of the sunscreen. Unfortunately, the addition of waterproofing
agents increases the cost of the formulation and may cause a deterioration of the
product’s aesthetic properties.
USE OF SURFACTANT-FREE DISPERSIONS IN SUN CARE

It is, therefore, easy to understand the need and desirability of finding an
alternative approach to the manufacture and formulation of conventional
emulsion-based sunscreen systems. Ideally, the resulting formulation would
have the same, or improved, aesthetic properties and would be prepared
without the use of traditional surfactants and emulsifiers. But where can such a
system be found? What means can be employed that will allow two immiscible
substances to mix? The answer to these questions appears to lie more in the realm
of physics than chemistry. Another approach does, indeed, exist.
Properties of Lamellar Phase Dispersions

It has been found that familiar hydrophobic materials (i.e., oils, waxes, silicones,
etc.) can be formed into stable aqueous dispersions by the application of an
extraordinary high-pressure, high-shear process that utilizes unique blends of
alkylated phosphatidyl choline. Molecules of phosphatidyl choline and certain
other phospholipids will form assemblies with one another in water at extremely
low concentrations with a low input of energy. These assemblies are typically
bilayers with the polar head group of the molecule interacting with the external
and internal aqueous phases. Concurrently, the nonpolar, aliphatic portions of
several molecules interact with one another or with a nonpolar fluid to form
the bilayer.
Phosphatidyl choline can form up to 11 different stereochemical assemblies
in water depending on the alkyl groups present, the phase transition temperature
of the molecule, the concentration of phosphatidyl choline present, the tempera-
ture at the time of formation, and the shearing energy applied during formation.
Some of these assemblies are more thermodynamically stable. Typically, assem-
blies formed above the temperature at which the molecule changes the structural
character of the phospholipid (i.e., transition temperature) are more stable
because of the lower entropy present. However, assemblies often transition to
a less stable assembly as the system is cooled. Blends of phospholipids generally
form more stable assemblies probably due to the synergistic packing of the phos-
pholipids. Ideally, if one could introduce energy without the use of heat, then it
would be possible to form more stable assemblies. One type of more stable
assembly is known as the lamellar phase (La).
A solution to this problem is the introduction of high energy input at low
temperatures. This can be achieved by exposing phospholipids to extremely
high shear rates under extreme pressure. Such shear is achieved by having the
fluid physically diverted into two channels that impinge upon each another in a
chamber at velocities that can approach 500 m/s. Further, the shearing action
resulting from this geometry takes place under extremely high pressures
ranging from 10,000 to almost 50,000 lb/in.2 (psi). Upon exiting the chamber,
the fluid expands as it returns to atmospheric pressure, and this causes an
ultraefficient breakup of the hydrophobic material. Under the right combination
of shear and pressure, enough energy can be imparted to allow almost instan-
taneous formation of extremely small droplets of the hydrophobic fluid which
are stabilized by the concomitant formation of La phospholipid assemblies.
Since the formation process is almost instantaneous, the amount of time that
the process media needs to be exposed to high shear rates and extremely high
pressures can be very short indeed! This time duration is so short, in fact, that
the phospholipid assemblies formed do not have time to disassemble before
470 Wilmott
they are no longer exposed to the shear and pressure conditions used to form
them. Remarkably, by employing this procedure, lipophilic materials can be
successfully incorporated into an otherwise all-water-based product.
The most important state in which the phospholipid assembly can exist for
generating stable oil-in-water dispersions is the fluid lamellar or La phase, also
known as the liquid crystalline phase. The liquid crystal phase exists as a
transition between the solid and liquid states. The existence of this phase is
only possible above the gel-to-liquid crystalline transition temperature (i.e.,
the required energy level) of the phospholipid or mixture of phospholipids
used. The gel-to-liquid crystalline transition temperature is defined by the
amount of work input needed to change the structural character of the native
phosphatidyl choline molecule that exists as a less stable Lb phase (also known
as a gel phase) to a more stable La phase. The La phase has two phopholipid
assemblies that can form. The first type is the usual unilamellar or multilamellar
phospholipid bilayer. This bilayer has large regions of water between the
bilayers. Figure 22.2 is an illustration of a unilamellar liposome containing an
encapsulated aqueous phase.
The second type of assembly that can form is the result of a conversion that
occurs in the presence of relatively large amounts of hydrophobic materials and
water. Here, the phospholipids rest at the surface of the hydrophobe droplet. The
lipophilic tails of the phospholipids extend into the hydrophobe while the more
polar heads of the phospholipids interact with the surrounding water to
produce a micelle-like structure. Unlike many emulsions prepared by conven-
tional means, the amount of hydrophobe that can be accommodated into a
stable, water miscible dispersion can be greater than 50% by weight. Different
Figure 22.2 Liposome bilayer.

hydrophobes vary in their ability to be incorporated into the stable La phase

configuration. Generally, nonpolar hydrophobes can be incorporated much
more easily than more polar ones. Higher-purity hydrophobes will usually be
capable of incorporation at higher levels than those of lower purity. Most silicone
derivatives can be incorporated at very high levels. Figure 22.3 is an illustration
of a particle containing a high level of an oil whose surface is stabilized by the
presence of phospolipid molecules.
The critical aspect of the production of stable La phase dispersions is pro-
cessing at low temperatures and using high energy input. The process used must
exceed the energy level requirements needed for the transition from the gel phase
to the liquid crystalline phase without actually heating the system to the transition
temperature. The La phase assembly must be formed in a fraction of a second,
and the conditions that allowed the assembly to form must then be removed
immediately after the assembly formation is complete. The result of this
process is a stable dispersion of highly concentrated hydrophobes that can, there-
after, be freely dispersed in water or water-based products. Typically, the particle
size of the micellar structures created during the process will be from 100 to
500 nm in diameter. This size is about 1/10 to 1/50 the size of particles produced
by standard emulsification techniques. Further, the high-pressure, high-shear
processing described earlier is so efficient that the distribution of particle sizes
for the micelles is extremely narrow.
While a small amount of phospholipid is required for the formation of La
dispersions, the resulting product can clearly be considered to be surfactant free.
The phospholipid molecules contained in the La dispersions have the tendency to
self assemble into micelles even in the absence of a hydrophobe. This happens
even when the concentration of phospholipid is extremely small (less than
Figure 22.3 Micelle-like phospholipid assembly of an oil.

472 Wilmott
10210 mM). As a result of this behavior, the phospholipids produce essentially

no irritation when applied to the skin. Further, they do not promote skin
barrier damage, but rather promote its repair since phospholipids constitute a
critical component of the cellular membrane. Oil dispersions made by the
high-pressure/high-shear process, using these phospholipids, have a surface
tension that is essentially the same as that of water. Figure 22.4 illustrates a
comparison of the surface tension of pure water (73 dyn/cm), an La dispersion
(71 dyn/cm), and a conventional oil-in-water emulsion (25 dyn). Figure 22.5
depicts the contact angle of a droplet of water on skin treated with an La
dispersion (618), a cationic emulsion (378), an anionic emulsion (138), and a
conventional nonionic emulsion (158). These data suggest that La dispersions
are truly different from surfactant-based emulsions and, in fact, may be con-
sidered surfactant free.
One of the most interesting aspects of the La phase dispersions made by the
high-shear/high-pressure process is the viscosity of the final dispersion. Typi-
cally, any stable emulsion containing 25% or higher concentration of petrolatum
will have a Brookfield LVT viscosity measuring over 100,000 cP. By contrast, a
high-shear, high-pressure processed dispersion of 25% petrolatum in water will
have a much lower apparent viscosity in the range of less than about 400 cP as
recorded by a Brookfield LVT viscometer. As a result of this low viscosity,
such dispersions can be readily sprayed by means of a finger-actuated pump
sprayer. This astonishing difference is entirely due to the type of dispersion
produced by the high-shear, high-pressure process. A formula containing 50%
petrolatum, processed by the high-shear, high-pressure process described, is a
stable, elegant lotion with an apparent Brookfield viscosity of approximately
4000 cP. The same formula made by conventional homogenization has an
Figure 22.4 Surface tension of La dispersions and a conventional emulsion.

Figure 22.5 Contact angle of water on skin after treatment with La dispersion, cationic
emulsion, nonionic emulsion, and anionic emulsions.
initial viscosity of 360,000 cP, is extremely inelegant, and is not stable at room
temperature for more than 7 days. Further, the high-pressure, high-shear
process imparts a negative charge or zeta potential on the surface of the
micelle that repels it from neighboring micelles. Therefore, the hydrophobic
micelles are free to move past one another, thereby creating a low-viscosity,
fluid environment.
La dispersions can sometimes provide a method to incorporate ingredients
that do not lend themselves to processing by any conventional emulsification
system. For example, it is possible to make stable 30– 50% La phase dispersions
of fluorinated materials such as polytetrafluoroethylene and perfluoropolymethy-
lisopropyl ether. These dispersions can be further diluted in water to achieve the
desired aesthetic or performance property.
La dispersions can be made with virtually any hydrophobic material by
carefully controlling the selection of phospholipids and the processing conditions
474 Wilmott
during manufacture. One interesting property of these dispersions is that can alter
the aesthetic properties of virtually all materials. This feature results in the oppor-
tunity to create new sensations with familiar materials. Conventional materials
such as petrolatum, lanolin, waxes, and natural oils are given a new “life” and
purpose. Since the micelles of each hydrophobic material are made the same
way, they are all independent of any surfactant, and because they have approxi-
mately the same particle size and negative surface charge, there is no tendency
for the micelles to coalesce. High-pressure, high-shear manufactured dispersions
of various low-polarity lipophilic agents (lipophiles) mix together readily,
without issue. The practice of balancing the hydrophilic and lipophilic emulsi-
fiers (HLB) depending on the composition of the lipophilic phase that is used
so commonly in the preparation of standard emulsion systems is now obsoleted
by La systems. Thus, a virtually infinite array of lipophilic dispersions can be
mixed, in any proportions, without creating any instability in the final blend.
La Dispersions of Ultraviolet Absorbers

The principle of forming La dispersions can be applied to most nonpolar com-
pounds. Because of their properties, La dispersions are particularly useful in
sunscreens.
Dispersions of Organic UV Absorbers

It is relatively straightforward to prepare homogenous dispersions containing
30 –50% of the UV absorbers ethylhexyl methoxycinnamate, octacrylene, octyl
salicylate, homosalate, and other fluids. Because these dispersions are prepared
without the use of surface-active agents, they produce a uniform, continuous
film on the skin. This property typically results in SPF values that are consider-
ably higher than in conventional emulsions containing an equivalent amount of
the same UV absorber(s). An example of such a homogenous dispersion is
SolareaseTM OMC-50, which contains 50% ethylhexyl methoxycinnamate in
an aqueous base.
Heterogenous dispersions containing mixtures of fluid, nonpolar UV
absorbers can also be readily formed. Octocrylene, homosalate, octyl salicylate,
and ethylhexyl methoxycinnamate can be mixed in virtually any ratio to form a
homogenous solution. This system can then be subjected to the high-pressure,
high-shear conditions described earlier to create the La dispersion. As will be
seen later in the chapter, the heterogenous dispersions formed by mixing two
or more nonpolar, fluid UV absorbers typically result in higher SPF values
than the mixing of homogenous dispersions of the individual UV absorbers.
Dispersions of the solid UV filters, such as benzophenone-3 and avoben-
zone (butyl methoxydibenzoylmethane), can also be prepared. First, the UV
absorber is dissolved in a suitable solvent and then the solution is subjected to
the high-pressure, high-shear conditions needed to produce the La dispersion.
Serendipitously, the fluid, nonpolar UV absorbers are excellent solvents for the
solid UV absorbers. This is particularly true for ethylhexyl methoxycinnamate

and octacrylene. For example, one part of benzophenone-3 can be dissolved in
three parts of ethylhexyl methoxycinnamate. This solution can then be dispersed
in a water phase at a 40% level via high-pressure, high-shear mixing. Silmilarly, 1
part of avobenzone can be dissolved in 3.75 parts of ethylhexyl methoxycinna-
mate. This solution can then be dispersed in an aqueous phase at a 47.5%
level. In the final example, a solution is prepared by dissolving 3 parts of
avobenzone and 4 parts of benzophenone-3 with 12.5 parts of ethylhexyl meth-
oxycinnamate. This solution is dispersed in an aqueouse base at a 39% level
using high-pressure, high-shear mixing. These examples are commercially avail-
able from Collaborative Laboratories as Solarease OMC/B3, Solarease II, and
Solarease Plus, respectively.
As can be readily observed, a wide variety of homogenous and hetero-
genous La dispersions can be made that contain organic, hydrophobic UV absor-
bers. A summary of some of the dispersions that will be considered further is
found in Table 22.1.
Physical Sunscreen Suspensions

It is interesting to note that the high-pressure, high-shear processing conditions
that produce La dispersions of hydrophobic fluids in water can also be used to
disperse very fine particulate matter in a suspending fluid. Coated, ultrafine
TiO2 and ZnO are examples of particulates of interest in the formation of effec-
tive sunscreen products. The thorough breakup of any aggregates of these
materials or blends thereof will permit the addition of 50% or greater loading
of the coated or uncoated particulates into a suitable suspending fluid such as a
benzoate ester. The turbulent mixing conditions will create stable particulate
aggregates of less than 75 nm in size, which optimizes the UV-A and UV-B
absorbance of the TiO2 and ZnO. This enhances the SPF value of the final
sunscreen product into which they are incorporated. Further, it also minimizes
the white cast often associated with the use of TiO2 and ZnO. Some of the
suspensions prepared using high-shear mixing that will be considered further
in this chapter are summarized in Table 22.2.
These products are commercially available from Collaborative Labora-
tories as TiO-Sperse Ultra, Z-Sperse Ultra, and TZ-Sperse Ultra. However,
suspension of coated ultrafine TiO2 and ZnO in a variety of suspending fluids
is available from many suppliers to the cosmetic and OTC drug industries.
FORMULATING WITH DISPERSIONS

Defining a Semiquantitiative Aesthetic Scale
A series of La dispersions can be prepared that have a range of aesthetic proper-
ties from “very light” with no residual feel to “very emollient” with a noticeable
and prolonged residual feel. This range of properties permits the generation of a
476
Table 22.1 Homogenous and Heterogenous Sunscreen Dispersions
Dispersions (%UV absorbers)

UV absorber 1 2 3 4 5 6
Ethylhexyl methoxycinnamate 50.0 37.5 30.0 25.0 21.5 30.0

Octacrylene 28.5
Octyl salicylate
Benzophenone-3 10.0 8.0
Butyl methoxydibenzoylmethane 10.0 6.0 12.0
Total UV absorber 50.0 47.5 40.0 39.0 50.0 42.0
Trade name SolareaseTM SolareaseTM SolareaseTM SolareaseTM SolareaseTM SolareaseTM
OMC II OMC/B3 Plus OMC/OS
Note: Dispersions are sold by Collaborative Laboratories, Stony Brook, NY.

Wilmott
Table 22.2 ZnO and TiO2 Suspensions
Suspensions (%UV absorbers)

UV absorber 1 2 3
Ultrafine TiO2 60.0

Micronized ZnO 50.0
Total UV absorber 60.0 50.0
Trade name TioSperse Ultra Z-Sperse Ultra TZ-Sperse Ultra
Note: Suspensions are sold by Collaborative Laboratories, Stony Brook, NY.

The inorganic UV absorbers are suspended in Finsolv TN.
spectrum of tactile sensations that can be combined to create virtually any aes-
thetic experience. An arbitrary aesthetic scale of 1 –1000 can be established to
describe the aesthetic properties of a given dispersion. Those having a light,
rapidly absorbing property would be on the low end of the scale. Dispersions
having a more unctuous, long-lasting effect would be designated with a value
at the higher end of the scale. Other lipophilic dispersions could then be assigned
intermediate values depending on the degree of tactile properties they demon-
strate. For example, a low-viscosity, hydrogenated polyisobutene dispersion is
assigned the number 100 for its light tactile impression and fleeting after feel.
By contrast, a cetearyl alcohol dispersion is assigned a value of 900 because of
its pronounced emolliency and noticeable, prolonged “waxy” after feel.
Similarly, cylcomethicone, phenyl trimethicone, a higher-viscosity hydrogenated
polyisobutene, petrolatum, gelled silicone, and gelled hydrogenated poly-
isobutene have been assigned numbers of 200, 300, 400, 500, 600, and 700,
respectively. Recently, dispersions of grape seed oil, cotton seed oil, olive oil,
mineral oil, and cocoa butter have been developed. These have been assigned
numbers of 250, 450, 650, 750, and 850, respectively.
Mixing these dispersions creates a virtually limitless range of tactile
properties. Statistically speaking, the mixing of the simple 15 aesthetic-
modifying dispersions described, can produce 15 factorial combinations (i.e.,
1.307 1012) when the concentration of each active modifier is constant!
Table 22.3 is a chart that illustrates the effect of various aesthetic-modifying dis-
persions on the properties of a final product. When the concentrations are varied,
almost limitless numbers of combinations of aesthetic behavior are possible. This
effect is analogous to that obtained in the color field, where the blending of three
primary colors (red, blue, and yellow) can create virtually any shade of color that
exists simply by varying the ratio of each of these primary colors. History shows
that with these three agents, artists have been able to produce countless great mas-
terpieces that possess myriad shades of color.
La dispersions of lipophilic performance materials (i.e., actives) can also be
readily prepared. These materials provide auxiliary functionality to the finished
478
Table 22.3 Properties of Aesthetic Modifying Dispersions
Absorbancy/
Aesthetic modifiera Initial feel playtime Residual Comments
AM 100 Very light Short Low, smooth Increases opacity of final product; oil free
AM 200 Very light Short Emollient with smooth afterfeel Helps to reduce any tackiness in finished
product; imparts a matte finish
AM 300 Light Medium Light, silky afterfeel Helps to minimize tackiness in finished
product; provides “dry” emolliency to the
end feel
AM 400 Light but with Medium Emollient with slight tackiness Use in products for normal– oily skin; consider
richer texture using AM 200 or AM 300 to eliminate any
tack; increases opacity of final product
AM 500 Rich Medium Slightly unctuous rub in with Tackiness can be reduced with AM 200 or AM
rich, slightly tacky afterfeel 300; provides good residual feel
AM 600 Elegant texture Short Emollient, silky afterfeel Good moisture barrier; ideal for sunscreens
and waterproofing; reduces tack and drag
AM 700 Rich Long Unctuous, slighty tacky Excellent waterproofing agent for sunscreens
emollient afterfeel
AM 800 Rich, heavy Long Unctuous, waxy afterfeel Tackiness can be reduced with AM 200 or AM
300; increases viscosity
AM 900 Very rich Very Long Waxy Increases opacity of final product; adds body
with elegant waxy afterfeel; reduces
tackiness
a
Asthetic modifiers are oil-in-water dispersions manufactured by Collaborative Laboratories.
Wilmott
sunscreen product. Materials such as retinoids, vitamin E (a-tocopherol),

a-bisabolol, polydimethylsiloxane, essential fatty acids, and petrolatum can be
made into stable dispersions in order to provide the finished sunscreen with a
range of useful properties. These include antiaging, skin whitening, antioxidant,
anti-inflammatory, moisturization, and skin protectant features. In recent years
the practice of combining UV absorbers and additional functional agents has
become common. Many, if not most, of the moisturizers and other treatment
products currently being marketed contain UV absorbers. This trend clearly
reinforces the recognition that the protection of the skin from damaging radia-
tion is very important. Dispersions of UV absorbers and dispersions of other
hydrophobic actives are completely compatible with the La dispersions used to
modify the aesthetic properties.
Since all of the dispersions discussed thus far are made essentially devoid
of traditional surfactants, they offer a powerful new degree of flexibility since
they are compatible with the sophisticated delivery systems being created for
pharmaceutical and personal care applications. Liposomes, nanospheres, encap-
sulates, and many other types of delivery systems maintain their integrity when
mixed with La dispersions. By contrast, emulsifiers and other surfactants rapidly
disrupt such systems, which makes them valueless in the formulated product.
Preparing the Final Formulation

Since the La dispersions are freely miscible with water, they can be infinitely
diluted if desired. The dilution process simply reduces their viscosity.
However, if the water is first thickened with a natural or synthetic rheologically
modifiying agent, then the addition of the La dispersions creates a product that
looks and feels like a traditional emulsion system. Accordingly, the preparation
of surfactant-free, La-dispersion sunscreen formulas requires three components:
a thickened water phase, a selection of La dispersions to produce the desired aes-
thetic properties, and one or more approved UV absorbers. The UV absorber is
preferably incorporated as an La dispersion (see the section on La dispersions
of UV absorbers). This combination of components provides the final product
with its aesthetic and functional properties. They may be combined concurrently
or sequentially. Since the particle size of the lipophilic dispersions is already pre-
established by the high-pressure, high-shear processing, they can be simply
mixed into the thickened water phase with gentle agitation at room temperature.
The rheological properties demonstrated are primarily due to the presence of the
thickening agents employed. Examples of such rheological modifying agents
include carbohydrate polymers such as xanthan gum or acrylate-based polymers
like carbomer. Depending on the amount of the thickening agent or agents used,
the final form of the formulated product can be designed to be a thick cream, a
soft cream, a lotion, a serum, or even a low-viscosity fluid. Virtually every
aqueous thickening agent is compatible with the La dispersions. However,
materials such as xanthan gum, methacrylate polymers or copolymers, starches,
480 Wilmott
and silicates that introduce thixotropy (i.e., viscosity decreases with time at a
constant shear rate) permit the formulation of elegant finished goods. Other
potentially useful polymeric thickening materials can be found in Table 22.4.
These thickened water phases should contain little, and preferably no, sur-
factant. The presence of surfactant can perturb the stability of the surfactant-free
dispersions.
Surfactant-free sunscreen preparations are completely independent of the
complex processing conditions required to make conventional emulsions. No
heat or extraordinary processing conditions are required. More remarkably,
these systems are far more stable than their emulsifier-based counterparts. The
hydrated thickening agent(s) provide a matrix into which the La aesthetic and
performance dispersions are embedded. As long as the thickening agent retains
its integrity at various temperatures, the product will maintain its stablility.
Thus, unlike ordinary emulsions, these dispersions have the potential to be
thermodynamically stable indefinitely! Products can be made that are indistin-
guishable from standard emulsion systems. More importantly, formulations
with unique aesthetic and performance properties can be prepared that enhance
the enjoyment of the customer during use. Formulas 1 –3 represent different
forms of sunscreen prepared using a surfactant-free approach.
THE ADVANTAGES OF SURFACTANT-FREE SUNSCREENS

Surfactant-free formulating of sunscreens has many advantages. The time of
development, from concept to the market place, is dramatically reduced. There
is no longer a need for the preparation of multiple, redundant formulations.
Laboratory efficiency can be increased dramatically. Typically, surfactant-free
formulations can be prepared in 10–15 min. This allows a formulator to prepare
30 or more prototypes daily. This acceleration in the speed of formulation variation
is amenable to the effective use of statistically designed experiments. The aesthetic
and rheological properties of the product can be evaluated immediately. There is no
need to wait overnight to determine the properties of the product, as is often the
case with standard emulsions. Greater flexibility and rapid formulation changes
are possible. Since the products are devoid of traditional surfactants, they are
less irritating to the skin. A much wider range of aesthetic product types can be
made. The compounding of surfactant-free formulations is a cold process that
readily scales to manufacturing conditions. The need for multiple pilot batches
to optimize the processing conditions is virtually eliminated.
Surfactant-free formulations have distinct advantages in manufacturing as
well. They are significantly less expensive to produce. The process conditions are
uncomplicated. Labor, overhead, and processing time can be reduced from 50%
to 75%. This improvement in production efficiency results in plant capacity
increases without any additional capital investment. If capital equipment is
needed, it will generate savings of about 70– 80% as compared to the processing
equipment needed for the manufacture of conventional emulsions. Since no
Table 22.4 Rheological Modifiers
Type Thickening agent
A. Carbohydrate 1. Algin 19. Gellan gum

2. Calcium alginate 20. Guar gum
3. Propylene glycol alginate 21. Hydroxypropyl quar
4. Carrageenan 22. Guar hydroxypropyltrimonium chloride
5. Calcium carrageenan 23. Hyaluronic acid
Surfactant-Free Sun Care
6. Sodium carrageenan 24. Dextran

7. Agar 25. Dextrin
8. Cellulose gum 26. Locust bean gum
9. Carboxymethyl hydroxyethylcellulose 27. Mannan
10. Hydroxyethylcellulose 28. C1-5 aklylgalactomannan
11. Hydroxypropylcellulose 29. Starch
12. Hydroxypropylmethylcellulose 30. Hydroxyethyl starch phosphate
13. Methylcellulose 31. Hydroxyethyl distarch phosphate
14. Ethylcellulose 32. Pectin
15. Chitosan 33. Sclerotium gum
16. Hydroxypropyl chitosan 34. Gum tragacanth
17. Carboxymethyl chitosan 35. Xanthan gum
18. Chitin
B. Polymeric 1. Carbomer 7. Polyacrylic acid
2. Sodium carbomer 8. PVM/MA decadiene cross-polymer
3. Acrylate/C10-C30 alkyl acrylate cross-polymer 9. Sodium acrylate/vinyl isodecanoate cross-polymer
4. Acrylic acid/acrylonitrogen copolymers 10. Ethylene acrylic acid copolymer
5. Ammonium acrylate/acrylonitrogen copolymer 11. Ethylene/VA copolymer
6. Glyceryl polymethacrylate 12. Acrylate/acrylamide copolymer
(continued )
481
482

Type Thickening agent
13. Acrylate copolymer 18. Ethyl ester of PVA/MA copolymer

14. Acrylate/hydroxyester acrylate copolymer 19. Isopropyl ester of PVP/MA copolymer
15. Acrylate/octylarylamide copolymer 20. Polyvinyl pyrrolidone (PVP)
16. Acrylate/PVP copolymer 21. Sodium polyacrylate
17. AMP/acrylate copolymer
C. Inorganic 1. Bentonite 6. Sodium maganesium silicate
2. Quaternium-18 bentonite 7. Lithium magnesium silicate
3. Hectorite 8. Silica
4. Quaternium-18 hectorite 9. Hydrophobic silica
5. Magnesium aluminum silicate
D. Protein/Peptide 1. Albumin 5. Milk protein
2. Gelatin 6. Wheat protein
3. Keratin 7. Soy protein
4. Fish protein 8. Silk protein
Wilmott
heating and cooling is required, energy savings can be greater than 90%. There
are fewer materials to compound, and no subphases are required. Quality is
dramatically improved since it is much easier to insure batch-to-batch reproduci-
bility. There is little waste, and virtually no “rework” of a batch is required. Kettle
dwell time is greatly reduced, and the product can be transferred directly to the
filling line once ingredient additions are completed. In fact, continuous proces-
sing is possible. Finally, the ease of manufacturing enables the product made
with La dispersions to be exactly the same regardless of the manufacturing
location anywhere in the world.
Perhaps most importantly, the consumer benefits from the use of surfactant-
free sunscreen formulations. The La-based systems are potentially more effica-
cious and less irritating. They will therefore have much greater consumer
appeal. The use of La dispersions to produce surfactant-free sunscreens results
in dramatically higher SPF values for the same amount of UV-A and UV-B absor-
bers. As stated previously, since no surfactant is present, the vehicle has a surface
tension essentially the same as water. When applied to a surface like hair or skin,
the lipid barrier of the substrate is not compromised. Penetration of the UV
absorber is then controlled by the nature of the delivery system and not by the
properties of the vehicle. The use of a surfactant-free base typically provides
lower penetration of the vehicle components into the skin and, consequently, irri-
tation potential is reduced as compared to standard emulsion. Because of the low
penetration, the uniformity of the resulting layer of product on the skin allows for
an even distribution of the active or the delivery system at the skin surface. This
property is readily confirmed when 20.0% of an La dispersion containing 37.5%
ethylhexyl methoxycinnamate and 10.0% butyl methoxydibenzoylmethane is
added to a surfactant-free vehicle so that the concentration in the final product
is 7.5% and 2%, respectively. The SPF performance of this formula is compared
with a conventional surfactant-based emulsion containing the same level of
sunscreen (see Table 22.5). In this example there is essentially a doubling of
the SPF value when the surfactant-free vehicle is employed. Another added
advantage observed is that the surfactant-free formula is essentially waterproof
whereas the conventional emulsion vehicle is not. In fact, the conventional emul-
sion vehicle would require the addition of supplemental waterproofing agents to
achieve this effect. Table 22.6 illustrates sunscreen formulas that have a variety
of SPF values. All of these products have an SPF value that is higher than
expected for the amount of UV absorbers present!
It has been observed that the SPF efficacy of sunscreens made with La dis-
persions that contain a combination of UV absorbers, is generally much higher
than that of sunscreens that contain combinations of dispersions containing
only one absorber in each dispersion. This is probably due to the synergistic
effect that occurs when different UV absorbers are in close proximity to one
another. This effect is even more readily observed in Table 22.7, which lists a
series of sunscreen formulations that were tested by an in vitro SPF method
using the SPF 290S from Optometrics, Inc. with software from Lab Sphere.
484 Wilmott
Table 22.5 SPF Efficacy of Surfactant-Free vs. Traditional
Ingredients A B
Moisturizing base 35.25

Deionized water 18.25 63.50
Pemulen TR-1 0.20
Keltrol 0.20
AMC 1.00
AM 200 9.50
AM 300 4.50
AM 400 11.50
AM 400 11.50
Solarease II 20.00
Micromerol 5.00
Hampene Na-2 0.05
Glycerin 1.00
Germazide MPB 1.25
Seamollient CL 0.75
DC 345 Fluid 5.00
Isopropyl Palmitate 7.00
Stearic Acid 3.00
Soybean Oil 2.00
Amphisol K 0.80
Polyprepolymer 2 0.30
Escalol 557 (OMC) 7.50
Parsol 1789 2.00
Triethanolamine (99%) 0.45
Totals 100.00 100.00
In vivo SPF value 16.85 8.18
The mixing of La multicomponent dispersions, with free UV absorbers and

inorganic TiO2 suspensions can produce SPF values that are incredibly high!
This phenomenon permits products with very high protection with lower UV
absorber levels. Similarly, SPF values of 30 or less can be generated with a
very low level of UV absorber. This permits the formulation of products with
elegant aesthetics.
Unlike standard emulsion-based sunscreens, which demonstrate large var-
iances in SPF efficacy with changes in composition, the surfactant-free formulas
do not! The SPF values for a given concentration of UV absorbers are remarkably
consistent regardless of the type or amount of “oils” added to modify the aes-
thetics. This effect is valid provided the oils are added as La dispersions.
Table 22.8 illustrates a series of sunscreen lotion and cream products made
with a variety of predispersed oils to modify the aesthetic properties. The static
and water-resistant SPF values of these formulas vary by less than two units.
Table 22.6 Sunscreen Composition vs. SPF Efficacy
Ingredients A B C D E F
Moisturizing base 35.25 35.25 35.25 35.25 35.25 35.25

Deionized water 9.25 0.00 0.00 4.25 23.25 18.25
AMC 1.00 1.00 1.00 1.00 1.00 1.00
AM 200 9.50 9.50 9.50 9.50 9.50 9.50
AM 300 4.50 4.50 4.50 4.50 4.50 4.50
AM 400 11.50 10.75 9.75 11.50 11.50 11.50
AM 400 11.50 10.75 9.75 11.50 11.50 11.50
Octacrylene 4.00 4.00 4.00
Solarease 25.00 25.00
Tiosperse ultra 10.00 10.00
SS OMC/Octacrylene 30.00
Solarease plus 30.00
Solarease OMC 15.00
Solarease II 20.00
Totals 100.00 100.00 100.00 100.00 100.00 100.00
In vivo SPF value 21.40 35.90 34.39 46.89 15.54 16.85/
16.65 WR.
In vitro SPF value 32.76 33.97 33.30 49.99 22.10
BEYOND CONVENTIONAL SUNSCREENS

The use of UV-B and UV-A absorbers in consumer products has expanded
dramatically in recent years. Originally, they were added to minimize the pro-
duction of sunburn in traditional sunscreen products. Initially, they were used at
low levels to minimally reduce erythema while still permitting the development
of a luxurious tan. As research revealed the negative physiological consequences
of sun exposure, the amount of UV absorber added to sunscreens increased. Ulti-
mately, levels of UV absorbers were incorporated to produce extraordinarily high
SPF values. Marketers realized that the need for UV protection had to be expanded
to every day use. This became particularly important because some of the more
aggressive skin treatment products and various dermatological procedures
thinned the stratum corneum leaving the underlying tissue more vulnerable to
UV damage. As a result, UV absorbers were added to moisturizers, lipsticks, foun-
dations, and eye creams. They were even added to hair care products to minimize
the negative effect of UV radiation on the structure of the hair and to protect its
natural or artificial color. The ubiquitous use of UV absorbers is likely to continue
as more sophisticated treatment products are developed.
Surfactant-free formulating is likely to be the vehicle of choice for the next
generation of physiologically active materials. As mentioned earlier, many of
these actives are denatured or otherwise destabilized by the presence of
surface-active agents. Further, the integrity of liposomes and other delivery
486
Table 22.7 Sunscreen Composition vs. In Vitro SPF
Ingredients 1 2 3 4 5 6 7 8 9
Cationic/acid 30.0 30.0 30.0 19.3

stable base
Lotion base 37.0 37.0 37.0 34.3 37.0
Germazide MPB 0.7 0.7 0.7 0.7 0.7 0.7 0.7 0.7 0.7
Deionized water 14.3 17.3 9.3 2.3 12.3 5.3 10.3
AM-100 5.0 5.0 5.0 5.0 5.0
AM-200 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0
AM-400 5.0 5.0 5.0
TioSperse Ultra 25.0 25.0 25.0 25.0
Solarease OMC-50 15.0
Solarease OMC/B3 25.0 25.0 25.0
Solarease Plus 30.0 30.0 30.0 30.0 30.0
Solarease OC/OS 25.0 25.0
Octacrylene 7.0 10.0 7.0 7.0
Octyl salicylate 5.0 5.0 5.0 5.0
Homosalate 5.0 5.0
Total 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0
In vitro SPF value 51.5 61.3 48.1 57.8 66.3 71.5 75.6 80.3 73.5
Wilmott
Table 22.8 Base Composition vs. SPF Level
Moist Moist Moist Moist Moist

cream, lotion, cream, cream, lotion,
Ingredients very dry very oily dry very dry very dry
Moisturizing base 44.00 48.40 32.55

Lotion base 35.00 37.00 4.75
Deionized water q.s. q.s. q.s. q.s. q.s.
AMC 4.75 5.00 4.75 4.25
AM 900 13.00 10.00 7.90
AM 100 5.00 4.13
AM 200 5.00 7.13
AM 300 7.13
AM 400 6.50 6.50
AM 500 10.00
AM 600 2.75 2.75 10.00
AM 700 10.00
Solarease II 20.00 20.00 20.00 20.00 20.00
Totals 100.00 100.00 100.00 100.00 100.00
Performance
Static SPF 20.28 20.00 20.56 20.28 20.28
Water-resistant SPF 19.72 19.48 20.00 18.92 18.68
systems is maintained using an La-based formulation system. This permits the

optimal penetration of the desired physiologically active ingredients, while retard-
ing the penetration of unwanted materials. Figure 22.6 shows the long-term
stability achieved by means of an La-based system when it contains liposomes
compared with the stability of liposomes in a conventional emulsifier-based
Figure 22.6 Compatibility of liposomes in a surfactant-free system vs. a conventional

emulsion.
488 Wilmott
emulsion. Essentially, there is no loss of liposome integrity with the surfactant-free

approach! As a result, new products can be developed that significantly repair
various skin disorders. When UV absorbers are added to these products they
provide the protection from UV radiation that can compromise these improvements.
Such products are likely to be the future of cosmetic and dermatological skin care.
CONCLUSION
Sunscreen products prepared using La-based dispersions in a surfactant-free for-
mulating system offer many advantages vs. the conventional emulsifier-based
methods. This approach results in greater SPF potency that is water resistant. It
offers unlimited aesthetic and form versatility in a vehicle that elicits virtually
no irritation. It is also compatible with delivery systems and the next generation
of therapeutic agents.
When one combines this with the myriad manufacturing benefits, it makes
surfactant-free formulating the method of choice for future sunscreen products.
New, unique aesthetic properties can be imparted to the formulated product,
thereby creating more elegant systems that heighten the enjoyment of using the
preparation. Since the quality of the product can be maintained so tightly, the
consumer will experience the same benefits and enjoyment from purchase to
purchase and from application to application. Brand loyalty will increase with
greater compliance with the usage directions. This will provide the incentive to
use the sunscreen correctly, which will enable to consumer to get the maximum
SPF protection offered by the product.
REFERENCES
1. Effendy I, Maibach HI. Surfactants and experimental irritant contact dermatitis.
Contact Dermatitis 1995; 33(4):217– 225.
2. Barany E, Lindberg M, Loden M. Biophysical characterization of skin damage and
recovery after exposure to different surfactants. Contact Dermatitis 1999; 40(2):98 –
103.
3. Rhein LD. Review of properties of surfactants that determine their interactions with
stratum corneum. J Soc Cosmet Chem 1997; (5):253 – 274.
4. Rieger M. Surfactant interaction with skin. Cosmet Toilet 1995; 110(4):31 – 50.
5. Kawasaki Y, Quan D, Sakamoto K, Maibach H. New technique for the determination of
skin lipid structure: ESR studies on the influence of anionic surfactants on human skin.
18th International IFSCC Congress, 1994:37 – 50.
6. Casterton PL, Potts LF, Klein BD. Use of in vitro methods to rank surfactants for irritation
potential in support of new product development. Toxicol In Vitr 1994; 8(4):835–836.
7. Bielfeldt S. A comparison of dermatophysiological methods to detect the influence of
surfactants on the human skin. Parfuem Kosmet 1990; 71(5):312 –318.
8. Walters KA. Methods for predicting the effect of surfactants on skin. Seminar at In
Cosmetics, Birmingham, UK, 1990.
9. Zeidler U. Physico-chemical in vitro methods for determination of the skin compa-
tibility of surfactants, J Soc Cosmet Chem Jpn 1986; 20(1):17 – 26.
APPENDIX 1
Sunscreen Formulations
Formulation 1
Suncare: SPF 15 Lotion
Formulation
Phase Ingredient Function Wt.%
A Moisturizing base Viscosity control 35.25
Deionized water 16.75
Advanced moisture complex Moisturization 1.00
Aesthetic modifier-200 Emollient 9.50
Solarease II Sunscreen 20.00
Germazide MPB Preservative 0.50
Liposomes C and E Antioxidant 1.00
Total 100.00
Mixing Procedure
1. Weigh the moisturizing base into a vessel large enough for the
entire batch.
2. With propeller and sweep agitation add deionized water and mix
until a smooth, uniform lotion results.
3. With continued mixing, sequentially add the remaining ingredients
ensuring that the product is smooth and uniform before adding the
next ingredient.
This formula is offered for informational purposes to represent a particular product concept. There
is no expressed or implied warrantee regarding its use in commerce. The authors are not respon-
sible and should be held harmless for any regulatory, legal, performance, or safety liabilities that
that may result from its use. Each individual or company is encouraged to conduct the appropriate
due diligence to insure that the formula meets internal corporate standards.
490 Wilmott
Formulation 2
Suncare: SPF 50 Plus Cream—Mixed Chemical and Physical Sunscreens
Formulation
A Cationic/acid stable base Viscosity control 18.30
Germazide MPB Preservative 0.70
B TioSperse Ultra TN Sunscreen 25.00
Solarease OMC/B3 Sunscreen 25.00
SanSurf OC/OS Sunscreen 25.00
Eusolex HMS Sunscreen 5.00
Total: 100.00
Mixing Procedure
1. Weigh cationic/acid stable base into a vessel large enough for the
entire batch.
2. Add Germazide MPB with propeller or sweep agitation.
3. Sequentially add ingredients in B to the main batch.
4. Mix entire batch until it is smooth and uniform. Use homogenizer to
increase smoothness and gloss.
Formulation 3
Suncare: SPF 50 Plus Cream—Chemical Sunscreen
Formulation
A Lotion base Viscosity control 37.00
B Germazide MPB Preservative 0.70
Solarease Plus Sunscreen 30.00
Uvinul N-539-SG (octocrylene) Sunscreen 10.00
Total: 100.00
Mixing Procedure
1. Weigh lotion base into a vessel large enough for the entire batch.
2. Slowly add deionized water to the main batch and mix with propel-
ler or sweep agitation until the system is smooth.
3. Sequentially add ingredients in B and mix until smooth.
4. Mix entire batch until completely uniform. Use a homogenizer to
achieve a smooth, glossy appearance.
23
Fragrancing of Sun Care Products
Felix Buccellato
Custom Essence Incorporated, Somerset, New Jersey, USA
Suntan Lotions, Creams, and Sprays 495

Fragrancing Sunscreens 501
Fragrance Safety and Photosensitization 502
Stability of Fragrances in Sunscreen Products 502
Color Stability: Ensulazole (INCI Name Phenylbenzimidazole
Sulfonic Acid) 503
Reactive Acid and Amine Groups 503
Odor Stability 504
Future Developments 504
Fragrance Appropriateness 505
References 506
Generations ago, people realized that the sun is not particularly good for the skin.
We probably became “Cave Man” to escape the elements, one of which was the
relentless rays of the sun.
The sun is also the reason why we developed melanin in our skin—to help
protect us from the damaging rays. After some time man sought to control his
environment, fashioning clothing, head gear, hats or cloth all with the same
purpose, to protect his skin from the sun. As society became more sophisticated,
493
494 Buccellato
we began to learn as a collective and share resources. We used clothing, parasols

and then science and chemistry in the early 1900s. It is always a source of wonder
and amazement how we can adapt and change our lives.
I always have a reservation when using the term “first” when it comes to
any use or discovery. Experience has told me over and over that the first in any-
thing is an elusive term which usually means “first recorded history.” It is nearly
impossible to say who was first, but a good bet is that Nature is usually first and a
great teacher when it comes to absorbing ultraviolet (UV) rays. Some of the first
ointments, developed in the early 1900s, contained natural sunscreens or UV
absorbers like quinine from South American cinchona trees, and cinnamates
from cinnamon bark (1).
It appears that the first commercial availability and use of sunscreen was
developed in 1928 for the military during World War II (2). It was a chemical
mixture of salicylates and cinnamates. The US Army was using red veterinary
petrolatum (“red vet pet”) prior to that time. The need to protect men who are
required to spend time in the sun drove the development of new sun protection
agents such as para amino benzoic acid (PABA) as well as various salicylates
and cinnamates.
Things have changed slightly since that time. The largest share of the
market is still dominated by sunscreens that use a combination of salicylates
or cinnamates. What has changed is our understanding of the nature of sunlight,
the various UV rays and wavelengths being generated by nuclear fusion, and
the protective layer of ozone in our atmosphere, which thankfully filters out
wavelengths less than 290 nm (1 nm ¼ 1 billionth of a meter). We have
come to understand that the types of UV rays that cause skin damage have
ranges of 320– 400 nm (UV-A) and 290 –320 nm (UV-B). We have also
learned that UV-B, while constituting about 1% of the total UV radiation
that reaches the surface of the earth, causes 98– 99% of the erythema (skin
redness) and is the major source of skin cancer. UV-A does not cause
sunburn but intensifies the effect of UV-B and inflicts its own type of
damage (2). Currently one in five Americans develop skin cancer at some
point in their lives (1).
We have discovered that certain chemicals have the ability to absorb
specific wavelengths and as a result act as “sunscreens.” These various types
of chemicals, many salicylates and cinnamates along with some others, are the
components used in sunscreen lotions that have allowed us expose ourselves to
UV rays and minimize the cumulative damage that is caused by the sun’s rays.
There are 17 sunscreens approved by the Food & Drug Administration for
use in the USA and 25 being used in Europe.
I have listed below some synonyms (Table 23.1) to help minimize
confusion and help understand the table of products listed below.
Products using sunscreens: almost every product (several hundred avail-
able) uses a combination of sunscreens for providing a specific sun protection
factor (SPF). In the suntan area, the most commonly used are octinoxate,
Fragrancing of Sun Care Products 495
Table 23.1 Synonym Chart
Name Synonyms
Octinoxate Ethyl hexyl p methoxy cinnamate

Octisalate Octyl salicylate, 2 ethyl hexyl salicylate
Avobenzone Parsol 1789 (trademark), Giv-Roure, butyl methoxy
dibenzoylmethane
Ensulazole Phenyl benzimidazole sulfonic acid
Oxybenzone Benzophenone-3
octisalate, oxybenzone, and octocrylene or homosalate, used ubiquitously in the

Coppertone line.
SUNTAN LOTIONS, CREAMS, AND SPRAYS

There are hundreds of products (SKUs) of various types of suntan lotion or cream
products that are specifically designed to protect the skin from sunburn. They
provide from SPF 2 to SPF 70 for the extreme Ozone brand sunblock. They
are available for adults, children, and babies.
Each product contains at least two different sunscreens, with many using four
or five UV absorbers or reflectors and is normally a combination of materials.
The most frequently used sunscreens are homosalate, octyl methoxy
cinnamate, octyl salicylate and oxybenzone. Note that inorganic sunscreens
like titanium and zinc oxides reflect and scatter sunlight. [TiO2 absorbs short
wavelengths and reflects longer wavelength light rays (3).]
I have tabulated the sunscreen products in alphabetical order by manufac-
turer for comparison purposes.
They are presented in the product table (Table 23.2) under the following
headings.
As can be seen from Table 23.3, the variety of fragrances used is quite
small for the number of products used.
Bain de Soleil—a red gel (similar to red veterinary petrolatum?)—is truly
unique in the sun protection market. It is the only one with a spicy oriental
fragrance and is arguably more popular in Europe than in the USA. The color
and the packaging are appropriate (packaging that blocks out light and prevents
discoloration from light induced fragrance/base reactions) for that type of
Table 23.2 Guide to Sections I – III of Table 23.3
Section Products Number of products
I Suntan products 53
II Skin treatment products 31
III Lip balm products 24
496 Buccellato
Table 23.3 Product Table by Manufacturer

Sunscreen Fragrance
Products SPF agents used type
Section I—sun protection

Bain de Soleil
Orange Gelee 4 Octinoxate, octisalate spice, oriental
Banana Boat (Sun
Pharmaceuticals)
Baby Magic Sun 48 Homosalate, octinoxate, octisalate, tropical fruit, coconut
Block Spray oxybenzone, TiO2
Suntannicals 8 Octinoxate, octisalate Melon, fruity
Faces Plus 23 Octinoxate, octisalate, oxybenzone, No fragrance
Sports Block 50 Octinoxate, octisalate, oxybenzone, Fragrance free
octocrylene
Vitaskin 30 Octinoxate, octisalate, Fragrance free
oxybenzone, avobenzone
Dark Tanning Lotion 4 Octinoxate, padimate O Coconut, banana
Ultra Sun Block 30 Octinoxate, octisalate, oxybenzone, TiO2 Fragrance free
Protective 8 Octinoxate, octisalate, Padimate O Coco banana
Tanning Oil
Protective 4 Octisalate, padimate O Coco banana
Tanning Oil
Kids 30 Octinoxate, octisalate, Fragrance free
oxybenzone, TiO2
Protective 15 Octinoxate, oxybenzone, Coco banana
Tanning Oil octocrylene, padimate O
Hair & Scalp 15 Octinoxate, octisalate, oxybenzone Orange flower
Protector
Bath & Body Works
Sunscreen 15 Octinoxate, avobenzone Coconut, tropical
Blue Lizard
Sun Cream 30þ Octinoxate, oxybenzone, Fruity floral
ocotcrylene, zinc oxide
Dermatologic
Cosmetic Labs
Essential Skin 30 Homosalate, octinoxate, octisalate, No fragrance
Protection butyl methoxy dibenzoyl methane,
benzo phenone 3
Eckerd Drug
Eckerd Baby 45 Octinoxate, octisalate, Baby powder
oxybenzone, octocrylene
Eckerds 30 Homosalate, octinoxate, octisalate, Orange flower
oxybenzone, avobenzone, octocrylene
Eckerds 15 Octinoxate, oxybenzone, Orange flower
Eckerds (note: same 45 Homosalate, octinoxate, octisalate, Orange flower
as SPF 30) oxybenzone, avobenzone,
octocrylene
(continued )

Sunscreen Fragrance
Eckerd Baby Spray 45 Octinoxate, octisalate, Baby powder

Eckerds 8 Homosalate, oxybenzone Orange flower
Faulding Products
Sea & Ski Faces 50 Octinoxate, octisalate, Fragrance free
oxybenzone, zinc oxide
Hawaiian Tropic
Golden Tan 6 Octinoxate, octisalate, Coconut
Barbie 30 Octinoxate, octisalate, oxybenzone, Strawberry
octocrylene
Dark Tan Gel 2 Ensulizole Coco banana
Baby Faces 50 Octinoxate, octisalate, TiO2 Fragrance free
Ozone (Note SPF 100 70 Homosalate, octinoxate, octisalate, Coconut
from Bioderma) oxybenzone,
TiO2, octyl dimethyl PABA
Kids Splash 30 Homosalate, octinoxate, octisalate, Lime kiwi
octocrylene (strawberry)
L’Oreal
Ombrelle Anti Aging 15 Octisalate, avobenzone, octocrylene Fragrance free
Age Perfect Anti 15 Octinoxate, ensulazole Rose floral
Wrinkle
Revitalift Complete 18 Octinoxate, ensulazole Mild floral rose
Neutrogena
Healthy Defense 30þ Homosalate, octinoxate, Creamsicle
octisalate, avobenzone
Ultra Sheer Day 30 Homosalate, octinoxate, octisalate, Herbal floral
Dry Touch oxybenzone, avobenzone
Schering-Plough
Coppertone Oil Free 30 Homosalate, octisalate, oxybenzone, Fragrance free
avobenzone, octocrylene
Coppertone Ultra 30 Homosalate, octinoxate, Orange flower
Sweat Proof octisalate, oxybenzone
Coppertone Sun 15 Octinoxate, oxybenzone Orange flower
Block Lotion
Coppertone Ultra 30 Homosalate, octinoxate, oxybenzone Orange flower
Sweat Proof
Kids Trigger Spray 30 Homosalate, octinoxate, Orange flower
octisalate, oxybenzone
Lotion & Splash 30 Homosalate, octinoxate, Orange flower
Coppertone octisalate, oxybenzone
Dry Oil Coppertone 4 Homosalate, oxybenzone No fragrance, SDA 40
Spectra Coppertone 30 Homosalate, octinoxate, octisalate, No fragrance
octocrylene, zinc oxide
Oil Free Coppertone 30 Octinoxate, octisalate, No fragrance
(continued )
498 Buccellato

Sunscreen Fragrance
Kids Coppertone 50 Homosalate, octinoxate, octisalate, Fragrance free

Sun Block oxybenzone, octocrylene, zinc oxide
Dry Oil Coppertone 15 Homosalate, octinoxate, No fragrance
Kids Coppertone 30 Homosalate, octinoxate, octisalate, Orange flower
Sports Gel 30 Octisalate, oxybenzone, Orange flower
Coppertone Parasol 1789, octocrylene
Kids Coppertone 40 Homosalate, octinoxate, Orange flower
Kids Spray 30 Homosalate, octinoxate, Orange flower
Lotion Coppertone 4 Octinoxate, avobenzone Orange flower
Water Babies 45 Homosalate, octinoxate, Floral fresh
Faces Coppertone 30 Homosalate, octisalate, oxybenzone, No fragrance
svobenzone, octocrylene
Coppertone 50 Homosalate, octinoxate, Orange flower
Spectra Triple octisalate, oxybenzone
Stop & Shop 30 Homosalate, octinoxate, oxybenzone, Orange flower
octisalate
Section II—skin treatments
Products other than suntan lotion (products by company) 31 products out of 200 products
(about 15.5%) containing sunscreens of some type
Almay Incorporated
Age Decelerating 15 Octinoxate, octisalate, Fragrance free
Cream oxybenzone, avobenzone
Avon Incorporated
Biologique þ 15 Octinoxate, oxybenzone No fragrance
Retroactiv None Benzophenone 4 No fragrance
Antibac. Moisturizing None Benzophenone 2 No fragrance
Gel
Beieresdorf
Eucerin 30 Octinoxate, avobenzone, octocrylene, No fragrance
zinc oxide, ensulizole
Nivea Q 10 4 Octinoxate Soft floral
Nivea Visage Anti 15 Octinoxate, octisalate, oxybenzone Soft floral
Wrinkle Lotion
Bristol Meyers Squibb 20 Octinoxate, octisalate,
Zinc oxide
Keri Moisturizing 15 Octinoxate, oxybenzone Rose floral
Lotion
Keri Revitalizing 15 Ocitnoxate, benzophenone 3 Soft floral
(continued )

Sunscreen Fragrance
Banana Boat Max 50 Octinoxate, octisalate, No fragrance

Sun Block oxybenzone, octocrylene
CHANEL Age Delay 15 Octinoxate, oxybenzone, avobenzone Mild floral,
sophisticated
Cheesborough Ponds
Vaseline Renewal 5 Octinoxate, TiO2 Light herbal
Protection
Guthy-Renker
Natural Advantage 15 Octinoxate, oxybenzone, octisalate, TiO2 Thea sinensis/
Moisturizer Matricaria oil
Galderma Labs
Cetaphil Facial 15 Avobenzone, octocrylene No fragrance
Moisturizer
Johnson & Johnson
Retinol Actif Pur 15 Octinoxate, avobenzone No fragrance
Ocean Potion 15 Octinoxate, octisalate, avobenzone Creamsicle, orange,
vanilla
Ocean Potion Baby 50 Octinoxate, octisalate, oxybenzone, Fragrance free
Parasol 1789, octocrylene
L’Oreal
Age Protection 15 Octinoxate, ensulizole Rose floral
Futur - e Moisturizer 15 Octocrylene, ensulizole Floral
Revitalift Complete 18 Octinoxate, ensulazole No fragrance
Age Perfect Cream 15 Octinoxate, ensulazole No fragrance
Visible Results 15 Octinoxate, TiO2 No fragrance
Neutrogena 20
Visibly Younger 20 Octinoxate, avobenzone No fragrance
Hand Cream
Visibly Younger 15 Octinoxate, octisalate No fragrance
Hand Cream
Healthy Defense 30 Octinoxate, octocrylene, No fragrance
Moisturizer zinc oxide, ensulizole
Face Lotion 20 Oxtinoxate, octisalate No fragrance
Olay–Proctor &
Gamble
Protective Renewal 15 Octinoxate, octisalate No fragrance
Lotion
Provital, Day Lotion 15 Octinoxate, zinc oxide Fresh floral
Complete All Day 15 Octinoxate, zinc oxide Fragrance free
Complete Moisturizer 15 Octinoxate, octocrylene No fragrance
Lotion
Wakefern
Lotion Shop Rite 4 Octinoxate, oxybenzone Orange flower
(continued )
500 Buccellato

Sunscreen Fragrance
Section III—lip balms: 34 units on market shelf, 24 using sunscreens (65%)

Sport Sunblock 30 Homosalate, octinoxate, oxybenzone, No flavor
padimate O
Blistex
Ultra 30 Homosalate, octinoxate, oxybenzone, No flavor
menthyl anthranilate 4.8%
Clear Advance 30 Homosalate, octinoxate, octisalate, No flavor
avobenzone
Complete Moisture 15 Octinoxate, oxybenzone Flavored
Lip Balm 15 Oxybenzone, padimate o Flavored
Medicated Lip Balm 15 Oxybenzone, padimate O Menthol, camphor,
flavor
Herbal Answer 15 Octinoxate, octisalate Chamomile,
Helianthus annus
Lip Tone 15 Octinoxate, menthyl anthranilate No flavor
Berry Lip Balm 15 Oxybenzone, TiO2 , padimate O Berry flavor
Silk & Shine 15 Octinoxate Flavored
Chapstick
Fruit Smoothies 15 Octinoxate, oxybenzone Natural fruit, flavors,
vitamins
Lip Balm 15 Octinoxate, oxybenzone Tropical
Lip Balm 15 Octinoxate, octisalate Strawberry, kiwi
Lip Balm 15 Octinoxate, oxybenzone Wild crazeberry
Lip Balm Ultra 30 Octinoxate, octisalate, Flavored
Lip Balm 15 Octinoxate, oxybenzone No flavor
Lip Balm Moisturizer 15 Octinoxate, oxybenzone Vanilla, mint
Stick
Lip Balm Moisturizer 15 Octinoxate, oxybenzone Aloe, No flavor
Squeeze
Lip Balm Regular 4 TiO2 , padimate O Fragrance
Lip Balm Regular 4 Padimate O Cherry fragrance
Hawaiian Tropic
Lip Balm Sun Block 45 Homosalate, octinoxate, octisalate, Herbal
Lip Balm Sun Block 45 Homosalate, octinoxate, octisalate, Orange
oxybenzone
Lip Balm Sun Block 45 Homosalate, octinoxate, octisalate, Coconut
oxybenzone, octrocrylene
NO AD
Lip Balm 30 Octinoxate, octisalate, oxybenzone, TiO2 Berry, tropical
fragrance. This oriental fragrance type is very good but may not be color stable in
a white lotion or cream like many of the usual sun tan products sold in the USA.
The Coppertone brand appears to have used the same floral jasmine (though
closer to orange blossom) fragrance for almost all their products. This seems
appropriate, knowing that Benjamin Green, the pharmacist who developed the
Coppertone line in 1944, was from Florida. It is a mixture of cocoa butter and
jasmine and it has served the manufacturers well, establishing their brand identity
(4). The Hawaiian Tropic brand has always been characterized by a tropical
coconut. Overall, the US market is saturated with coconuts. The notable excep-
tion is the strawberry fragrance added to the Barbie brand for children. Seventeen
out of 50 products are fragrance free. These are for sensitive skin, baby products,
or for facial use.
FRAGRANCING SUNSCREENS
The wide variety of sunscreen bases and materials used does not pose a signifi-
cant problem with regard to fragrance. When we examine the structures of the
sunscreen molecules we see that many of them have bifunctionality, both
ketones and phenols, along with various points of unsaturation. One might
suspect that these groups would be reactive or unstable. One might also
suspect that the sunscreens could react with the various functional groups or
materials used in fragrances. The fragrance molecules cover a wide range of
functional groups themselves. They include, but are not limited to, terpenes
(unsaturated hydrocarbons), alcohols of all types, primary, secondary, and
tertiary, as well as diols, ketones, aldehydes, amines, esters, lactones, and a
variety of bifunctional or multifunctional groups. The full range can occur in a
single fragrance, and often all these functional groups and more are present in
a single natural product. One might anticipate that the sunscreens would react
with many or at least some of the fragrance ingredients. This in fact does not
appear to be the case. Most fragrance ingredients and indeed a variety of
blends seem to be stable, with a few notable exceptions that are common to
many creams and lotions as will be noted later. This may be more a function
of the medium than the materials. It has been my experience that the environment
or the medium of the product is more determinate than the materials. It seems that
the same materials which are reactive in a water based system react more readily
and frequently than in a system where a minimum amount of water is used. This
appears to be the case with suntan lotions or creams.
The base odors and the odors of the sunscreens themselves are quite mild
and easily mixed or masked with the use of low levels of fragrance. They may
range from 0.1% to 1.0% on the high end. They are actually very easy media
to work with. The base odors are generally very mild, they are not very reactive,
application to the skin provides a broad surface from which fragrance can
emanate, and a wide variety of types could be employed. This, however, does
not appear to be the case. Almost all the sun care fragrances on the market
have followed a market leader and are of either the floral orange blossom type
like Coppertone or the coconut type like the Hawaiian Tropic brand. This does
not appear to be caused by stability requirements or for any other reason than
following the lead of a successful product. The changes in the market are not
due to a shift in this thinking, rather it is due to the introduction of fragrance
502 Buccellato
products marketed for young children and infants. The fragrances have followed
suit to accommodate the image of kids, Strawberry for Barbie from Hawaiian
Tropic and powder florals for Baby Magic.
The skin treatment products which are made for adults employ milder floral
fresh and clean aromas that are more appropriate for the market.
FRAGRANCE SAFETY AND PHOTOSENSITIZATION

It has long been established that fragrances add a measure of acceptability to a wide
variety of products, and sunscreen products are no exception. However, when the
objective is to prevent skin damage and provide protection from the sun, fragrances
are not always necessary or desirable. The modern bases used in sunscreen and
their lack of background or base odor permits perfectly acceptable products to
be designed and marketed without any fragrance whatsoever. The elimination of
fragrance also removes another factor or potential source of skin irritation and a
variety of reactions that may take place in the presence of UV rays.
There are a few items that have a potential to be photosensitizers or cause skin
irritation after being exposed to UV rays. They are usually citrus products like
lemon, lime, or bergamot which contain a class of chemicals called psoralenes or
bergaptenes. The fragrance industry has guidelines regarding their use or nonuse
in skin applications. The fragrance industry follows the guidelines of the Research
Institute for Fragrance Materials (RIFM) and the International Fragrance Associ-
ation (IFRA). When the citrus products mentioned above are used, they are
employed at 10 times below their no-effect level, providing a large margin of safety.
STABILITY OF FRAGRANCES IN SUNSCREEN PRODUCTS

Most fragrance ingredients are stable in the fairly mild sunscreen and moisturizer
bases and as a result do not pose a severe restriction on the types of fragrance that
could be used. Having said that, it is somewhat puzzling that a greater variety of
fragrances has not appeared in the suntan product market. Are we all coconuts?
There are a few basic considerations such as color stability (not fragrance or odor
stability) that can arise with fragrance/fragrance or fragrance/base or light
induced color changes that can seriously affect the color and appearance of a
product but not have much olfactory or performance effect.
A review from Custom Harley Davidson Motorcycle Parts & Accessories
appeared in April 2000. Paul (in sales department), comments on his experience
trying dozens of sunblockers over the years and succinctly says, “I’ve trashed a
lot of them. Some burned my eyes and some were so greasy they caused my
hands to slip off the grips. My bike smelled like the beach for months.” He
winds up recommending Coppertone to go with SD-40 alcohol. This is an
unlikely source for an on-target evaluation of the sunscreen market. I have
personally received many comments about the odor and greasiness of creams
and lotions and the difficulties in using these products.
Application by pump spray is easier and more evenly distributed, and does
not leave streak marks as creams do when you try to apply them on yourself. The
odor is in fact milder, perhaps because you tend to use less, thereby delivering
less fragrance as well as less salicylates that contribute to the odor profile.
Why do not these sprays out sell the creams and lotions?
It could be price, but as our biker friend points, out he has used a small
pump spray for months and it is waterproof and does not run and burn his eyes
when perspiring! The buying public does respond negatively to higher priced
items as their perceived value is less. They very rarely have the time or incli-
nation to do a cost/use study on a product. It appears that there could be an
opportunity for some clever and focused marketer to gain a niche and develop
a part of the market for people who desire the attributes of a pump spray (5).
COLOR STABILITY: ENSULAZOLE (INCI NAME

PHENYLBENZIMIDAZOLE SULFONIC ACID)
Reactive Acid and Amine Groups
Vanillin, a multifunctional aroma chemical (3 methoxy, 4 hydroxy benzaldehyde),

has two reactive groups, the aldehyde group and the hydroxyl group, that can
either form Schiff’s bases or react with trace metals or other fragrance ingredients.
They have a tendency to turn the base from any shade of pink or red to dark brown.
While the odor and performance do not suffer, the appearance has been degraded
enough to cause consumers and, as a result, marketers to want to avoid this
condition.
There are other materials like phenols, hydroxy cyclopenteneones, and
unsaturated phenols, often multifunctional, that should be avoided because
they cause the same type of problems.
Normally unstable fragrances would be true vanilla, spices, orientals, and
berry fragrances of any type which can cause color problems. Many of these
effects can be mitigated to some degree but the character of the fragrance
usually suffers to some degree.
504 Buccellato
Fragrances that are good for color are generally fresh clean, floral, or lightly
herbal fragrances or use expensive decolorized versions of raw materials or
natural products. Rose, a perennial favorite, is a widely acceptable cosmetic
aroma that exhibits very good stability in a wide variety of applications. Rose
is often the base accord or floral base upon which many floral fragrances or
twists, including herbals, are constructed.
ODOR STABILITY
From an olfactory viewpoint, all natural citrus products in general should not be
used in these types of products. All citrus products are constituted of mostly limo-
nene, a cyclic unsaturated terpene, and many other unsaturated terpene hydrocar-
bons that react with oxygen and develop an off-odor similar to turpentine. In
addition, the unsaturated terpenes react with oxygen and will create a vacuum in
the package, causing it to warp and bend. This is commonly referred to as “panel-
ing” and produces an unsightly package, usually within 60 days or less. The odor
change begins immediately and is quite noticeable within 30 days. Additionally,
the more odor-active components of citrus oils are aldehydes, both saturated and
unsaturated, that also oxidize readily, eventually altering the odor significantly,
and in many cases the odor will seem to have vanished. This is due to the active
odor components, often aldehydes, that have been oxidized to the corresponding
acids, which have a much lower odor impact. When citrus is used, it is usually
in smaller amounts in conjunction with another type of aroma like cream or
vanilla to make a creamsicle. This is one of the types currently being used.
Some of the effects of color and odor instability can be reduced using anti-
oxidants and, ironically, different and specialized UV absorbers which help
prevent light induced oxidation or cross fragrance and base reactions.
FUTURE DEVELOPMENTS
There are some concerns that current UV absorbers form free radicals on the skin
following absorption of UV radiation. Antioxidants are used to try and neutralize
the free radicals formed. A novel material called Optisol, a patented product
which modifies the structure of titanium and zinc oxides, is promising to elimin-
ate the problem of formation of free radicals and additionally extending the life of
other active ingredients.
More recently, researchers are studying coral reefs which have developed
mycosporine-like amino acids (MAAs). As a result of this discovery and
research, new synthetic ingredients related to MAAs may soon become available.
They will be highly efficient at capturing, absorbing, and dissipating the UV
energy. Additionally, they promise to cause less allergic reactions than commer-
cial sunscreens and exhibit greater stability (1). Combination functional products
like anti-aging creams, face lotions, creams, and lip glosses with sunscreens are
already on the market. Pediatricians warn parents that the West Nile Virus rarely
makes people sick but using an insect repellent with more than 10% diethyl-m-
toluamide (DEET) can be deadly for small children as it is a neurotoxin. The
combination product incorporating a sunscreen may help DEET be absorbed
more into the skin, thereby putting small children at greater risk (6). These
new materials may all benefit from a fragrance which can be tailor-made to
suit the image and utility of each product. It would certainly be beneficial to
market a new product with new claims of efficacy and safety and have a
unique corresponding fragrance to enhance the image and branding of the new
product. There are few technical reasons limiting the types of fragrances that
could be used in a sunscreen product other than some of the stability guidelines
mentioned above. It usually requires the imagination of a courageous marketer or
the naiveté of an entrepreneur with a different vision and desire to do something
independent and new to the market.
Fragrance Appropriateness
As mentioned above, it is somewhat surprising that the number of fragrances used
in most of the suntan products are so few. I realize that once a market and product
is established and is well known as in the case of the Coppertone and Hawaiian
Tropic brands, it is extremely difficult to replace or to add a competing product
with a different aroma. The fragrance identifies a successful brand name and any
decision to replace or modify the aroma requires careful consideration. It appears
that both Schering Plough (Coppertone) and Tanning Research (Hawaiian
Tropic) have found the appropriate fragrance for their respective products. The
Coppertone brand is a jasmine/orange blossom aroma that ties in to Florida’s
Sunshine State, and the Orange Groves and Hawaiian Tropic brands are very
closely associated with the coconut/pina colada Hawaiian Vacation theme.
The new skin treatment products coming out the cosmetic section of the
market have a free reign to utilize new and different fragrances that are more
appropriate for their image or brand. This is clearly seen in the case of
Chanel’s Age Delay cream, which uses a sophisticated and light modern floral
aroma. In the case of Procter & Gamble’s Olay brand they have used a very
pretty rose floral which has always been regarded as the single most important
floral aroma in the cosmetic world. This dates back to ancient Egyptian and
Roman times, when rose petals were used to add fragrance to baths. The rose
aroma has been a basic in cosmetics since that time, and little has changed
over the millennia. Modern perfumery still uses rose but with new nature identi-
cal synthetics that are available for enhancing nature. These materials, like
damascenone, and a variety of damascones as well as other specialty aroma
ingredients, are synthetic but nature-identical and commercially available with
the advantage of continuous supply for the cosmetic market. This philosophy
of developing nature-identical materials providing a continuous, reliable
supply is one of the three legs of perfumery material development. The other
506 Buccellato
two, synthetic materials with unique odor properties and synthetic materials with
unique functional stability, provide a wide variety of fragrance ingredients from
which to build new and unique fragrances for new and unique products. I am
certain the future of sunscreens and new sunscreen products will utilize the
new materials. New appropriate cosmetic aromas will be developed and utilized
for them as society becomes more cognizant of the danger of overexposure to our
life- and energy-providing sun.
REFERENCES
1. Chen I. The biology of sunscreen. Discover 2003; 24(6).
2. Kim JJ, Lim HW. Primary Care Cancer 2000; 20(5).
3. Reisch M. Sci Techno 2002; 80(25).
4. Coppertone Solar Research Center. The History of the Solar Research Center. 1.
5. Bikers Sun Block Internet article April 11, 2000. Custom Harley Davidson Motorcycle
Parts & Accessories, Paul in Sales.
6. O’Connell J. Academy of Pediatrics, Hubbard Broadcasting Inc. 2003.
24
Formulating Natural Sun
Care Products
Timothy Kapsner, Peter Matravers, Ko-ichi Shiozawa,

and Patricia Peterson
Aveda Corporation, Minneapolis, Minnesota, USA
Introduction 508
Formulation Focus 508
UV Absorbing Ingredients 509
Increasing SPF 511
Natural Fragrances 512
Natural Standards 513
Points of Difference 514
Environmental Concern and Aromatherapy 514
The Environmental Principle 514
Aromatherapeutic Principle 514
Natural Aromas as they Relate to Sun Care Products 515
Preservatives 516
Next-Generation Sun Care 518
Biological Effects Due to Sun Exposure 518
Conclusions 519
References 520
507
508 Kapsner et al.
INTRODUCTION
The word “natural” has evolved, over the past several years, to mean the exclu-
sive use of plant-based ingredients to create a finished product. Consumers now
seek out products that claim to be “natural” or “all-natural,” even though the FDA
has not issued regulations to define the term “natural” when applied to cosmetics.
Just recently, C&T Magazine reported, “new ingredients—vitamin C and natur-
als such as aloe vera and chamomile are also finding their way into sun product
formulations to make them more attractive to customers” (1). The sunscreen
development process, therefore, must not stop at adding a few natural ingredients
to an otherwise traditional product. It must start with a re-examination of all the
components that make up a sunscreen, with an eye to maximizing the efficacy and
sustainability of each. Then, and only then, can a formulator put together a
sunscreen product that is truly “natural.”
In a practical sense, very few products fulfill this condition but instead rely
on any number of non-plant-based ingredients to perform certain functions.
These ingredients are generally petroleum based. Our goal and mission has
been to avoid depleting finite resources of fossil fuels by substituting renewable
plant sources. There are also other advantages to using plants as a resource:
. Supports local farmers
. Diversifies and strengthens local economies
. Supports and sustains indigenous peoples
. Uses a renewable resource
We have continued to improve our product development efforts as our mission
has evolved. We now find ourselves facing tough questions about the impact
of our products on the fragile ecosystem of our Earth.
FORMULATION FOCUS
We have explored several new product areas in the last few years and, following a
precautionary principle, the Research and Development staff is taking steps to
focus on ingredient issues in the product development process. In formulating
sunscreen products there are two areas of interest that have been addressed.
The first challenge is to address the health and safety questions being raised
for certain widely used active ingredients and preservatives. A very active search
for natural preservatives and physical sunscreens is attempting to address this
issue. UV radiation contains a tremendous amount of energy, and this energy,
besides causing the damage it does to the skin, can also break down the
molecules that are intended to absorb or reflect it. Studies have shown that
some of the organic sunscreens are photochemically unstable (2; see also this
volume, Chapter 17 by Craig Bonda). A safety review that takes this into
consideration would be beneficial when evaluating sunscreen ingredients
and products. Mineral replacements, including titanium, zinc, and iron
Formulating Natural Sun Care Products 509
oxide-based compounds, are being used to avoid these concerns with organic
sunscreen actives (3). Titanium dioxide is found in many minerals and is
highly abundant. It is estimated that the world’s mineral resources contain in
excess of 1 billion tons of titanium dioxide (4). After the valuable minerals are
separated, the remaining sands are returned to the deposit and the land reculti-
vated. In the USA, titanium-rich sands are mined in Florida and Virginia. It is
our goal to assure responsible mining of these materials.
The second challenge is our continuing effort to replace petroleum-
based synthetic ingredients or petroleum-processed natural ingredients with
plant- and mineral-based alternatives. These alternatives must provide a
similar level of functionality, benefit, and elegance to the consumer without
introducing additional negative environmental impacts or related hazards. For
example, zinc oxide is a Category I sunscreen in the USA but not in the European
Union (EU), since the EU has concerns regarding pollution at zinc oxide
manufacturing sites (5).
Most important for the consumer is “wearability”. The best-intentioned
product will be a complete market failure if the user is not provided with an
elegant, effective product. At the same time, the use of plant and mineral-based
materials that may adversely affect threatened or endangered species should be
strenuously avoided. This requires careful investigation of ingredient options,
which often slows down the product development process. Further, renewable
resources should be used wherever possible in products and packaging.
The intent, however, is to go beyond reducing the “footprint” on the
environment—of just doing “less bad in the world”—to become a restorative
force, where there is actually measurable benefit from “doing good”. A truly
sustainable business model must incorporate elements of providing for current
needs without compromising the ability of future generations to provide for
their needs. As difficult as this concept of sustainability is to understand and to
put into daily practice, we have made some small steps in the direction we
want to go and where we think others may want to go as well.
UV ABSORBING INGREDIENTS
The sunscreen final monograph, published on May 21, 1999, lists 16 Category I
active ingredients (6). These 16 active ingredients vary significantly in their
physical and chemical properties, and there are many considerations as to
which ones to use in building a sunscreen product. The easiest, and most
common, way to classify the active ingredients is in which part of the UV spec-
trum they are active. When considering which active ingredients should be used
to formulate natural sun care products, however, another way of classifying the
active ingredients may be more relevant. Titanium dioxide and zinc oxide are
the two Category I actives that are inorganic pigments. All of the other actives
are synthesized organic compounds. A natural sunscreen should use natural
ingredients; this applies especially to the active ingredients. The FDA does not
510 Kapsner et al.
currently allow the claim “natural sunscreen” to be used in marketing a sun care
product. A marketer can claim that their sunscreen contains natural ingredients.
Some of these natural ingredients may, among their other functions, also increase
the SPF of the product. There are, however, no active ingredients that the FDA
will allow a sunscreen manufacturer to call “natural”. This begs the question
as to what active ingredients should be used in natural sun care products.
Titanium dioxide and zinc oxide are minerals, which, according to Webster’s
New College Dictionary, are naturally occurring inorganic substances. The
organic food industry allows mined minerals to be used in certified organic
processed products. By the time titanium dioxide and zinc oxide find their way
into a sunscreen, however, they have been processed in one or more ways to
make them more compatible and more effective. Many different types of coatings
and dispersants, sometimes natural and sometimes not, have been added.
Anyone who has ever used paints or color cosmetics knows that the main
function of titanium dioxide and zinc oxide in those products is to opacify them.
They do this very well in sunscreens also. Early versions of sunscreens containing
only these two pigments left an unacceptable white residue on the skin, and were
thus not very popular. This challenged the producers of these ingredients to
improve them, and they soon responded with micronized versions, with much
smaller particle sizes, which significantly reduced the whitening. Further refine-
ments of the micronization technology resulted in the recent discovery that there
is a specific particle size range that gives the lowest whitening but still reflects
UV radiation (7). Other chapters of this book deal extensively with the selection
and technology of the inorganic sunscreen actives.
As improved as these new pigments are, these materials are still difficult to
work with, and it is not unusual for the final product to lend a significant—and
undesirable—white chalky sheen to the skin, sometimes with a bluish cast.
Manufacturers and formulators have found a number of ways to overcome this
challenge, but it takes definite skill to avoid the “whitening” outcome. The key
to success is in first keeping the solid in suspension and preventing agglomeration
both in the product and on the skin, and then keeping the overall product from
drying out on the skin. Specific plant-based solvents and emulsifiers have been
introduced to do just that. For example, polyglyceryl-6 polyricinoleate is an
emulsifer based on natural glycerin and ricinoleic acid, which is said to be
particularly good at dispersing titanium dioxide. Two other emulsifiers, one a
blend of coco-glucoside with coconut alcohol and the other a blend of coco-
glucoside with cetearyl alcohol, will help keep the pigments dispersed in the
finished emulsion. Another new ingredient, dimyristyl tartrate, helps to stablize
the emulsion viscosity and improves water resistance.
Titanium dioxide pastes and slurries have been created to maintain a phys-
ical distance between the particles and therefore prevent agglomeration. One of
the newest entries in this ingredient category uses alkyl benzoates to disperse the
titanium dioxide or zinc oxide in a solid flake. This keeps the pigments finely
dispersed until they go into the emulsion, resulting in a finer dispersion in the
finished product. Another approach to the challenge of dispersing solid materials

may be to formulate a water-in-oil or water-in-silicone lotion, with the solid
titanium or zinc well dispersed in the internal water phase. The external silicone
or oil phase then creates a nonevaporating moisture layer on the skin, thus main-
taining physical distance between the particles to prevent agglomeration, while
also preventing dry-out and whitening. These emulsions are also waterproof
(without the need for film-forming resins) and therefore more effective for
outdoor and beach products. A raw material based on natural ingredients used
for this approach is a blend of cetearyl alcohol, dicetyl phosphate, and ceteth-
10 phosphate. This material helps create an emulsion with good shear-thinning
properties, and also improves the deposition of oils on the skin, improving
water resistance.
Unusually stable and functional gel matrix emulsions are especially suited
for physical sunscreens. Not only are the solid particles held tightly in the matrix,
but the emulsion forms a hydrophobic film on the skin to effectively prevent
agglomeration, add waterproofing, and boost overall SPF by virtue of these
inherent emulsion characteristics. An emulsifier blend created for this purpose
contains polyglyceryl-10 pentastearate, behenyl alcohol, and sodium stearoyl
lactylate.
INCREASING SPF
A sunscreen is, of course, an OTC drug product. As such, it is subject to the
requirements of the sunscreen monograph. This means that the active ingredients
added to achieve the SPF must be on the Category I list and must be used in
concentrations prescribed by the monograph.
There are, however, many ways to enhance the performance of a natural
sunscreen. The organic sunscreens absorb UV radiation because they contain
aromatic rings that are conjugated with a carbonyl group and also contain
electron-donor groups in either the ortho or the para positions on the aromatic
ring (8). Structures very similar to this are abundant in nature, so these natural
materials should also have some UV absorption. For example, ethylhexyl meth-
oxycinnamate is a Category I sunscreen active. Galanga extract (a rhizome in the
ginger family, commonly used in Thai cooking) contains high levels of ethyl
methoxycinnamate, a safe, natural material with a structure very similar to the
Category I ingredient. Other cinnamic acid derivatives can be found in sage,
thyme, and rosemary. Flavonoids are naturally occurring polyphenolic molecules
that contribute color to many plants. Some plant extracts, such as ginko biloba,
contain flavonoids which absorb UV as well as visible radiation, and thus may
boost the SPF of a sunscreen (9).
Many other natural extracts have UV absorption. Annatto is a well-known
food colorant; what is not so well known is that in addition to absorbing visible
light, it also absorbs UV radiation. Gamma oryzanol, which is extracted from rice
bran oil, also absorbs UV radiation and can boost the SPF of a natural sunscreen.
512 Kapsner et al.
Licorice (Glycyrrhiza glabra) extract is reported to be as effective as ethylhexyl

methoxycinnamate in absorbing UV rays. Lawsone, the functional ingredient in
henna, is a known UV absorber and approved sunscreen blend ingredient.
Calophylum inophylum seed oil has some UV absorption and also acts as an
antioxidant, which may add a further benefit in a natural sunscreen as a free-
radical scavenger (10).
Pongamol is a natural material extracted from the karanja tree, which grows
in India. This material is reported to enhance the UV protection of sunscreen
actives and to broaden UV absorption, especially into the UV-A region (11).
Two other plant extracts that have been tested to have UV absorption are
coffee extract and wild pansy extract. Other natural materials that have been,
or are being, evaluated as natural UV absorbers are rutin, helichrysum italicum,
lupinus albus, rhamnus frangula, naringin, neohesperidine, luteolin, and
aloin (12).
Although private industry has made most of the contributions to the
advancement of sunscreen chemistry, the USDA has also recently announced a
significant advance. They have applied for a patent (13) on a material they are
calling “soyscreen.” This material is produced by reacting soybean oil with
ferulic acid, which has UV absorbing properties. The result is a molecule that
absorbs UV rays and is oil soluble, so it should stay on the skin. The manufactur-
ing process is low energy and uses an enzyme that can be recycled, so this ingre-
dient gets high marks for environmental responsibility. The finished ingredient is
biodegradable, so it will not accumulate in the environment. This material will
presumably be available soon for licensing.
NATURAL FRAGRANCES
In the last few years, it has become more and more popular to see the term
“natural” associated with cosmetic products and fragrances. For many people,
if a product contains some natural ingredients, along with synthetics, it is still
considered to be natural. By all-natural fragrances, however, we mean that the
fragrance contains no synthetic ingredients at all. Natural fragrances should be
prepared with aromatic materials obtained from plant sources. Many of these aro-
matic plant materials, such as rosemary, rose, and jasmine, possess antioxidant
activity as well.
Natural aroma ingredients include the following:
Essential oils: These are obtained through steam distillation process,
for example, oils of lavender, rose, thyme, ylang ylang, etc., and also
by physically extracting the rind of citrus fruits, for example, bergamot
oil, lemon oil, orange oil, grapefruit oil, etc.
Absolutes: A plant is treated with a solvent to extract the oil mixed with
vegetable wax. This first-phase material is called a “concrete” because
of its hard texture. Then the concrete is dissolved with ethanol to
produce an absolute, for example, most flowers, such as jasmine,

mimosa, geranium, rose, lavender, clove, clary sage, neroli, etc.
CO2 extraction: Supercritical CO2 is used as a solvent to extract oils from
plants such as seeds, resins, and barks. Then, lowering the pressure, the
CO2 becomes a gas and evaporates, leaving behind the extracted CO2
absolute.
Enfleurage: Plants are steeped in fat (beef, suet, or lard) on plates, which
will absorb their fragrance. It is used mainly for jasmine and tuberose.
This technique, first reported by the ancient Egyptians, is hardly prac-
ticed anymore due to its high cost. Solvent extraction methods have
replaced this process.
Resinoids: obtained through the application of alcohol to resins, for
example, benzoin, labdanum, galbanum, opoponax, peru balsam,
styrax, tolu, etc.
Isolates: These are obtained from essential oils by heating them and sep-
arating a major component of the essential oil, for example, linalool
from coriander oil, geraniol from palmarosa oil, methyl salicylate
from wintergreen oil, eugenol from clove bud oil, anethol from anis
oil, etc.
Natural chemicals: These are obtained by treating isolates with physical
processes (mixing, heating, stirring, washing, etc.), or with fermentation
or enzymatic action to connect them with other natural components, for
example, linalyl acetate (linalool þ vinegar), geranyl acetate (geraniol þ
vinegar), etc.
Natural Standards
These items are natural as defined by the following standards, which are adhered
to by the cosmetic and food industries:
1. The FDA definition of “natural” in the context of flavor, given by 21
C.F.R.101.22(a)(3) (14). (The FDA has not issued regulations to
define the term “natural” when applied to cosmetics.)
2. The terms and definitions laid down in the Norme Francaise T 75-006
issued in October 1987 by the French standardization organization
AFNOR (Association Francaise de Normalisation). [The International
Fragrance Association (IFRA) General Assembly subsequently
adopted this in October 1989, as the statement on Natural Fragrances.
The IFRA Board of Directors then circulated this on June 14, 1991, to
all members of the Association.]
3. The term “natural flavouring substance” mentioned in the Code of
Practice as 88/388/EEC, article 1 for the Flavour Industry, issued in
October 1989 by the International Organization of the Flavour Industry
(IOFI) (15).
514 Kapsner et al.
Points of Difference
The major differences between mainstream perfumery and natural perfumery are
1. Mainstream perfumery uses mainly synthetic sources with a palette
ranging from 5000 to 30,000 materials. They have a variety of
scents available that are inexpensive powerful aromas with a long
shelf life.
2. Natural perfumery uses a limited number of natural essential oils and
extracts. Among the 250,000 species of flowering plants (16) only
about 3000 plants carry essential oils, of which only 200 or so plants
yield their oil readily. They have a limited variety of scents available
that are expensive and subject to change due to climatic, geographical,
and political changes. They are generally weak aromas with a short
shelf life.
Environmental Concern and Aromatherapy

Until 10 years ago, or so, natural fragrances were considered an alternative. Due
to the recent resurgence in environmental concern and interest in aromatherapy,
natural aromas are gaining in popularity and are in serious demand with the
general public today. All indicators point to this trend continuing and growing
in the future. Natural products are now found in every category from hair and
skin care to cleaning products.
The Environmental Principle

We feel by using natural ingredients, we are doing our part to help nature to stay
in good health and beauty. We avoid using materials that can eventually hurt the
environment in any of the following ways:
. If used or handled improperly, they can contribute to pollution.
. They are a depletable resource.
. They are slow to degrade.
Even Mother Nature cannot reproduce petrol, which makes its use not environ-
mentally sustainable. On the contrary, Mother Nature can produce every year
all the plants that supply us with the beautiful essential oils, absolutes, and
other natural materials that we need—mimosa in February, violet in May, rose
and jasmine in July, etc.
Aromatherapeutic Principle
Aromatherapists believe that essential oils possess beneficial effects, from the
medical and pharmaceutical points of view, such as sedating and stimulating
effects, antiseptic and disinfectant effects, spasmolytic and diuretic effects, and
so on. They firmly believe that essential oils have the power to cure people.
From their point of view, perfumers are using only one small aspect of what
these essential oils can offer. Dr. Jean Valnet and Robert Tisserand were the
pioneers of this practice. Dr. Valnet’s book, published in 1964, made a great
impact on the world of aromatherapy; these days more and more people are
studying and practicing this discipline (17). The result of this study and practice
is a considerable body of knowledge regarding the beneficial effects of natural
essential oils. The calming effect of natural rose oil and the stimulating effect
of peppermint are well known. A talented perfumer can create natural aroma
blends that complement and enhance these benefits. With this approach, the
exclusive use of natural aroma materials can be perceived not as a challenge
or a restriction, but as a tremendous opportunity.
Natural Aromas as they Relate to Sun Care Products

For sun care products (presun, sunscreen, and after sun) it is most important to
avoid what are considered the phototoxic groups of oils. The photosensitizing
components in essential oils are the furanocoumarins such as bergaptene and
psoralen. Photosensitization is the process by which the skin is made more
sensitive to UV radiation. The furanocoumarins absorb the UV radiation very
easily and then reradiate this energy into the skin causing the skin to burn
faster (as well as tan faster as bergamot was used in sun tanning preparations
in the past) (18).
Phototoxicity is defined as a skin reaction that occurs after exposure to UV
light. In the case of sun exposure, sunburn appears much more quickly, evidenced
by the usual redness (erythema) which will disappear within 1– 3 days and is
followed by mild tanning. Another reaction to furanocoumarin containing
compounds is a photoallergy or an allergic response. Photoallergy is also
known as berloque dermatitis, and it usually occurs on areas such as the neck
and chest, which are exposed to sunlight (18). The perfumer should always
be careful of the phototoxic essential oil concentrations in the final product
(19). Because of this risk, in the perfume industry the perfumer only uses the
furanocoumarin-free bergamot. The oils listed below contain a much smaller
amount (less than 0.5%) of furanocoumarin, which makes their phototoxicity
negligible.
Rutaceae Apiaceae
Bergamot (highest possibility) Angelica root
Fig leaf Cumin
Lemon (expressed) Opoponax
Lime (expressed)
Orange (bitter, expressed)
Mandarin
Grapefruit
Rue
516 Kapsner et al.
The IFRA has also issued a list of restricted oils, which includes angelica
root, cumin, and bergamot essential oils. Among the others in this list are oils
such as baume de Perou, cassia, cinnamon, sassafras, verbena, anise, aspic,
basil, clove, corriander, hyssop, sage, and tansy flower, which are on this list
for other reasons (20). Other than these groups of essential oils to avoid, there
are no known phototoxic contraindications to using the remaining oils as a part
of sun care product formulations.
Natural aroma ingredients are very complex mixtures of dozens, if not
hundreds, of components. As well as having subtle aromatic effects, these
natural compounds have many beneficial effects on the skin. Chamomile oil
contains significant amounts of bisabolol, which is a known anti-irritant.
Lavender oil is also known to soothe the skin. These benefits can be put to use
by formulating the aromas from natural essential oils and other natural aroma
compounds in natural sun care products.
PRESERVATIVES
Preservation is probably the most difficult task for a formulator to accomplish
while holding true to the mission of developing a natural sun care product. For
a sunscreen product to be safe, it must be adequately preserved. Doing this
with natural, or naturally derived, ingredients is a serious challenge indeed.
Through the 1970s, formaldehyde was the most common cosmetic pre-
servative. It had several advantages, being inexpensive, highly effective, and
relatively stable. With the widespread use of cosmetics, household, and industrial
products, however, toxicity issues led to its downfall. It is very difficult to find an
effective preservative that is also nontoxic to humans, other animals, and plants,
and safe for the environment. (After all, the function of a preservative is to kill,
or control the growth of, microorganisms.) As formaldehyde fell from favor,
another class of preservatives was created, those that produce formaldehyde on
demand (called formaldehyde donors). While much safer than pure formal-
dehyde, their use is also being questioned today, and they also do not have a
place in natural sunscreens.
One of the most difficult aspects of marketing cosmetic products worldwide
is preservation. Two major markets, the European Union and Japan, have a posi-
tive list of allowed preservatives. Japan’s list is the most restrictive. Of those,
a few could be considered for use in natural sunscreens: benzoic and sorbic
acids and their salts, benzyl alcohol, phenethyl alcohol, and phenoxyethanol
(21). While judicious use of these ingredients may adequately preserve a
product, staying true to the spirit of formulating a natural sunscreen calls for
a more creative approach to preservation.
There are many natural ingredients that can contribute to preservation.
Many essential oils have antimicrobial properties. Some of the more effective
ones are sage, thyme, and oregano (all of which have significant levels of
thymol), tea tree, lemongrass, clove, and cinnamon. Any essential oil used at
a high enough level to assist in preservation will, of course, have a significant

impact on the aroma of the finished product. Careful selection of the essential
oils used to fragrance a natural sunscreen will certainly help in its preservation.
Although foods do not have the long shelf-life requirements that cosmetics
do, considerable work has been done to determine how best to preserve foods.
The most useful natural ingredients from this work are the acids, citric, lactic,
and sorbic. Although citric acid does not have a significant direct antimicrobial
effect, it can enhance the effect of other ingredients by lowering the pH and
chelating metal ions. Lactic and sorbic acids do have antibacterial and antifungal
effects. In addition to the acids, saponins and flavonoids may give a boost to
antimicrobial systems (22). Polyphenols are known to have an antimicrobial
effect. Green tea extract is high in polyphenols and flavonoids, and can also
give an antimicrobial boost (23). Grapefruit seed extract has been used in cos-
metics for many years as a natural preservative. It has a significant advantage
over other natural preservatives in being water soluble. Benzyl alcohol has
been used in cosmetics for many years. Natural benzyl alcohol, though expens-
ive, is available. Its use is restricted to fairly low levels in some countries.
The need in the cosmetic industry for natural preservatives has spurred
considerable research and the introduction of many interesting ingredients.
Hinokitiol is an exudate from a cedar tree. Although extremely expensive, it is
highly effective at low levels. Asparagopsis armata extract is a seaweed extract
that contains natural halogenated “macromolecules.” It is water soluble, fairly
expensive, and fairly effective. Olive leaf extract not only helps in preservation,
but doubles as a free-radical scavenger. Malaleuca alternifolia leaf oil and
leptospermum scoparium oil consist of fractions from several Australian essential
oils. They have a strong essential oil aroma but can help in preservation. A
plant extract blend of Origanum vulgare L. (Apiaceae), Thymus vulgaris
L. (Apiaceae), Cinnamomum zeylanicum Nees (Lauraceae), Rosmarinus
officinalis L. (Lamiaceae), Lavandula officinalis L. (Lamiaceae), and Hydrastis
canadensis L. (Ranunculacea) also has a significant antimicrobial effect. Short-
chain fatty acids, such as caprylic and capric, can have an antimicrobial effect
(24). Unfortunately, however, they also tend to be fairly irritating. Creative
chemists have come up with glyceryl esters of these materials, glyceryl caprate
and glyceryl caprylate, which seem to retain some of the antimicrobial effect
but with less irritation.
In addition to adding ingredients specifically for their antimicrobial effect,
sunscreen formulas can be modified to make a more “hostile” environment for
microbial growth. Lowering the water activity of a formula, by adding inorganic
salts or glycerin, can help significantly. Moving the pH away from neutral (above
8 or below 5) will itself discourage microbial growth. Cationic emulsifiers such as
cocamidopropyl PG-dimonium chloride phosphate can also help. Ethanol, if used
at a high enough level, can preserve a product by itself. Unfortunately, it is also a
very effective solvent, and can dry the skin. Judicious use of low levels of ethanol
can reduce the requirement of other preservatives.
518 Kapsner et al.
As traditional preservatives fall from favor, creative formulators have

explored other, more natural ways to accomplish this important task. The
many new ingredients and techniques now available ensure that a natural
sunscreen need not be significantly less natural just because it is adequately
preserved.
NEXT-GENERATION SUN CARE

The next-generation sun care products must address all detrimental sun damage
beyond just UV shielding. Current SPF measurement addresses only UV-B
erythema redness and does not account for the silent cellular damage—a time
bomb for disaster on prolonged exposure.
Advanced sun care should address the following biological effects, thus
providing total protection during and after sun exposure.
Biological Effects Due to Sun Exposure

1. Erythema UV-B damage on skin epidermis.
2. DNA damage by UV-A in skin dermis.
3. Photoaging process begins with the release of collagenase and elastase
enzyme ultimately causing skin sagging and wrinkles. This process is
regulated by matrix metalloproteinase (MMP) and tissue inhibitors of
matrix proteinase (TIMP).
4. Immunocompromised.
5. Inflammatory cellular reactions.
6. Free radical generation in the skin.
7. Skin barrier protection compromised; skin dehydration.
Today we have a better understanding of the mechanisms of the above bio-
logical effects and have identified active ingredients to augment, prevent, and
protect these destructive processes (25).
Sun exposure biological effects Solution

Erythema UV-B, UV-A, UV-A and UV-B protection with ZnO and TiO2 ,
and DNA damage phytothergenetic sunblock Cajolone, and
isoamyl salicylate from potatoes and oil of
wintergreen
DNA damage DNA repair by liposomes from biofermentation of
Micrococcus lutenus; it contains endonuclease,
which recognizes UV damage and repairs
UV-DNA damage
Photoaging Collagenase and elastase inhibition by wheat
cerasomes
TIMP enrichment by white lupin flower peptides
Sun exposure biological effects Solution

Immunocompromised Plankton have evolved to protect themselves from
sun exposure as they need UV light to
manufacture energy; they contain photolyase
which clears and reverses damage caused by
shorter-wavelength UV; this ingredient is
available as photosomes
Inflammatory reaction to the sun A complex from algae, blue chamomile, and
sucrose; licorice extract
Free radical Free radical quenching by antioxidants from
rosemary, astaxanthin, grapefruit seed extract,
and jasmine absolute (hexane free)
Skin barrier compromised Skin barrier replenishment by organic ingredients
jojoba oil, almond oil, quinoa protein, and
Aloe Vera
We should look well beyond simply treating the skin’s surface for preven-
tion of sun damage. Sun protection can—and should—focus on integral skin
metabolism and immunological processes for true sun protection. This next-
generation sun care should also improve skin health for future sun exposure as
well as with continual skin integrity enhancement (e.g., reverse photoaging).
The ingredients listed in the table all speak to strengthening specific skin
mechanisms, instead of simply “grabbing” damaging UV rays with resonance
structures. Instead, this approach assumes that the skin itself can act as its own
effective barrier to sun damage. It may also be possible to take a step beyond
even this approach and use nutrition and other internal processes to further aid
in overall sun protection. It is our approach, then, to see skin processes as a
whole, working together in preventive and repair processes, rather than rely on
a few ingredients to play such a vital role in sun protection.
CONCLUSIONS
Formulating natural sun care products is no easy task. It demands a vast
knowledge of plant sources and functions as well as excellence in formulation.
Development times are likely to be long; the final product is likely to be more
expensive and perhaps less versatile than its synthetic counterparts. As mentioned
earlier in this chapter, current FDA regulations do not allow a sunscreen product
to be labeled and marketed as totally natural. As seen in this discussion, however,
significant advances are being made in all categories of natural ingredients
needed to build a sunscreen: emulsifiers, UV absorbers, aromas, and preserva-
tives. As these frontiers continue to advance, there may come a time when the
sunscreen monograph process will be required to re-examine the claim of a
natural sunscreen.
520 Kapsner et al.
The effort of attempting to create natural sun care products, if done with
conscience, is worth the outcome. It is our desire to make a positive impact on
the world, from the perspective of maintaining consumers’ health as well as initi-
ating positive environmental policies with measurable outcomes. Above all, we
recognize that we are only on this earth for an instant; we are guardians for our
children’s children.
REFERENCES
1. Rasmussen R. Cosmet Toilet Mag 2003; 118(2):5.
2. Shaath NA, Fares H, Klein K. Photodegradation of sunscreen chemicals. Cosmet
Toilet 1990; 105:41 –44.
3. Pinell SR. Dermatol Surg 2000; 26:309 – 314.
4. Fairhurst D, Mitchnick M. Particulate sunblocks. In: Lowe NJ, Shaath NA,
2nd ed. New York: Marcel Dekker, 1997.
2005:173 –198.
6. Food and Drug Administration. Final rule for sunscreen drug products. Fed Reg 1999;
27666.
7. Presperse Incorporated. Product Literature, Ti-Sphere, 2003.
8. Shaath N. Chemistry of sunscreens. In: Lowe NJ, Shaath NA, Pathak MA, eds.
Marcel Dekker, 1997.
9. Lee KT. Preliminary studies on natural plant extracts as sunscreen agents. IFSCC
Congress: Science and Beauty at the Dawn of the Third Millennium, Cannes,
France, Sept. 14– 18, 1998:1 –8.
10. Plant Sun International. Product Literature, Scaveng Oil, 2003.
11. Quest International. Product Literature, Pongamia Extract, 2003.
12. Proserpio G. Cosmet Toilet 1976; 91:34– 46.
13. US Patent No. 6,346,236.
14. Food and Drug Administration. Code of Federal Regulations. Washington, DC: FDA,
Title 21, Section 101.22(a)(3).
15. International Organization of the Flavor Industry. 88/388 EEC Article 1, October
1989.
16. Pelt JM. Les Plantes: Amours et civilisations vegetal. Librarie Artheme Fayard,
1980– 1981.
17. Valnet J. The Practice of Aromatherapy. Rochester, VT: Destiny Books, 1980.
18. Guba R. Specification Sheets. The Center for Aromatic Medicine, 1995.
19. Tisserand R, Balacs T. Essential Oil Safety: A Guide for Health Care Professionals.
Churchill Livingstone, 1995.
20. Ryman D. Aromatherapy: Complete Guide to Plant and Flower Essences for Health
and Beauty. Bantam Books, 1993.
21. Steinberg DC. Preservatives for Cosmetics. Cosmet Toilet, 1996; 111:42.
22. Otshudi AL, Foriers A, et al. In vitro antimicrobial activity of six medicinal plants
traditionally used for the treatment of dysentery and diarrhoea in Democratic Republic
of Congo (DRC). Phytomedicine 2000; 7(2):167 –172.
23. Elmets CA, Katiyar SK, Yusuf N. Photoprotection by green tea polyphenols. Shaath
NA, ed. Sunscreens: Regulations and Commercial Development. 3rd ed. New York:
24. Kabara JJ, Orth DS, eds. Preservative-Free and Self-Preserving Cosmetics and Drugs:
Principles and Practice. New York: Marcel Dekker, 1997:120 – 123.
25. Pinnell FR. Cutaneous photodamage, oxidative stress and topical protection. J Am
Acad Dermatol 2003; 48(11):1– 19.
Consumer Products with
Ultraviolet Filters
25
Recreational Sunscreens
James P. SaNogueira
Playtex Products, Inc., Allendale, New Jersey, USA
Introduction 525
Sunscreen History 526
Market Share and Trends 526
Formulations 527
Consumer Benefits and Performance Needs 527
Usage and Performance Needs During UV Exposure 528
Water/Sweat Resistance 529
Sunbathing/Suntanning Products 531
Fast Drying Sunscreen Gel 532
Additional Considerations 532
Patents 532
Photostability 533
Conclusions 533
References 533
INTRODUCTION
What are recreational sunscreens and what sets them apart from other types of
products that attenuate UV rays? Is the term “recreational sunscreen” an oversim-
plification? After all, it includes many types of products whose performance and
benefits vary widely. Other terminology such as “beach products,” for example,
can be even more misleading as descriptors of products used under demanding
525
526 SaNogueira
conditions and in a wide variety of situations. Often, sunscreen products that offer
the type of performance attributes and benefits of recreational sunscreens are
required as an important part of a daily photoprotection regime. This is especially
important for those who are frequently exposed to UV radiation, perhaps for long
periods because of their occupation (not recreation) outdoors.
Perhaps a good definition of recreational sunscreens is, those products
which provide UV attenuation as the primary benefit, with other benefits being
added to segment performance and appeal to consumers who have specific
secondary benefit needs. Thus, recreational sunscreens are differentiated from
products whose primary purpose is the delivery of other skin care benefits and
which are designed to also offer the additional benefit of UV protection.
In all, this chapter is dedicated to the discussion of products that must go
beyond the addition of UV attenuation to moisturizers, makeup, and other skin
care products whose users require benefits different from and even beyond
those afforded by products offering UV protection as a secondary benefit.
SUNSCREEN HISTORY
The use of sunscreens predates the discovery and use of our “modern” ingredients
and products used to attenuate UV radiation. Beauty, social status, and even
health and comfort drove the ancients to find ways to help protect their skin.
As they worked in the fields and began traveling and resettling around the
world in areas where the incidence of UV radiation outmatched their genetic
code, effective compositions were developed over time to protect their skin.
Some of these ingredients are still used today. While this is the topic of a previous
chapter (1), it is mentioned here to help demonstrate that the use of “recreational”
sunscreens predates the modern area of vacations in the sun.
MARKET SHARE AND TRENDS

In terms of market growth, recreational sunscreens have enjoyed steady growth
over the last 20 years as people have become more aware and concerned with pro-
tecting themselves from UV rays. Today, the recreational sunscreen market
stands at over $450 million in the USA alone. The chart below illustrates the
growth in sales over time (2).
Growth in Recreational Sunscreen Sales
2003,
Year 1997 1998 1999 2000 2001 2002 YTD (Sept)
Sales in millions ($) 458 499 551 572 634 470a 451a
% Increase 2.8 10.4 3.9 10.4 0.9 26.0
a
Excludes Walmart sales figures.
Source: AC Nielsen Scantrack data, total USA, provided by Playtex Products Inc.
Recreational Sunscreens 527
Major US Manufacturers/Marketers Dollar Sales
2002 2003, YTD (Sept)

Banana Boat 21.7 21.9
Coppertone 30.5 31.1
Neutrogena 12.8 14.4
Hawaiian Tropic 8.7 9.8
Source: AC Nielsen Scantrack data, total USA, provided by
Playtex Products Inc.
Microbrands and store brands also exist, with the former shrinking as a
whole over time while store brands have shown growth. Recreational sunscreens
are largely seasonal products in most areas of the USA and in countries with
similar climates. Sales of recreational sunscreens are highly dependent on the
weather, particularly in the time frame of major summer holidays and vacation
periods. This translates into a challenge for marketers and retailers alike in
terms of forecasting, manufacturing, and stocking sunscreen products.
FORMULATIONS
To the formulator, the structure of the sunscreen business provides both
challenges and opportunities. Approximately 20% of annual sales of sunscreen
products come from new product introductions year in and year out. Conse-
quently, there is a constant challenge to develop new products that offer benefits
and features that will help to capture incremental sales volume and profit as well.
Sunscreen formulators have to respond very quickly to meet the timing of this
seasonal business while insuring that the products delight consumers, are econ-
omically and technically feasible, and can be executed on time. In the USA, as
all products with an SPF are OTC drugs by definition, formulators must also
meet regulatory requirements that are a moving target at present.
The market trend over time has been toward higher SPF products and an
increasing number of products that offer meaningful levels of UV-A protection
through the addition of avobenzone, or titanium dioxide and zinc oxide. More
modern formulas use ingredients that help to boost or maintain the photostability
of the sunscreen active ingredients. Recent market trends include a focus on
improved aesthetics, convenient application/usage, and specialized applications
or subsegments.
CONSUMER BENEFITS AND PERFORMANCE NEEDS

As noted earlier, recreational sunscreens cover a wide spectrum in terms of per-
formance requirements and the consumer benefits that they need to deliver to
insure efficacy and provide consumer satisfaction. Some consumers desire
528 SaNogueira
products that help to make sunbathing a more enjoyable experience by providing

a luxurious or oily skin feel, a high degree of shine, and tropical scent with
minimal protection while others seek fast absorbing fragrance-free products
with high protection that stays on in water and after perspiration. Over time
the number of product forms, methods of delivery, and varying product
aesthetics/sensory characteristics have continually expanded. Of course
this extends to everything in between, additional benefits and an abundance
of product forms, that is, lotions, creams, oils, sprays, sticks, gels, pastes, and
mousses. Sunscreens combined with skin protectants are classified as “dual
drugs” because they cross two monographs. Sunscreen products with insect
repellants such as DEET help to provide dual protection against the sun and
mosquitoes in one product.
Visual signals have been added to products; these include indicators rep-
resented by the addition of color to the entire product or to colored microcapsules
to help consumers see where the product has been applied and where they have
missed. Shine enhancers have been added to give the skin more gloss when
sunbathing, glitter has been added to give the skin a shimmering appearance.
Recreational sunscreen products also cover a wide range of other skin care
benefits. The emulsions used to deliver sunscreen actives also have the capability
to effectively deliver all the skin care benefits of more cosmetic products.
Moisturization, antiaging, antioxidants, vitamins, botanicals, skin protectants,
alpha and beta hydroxy acids, pigments, etc, can and are delivered effectively
by recreational sunscreens. Recreational sunscreens provide robust protection
to the skin against UV damage, outperforming the so-called daily photoprotec-
tion products, while enhancing the appearance and condition of the skin as
effectively as cosmetic products without UV protection.
USAGE AND PERFORMANCE NEEDS DURING UV EXPOSURE

Formulators approach the design of sunscreen formulas based on the particular
application and intended product concept and positioning in the marketplace.
Although there is often some overlap of product benefits across segments,
there are normally one or more differentiating attributes offered by a particular
positioning that must be accounted for in the product design.
Recreational sunscreens are designed to deliver product performance that
will meet a variety of consumer needs as dictated by their personal preference
for aesthetics, activity, and amount of protection. Differences in the level and
type of physical activity can influence the need for product substantivity (water
resistance/sweat resistance, resistance to rub-off/toweling. Over the years
specialized products based on increased levels of substantivity marketed to
people who take part in surfing, water skiing, snorkeling, etc., have led to market-
place successes. The point of usage and the environmental conditions for rec-
reational products are generally more diverse and must also be accounted for
in the product design. As such this presents both a challenge and an opportunity to
formulators, package engineers, and marketers alike.
WATER/SWEAT RESISTANCE
Sunscreen formulations can be made water resistant by using one or more formu-
lation techniques to help form a film that will keep sunscreens on the skin upon
immersion in water or exposure to perspiration. Some product forms such as
water-in-oil or water-in-silicone emulsions are inherently more waterproof than
their counterpart oil-in-water emulsions and can sometimes be formulated with
little or even no additional “waterproofing” ingredients. Water-in-oil emulsions
have the added advantage of providing instant waterproofing and SPF efficacy
as they more readily form a continuous film of sunscreen in an inherently water-
proof layer. Emulsions of this type can also offer “instant” efficacy as illustrated
in patent art (3) and by recent launches of products offering instant waterproofing
and SPF efficacy.
An example of a high-SPF water-in-oil sunscreen formulation is given. A
crystalline organic sunscreen (bisethylhexyloxphenol methoxyphenol triazine,
tinasorb S), a sunscreen ester in the oil phase, and titanium dioxide powder
that is dispersed in the water phase are featured in this formula. Glycerin is
added to help with skin moisturization. This type of formula lends itself to
being instantly effective and resistant to both fresh-and saltwater (4).
Sun Protection Lotion with High SPF
Phase A
Cetyl PEG/PPG—10-1 dimethicone 2.5
Cetyl dimethicone 1.0
Diethylhexyl carbonate 6.5
C12– C15 alkyl benzoate 4.0
Macadamia nut oil 2.0
Tocopherol acetate 0.5
Tinasorb S 3.0
Octinoxate 6.5
Phase B
Allantion 0.5
Sodium carboxymethyl betaglucam
Glycerin 2.0
Sodium chloride 0.5
Tegosun 40 (TiO2 and glycerin and 12.2
isolaureth—4-phosphate and vinyl
buteth-25 and sodium maleate)
Copolymer
Water 52.0
Preservative q.s.
530 SaNogueira
Any number of optional ingredients such as fragrance, color, additional anti-

oxidants, or aesthetic modifiers could be added or substituted. Various levels and
combinations of sunscreen actives as found in the various versions of the proposed
FDA, TFM, and FM dating back to 1978 and or other internationally available
sunscreens could also be added or substituted (see section on sunscreen actives).
Oil-in-water emulsions normally require one or more waterproofing ingre-
dients in order to retain sunscreen actives on the skin. Careful choice of the type
and amount of emulsifier used in emulsions can limit the need for waterproofing
agents by avoiding or reducing the tendency of the product to re-emulsify when
exposed to water. Generally speaking, oil-in-water emulsions require longer to
set up a fully effective continuous film on the skin than water-in-oil emulsions
and being composed of a water-soluble continuous phase, are more likely to
mix readily with water and require a set time before becoming waterproof.
Depending on the thickeners and emulsifiers used, this type of emulsion may
also be more or less sensitive to salts.
Product forms such as certain types of gels and sprays are solutions that rely
on volatile components as carrying agents that flash off or evaporate upon
application leaving behind a film of sunscreen ingredients, solubilizers, and exci-
pients. Waterproofing ingredients are useful not only in keeping the sunscreen on
the skin, but also in helping the sunscreen form an effective layer as it is rubbed
onto the skin and the volatile components evaporate or “flash off” from the skin.
Waterproofing agents work via two basic mechanisms. The most traditional
approach is the use of film forming ingredients that help the sunscreen to stay on
the skin after the waterproofing agents form a hydrophobic film that binds or
anchors at least temporarily to the skin. A second mechanism works by increasing
the viscosity of the oil phase ingredients, in turn helping to reduce the mobility of
the sunscreen and causing them to deposit onto the skin from the emulsion upon
application and dry-down of the product film. A poster presented by Rerek (5)
discusses the mechanism of waterproofing via thickening of lipids.
Some of the commonly used waterproofing ingredients are listed in the
following table. This is not a complete listing but does serve to illustrate some
of the different types of waterproofing chemistries that are used. The choice of
waterproofing ingredients can be dependent on the overall formulation type,
the oil phase load, the desired skin feel, and the particular application. Combi-
nations of different waterproofing ingredients are often helpful in achieving the
desired results.
Waterproofing Ingredients
Typical usage
Trade name INCI name range (%)
Ganex V-220 PVP/eicosene copolymer (1– 3)
Lexorez 100 Adipic acid/diethylene (1– 4)
glycol/glycerin cross-polymer
Typical usage
Trade name INCI name range (%)
Allianz OPT Acrylates/C12– 22 (1 – 3)
akylmethylacrylate copolymer
Performa V1608 C30– 38 olefin/isopropyl (0.5– 3)
maleate/MA copolymer
PA-18 Resin Octadecene/MA copolymer (0.5– 2)
Panalene 300 Hydrogenated polyisobutane (1 – 5)
Lexorez 200 Trimethylpentadiol/adipic acid/ (1 – 4)
glycerin cross-polymer
Performalene 400 Polyethylene (0.5– 3.0)
Fomblin HC/PC-1000 Polyperfluroethoxymethoxy (0.5– 3)
difluroethyl PEG phosphate
An example of a typical waterproof water-in-oil sunscreen follows. This

formula features the use of TiO2 as the sole sunscreen ingredient, approximate
SPF 15.
%w/w
Phase A
Stearyl alcohol 2.00
Estol 1543 5.00
Prisorene 3631 5.00
Tween 60 2.00
Solaveil CT-100 11.11
Phase B
Demineralized water 56.49
Arlatone 2121 2.50
Rewoderm S1333 0.20
Phase C
Veegum Ultra 0.80
Sodium lactate (50%) 0.40
Germaben II 1.00
Source: Formula courtesy of Uniquemia, formula reference 5468*1.
SUNBATHING/SUNTANNING PRODUCTS
Sunscreen products designed for “sunbathing” are less concerned with duration
and even waterproofing in many cases. The users of these products are more
interested in relaxing in the sun and are usually intent on tanning, although
there are a number of these types of products that offer a higher SPF reflecting
the consumers desire to protect their skin while sunbathing. There is a general
belief among some sunbathers that oils and a shiny appearance attract the sun
532 SaNogueira
and help to facilitate tanning. Others simply enjoy the look, feel, and fragrance as
they relax and bask in the sun.
The predominant form of these products is tanning oils, which includes
“dry oils” and tanning sprays. Tanning gels, butters, and lotions are also
common forms used to deliver a combination of UV protection, shiny appear-
ance, and tropical fragrance.
Spray forms in various configurations have become more popular, with
both lotions and alcohol-based formulas being delivered in a mist from a
number of packaging options such as finger pumps, trigger sprays, and bladder
sprays. This form provided the benefit of fast and easy application for consumers
and in some cases could allow application without rubbing the product in.
A number of new products have been launched into the sports segment
offering benefits of fast drying formulas that tend to be dryer in feel and have
less of a tendency to leave skin feeling oily or slippery.
Fast Drying Sunscreen Gel

This oil-free quick drying SPF 23 sunblock formula demonstrates a product
designed to evaporate quickly leaving behind an effective water and sweat resist-
ant layer of sunscreen. The fast drying and relatively nongreasy skin feel is par-
ticularly attractive for use in sport applications.
This formula demonstrates an alcohol-based sunscreen that dries quickly.
The amount of alcohol can be increased to give a drier feel. The octocrylene
in the formula not only provides UV protection, but also helps to photostabilize
the octinoxate and aids waterproofing due to its affinity for skin.
Phase A
Sodium polyacrylate (Rapthix TM A-100) 1.00
Phase B
Ocitnoxate 7.50
Oxybenzone 4.00
Octisalate 5.00
Octocrylene 7.00
Phase C
Alcohol 20.00
Butylated PVP (Ganex R P-904LC) 0.10
Source: Formula courtesy of ISP.
ADDITIONAL CONSIDERATIONS
Patents
Those who formulate sunscreen products will find that the patent art presents dif-
ficult challenges as they construct their products. Published patent applications
also present problems during the course of product development. Therefore, it is

necessary for the formulator not only to be an expert in product design, but also to
be conversant in the patent art and, importantly, the prior art that may help them
to add perspective to the relevance or importance of published patents and appli-
cations. Unfortunately, some patents have become more about business strategy
and less about true discovery and science. Nonetheless, there are important
patents in the sunscreen area, that deal with photostabilization. In particular,
the use of naphthalates, maleates, and glycoside dioleate esters are among the
more recent patents issued. Other important patents include the use of coatings
to increase the compatibility of inorganic sunscreens with avobenzone, thereby
preventing degradation or crystallization of the organic sunscreen.
Photostability
Photostability is an important concern for recreational sunscreens and other pro-
ducts that have an SPF. This concern has been slower to develop in the USA than
in Europe where photostability has become a market claim as well as a scientific
issue. Achievement of efficient formulas and high levels of UV-A protection
require the formulator to take photostability into account in the product design.
This issue may in some ways have a greater impact on recreational sunscreens
because of the duration of sun exposure vs. incidental or intermittent
UV exposure for other products. The chemistry of sunscreen photostability is
well covered elsewhere in this book, but deserves mention here as an important
and emerging issue.
CONCLUSIONS
Recreational sunscreens are a diverse category of products that offer robust UV
protection as the primary benefit under a variety of consumer habits and practices
and use conditions. Water and sweat resistance, resistance to rub-off, and dur-
ation and amount of UV energy exposure are the primary areas of differences
between recreational and other types of sunscreens, both of which can and do
deliver a multitude of other skin care benefits.
REFERENCES
1. Giacomoni PU. Sun protection: historical perspective. In: Shaath NA, ed. Sunscreens:
2005:71– 81.
2. AC Neilsen Scantrak data, supplied by Playtex Products, Inc.
3. Stewart, E. US Patent 6,197,281, Amon-Re.
4. Degussa/Goldschmidt AG, Happi, March 2003:22.
5. Rerek M. SCC Meeting, Proceedings, December 2001:27.
26
Daily Use Sunscreens
Peter J. Lentini
The Estee Lauder Companies, Melville, New York, USA
Introduction 535
Biology 536
Engineering 536
Marketing 537
History 538
Current Market 539
Conclusions 540
References 540
INTRODUCTION
For the majority of their history, sunscreen preparations were relegated to the
realm of overexposure, for those who spent an inordinate amount of time in
the sun, such as lifeguards, athletes, etc. Little or no consideration was given
to the average person, who can accumulate a tremendous amount of sun
damage through intermittent or incidental exposure. Sunscreens were the
product one took on vacation or to the beach. Rarely, except for those with hyper-
sensitivities, were they used on a daily or regular basis, until recently. Marketers
of skincare products have capitalized on the need for daily protection, and it is the
intent of the author to discuss the need, implications, engineering, marketing, and
positioning that goes behind this growing area of skin care.
535
536 Lentini
BIOLOGY
Numerous studies conducted over the past few decades indicate a strong corre-
lation between UV exposure and photoaging, accumulation of lines and wrinkles,
and various lesions and cancers. While large doses (long-term exposure) produce
the fastest deleterious effects, it has been purported that intermittent suberythmal
doses can elicit similar responses. English et al. (1) report on site specific exposure
to UV during childhood correlating to squamous cell carcinoma, more strongly
associate this form of UV-dependent carcinogenesis to historical exposure than
to adult exposure, and describe it as the more classic model of photodamage
(gross dose dependence). Koh (2), reporting on melanoma, another UV induced
carcinogenesis, and far more deadly and controversial, states that this particular
diseased skin state is far more dependent on intermittent exposure to the sun,
especially earlier in life, and more influential on long-term skin health than
simple cumulative exposure. Darlington et al. (3) report on yet another exposure
marker, solar keratoses, and conclude that this precancerous state is reduced by
about 25% with the introduction of a daily use (discretionary) sunscreen. What
this points to is a variety of exposure patterns resulting in sun damage. Classic
dose-dependent damage from UV may no longer be the primary modality.
Take into consideration something like driving to work every day. Walking
to and from your car, home, office, mall/shopping center, wherever, can lead to
something like a 12 h of “exposure” per day. Adding this up over the course of a
working year, assuming 50 weeks of work, one accrues about 125 h of UV
exposure. While this may not all be in direct sunlight at noon in Arizona, it
shows clearly how this intermittent/incidental exposure can add up and add up
quickly, and actually amounts to more than one would get on a typical Caribbean
vacation. Further to this, recent research from a variety of sources demonstrates
the insidious accumulated damage from suberythemal exposure. Ishitsuka et al.
(4) report a greater reduction in the number of viable Langerhans cells subjected
to intermittent suberythemal UV exposure than to a single high dose, and
researchers at The University of Pennsylvania School of Medicine found
similar results at 12 MED for a variety of markers, including Langerhans cells
reduction, stratum cornea thickening, dermal inflammatory infiltrates, and depo-
sition of lysozyme on elastin fibers, while a single large dose of UV did not elicit
these responses (5). The bottom line is that one will accumulate sun damage from
a variety of exposure modalities, both early and throughout adult life, and this
intermittent and incidental exposure may be as damaging as a sunburn.
ENGINEERING
Traditionally, one would apply a sun protection product to alleviate daily
exposure. Unfortunately, the form does not lend itself to daily use. Sun protection
products come primarily in two forms: beachwear and dailywear. An understand-
ing of the forms and their differences seems appropriate. Beachwear products are
Daily Use Sunscreens 537
generally higher-SPF products (domestically .15), wear and water resistant, and
provide little else aside from sun protection. They can be emulsions or anhydrous
products, and are generally “heavier” in feel than most other skin care products,
due to the sunscreen content and various emulsifiers and resins used to impart
stability and wear/water resistance. Some are intentionally made to be very
shiny in appearance on skin, to enhance the look of a sun-kissed body. They
may also contain large amounts of film-forming agents used to thicken the film
of sunscreens as the product dries on the skin, to increase path-length and the effi-
ciency of the screening system. The claims one can make on the said product are
restricted by the FDA, and refer specifically to verbage approved in the sunscreen
monograph (same as for daily wear). Base selection for daily wear thus becomes
a very important consideration, as it will dictate overall performance and product
acceptance, and ultimately, use compliance. Dailywear needs to be lightweight
by comparison to the beach product, and generally carries an SPF of 15 or
less. The lighter texture lends to layering, which is an important consideration
for dailywear, as one will have to accommodate items such as makeup on top
of the daily protection product if one is to expect use compliance. Furthermore,
the selection of the sunscreen system becomes very important. As opposed to
what one would do for a high-SPF beachwear product, where the SPF number
usually drives the development, safety and texture become primary consider-
ations, as it is well known in the literature that certain combinations of sunscreens
can cause adverse reactions and sensitivities (6). During the early 1990s, when the
popularity of dailywear facial sunscreen products rose, the first entries were basi-
cally beachwear modifications, and suffered from many of the weight- and shine-
related drawbacks described earlier. Over time, these early entries paid the price in
the marketplace, and were eventually replaced by more elegantly engineered pro-
ducts based on well-tolerated combinations of category items, such as micronized
TiO2 and octylmethoxycinnamate, in relatively lighter-textured bases. Both
category items benefit from wide consumer acceptance from an irritation and
allergy perspective, and depending on the base selection, can be quite transparent
and matte, so layering with makeup, for example, can be achieved with little or no
deleterious effects to the makeup wear or appearance. Furthermore, the consumer
receives the ever-important immediate gratification, that feeling of being moistur-
ized or smoothed to the touch, and will, most likely, continue to obtain the appro-
priate photoprotection on a regular basis because the product makes the
consumer’s skin feel and look “better”.
MARKETING
Translating this to a marketing opportunity requires the development of yet
another need, as prevention and protection are difficult concepts to market on
their own. As opposed to a beachwear product, where one is selling the preven-
tion of sunburn, dailywear, from a sun protection perspective, sells better skin
health 10– 20 years down the road. As such, there remains a strong possibility
538 Lentini
of noncompliance, and one needs to “hook” the consumer to the product in order
to gain the purported long-term benefit (Table 26.1). By positioning the product
as a moisturizer used every day, for example, that happens to provide SPF 15 pro-
tection, one can depend more on the likelihood of compliance to daily appli-
cation. Marketers have covered a wide range of “needs” for daily use,
inclusive of, but not limited to, moisturization, antioxidant protection, vita-
mins/minerals, humectancy, myriad botanical extracts, and essential lipids.
These daily requirements are positioned almost as a daily dietary supplement
for the skin and the more successful entries truly hone in on these needs, and
the protection seems almost ancillary.
HISTORY
A historical perspective seems appropriate here. The prestige entries of the early
to mid 1990s encompass the most appropriate examples of this positioning. Three
particular entries come to mind. Clinique’s City Block, Estee Lauder’s Daywear,
and Lancôme’s Bienfait Total. All three entries appeared in the early to mid
1990s, and were reasonably successful sellers for their marketers. The first
two entries actually grew to become branded franchises within their lines, an
indication of their continued success.
City Block Oil-Free Daily Face Protector SPF-13 debuted in the spring of
1991 featuring UV-A and UV-B protection, no “chemical” sunscreens, and no
fragrance. Targeting city dwellers, this fairly lightweight inorganic susncreening
system provided a matte finish and good compatibility with makeup. According
to the manufacturer, “even in the city, most days allow for a little sun on your
face” (7). Backed by the dermatological support mentioned earlier, the consumer
Table 26.1 Beachwear vs. Dailywear: General Trends
Beachwear Dailywear
Sunscreening system Multiple screens, high One to two materials only;

percentage; organic with organic/inorganic hybrid
filmogens
Product form Heavy lotion, cream, or Light oil-in-water emulsion
anhydrous spray/gel
Emulsifier type/content Soap or high HLB nonionic Gentler, polymeric or
biomimetic
Ancillary items Humectants, high-fragrance Moisturizers, antioxidants;
load, shine-enhancing lipids, treatment items,
esters optics for matte finish
Claims Protection and prevention Myriad positioning, but
with an eye toward the
FDA monograph verbage
Note: HLB is hydrophilic –lipophilic balance.

Daily Use Sunscreens 539
was hooked into daily use by the sheerness of the formula, and the linkage of
daily exposure to UV and premature wrinkling. This is more the exception
than the rule so far as positioning is concerned, although even here, the SPF
claim was sublined. Bienfait Total debuted to mixed reviews in the spring of
1994, including an investigation of claims by the National Advertising Board
of the Better Business Bureau. The product faired well in support of the “physico-
conversion” of a glyceryl phosphate into a moisturizing entity by the skin’s
own enzymatic processes, and the product sold well, especially in the EEC.
Once again, the protection of SPF 15 was secondary to the alpha-hydroxy acid
claims of smoother skin, moisturization benefits, and “total well-being” (8).
Finally, in the spring of 1995, Lauder introduced Daywear Super Antioxi-
dant Complex, “a cucumber-scented, protective morning moisturizer for skin
showing premature signs of aging caused by indoor and outdoor pollution” (9),
with little or no mention of the SPF 15 protection afforded by the formula. The
antioxidant cocktail featured in the formula addressed a number of consumer con-
cerns, including radical scavenging, traditional vitamins, and state-of-the-art
delivery of ingredients. Lauder’s marketers hailed this product as “a one-step
environmental plan” for skin care (10). While the protection was subverted in
positioning for many years, the introduction of a retinol repair product in the
late 1990s by Lauder allowed for the product’s repositioning and reintroduction
as a powerful UV protector for those needing it when using retinoid therapies.
The product line continues to sell very well at the time of publication.
CURRENT MARKET
A recent review of skin care introductions, both domestically and internationally,
shows an increase in the number of skin care products providing UV protection.
Looking at two mass marketers, P&G (Olay) and Biersdorf (Nivea), one of every
two moisturizers they offer for facial care carries UV protection. Similar trends
are seen among the prestige marketers as well, running about one out of four
facial moisturizer entries providing protection (11). Both marketers have cap-
tured the essence of daily-use protection in creating a need for application. In
the case of the Nivea Visage entries, the “need” is for CoQ10, an antioxidant
requiring application on a daily basis to be effective. The sunscreening systems
rely heavily on octyl methoxycinnamate and the oxides of Zn and Ti, a
“hybrid” system maximizing transparency, efficiency, and safety at the SPF 15
level. The emulsion systems used in these products are polymeric in nature,
similar in approach to that of the prestige marketers, conveying inherent safety
in a daily-use setting via the stratification of the sunscreening agents on the
surface of the skin, significantly reducing the likelihood of penetration and a neuro-
sensory event or allergic reaction. The more successful entries will follow this
prescription: surface-attenuated sunscreens (particles or otherwise), light skin
feel with a matte finish, and a daily need/requirement in the form of a botanical
extract or nutrient, to ensure daily application.
540 Lentini
CONCLUSIONS
While the form has been around for over a decade, the daily-use sunscreen
remains an underutilized product form. While all indications are that this cat-
egory continues to grow in volume (12,13), the message seems to fall on some
deaf ears. The Sun Safety Alliance reported earlier this year that skin cancer con-
tinues to rise at a rate of over 6% per year. They have, however, pushed through
legislation in several states, including California, providing funding for sun edu-
cation, targeting school children, and providing at least a baseline education in
sun protection. The Alliance has also provided for children to self-apply sunsc-
reen during the school day without the need for a physician’s note or prescription
(14). Hopefully, the education and application will change habits and signifi-
cantly reduce the childhood exposure so closely related to the more serious inter-
mittent-or-casual-exposure-related diseases, and the next generation of sun
worshippers will grow up healthier and more aware of the potential damage
caused by this mode of exposure.
REFERENCES
1. English DR, Armstrong BK, et al. Case-control study of sun exposure and squamous
cell carcinoma of the skin. Int J Cancer 1998; 77:347 – 353.
2. Koh HK. Cutaneous melanoma. New Engl J Med 1991; 325(3):171 –182.
3. Darlington S, et al. A randomized controlled trial to assess sunscreen application and
beta carotene supplementation in the prevention of solar keratoses. Arch Dermatol
2003; 139:451 – 455.
4. Ishitsuka Y, et al. Repeated irradiation with suberythemal UVB reduces the number of
epidermal Langerhans cells. Arch Dermatol Res 2003; 295(4):155– 159.
5. Lavker RM, et al. Cumulative effects from repeated exposures to suberythmal doses of
UVR in human skin. J Am Acad Dermatol 1995; 32(1):53 –62.
6. Foley P, et al. The frequency of reactions to sunscreens: results of a longitudinal
population-based study on the regular use of sunscreens in Australia. Br J Dermatol
1993; 128(5):512– 518.
7. Clinique City Block Oil-Free Daily Face Protector—SPF-13. Product Alert, June 24,
1991. Marketing Intelligence Service, 1991.
8. Lancome Bienfait Total claims substantiated, NAD concludes. The Rose Sheet, Jan
16, 1995; 16(3).
9. Lauder attracts moisture. Soap, Perfumery & Cosmetics, Oct 1995; 68(10):12.
10. Lauder’s DayWear: health food for skin. Women’s Wear Daily, May 26, 1995:4.
11. New Coalition Launches Crusade against Skin Cancer Caused by Sun Exposure.
New York: PR Newswire, Apr 22, 2003.
12. The sun’s out: what’s driving the suncare category. Beauty Fashion, May 2003:33.
Kline and Company.
13. Halliday S. New technology: when skincare met suncare. World Global Style
Network, Apr 4, 2003.
14. Mathews I, Marcoulet N. Suncare trends review. Int Cosmet News 2003:37.
27
Valuable Properties for Baby
and Kids Segments
Dennis L. Lott, Kelly Lewellen, and Glenn Wiener

Tanning Research Laboratories, Inc., Ormond Beach, Florida, USA
Introduction 542
Review of Baby Segment 543
Review of Kids Segment 544
Sunscreen Actives 545
Zinc Oxide 546
Octinoxate 546
Homosalate 546
Octisalate 546
Oxybenzone 546
Octocrylene 546
Avobenzone 546
Baby Product Specific Strategies 547
Selection of Sunscreens/Carrier System 547
Sunscreen Optimization 548
Barrier Function Protection 549
Kids Product Specific Strategies 551
Formulation Types 552
Emulsions 552
Sticks 553
541
542 Lott, Lewellen, and Wiener
Lip Balms 553

Alcohol Sprays 553
Testing 554
SPF and Water Resistance 554
Migration 554
Hypoallergenicity 554
Moisturization 555
Photostability 555
Conclusions 555
References 555
INTRODUCTION
It has been shown that sun damage sustained early in life is a precursor to skin
damage later in life. Specifically, recent studies revealed that severe sunburn
before age 18 is a positive risk factor in developing melanoma (1,2). Addition-
ally, it has been noted that almost 80% of total lifetime exposure is obtained
by 18 years of age (3). Due to the great importance of sun protection during
these early years, this chapter will address the characteristics of Baby and Kids
segment products.
Several organizations have Baby and Kid specific programs to educate and
promote UV protection. Use of sunscreens as well as sun avoidance and proper
clothing are integral parts of these programs. A quick review of some of the
organizations follows:
. The Cancer Council Victoria was one of the leaders in developing pro-
grams to encourage UV protection for children. In 1980 a cartooned
seagull singing “Slip! Slap! Slop!” helped spread the message of the
importance of UV protection to the young people of Australia. The
name SunSmart was adopted by the program in 1988. The program is
credited with slowing down the rate of skin cancer for Australians (4).
. The US Department of Health and Human Service’s Center for Disease
Control and Prevention developed Guidelines for School Programs to
Prevent Skin Cancer (5).
. The Skin Cancer Foundation has a “Children’s Sun Protection
Program” that reaches out to schools, camps, and day care centers
throughout the USA (6).
The overall US mass sun care market is estimated at about $600 million in factory
sales to traditional food, drug, and discount stores. At retail, sun care items are
often grouped together by segments, not brands. The Baby and Kids segments
are part of the overall sun care category, and represent the only segments
Valuable Properties for Baby and Kids Segments 543
within the category based on age. Sun care is typically divided into 12 segments
as follows:
Tanning: These are low SPFs, 4 and below. There are items in this category
that have no protective sunscreens that are referred to as “0 SPF” (the
correct terminology should be “1 SPF”).
Indoor: Products designed for tanning bed parlors or home tanning bed use.
They are usually limited to moisturizers and products containing “accel-
erators” such as riboflavin or tyrosine.
Sunless: These are products containing artificial tanning agents and/or
bronzers. Typically, dihydroxyacetone and caramel are the ingredients
of choice.
Protection: SPF products of 15 and higher. The higher-SPF products
appear to be growing faster.
Sun lip care: Lip balms with sunscreen, almost all are SPF 15 or higher.
Sport: Products designed for active users. Almost all are SPF 15 or higher,
and are characterized by light texture and nongreasy feel.
Baby: High-protection products with SPFs of 30 or higher. They almost
always have a “Baby” type fragrance.
Kids: High-protection products with SPFs of 30 or higher, with additional
claims that address the active lifestyle of children.
Skin: This segment includes “oil free” and “faces” type products.
Moderate: SPF 5– 14 products. While this segment provides some protec-
tion, the consumer’s goal is probably tanning.
After sun: Products that do not offer any SPF and are sold in the sun care
section specifically for after sun exposure use. Moisturization is a key
attribute.
Burn relief: May or may not contain actives from other monographs.
Actives might include materials such as lidocaine or camphor, both of
which are listed in the External Analgesic Drug Products for Over-
The-Counter Human Use Monograph (7). Aloe type gels are very
popular in this category.
Table 27.1 illustrates the approximate percent product sold by segment. The data
are an estimate for all outlets based on data supplied by permission from
A.C. Nielsen.
REVIEW OF BABY SEGMENT

The Baby segment was born in 1986 with the launch of Tanning Research Labs,
Inc., Hawaiian Tropicw Baby Faces and Tender Places product. It was the first
sun care product to break the 15 SPF barrier with an SPF of 22. In the following
year, the Baby segment was in the forefront again when Schering-Plough, Inc.
broke another barrier with the introduction of Coppertone Water Babiesw, a
product line designed specifically for babies that carried an 80 min waterproof
Table 27.1 Approximate Percent Product Sold

by Segment
Approximate percentage
Segment of market
Indoor 2 –2.5
Sunless 15–20
Protection 18–22
Sun lip care 1 –2
Sport 10–15
Baby 5 –8
Kids 5 –8
Skin 9 –13
Tanning 12–15
Moderate 3 –6
After sun 1 –3
Burn relief 6 –8
claim. In August 2003, the US baby sun care segment exceeded 7% of the total
sun care category in dollar sales according to A.C. Nielsen.
Today the Baby segment is dominated by a handful of products. There are
approximately 10 products that account for 80% of the sales in this segment. Over
95% of the sales come from products made by Schering Plough’s Coppertonew,
Playtex’s Banana Boatw, Tanning Research’s Hawaiian Tropicw, and various
Private Label brands. Generally speaking, Baby products focus on the age
group from 6 months up to 6 years. The sunscreen monograph (8) mandates
that products carry a warning stating that sun care products are not intended
for infants under 6 months of age without physician advice. Common product
attributes within the Baby segment are
Fragrance: It is a characteristic baby powder type.
SPF: Baby products are SPF 30 and above.
Packaging: Typically pink.
REVIEW OF KIDS SEGMENT

Introduction of a Kid’s segment was a natural progression after the success of
the Baby segment. In 1994 the first Kids products were introduced under the
Coppertonew Brand. While there is no set age range for the Kids segment, it
normally encompasses children up to 10 or 11 years of age. A review of the Kids
segment reveals differences and commonalities when compared with the Baby
segment. Unlike the Baby segment, the Kids segment is not dominated by as
small a number of products; approximately 15 products account for 80% of
sales. Over 92% of the sales come from products made by Schering Plough’s
Coppertonew, Playtex’s Banana Boatw, Tanning Research’s Hawaiian Tropicw,

and various Private Label brands. Additionally, the product mix is varied with
no one fragrance type that dominates this segment. Products range from non-
fragranced, to fruity, to indistinguishable from the main stream product line.
Product appearance ranges from colored, to disappearing color to indicate coverage,
to glittered, to plain white lotion. Product claims are perhaps more extensive in
this segment than any other, due to the nature of the end user, children. Claims
go from expounding on being gentle to being durable and therein lies difficulty
for the sun care chemist. Probably, the area with the most variety is the packa-
ging. The Kids segment encompasses all package forms and the artwork is defi-
nitely not sedate. There is one consistent theme throughout the Kids as in the
Baby segment, high SPFs. A majority of the products offered are SPF 30 and
above. According to A.C. Nielsen, the kids segment represented over 6% of
the US suncare market in dollar sales as of early August 2003.
SUNSCREEN ACTIVES
Sunscreen products in the USA are regulated as drugs. Presently, the current
regulation is the 1999 Final Monograph (8). The active ingredient list is a
relatively short one and those commonly found in Baby and Kids products are
even fewer. Before formulation work begins the ingredients should be reviewed
keeping the formulation type and what is to be accomplished in mind, and being
cognizant that the monograph does not allow all combinations. The following is a
list and brief description of actives that are routinely found in Baby and Kids
products.
Titanium Dioxide
This is a particulate mineral sunscreen that is primarily a physical block but also
performs as an absorber. The material blocks both in the UV-B and in the UV-A
range, but is usually referred to as a UV-A blocker. However, due to the cosmetic
disadvantage that at high concentrations it can produce opaque whitening
products, it is frequently supplied as very small nano particulates. Once it has
been reduced to this size, the material performs primarily as a UV-B sunscreen.
Nano particles have recently come under a great deal of criticism as being envir-
onmentally unacceptable (9). Also, it is believed that titanium dioxide serves as a
semiconductor on the skin and can catalyze photolability in organic sunscreens
(10,11). Titanium dioxide is reported to induce photooxidation of lipids (12).
Unlike organic sunscreen actives, incorporation of titanium dioxide requires
the formulator to consider particulate surface properties to ensure system com-
patibility and efficacy. Fortunately, advances in surface treatments allow
titanium dioxide’s obstacles to be effectively addressed and overcome. Inorganic
treatments such as aluminum hydroxide are capable of controlling photocata-
lytic activity by capturing hydroxyl radicals and improving photostability by
preventing the reduction of Ti(IV) to Ti(III) (13). Numerous other treatments,

both inorganic as well as organic, are commercially available today.
Zinc Oxide
Another particulate sunscreen, zinc oxide, is also an approved skin protectant
active as well as a sunscreen active. However when used as a sunscreen, many
of the same observations as those for titanium dioxide are appropriate with the
exception that it is a more recognized UV-A protectant.
Octinoxate
This is a powerful UV-B sunscreen that also shows absorbance in the short-
wavelength UV-A region. It is easy to formulate with as it is a good solvent.
The problem with octinoxate is its photolability, especially in conjunction with
avobenzone.
Homosalate
Homosalate is a relatively weak sunscreen that has a narrow UV-B absorption
band. Commercially available homosalate has two isomers. Homosalate is not
difficult to formulate with.
Octisalate
The same observations as for homosalate although cis/trans isomerism is not
possible. It is recognized as a solubilizer for the solid sunscreens avobenzone
and oxybenzone.
Oxybenzone
This sunscreen is a UV-B and short-wavelength UV-A screen. It is a good
sunscreen to use in combination with other actives. It has been reported to
cause irritation, but this is more likely the case of not being properly formulated.
Oxybenzone is relatively difficult to solubilize. Many products on the market start
out with oxybenzone in a saturated solution in the emulsion’s oil phase. As the
product ages the oxybenzone falls out of the solution resulting in gritty, needle-
like crystals. These crystals can not only be irritating, but may cause the
product to be subpotent. Oxybenzone is very photostable in most formulations.
Octocrylene
A strong UV-B sunscreen with a relatively broad absorbance band. It is a good
sunscreen to use in combinations and is photostable.
Avobenzone
This is a long-wavelength UV-A absorber. It is used in combination with UV-B
absorbers to provide broad-spectrum products. It is not a photostable sunscreen
in many formulations. The formulator must be very careful when using this
ingredient. It probably should not be used with octinoxate, and the preservative
system is critical.
BABY PRODUCT SPECIFIC STRATEGIES

When formulating a product for the Baby segment, sun care chemists must take
into consideration important factors in order to satisfy both parent and baby.
Baby skin has a higher moisture content than an adult’s skin, which is ordinarily
thought of in a positive manner. However, due to baby skin being thinner and the
stratum corneum having a looser structure when compared to typical adult skin,
baby skin barrier function is weaker. A weak barrier function could promote high
transepidermal water loss and greater exposure to external stimuli (14). The good
elements are not readily locked in and the bad elements are not readily locked out.
To accommodate for these differences, Baby products should therefore possess
the following properties:
. Must deliver a high SPF, capable of absorbing a large amount of
UV-A/UV-B irradiation.
. Must be gentle to the underdeveloped baby skin, minimizing risk of
irritation and sensitization.
. Must minimize levels of any defatting surfactants which can further
weaken barrier function.
. Must possess a high level of occlusivity to reduce entrance of external
elements and escape of internal moisture.
. Must be highly moisturizing to continually hydrate skin.
Products formulated to properly fit (both physically as well as functionally) into
the aforementioned pink bottles are nearly all emulsions. Emulsions give the sun
care chemist the opportunity to effectively deliver a combination of lipophilic
and hydrophilic ingredients to baby skin. If formulated correctly, these emulsions
can possess most, if not all of the properties listed above. To translate successful
completion of these tasks, Baby product marketers present their products with
claims including hypoallergenecity, nonstinging, nonirritating, fragrance free,
PABA free, waterproof, nonmigrating, and pediatrician tested.
Selection of Sunscreens/Carrier System

To provide a high SPF with broad-spectrum protection, a combination of UV-A
and UV-B sunscreens should be formulated into the composition in such a
manner that all crystalline sunscreens avobenzone, oxybenzone, methylbenzyli-
dene camphor, and ethylhexyl triazone (methylbenzylidene camphor and
ethylhexyl triazone are not currently approved for use in the USA) are completely
and permanently dissolved. Recrystallization of one or more of these filters is
likely to result in a reduced absorbance profile, increased risk of emulsion

instability, undesirable product application, and aesthetics as well as a heightened
potential for irritation. Esters of salicylic acid (15) and cinnamic acid are good
solubilizers. Numerous other esters, ethers, alcohols, alkanes, and other classes
of compounds offer good solubilizing strength and should be considered based
on their compatibility with the system at hand. Perhaps some of the strongest
sunscreen solvents come from the amide and imide classes of compounds.
Highly polar dimethyl capramide and the eutectic mixture of butylphthalimide
and isopropylphthalimide are both capable of solubilizing large amounts of
crystalline sunscreens. However, levels should be kept at a minimum due to
the possibility of irritation associated with certain members of these respective
classes.
When formulating Baby sunscreens, one school of thought is to achieve
high SPF, broad-spectrum protection utilizing solely inorganic micronized
titanium dioxide or zinc oxide. A number of sunscreen marketers believe that
consumers associate irritation and eye stinging with Baby sun care products
formulated with one or more organic filters. High-SPF products have been
developed using inorganic filters, and numerous formulation challenges exist.
Methods and materials have been introduced to minimize whitening upon
application. Some may view this as a positive although the creative marketer
might look to the traditional whitening associated with particulate sunscreens
as a way to let Mom or Dad know that Baby does indeed have a thick, even
layer of lotion providing protection from UV induced damage. Other formulation
challenges include maintaining an even particulate dispersion in the finished
product, preventing the reaction of zinc with any free fatty acids, emulsion
separation, and preventing particulate photostability catalytic activity. Such
problems are appropriately addressed elsewhere and are beyond the scope of
this chapter.
Sunscreen Optimization
Baby skin, in its underdeveloped state, can be more prone to external irritants and
allergens. Formulating Baby sun care products requires minimizing of potential
irritants and allergens. Certain UV absorbers have the ability to cause contact
sensitization or photosensitization and therefore should be avoided or kept to a
minimum. This presents a challenge—Moms and Dads want higher-SPF products
to protect their baby, but traditionally to achieve a high SPF, high levels of UV
absorbers have been necessary. This rationale should be dismissed and con-
sidered old fashioned. To achieve high-SPF Baby products, formulators must
seek ways to increase SPF, utilizing carefully thought out and unique methods.
Absorbance curves for individual as well as blends of UV absorbers should
provide insight to help in optimizing a sunscreen blend, resulting in a high-
SPF, low-sunscreen-level product. The days of increasing every sunscreen in a
particular system in an attempt to raise SPF are over. Using the Beer – Lambert
relationship (16) (Eq. 27.1) in conjunction with sunscreen absorbance curves as

well as the erythemal action and appropriate solar spectra, it can easily be shown
that dilute sunscreen solutions are ideally capable of providing extremely high
SPF values.
AM
1¼ (27:1)
bc
In this equation, 1 is the molar absorptivity, A is the absorption of radiant energy,
b is the cell width, c is the concentration of the solute, and M is the molecular
weight of the solute. Unfortunately, applying a sunscreen emulsion to human
skin, irradiating it, and evaluating its ability to prevent an erythemal response is
not necessarily closely mimicked by shooting a UV beam through a quartz
cuvette and measuring how much and which parts of this beam are being absorbed
by the contents inside the cuvette. Formulating techniques are quickly improving,
but there still remains a large gap between the maximum UV absorbance and the
maximum attainable SPF. Properties including emulsion quality, evenness of
application, film formation, film uniformity, product migration, continued solubil-
ization of sunscreens, polarity of oil phase, and others dictate how well a sunscreen
chemist can succeed in optimizing a sunscreen’s effectiveness at absorbing UV
energy. Ratios of SPF to total UV absorber have gone up from less than 1 : 1 in
the past years to much higher values at present. A traditional SPF 40 may
contain as much as 35% sunscreen, thus about a 1 : 1 ratio. Products with ratios
of 4 : 1, and perhaps even higher, exist today. The unpublished Tanning Research
Laboratories, Inc., data shown in Fig. 27.1 indicate the expected SPF of an 8%
homosalate emulsion and a 15% homosalate emulsion when measured with an
Optometrics SPF290w monochromatic device and calculated using the 408 stan-
dard sun spectra. Increasing homosalate from 8% to 15% hardly changed the
expected SPF. Note that this SPF to percent sunscreen ratio is about 1 : 1.5 for
the 8% homosalate formula and 1 : 2.5 for the 15% formula. Thus, merely increas-
ing the sunscreen concentration is not always the answer.
Particulates can be helpful in boosting SPFs. Particulates bend photons,
increasing their path-length, and by the Beer – Lambert relationship, the absor-
bance of radiation (17). Other potentially irritating or sensitizing ingredients
such as fragrance, preservatives, and emulsifiers should also be carefully selected
and used at low, yet effective, levels.
Barrier Function Protection

Children and adults alike rely on relatively high levels of sebum to help control
homeostasis. Baby skin does not produce nearly as much sebum, which results in
inferior homeostasis. Transepidermal water loss is increased and potentially
harmful xenobiotics are not repelled as readily. Adding a defatting surfactant
to a Baby protection product will further weaken homeostasis. Anionic surfac-
tants, in particular the alkylaryl sulfonates, alkyl sulfonates, alkyl sulfates, and
1.5
8% Homosalate
15% Homosalate
1
absorbance
SPF ~ 6
0.5
SPF ~ 5
0
290 300 310 320 330 340 350 360 370 380 390 400
wavelength (nm)
Figure 27.1 Tanning Research Laboratories, Inc. data showing the expected SPF of an
8% and a 15% homosalate emulsion.
alkyl ether sulfates, are known to strip fats from skin (18). These groups of sur-
factants should be avoided entirely, as they not only defat but also can be irritat-
ing and sensitizing. Baby skin should not be subjected to defatting ingredients,
and taking this thought one step further, adding an occlusive agent will externally
strengthen homeostatic function. After a parent bathes their infant, they are sure
to coat them from head to toe with a highly occlusive lotion. Applying a protec-
tive sunscreen to their infant should provide the same occlusivity. Many such
occlusive agents exist, such as dimethicone and petrolatum. Occlusive agents
should be carefully chosen to minimize risk of irritation and sensitization.
Hydration of human skin, whether it be adult skin, child skin, or baby skin,
is an attribute that all sun care products should carry. Although the rationale
behind this statement changes from one category to the next, sun exposure,
whether accompanied by some level of outdoor activity or not, continually stres-
ses our skin. Both heat and saltwater are claimed to raise levels of transepidermal
water loss. Therefore, babies brought outside into the sunlight should always
have exposed areas treated with a moisturizing lotion. Technology in the
field of moisturization has blossomed and as a result, many highly effective
moisturizers, utilizing different modes of action, are available for use. For
example, occlusive agents, such as those previously mentioned, or humectants,
such as glycerine or sorbitol, can be used.
KIDS PRODUCT SPECIFIC STRATEGIES

Although no age limitations exist for this product segment, it is generally thought to
include the years from when an infant becomes active up to preteen status. Market-
ing strategists must address the wants and needs of two divergent consumers:
parents and children. Moms and dads will be influenced by gentleness, durability,
and convenience. Kids want fun and minimal intrusion on their life. Successful
products in this market have found unique ways to appeal to both groups.
Products are developed to meet a consumer demand. Unfortunately, one of
the ways marketers become cognizant of a demand is through consumer com-
plaints. One of the most common complaints coming from parents is eye stinging,
resulting from a sun care product migrating into the child’s eyes. It is not possible
to formulate products that do not sting if physical eye contact is made. Sunscreens
and necessary inactive ingredients will result in transient stinging and eye
watering if the product gets into eyes. Therefore the goal must be to produce
Baby formulations and especially formulations for more active Kids that resist
migration when used on the face.
Formulations must be rugged. One only has to make a trip to the beach and
observe children to understand how durable formulations must be. Kids are
usually very active, constantly in and out of the water with frequent toweling,
and generally playing in such a manner that could physically rub the product
off. Their activity also makes it difficult for moms to corral long enough to
apply sunscreen. Therefore, the product should be designed such that with
even one application, a child is protected for long periods of time under
extreme conditions. This means the product should be very water resistant
(this is the highest claim allowable by the proposed monograph, based on
80 min of water immersion, although even longer periods of water resistance
would be advantageous). The product should be nonmigratory. Kids at play,
especially in and around water, are more than likely not going to be wearing
head covers. Therefore, product must be applied to the face, around the eyes.
A product that does not stay where applied will cause eye stinging and increased
resistance by the child to further sunscreen use. The product must have rub resist-
ance. Kids will be on the ground, playing with toys and on playground equipment
and frequently toweling, making rub resistance very advantageous. The product
must be photostable. Sunscreens that lose their UV absorption characteristics in
the sun simply do not measure up to the standards necessary for this segment.
Adding to the dilemma for the formulators designing products for this
segment is the consumer’s desire for convenience. Many Kids segment leaders
are sprays. It appears that many moms and dads purchase sprays for ease of
application. This complicates the formulator’s life in that sprays must be of a
lower viscosity or more highly shear thinning than bottle or tube products to prop-
erly dispense from sprayers. Thus, the same characteristics that make for a good
functional product on the skin, waterproofing, nonmigration, rub resistance, etc.,
are somewhat contradictory to a light sprayable product.
Summarizing, the following are the characteristics of a good Kids product:
High SPFs
Very water resistant
Nonmigrating
Rub resistant
Photostable
FORMULATION TYPES
As was discussed previously, characteristics of products designed for the Baby
and Kids segments, such as high SPFs and good durability based on water resist-
ance and nonmigration, drive the types of formulations that are most suitable for
these segments. For example, oils cannot be used due to SPF limitations. The
writers have no knowledge of oils having SPFs higher than about 15. Aqueous
gels and aqueous spray gels are limited in that the water soluble sunscreens
available to the chemist limit the SPF to about 15 and prevent the formulations
from being waterproof. Therefore, the most common formulation types for these
segments are as follows.
Emulsions
Emulsions are by far the most common vehicle for not only the Baby and Kids
segments, but also for many other segments as well, especially protection seg-
ments. Emulsions are generally the most cosmetically elegant formula types
with widespread consumer acceptance. They are generally water in oil or oil in
water (the most common) types. Some mixed emulsion systems may also be
found. Regardless, they share a common trait in that they contain an oil phase
that delivers the active and “waterproofing” characteristics of the formula. The
emulsion format can be found in a wide variety of package forms: bottles,
sprays, tubes, and a variety of containers with dispensing pumps.
Since the emulsions can be so varied in form yet perform the necessary func-
tions needed in these segments, they present the greatest challenges for the formu-
lator. An emulsion paradoxically has several contradictions that must be solved:
1. An emulsion by definition is a mixture of oils and water—two sub-
stances that do not readily mix together and certainly do not easily
stay together in a homogenous mix to produce an elegant product.
2. An emulsion in the Baby and Kids segments must be waterproof. This
is somewhat strange since most of these emulsions will contain more
than 50% water.
3. Most common bacteria thrive in water and require it to live and grow.
Emulsions contain water. Not only can the products not have bacteria,
they must also not allow bacteria to grow after contact with air, human
touch, etc.
All of these contradictions provide challenges. The formulator is sometimes
additionally challenged by any further desired product characteristics. It is not
unusual for marketers to demand very specific fragrance, viscosity, and feel
characteristics. None of the other product types discussed later offer as many
challenges.
Sticks
Sticks are becoming more and more popular especially in the two subject seg-
ments discussed herein. This formula type is characterized by its wax-like struc-
ture and repel type package. The package size is almost always small, usually less
than 0.5 oz. The product is generally used for small specific areas such as nose
and ears. The main reason for the popularity is the ease of use that does not
necessitate hand contact with the product. Since the entire formula is oleaginous
it does not have many of the challenges presented by emulsion bases.
Lip Balms
Lip balms are very similar to sticks in form and function except they are specifi-
cally designed for the lips. The predominant difference is that they should contain
a “flavor” that is allowable for internal use rather than a “fragrance” designed for
topical use.
Alcohol Sprays
Alcohol sprays enjoy limited success in the category even though they are actu-
ally a very good dosage form for the Kids category. There is some resistance from
parents to the use of a product containing alcohol, but the product type has some
distinct advantages. Other than sticks and lip balms, it is probably the only for-
mulation type that can be dispensed directly and not require further hand appli-
cation to obtain a uniform coverage. It dries very quickly. It can be applied
uniformly over skin that is not clean. For example, children on the beach need
frequent reapplication of sunscreen. This can be difficult when rubbing is
required due to the inevitable sand and salt adherence to the skin. The disadvan-
tages associated with this formulation type are somewhat obvious: alcohol will
burn abraded skin, it is drying, and it is flammable.
Formulation challenges are generally easier for alcohol bases due to good
ingredient solubility in alcohol.
TESTING
One of the biggest development hurdles is how to evaluate formulas to determine
if they meet the attributes desired. Brief descriptions of many of the formal tests
are listed in the proceeding section, but it is up to the sun care chemist to develop
“in-the-lab” means to evaluate formula attributes quickly.
SPF and Water Resistance

SPF value is the UV energy, supplied by a solar simulator, usually a xenon arc
filtered with WG320, UG11, and dichroic mirrors, required to produce an
MED on protected skin divided by the UV energy required to produce an
MED on unprotected skin. This test is performed on Skin Types I, II, and III
test subjects (highly sensitive, very sensitive, and sensitive to sun). In the USA,
the labeled value is based on the average of a 20-subject test panel, adjusted
down to a 95% confidence interval. A water resistant or very water resistant
value is an SPF test that also includes a 40 and 80 min water immersion, respect-
ively, before exposure to the solar simulation radiation. Some products are
labeled with extended waterproof claims. These are substantiated by even
longer water immersions prior to irradiation. These extended waterproof
claims are beneficial to Kids, but extended waterproofing is not expected to be
allowed after adoption of a final sunscreen monograph.
Migration
There is no standardized test for migration, although this test has value. One of
the predominant complaint from moms concerning Kids and Baby products is
eye stinging. Sunscreen products will not cause eye damage, but will sting.
Therefore, the only recourse is to prevent the product from migrating into the
eyes. A migration test should measure the movement potential of a topically
applied product under high heat and humidity conditions that would lead to
perspiring.
A typical test protocol would be similar to the following. Test product and
two controls (a known migrating product and a known nonmigrating product) are
applied to circular delineated test sites on a test subject’s back. Under UV black
light, test sites are measured and recorded. The test subject is then placed in an
environmentally controlled room, with temperature at 100 + 28F and relative
humidity 30 –40%, to induce sweating. After 80 min of sweating, the test sites
are measured again under UV black light conditions. Test products that move
less than 10% will be considered nonmigrating and will be able to support a
nonmigrating claim.
Hypoallergenicity
Hypoallergenic tests are recommended for all Baby and Kids products. This
test measures the irritation and sensitization potential of products. Usually,
a 100-subject test panel is used in a two-part test. Briefly, the test includes occlu-
sive, semiocclusive, or open patches that are applied three times a week for 3
weeks on a subject and remain for 24 h after each application. A reaction indi-
cates that the product is probably an irritant. After a 7– 14 day rest period,
patches are reapplied on an untreated area for 24 h. The treated sites are observed
at 24 and 48 h posttreatment. A reaction indicates that the product is a sensitizer.
Moisturization
Moisturization is a popular claim for products in the Baby and Kids segment as
well as in most segments. This claim is usually validated by comparing treated
skin to untreated skin and a control treated area. Measurements are made with
an instrument such as a Corneometerw sold by Courage þ Khazaka, Cologne,
Germany. The product is said to be moisturizing if the treated site displays
higher moisture levels than untreated skin.
Photostability
Photostability is a subject that has received a great deal of attention, especially in
regard to the UV-A filter avobenzone. Other sunscreens also exhibit photolabil-
ity. Although there is no standardized method for measuring photostability, it is
extremely important that sunscreen products are photostable, especially Baby and
Kids products. The photostability determination test must be done on a thin film
of the product that is irradiated in sunlight or with a spectrum known to mimic
sunlight. A solar simulator spectrum suitable for SPF testing is not adequate to
measure photostability since products do not degrade in SPF spectra as they do
in sunlight. The importance of this cannot be overemphasized. If the product is
not photostable, the SPF reported from solar simulator testing will result in over-
estimation and an improperly labeled product.
CONCLUSIONS
Ultimately, the most important aspect is creating a product that appeals to the end
user, hopefully affecting adequate product usage leading to the needed protec-
tion. Inadequate usage is probably the biggest problem in protecting consumers
from UV skin damage. Study after study shows that consumers do not use
adequate quantities of the product to obtain the labeled SPF value. Baby and
Kids products simply must be formulated and packaged to attract purchase and
encourage adequate usage.
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2. Weinstock M, Colditz G, Willett W, et al. Nonfamilial cutaneous melanoma incidence

in women associated with sun exposure before 20 years of age. Pediatrics 1989;
84:199– 204.
3. Sun & Skin News. A Publication of the Skin Cancer Foundation, 2001; 18(2).
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28
Fabrics as UV Radiation Filters
Kathryn L. Hatch
Agricultural and Biosystems Engineering , The University of
Arizona, Tucson, Arizona, USA
Introduction 558
Fiber Distribution 558
Fiber Composition 559
Fiber Class Differences 559
Differences Within Natural Fiber Class 560
Differences Within Manufactured Fiber Class 561
Fabric Thickness 562
Dye Composition and Concentration 562
Comparison of Dyed Fabrics 562
Comparison of Dyes in Solution 564
UV-Absorbent Compounds 564
Optical Whitening (Brightening) Agents 564
Mill Applied 565
Detergent Ingredient Applied 565
Rinse-Cycle Fabric Softener Ingredient Applied 566
UV-Cutting Agents 566
Mill Applied 567
Detergent Ingredient Applied 568
Rinse-Cycle Fabric Softener Product Applied 569
Rinse Water Applied 570
Conclusion 570
References 571
557
558 Hatch
INTRODUCTION
Engineering fabrics to increase their capability to filter solar radiation, especially
the UV portion, has been of interest for a number of years (1 –18). The intent is to
label such fabrics and items made from them as solar (sun or UV ) protective
clothing. The American Society for Testing and Materials (ASTM ) standard
guide D6603 (19) defines UV-protective textile as “any textile whose manufac-
turer and/or seller claims that it protects consumers from ultraviolet (UV ) light,
claims the reduction of risk of skin injury associated with UV exposure, and/or
uses a rating system that quantifies the amount of UV protection afforded”. The
purpose of this chapter is to describe the ways in which fabric can be enhanced to
improve its UV-filtering capability.
FIBER DISTRIBUTION
Fabrics are manufactured assemblages of fibers or yarns that have substantial surface
area in relation to thickness and sufficient mechanical strength to give this assembly
inherent cohesion. The fundamental unit in all fabrics is therefore fiber, a unit of
matter with an extremely small diameter and a length at least 100 times longer
than its width. Most fibers are several thousand times longer than they are wide.
Cotton fibers, for example, range in length from 78 to 2 12 in. with diameters ranging
from 16 to 20 mm. Fibers are usually assembled into yarns before becoming part
of a fabric. Yarns, like fibers, tend to be cylindrical structures that are long in relation-
ship to diameter. Yarns are interlaced to form fabrics in the woven fabric class,
interlooped to form fabrics in the knit fabric class, and knotted and twisted to form
fabrics in the class with this same name. The fabric class in which yarns seldom
appear is called the nonwoven class, a class of fabrics made directly from fibers.
What is important to visualize is that this assembling of fibers into yarns
and assembling of yarns into fabrics means that fiber or yarn do not fill the
entire volume of the fabric. There are spaces between yarns creating holes
through the fabric from its face to back. Further, there are innumerable spaces
between fibers within yarns. Collectively, these “empty-of-fiber spaces” within
a fabric’s volume are referred to as interstices or voids.
The interstices/voids which have the major influence on the UV-filtering
capability of fabric are those between yarns because they provide a direct
pathway for UV directed perpendicular to the fabric surface (which is the
usual case in UV transmittance testing methods) to be transmitted. Such trans-
mitted rays are referred to as direct transmittance. The interstices/voids
between fibers within yarns also contribute to filtering as incident radiation
may be reflected from one fiber surface to another until transmitted through
the fabric. Incident UV that is transmitted through the fibrous portion of the
fabric is referred to as scattered transmittance.
The distribution of fiber/yarn within a fabric is the most important factor in
determining the fabric filtering ability. Fiber distributions that result in the least
Fabrics as UV Radiation Filters 559
surface area not containing fiber/yarn in otherwise identical fabrics (same fiber
composition, thickness, chemical content, etc.) lead to the higher percent block-
ing values, UV protective factor (UPF) values, and SPF (sun protection factor)
(SPF ) values. Pailthorpe (1) called the percentage of fabric surface area contain-
ing fiber/yarn the fabric’s cover factor. Assuming that the area covered with
fiber/yarn completely absorbed all incident UV, the relationship between
cover factor and the directly transmitted UV transmission through this ideal
fabric would be expressed as % UV transmission ¼ 100 2 cover factor. This
relationship is shown in Table 28.1. As is readily apparent, very small increases
in fabric cover factor make a substantial change in a fabric’s ability to filter UV.
FIBER COMPOSITION
The fiber composition of the fabric is a description of the class or classes of fiber
used to manufacture the fabric. Fabrics may be made entirely of fibers from one
fiber class, cotton, polyester, wool (laine), silk (soie), flax (linen), rayon
(viscose), lyocel, acetate (cellulose acetate), nylon (polyamide), olefin (polypro-
pylene), and acrylic (polyacrylonitrile), or from two or more fiber classes as
cotton and polyester. The difficulty in directly assessing differences in fiber
class filtering ability resides in finding or even engineering fabrics that are
alike in all respects except for fiber composition. There is always enough differ-
ence in thickness and cover factor of fabrics of like fiber composition so that the
fabric transmittance values would not reveal fiber content differences alone.
Fiber Class Differences

Excellent data on the ability of fibers from various fiber classes to filter UV is
provided by Crews et al. (2). They selected 43 undyed, not optically whitened,
Table 28.1 Relationship between

Cover Factor of an Ideal Fabric and
Filtering Ability (1)
Cover
factor Fabric SPF/UPF
80 5
90 10
93.33 15
95 20
97.5 40
98 50
99 100
99.5 200
560 Hatch
woven fabrics commonly found in clothing that were 100% cotton, 100% rayon,
100% nylon, 100% wool, 100% silk, or 100% polyester. Each fabric was charac-
terized by weave class, weight, thread count, yarn number, yarn type, thickness,
fabric cover, and cloth cover, and as bleached/unbleached. The percent UV
transmittance of each fabric was determined using a spectrophotometer with an
integrating sphere. Percent transmittance values for fabrics of like fiber compo-
sition were averaged resulting in transmittance results for fiber content groups of
25.1% (cotton fabric average), 27.3% (rayon fabric average), 24.1% (nylon fabric
average), 8.6% (wool fabric average), 14.6% (silk fabric average), and 23.2%
(polyester fabric average).
To determine the influence of fiber type alone on fabric percent transmit-
tance, the fabric characterization data were used in an analysis of covariance
procedure to calculate an adjusted percent transmittance for fabrics of like fiber
composition. The result of this analysis gave adjusted percent transmittance
values as follows: 26.9% (cotton), 26.0% (rayon), 20.6% (nylon), 18.2%
(wool), 16.8% (silk), and 15.3% (polyester). Analysis using Fisher’s LSD
technique revealed no significant differences in the adjusted values of cotton
and rayon and no significant differences in the adjusted values for nylon,
wool, and silk. So cotton and rayon fibers have similar ability to filter UV
radiation and nylon, wool, and silk fibers have similar ability to filter UV
radiation.
The major differences between the unadjusted and adjusted fiber percent
transmittance values were for wool (8.6% increased to 18.2%) and polyester
(23.2% decreased to 15.3%). The change in the wool values largely reflects the
fact that fabrics in the wool set were much thicker than fabrics in the other fiber
sets. Once the contribution of thickness to percent fabric transmittance was
accounted for in the covariate analysis, the percent transmittance due to the
wool fiber composition of the fabric was evident. Adjusting the polyester
values showed a decrease in UV transmittance, which makes sense because
polyester fiber is the only fiber studied by Crews et al. (2) made from a
polymer containing aromatic rings which are UV-absorbing entities. Because
cotton and rayon fibers are both made from cellulose polymers and silk, wool,
and nylon are all composed of amide polymers, the filtering abilities within
these classifications would be expected to be similar. It should be noted here
that these fiber values (or rankings) do not reflect SPF or UPF.
Differences Within Natural Fiber Class

Natural fibers are usually made into fabrics before the removal of naturally occur-
ring materials within or on the surface of the fibers. These naturally occurring
materials may or may not be removed from the fabric before it is worn in the
sun. The question is how much difference in fabric percent transmittance
occurs when the naturally occurring substances are removed. Crews et al. (2)
examined this question using two pairs of fabrics.
The first pair contained a bleached and unbleached print cloth. The
bleached cotton print cloth had a UV transmission of 23.7%, a value almost
twice as high as that of unbleached cotton print cloth with a UV transmission
of 14.4%. The reason the unbleached cotton had a lower percent transmittance
is because the natural pigment and lignins on the fabric act as UV absorbers.
The second pair consisted of silk fabrics, one fabric had the coating sur-
rounding silk fibers intact and the other fabric did not have the fiber coating
because it had been removed during bleaching. A comparison of the UPF
value for the crepe de chine silk fabric and the shantung silk fabric, which had
similar percent cover values of approximately 92 and similar thickness,
showed that the UV transmission through the bleached crepe de chine was four
times higher (21.8%) than that of the similarly constructed but unbleached shan-
tung (5.4%). They thought this difference was due to the natural pigments,
lignins, and other impurities in the unbleached silk fabrics acting as UV
absorbers.
Differences Within Manufactured Fiber Class

Fibers within a manufactured fiber class, such as the rayon (viscose) class, may be
modified by adding titanium dioxide (TiO2) to the fiber spinning solution or melt.
TiO2 a well-known inorganic UV-absorbing compound added to sunscreen
lotions (3), attenuates UV by absorption and scattering leading to “broad-
spectrum” (UV-A and UV-B) coverage. Wedler and Hirthe (4) explain the use
of TiO2 in manufactured fibers. They state that adding typical levels of white
pigment grade to manufactured fibers, 0.3% to produce semidull fibers and
1.5% to produce full-dull fibers, leads to some improvement in UPF of fabric
made with such fibers. High levels of sunburn protection with this grade are
not possible because increasing the concentration of white pigment grade TiO2
in the fiber creates fiber processing difficulties. However, using an ultrafine
grade of TiO2 not only eliminates the processing difficulty but also provides a
much higher number of particles per portion of fiber weight. More particles
means that more UV will be absorbed or reflected at the fiber level. Significant
improvement in fabric UPF can be achieved when fabrics have a high cover
factor.
No studies were found in the literature that demonstrated improvement in
fabric UPF due to the fact that fibers in the fabric contained TiO2. The closest
indication of the effect of TiO2 on the UPF values of fabric is provided by
Gambicher and coworkers (5). In their study which focused on comparing
in vivo and an in vitro testing methods, three viscose (rayon) fabrics made
from TiO2-containing fibers and four viscose fabrics without TiO2-containing
fibers were used. The TiO2 fabrics did have higher UPF values but these
fabrics also had higher fabric weights than fabrics made without TiO2 in their
fibers. Therefore, the entire increase in fabric UPF cannot be attributed to the
inclusion of TiO2.
562 Hatch
FABRIC THICKNESS
Fabric thickness has been found to be the most useful parameter for explaining
the differences in UV transmission of fabrics of like fiber composition when
differences in percent cover factor of those fabrics are also accounted for (2).
In this case, the incident UV has a greater distance to travel through the fabric
with more opportunity for certain wavelengths to be absorbed or reflected by
the fibers.
DYE COMPOSITION AND CONCENTRATION

Dyes are organic chemicals that are able to selectively absorb and reflect wave-
lengths of light within the visible range of the electromagnetic spectrum. A dye
molecule must have a conjugated system. Dye molecules may also absorb in the
UV range and those that do would be expected to contribute to the UPF value of
fabrics to which they are applied. Further, dyes with UV transmittance spectra
showing the strongest absorption in the UV-B region would be expected to
produce fabrics with higher UPF values. As fabric is dyed to a deeper shade
using the same dye, the UPF of the fabric should increase due to the greater
dye concentration in the darker fabric.
Dyes may be classed by application method or by chemical type. Appli-
cation classing is useful because knowing a dyes generic class reveals which
fibers can be colored with it. For example, dyes in the direct and reactive
classes can be used to color cotton fiber. Dyes in the acid class may be used to
color nylon, silk, and wool fibers. Each dye within an application class is often
identified by its color index name, a name composed of class name, dye hue
(color reflected by the dye), and a unique identifying number.
Comparison of Dyed Fabrics

Srinivasan and Gatewood (6) studied the effect of dyeing a white cotton fabric
with dyes of various colors (hues) but having different absorbance in the UV
region. The cotton fabric selected was a bleached print cloth because (a) it had
a UPF value low enough (4.0) for any improvements to UPF due to dye addition
to be detected and (b) it is a fabric often dyed and finished for summer garments.
Dyes from the direct classification were used because dyes from this class are
most often used to color cotton fabrics. The 14 dyes selected differed in chemical
classification. The hues were yellow (four dyes), red (three dyes), violet (one
dye), blue (three dyes), green (one dye), brown (one dye), and black (one dye).
After prescouring the print cloth, the direct dyes were applied to 5 g samples
of cotton fabric at theoretical concentrations of 0.5% and 1.0% on weight of
fiber (owf ). The 1.0% owf represents a medium depth of shade that would be
typical of summertime fabrics. A control sample was prepared by subjecting
the bleached print cloth to a blank dyeing process with all ingredients except
the dye to eliminate the effect of fabric shrinkage on percent transmittance and
therefore on calculated UPF. Specimens of dyed fabric were submitted for UV

transmittance assessment. The mean UV, UV-A, and UV-B percent transmittance
values were calculated from each scan and averaged for 16 scans (four speci-
mens two scans two replications). Then, the UPF values were calculated.
Analysis of variance was conducted on the UPF data to determine if the
application of dyes changed the UPF values of the cotton print cloth and
whether greater owf application lead to higher UPF values. The dyed fabric
UPF values are shown in columns 2 and 3 of Table 28.2. These data show that
increasing the concentration of the dye in the fabric leads to increased UPF
values. For each dye, the fabric UPF value is higher after the 1.0 owf application
of dye than after the 0.5% owf application. So, the darker fabric of each pair
would afford greater sunburn protection.
To determine the specific dye effect on the UPF of the fabric, the concen-
tration of the dyes in each fabric needed to be the same. This was not the case
because the dyes had different exhaust rates. To determine the percent exhaustion
from the dyebath, the absorptiometric measurements of the residual dyebath sol-
ution were compared with calibration curves prepared from dye solutions at
known concentrations based on the weight of the commercial dye.
Having the dye exhaust rate data made it possible to use analysis of covari-
ance treating concentration as a covariable. Fisher’s least significant difference
test was then used to determine which of the dyed fabrics differed in their
UPF values. The adjusted UPF values are shown in column 4 of Table 28.2.
Table 28.2 Selected Results of the Srinivasan and Gatewood Study (6)
Direct dye Fabric UPF Fabric UPF

used to after 0.5% owf after 1.0% owf Adjusted dyed
dye fabric dyeing process dyeing process fabric UPF
None 4.1
Yellow 12 13.1 18.6 17.8
Yellow 28 19.9 29.3 21.6
Yellow 44 18.4 28.6 25.3
Yellow 106 19.3 27.6 25.0
Red 24 27.6 37.1 31.3
Red 28 38.7 50.7 41.3
Red 80 17.3 24.7 20.3
Violet 9 20.9 28.8 23.5
Blue 1 21.5 30.2 25.5
Blue 86 16.2 18.6 24.0
Blue 218 13.1 19.0 16.6
Green 26 22.3 29.2 26.2
Brown 154 22.8 30.6 24.7
Black 38 29.8 40.2 33.7
564 Hatch
The adjusted results show that fabric color (hue) is not a reliable indicator of the
UV protection provided by dyed fabrics because dyes of the same hue produced
fabrics with varying UPF values when concentration level was identical. This
study also showed that black fabric does not necessarily provide the best
sunburn protection as one of the red dyes produced a fabric having a higher
UPF value than the fabric dyed black. Here, it is critical to remember that
color seen is due to one’s brain interpreting the visible rays that reach one’s
eyes. Color is not the result of “seeing” invisible UV radiation.
Comparison of Dyes in Solution

Srinivasan and Gatewood (6) also devised an equation similar to that used in cal-
culating the UPF of fabrics for evaluating dyes in solution based on their trans-
mittance values. This equation calculated the effective UV transmittance, which
is the relative effectiveness of dyes in improving the UV protection of a fabric,
based on the transmittance of dyes in solution weighted for solar spectral irradiance
and relative erythemal spectral effectiveness. Because this method takes into
consideration the effectiveness of both UV-A and UV-B transmittances and
because the concentrations of the dyes in the solutions can be more easily
controlled than in fabric, it led the researchers to conclude that determining the
effective UV transmittance of dyes in solution would probably be an excellent
procedure to screen dyes before going through the expense of applying them to
fabrics to investigate UPF effectiveness.
UV-ABSORBENT COMPOUNDS
In this manuscript, the term UV-absorbent compound is used to indicate colorless
compounds that have UV-absorbing capabilities. The major subclasses are
optical whitening agents (OWAs), also known as fluorescent whitening agents
(FWAs), and UV-cutting agents (UVCAs). The OWA compounds’ main
purpose is to whiten and brighten fabrics but they may also improve the UV
filtering. The UVCAs’ primary function is to enhance the UPF of fabrics to
which they are added while also contributing to the whiteness and brightness
of the fabric.
Optical Whitening (Brightening) Agents

OWAs whiten and brighten fabrics because they convert a portion of the incident
UV to a visible blue wavelength and reflect this as a visible blue wavelength. In
other words, OWAs cause fluorescence. More visible light reaches an observer’s
eye from the surface of a fabric containing OWA than from an identical fabric
without OWA. More specifically, OWAs absorb UV radiation near 360 nm and
re-emit it at about 430 nm. Secondarily, OWAs absorb UV, which they do better
in the UV-A region than in the UV-B region, in which they absorb poorly.
Additionally, they have a weakness at about 308 nm. The main thrust of work
with OWAs has been to select compounds from the OWA class, some being
modified to enhance UV-absorbing ability, to study how effective they are
compared to each other in increasing UPF values of fabrics and in enhancing
whiteness/brightness.
Mill Applied
Bleached cotton fabrics, nylon fabrics, and polyester fabrics may be enhanced in
the finishing mill by the addition of OWAs. Reinehr et al. (7) finished a cotton
poplin fabric (initial SPF 3.5) with three OWAs: a conventional stilbene
(OWA-1), a DSBP OWA (OWA-2), a mixture of OWA-1 and -2, and a modified
OWA (OWA-3), a compound similar in structure to OWA-1 but with carboxylic
acid and ester groups, which results in additional UV-B absorption. At identical
concentration of OWA on the fabric, the SPF values were 10 for OWA-1, 10 for
the mixture, 14 for OWA-2, and 22 for OWA-3. When OWA-3 was applied by
exhaust application the fabric SPF was 35 and when applied by padding it was
60þ, these values being higher due to greater concentration of the OWA on
the fabric. They concluded that OWAs make a positive contribution to improving
the sunburn protection of cotton fabric but in many cases do not achieve the pro-
tection level usually desired (i.e., the 30þ UPF required to classify a fabric as UV
protective).
Detergent Ingredient Applied
OWAs are a common additive to home laundry detergent formulations because
they deposit onto fabrics of certain fiber compositions (usually cotton and
cotton blends) during the wash cycle. There was interest in laundering both
nonwhitened and whitened fabrics.
Nonbrightened fabric laundering: Reinehr et al. (7) laundered non-

whitened cotton poplin fabrics with a detergent containing 0.2% OWA-3
compound (an OWA with improved absorption in the UV-B) and with 0.2% of
an OWA-1 compound (the traditional stilbene OWA). After five launderings,
the fabric laundered with detergent containing OWA-3 had an SPF double that
of the fabric laundered with the OWA-1 compound. The increase in whiteness
was the same for both treatments.
Zhou and Crews (8) laundered eight white summer-weight fabrics of
various fiber compositions 20 times using home laundering equipment. Some
swatches were laundered with detergent containing OWAs and others with deter-
gent without OWAs. Laundering fabric had increased UPF values due to fabric
shrinkage. In laundering fabric with detergent containing an OWA the UV-blocking
ability of the cotton and cotton/polyester fabrics was improved, but not that of
the polyester or nylon fabrics. The cotton sheeting showed a 10-fold increase
in mean UPF following 20 launderings with OWA (UPF 5.5 initially and UPF
57.1 after washing). One hundred percent cotton broadcloth showed an increase
of about sixfold (ending in UPF of 22). Some of the increase was probably due to
566 Hatch
shrinkage in the fabric, but that would be small. The cotton fabrics’ enhanced
blocking property was attributed to the ability of cotton fiber to absorb the
OWA compound, thus facilitating the buildup of OWA in the fabric. Buildup
may also be due to chemical affinity of the fiber for the OWA. At 20 launderings,
UPF still had not leveled off—so more laundering may lead to even greater
improvement.
Pre-brighten fabric laundering: Reinehr et al. (7) laundered swatches
of a prebrightened white 100% cotton poplin fabric (SPF 13) with a bright-
ener-free detergent and with a detergent containing 0.2% OWA-1 (a conventional
stilbene compound). After four to five washings in the brightener-free detergent,
the prebrightened fabric had an SPF of 5. After four to five launderings in the
0.2% OWA-1 detergent formulation, the prebrightened fabric swatches had an
SPF equal to or greater than the initial 13 SPF.
This research team also laundered a prebrightened blue cotton fabric (SPF
7) with a brightener-free detergent and a detergent containing 0.1% FWA-2 (con-
ventional DSBP). After 10 washings, the swatches laundered in brightener-free
detergent had an SPF of 5 while the SPF of the swatches laundered in detergent
containing FWA-2 reached 15. Using a dark blue prebrightened cotton poplin
fabric (initial SPF 24) showed that the SPF was reduced to 20 when the detergent
contained no FWA and showed improvement with FWA in the detergent.
Rinse-Cycle Fabric Softener Ingredient Applied
Reinehr et al. (7) softened a cotton fabric with two rinse-cycle fabric-softening
products: one containing a cationic OWA (OWA-4) and the other OWA-2.
Two formulations were used: one had 0.3% and the other 2.7% on weight of
after-rinse product of the softening compound. Whiteness of fabrics to which
the cationic OWA was added was better than for those fabrics softened with
OWA-2. There was little difference in the whiteness of fabrics laundered
with the softening products containing different amounts of cationic OWA.
However, fabric swatches laundered with the softener containing the higher
concentration of cationic OWA had higher SPF values than those swatches laun-
dered with the lower concentration of cationic OWA in the product (SPF of 30
compared to 12). The comparison treatment (OWA-2) resulted in an SPF of 5
at both concentrations.
UV-Cutting Agents
UVCAs are a classification of chemical compounds that lead to a significant
improvement in the sunburn protection capability of the fabric. The main
feature of UVCAs is that they have chromophore systems that absorb very effec-
tively in the UV region, enabling them to maximize the absorption of UV radi-
ation while in situ on textiles. UVCAs may be applied in the mill, added to a
laundry detergent formulation, be part of a rinse-cycle fabric softener formu-
lation, or be the main ingredient in a rinse-water additive product. UVCAs
should not be confused with UV-absorbing compounds whose purpose is to slow

down the solar degradation of PA (polyamide/nylon) fiber or enhance the light
fastness of dyes on automotive PES (polyester/polyethylene terephthalate)
fibers/fabrics.
Mill Applied
Hilfiker et al. (9) showed the effect of treating a thin (0.2 mm), slightly porous
(1.5%) cotton fabric with a triazine (UVCA-1) and with a hydroxyl-triazole
(UVCA-2). Theoretical values calculated using information about each com-
pound’s absorption spectra predicted that the maximum SPF of a treated cotton
fabric would be 67 for UVCA-2 and 25 for UVCA-1. The authors explained
that these differences are due to the fact that UVCA-1 has an upper absorption
limit of about 335 nm, so it can never yield a very high SPF, while the upper
absorption limit of UVCA-2 is 385. On the other hand, increases in SPF value
due to increased concentration of the compound in the fabric would be expected
to be greater for UVCA-1 than for UVCA-2 because the extinction coefficient of
UVCA-1 at 310 nm is higher than for UVCA-2.
The authors applied UVCA-2 to a poplin cotton fabric (110 g/m2, 0.6%
porosity, SPF 3.2) and a cretonne cotton fabric (144 g/m2, 4% porosity, SPF
6.8) so that the concentration of UVCA-2 on the fabric was in the range of
0 –0.02 g/cm3. They reported the measured SPF values of each fabric at each
concentration level and the SPF values obtained using their theoretical equation.
Agreement of the paired values was considered to be good in the absence of
any adjustable parameters. At the lowest concentration applied, the SPF was
12 for poplin and 12 for cretonne. At the maximum concentration applied, the
SPF for poplin was 103 and for the cretonne it was 19.
Reinert et al. (10) reported the results of adding different UVCAs from a
dyebath to fabrics of various fiber compositions, weights, and thicknesses. The
UVCA they applied to eight cotton fabrics, Cibatex UPF, was a water-soluble
oxaldianilide with two reactive groups. The UVCA applied to five wool, five
silk, six polyamide and polyamide elastin (spandex) blends was Cibafast W, a
monosulfonated benzotriazole derivative. The UVCA applied to the five polye-
ster and polyester blend fabrics, Cibatex APS, was a dispersion of a benzotriazole
derivative. In this study, the UVCA was added to the dye bath so that the fabric
was colored and UPF treated at the same time. All UVCAs were applied in the
standard amount of 2% owf with the dye. A blank dyeing was done. This
“dye” bath included only the UVCA at 2%.
While the exact improvement in UPF differs by specific fabric, trends are
the same. The UPF increased as the depth of shade increased and especially with
the addition of UVCA-2 to the dyebath. For example, the initial UPF values for
two of the eight cotton fabrics were 3 (Renforce fabric) and 5 (tricot fabric).
Dyeing of these fabrics with yellow dye F-4G to a pale yellow shade increased
the UPF to 7 for the Renforce fabric and to 5 for the tricot fabric. Dyeing to a
deep yellow shade resulted in UPFs of 7 for both. Adding 2% UVCA-2 to the
568 Hatch
dye-baths increased the UPF of the pale yellow fabrics to 20 (Renforce) and to
50þ (tricot). Adding UVCA-2 to the dyebath of the Renforce fabric containing
sufficient dye to color it to a deep shade of yellow increased the UPF to 34.
Jöllenbeck (11) describes a new UV-cutting compound for mill-finishing of
cotton and viscose fabrics. This UV-cutting agent, Solartex CEL (renamed Tino-
fast CEL), effectively absorbs in the 300 – 320 nm range of the electromagnetic
spectrum, the range in which the erythemal effect (the product of erythemal effec-
tiveness and spectral distribution) of UV radiation on the skin is at its highest.
UPF results are provided for cotton tricot knit fabric (UPF 5) after dyeing
and finishing with Tinofast CEL. Fabrics dyed to a dark shade with Cibacron
dyes blue F-GPN, red FB, and scarlet F-3G had UPF values .50 and with
yellow F-4G a UPF of 44. However, the fabric dyed to a light shade with the
same dyes resulted in UPFs of 10 (blue), 25 (red), 17 (scarlet), and 7 (yellow).
Adding 2 –4% Tinofast CEL to the dyebath resulted in UPF values for the pale
dyed fabric swatches of .50.
Jöllenbeck et al. (12) compared the UV-filtering ability of cotton fabric fin-
ished with 1,3-chlor-5-(40 -sulfophenyl)-s-triazine to that finished with Tinofast
CEL (bireactive oxalic acid derivative). The first compound, referred to herein
as UVCA-1, absorbs most in the UV-C and UV-B ranges. It is usually applied
to carpeting during space dyeing. The second compound, referred to herein as
UVCA-2, absorbs in both UV-A and UV-B, with its maximum absorption at
the maximum erythemal effectiveness.
UVCA-1 and UVCA-2 were applied to swatches of nondyed cotton tricot
knit with porosity of 0.2% and initial UPF of 5. When UVCA-1 was applied
at 1%, the UPF of the tricot was 31 and when applied at 4% it was 51 UPF. In
contrast, with 0.5% UVCA-2, the UPF was 107 and with 1.0% it was 183.
Detergent Ingredient Applied
UV-cutting compounds may be added to a detergent formulation with the expec-
tation that UV-cutting molecules will be deposited on fabric during the laundry
wash cycle and not be rinsed out during the subsequent rinse cycles. As was
the case with research involving the addition of OWAs to detergent formulations,
research included laundering prewhitened and not prewhitened fabrics.
In the earliest research report, Rohwer and Eckhardt (13) laundered cotton
fabric (not described) with two detergents types (powder and liquid), one formu-
lated without the addition of Ciba Tinosorb FD and the other formulated with
Tinosorb FD. They were interested in the effect of UVCA on the fabric white-
ness. Results showed that fabric whiteness was not diminished and in fact was
slightly increased when UVCA was included in the detergent formulation. This
result was confirmed by Eckhardt and Osterwalder (14) who laundered a prewhi-
tened cotton fabric with a UV-cutting compound incorporated into a detergent
formulation. They showed that the prewhitened fabric after such laundering
had increased whiteness. They also concluded that the UV-cutting agent did
not quench the initial whiteness and it contributed to the whiteness of the fabric.
Eckhardt and Rohwer (15) conducted a two-part experiment. The aim of

the first part was to determine whether a UV-A –UV-B absorbing compound
(FD), a molecule composed of two UV-B-absorbing moieties bound to a
UV-A-absorbing structure, when added to a detergent formulation at 0.1%
and 0.2% would lead to greater improvement in UPF of white cotton fabrics
than that achieved using the same base detergent formulation with traditional
OWA added (OWA-1 and OWA-2). The aim of the second part was to explore
the effect on the initial whiteness value of prewhitened fabrics as a result of
laundering with a UVCA-containing detergent.
In part 1, four not prewhitened cotton fabrics were selected, two knit and
two woven. The base detergent was AATCC (American Association of Textile
Chemists and Colorists) Standard Detergent 1993 WOB (without brighteners).
The UPF of the laundered not prebrightened swatches increased significantly
with the use of FD in the detergent formulation at both 0.1% and 0.2%.
A UPF of 15 was reached by the fifth wash with the FD-containing detergents.
In contrast, it took 10 washes for the swatches laundered with OWA-1 and
OWA-2 compounds at comparable percent detergent formulation to reach this
UPF value. The increase in UPF value was greater for the knitted fabrics than
for the woven fabrics, a result believed to be due to the greater absorption of
the compound on the knit fabrics.
In part 2, the prewhitened fabrics laundered with the FD detergent formu-
lation had whiteness values equal to those of the same fabric laundered for the
same number of cycles in detergent containing only the FWA. This was true at
0.1% addition and 0.2% addition.
Wang et al. (16) also studied the alteration in the UPF of fabric when laun-
dered with the Ciba FD compound. Swatches of two cotton fabrics—one a knit
fabric (jersey for T-shirts) and the other a woven fabric (a mercerized print
cloth)—were laundered in home laundering machines. The treatments were
laundering (a) without detergent, (b) in AATCC standard detergent without
OWA, and (c) in AATCC standard detergent containing a UVCA (Ciba Specialty
Chemicals Tinosorb FD).
After five cycles of laundering in water only, the UPF of the jersey fabric
increased from 4.7 to 7.1 and the UPF of the print cloth increased from 3.1 to 4.2.
These increases were due to shrinkage of the fabric. After five cycles of washing
in AATCC detergent with OWA, the UPF values were 6.0 for jersey fabric and
4.4 for print cloth. After washing the swatches once with detergent containing
UVCA, the UPF for jersey was 11 and for print cloth it was 7. By the fifth
wash cycle, the jersey fabric had a UPF value of 23 and the print cloth a value
of about 12.
Rinse-Cycle Fabric Softener Product Applied
Rohwer and Kvita (17) report the results of using a rinse-cycle fabric softener
containing a UVCA in the formulation when laundering bleached cotton
fabrics, some prebrightened and some not brightened. The fabric softener
570 Hatch
formulation was 1.6 g/L of concentrated fabric conditioner containing 6% Tino-

sorb FR (15% active) to make an initial 1:30 active-to-liquor ratio. Bleached
cotton swatches (UPF of 3.5) were laundered with 4 g/L of detergent without
UVCA added. In the final rinse cycle, 2%, 4%, 6%, 8%, and 10% concentrations
of the prepared 1:30 liquor ratio, UVCA-containing fabric softener were added.
The UPF of the cotton fabric increased with the number of wash/rinse
cycles and was higher as the concentration of the active softener ingredient
increased from 2% to 10%. At the 10% concentration, the UPF was 9 after one
rinse addition, 17 after three rinse additions, and 25 after five rinse additions.
Following laundering with the addition of rinse cycle fabric softener containing
UVCA, the prewhitened fabrics had the same whiteness values as the fabrics not
prewhitened. The absorbed energy is effectively transformed into fluorescent
radiation avoiding detrimental effects on prebrightened fabrics.
Rinse Water Applied

Tinosorb FD is also available for addition during the rinse cycle in a product in
which the Tinosorb FD is the major product ingredient. The sole purpose of the
product is to enhance the UPF value of the fabric. This rinse-cycle added
product’s name as test marketed is Ritw Sunguard. Kim et al. (18) repeatedly
laundered white cotton knit fabrics with this rinse-cycle product, with Ritw
Whitener and Brightener, with Tidew with Bleach, or with Wiskw Liquid to
determine the improvement in UPF values of two types of weft knit fabrics.
Fabric swatches for the study were cut from eight polo-style shirts made with
60% cotton/40% polyester pique-stitch weft knit fabric (blended pique) and
from eight undershirts made of 100% cotton jersey weft knit fabric). These
swatches were laundered repeatedly in home laundry equipment.
The UPF values of both fabrics improved from initial UPF values of 14.2
and 23.4 (jersey and pique fabric, respectively) with repeated laundering in the
four laundry treatments. After one laundering cycle with Sunguardw, the UPF
was 81.4 + 23.0 ( jersey fabric) and 39.6 + 8.3 (pique fabric) and with Ritw
Whitener and Brightener, the UPF was 30.5 + 6.1 (jersey) and 36.6 + 6.1
(pique). UPF values above 30 were obtained by the conclusion of the fifth laun-
dering with Tidew and with Wiskw. Specifically, the UPF values at this point
were 43.3 + 8.5 (jersey fabric) and 39.7 + 10.4 (pique fabric). There were stat-
istically significant differences in UPF values for fabric type and for laundry
product used in the wash. Adding just the Rit Sunguardw product to laundry
water resulted in the most rapid achievement of a 30þ UPF.
CONCLUSION
Without a doubt the most important factor controlling the degree of sunburn pro-
tection to be provided by a fabric is fiber distribution. When fiber fills a greater
percentage of the fabric volume, UPF value increases. This increase is due to the
reduction of directed UV radiation, radiation that passes through fabric unhin-

dered because there is no fiber in its path to absorb any of it.
The second most important factor is concentration. This means concen-
tration of fibers from fabric face to back (indicated often by thickness and
weight per unit area), of dyes on the fibers, of OWAs on the fibers, of UVCAs
on the fibers, and of TiO2 contained in modified manufactured fibers.
The third most important factor is the fiber composition of the fabric.
Polyester fiber and silk fiber have the greatest ability to filter incident UV, fol-
lowed by wool fiber and nylon fiber, with rayon fiber and cotton fiber having
the least filtering ability. No data were obtained to show the UPF values for
various fiber classes. Such data when available may change the rank order of
the fibers. The UPF value of all fabrics can be enhanced by dyeing them with
dyes that absorb in the UV as well as the visible range. Using dyes that absorb
strongly in the UV-B range leads to fabrics with higher UPF values than using
dyes that absorb weakly in the UV-B.
For cotton fabrics, the addition of UV-cutting compounds raises the UPF
value of the fabrics significantly. These compounds may be added in the mill,
during the laundry wash cycle when they are included in the detergent formu-
lation, during fabric softening in the rinse cycle when the fabric softener
product contains a UV-cutting compound, and to the rinse water as a dedicated
product. The UPF value of cotton fabrics can also be improved with the addition
of OWAs when the compound is applied at the mill or when the optical whitener
compound is included in a detergent formulation.
Fabrics (nylon, polyester, cotton, etc.) finished in the mill with OWAs will
enhance the UPF over identical fabric not so finished. The durability of this finish
depends on the compound selected and method of application. For prewhitened
cotton fabrics, the initial UPF value can be retained or improved by laundering
with detergent containing the OWA without loss of whiteness. Only cotton
fabrics not prewhitened/prebrightened in the mill can be improved by laundering
them in detergents and other products containing OWAs.
Another means of changing UV transmittance through textiles is fiber
modification. The addition of TiO2 to manufactured fibers increases the ability
of the fiber to absorb incident UV. The increase is related to the grade of
TiO2: ultrafine grade being able to reduce transmittance to much lower levels
than white pigment grade because the concentration of white pigment grade is
limited by the inability to process fiber past a certain concentration of the
pigment and to the fact that the smaller particle size of the ultrafine grade
places pigment particles closer throughout the fiber polymer matrix.
REFERENCES
1. Pailthorpe M. Textile parameters and sun protection factors. Textiles and Sun Protec-
tion Conference Proceedings. The Society of Dyers and Colourists of Australia and
New Zealand (NSW Section), 1993:32– 53.
572 Hatch
2. Crews PC, Kachman S, Beyer AG. Influences on UVR transmission of undyed woven
fabrics. Text Chem Colorist 1999; 31(6):17 – 26.
3. Dransfield GP. Inorganic sunscreens. Radiat Prot Dosim 2000; 91(1 – 3):271– 273.
4. Wedler M, Hirthe B. UV-absorbing micro additives for synthetic fibers. Chem Fibers
Int 1999; 49:72.
5. Hoffmann K, Kasper K, Gambichler T, Altmeyer P. In vitro and in vivo determination
of the UV protection factor for lightweight cotton and viscose summer fabrics: a pre-
liminary study. J Am Acad Dermatol 2000; 43:1009 – 1016.
6. Srinivasan M, Gatewood BM. Relationship of dye characteristics to UV protection
provided by cotton fabric. Text Chem Colorists Am Dyestuff Report 2000;
32(4):36– 43.
7. Reinehr D, Eckhardt C, Kaufmann W. Skin protection against ultraviolet light by
cotton textiles treated with optical brighteners. 4th World Surfactants Congress.
Barcelona: Asociacion Espanola de Productores de Sustancias para Aplicaciones
Tensioactivas, 1996:264 –276.
8. Zhou Y, Crews PC. Effect of OBAs and repeated launderings on UVR transmission
through fabrics. Text Chem Colorist 1998; 30(11):19 – 24.
9. Hilfiker R, Kaufmann W, Reinert G, Schmidt E. Improving sun protection factors of
fabrics by applying UV-absorbers. Text Res J 1996; 66:61 – 70.
10. Reinert G, Fuso F, Hilfiker R, Schmidt E. UV-protecting properties of textile fabrics
and their improvement. Text Chem Colorist 1997; 29(12):36 – 43.
11. Jöllenbeck M. New UV absorbers for sun protective fabrics. In: Altmeyer P,
Hoffmann K, Stücker M, eds. Skin Cancer and UV Radiation. Berlin: Springer,
1997:382 –387.
12. Jöllenbeck M, Härri H-P, Schlenker W, Osterwalder U. UV protective fabrics.
Proceedings of AATCC Functional Finishes and High Performance Textiles Sym-
posium, Charlotte, NC, January 2000:27 – 28.
13. Rohwer H, Eckhardt C. Laundry additive for the sun protection of the skin. SÖFW J
1998; 12(11):1– 4.
14. Eckhardt C, Osterwalder U. Laundering clothes to be sun protective. In: Cahn A, ed.
Proceedings 4th World Conference on Detergents: Strategies for the 21st Century,
Montreux, 1998:317 – 322.
15. Eckhardt C, Rohwer H. UV protector for cotton fabrics. Text Chem Colorist Am
Dyestuff Reporter 2000; 32(4):21– 23.
16. Wang SQ, Kopf AW, Marx J, Bogdan A, Polsky D, Bart RS. Reduction of ultraviolet
transmission through cotton T-shirt fabrics with low ultraviolet protection by various
laundering methods and dyeing: clinical implications. J Am Acad Dermatol 2001;
44:767– 774.
17. Rohwer H, Kvita P. Sun protection of the skin with a novel UV absorber for rinse
cycle application. SÖFW J 1999; 125(8):1– 5.
18. Kim J, Stone J, Crew P, Shelley II M, Hatch K. Improving knit fabric UPF using con-
sumer products: a comparison of results using two instruments. Fam Cons Sci Res J
2004; 33(2):141– 158.
19. ASTM International. D6603 Standard Guide for Labeling of UV-Protective Textiles.
Annual Book of ASTM Standards, Volume 07.01. Philadelphia, PA: ASTM, 2002.
29
Sunless Tanning and Tanning
Accelerators
Anthony D. Gonzalez and Robert E. Kalafsky

Avon Products, Inc., Suffern, New York, USA
Introduction 574
Tanning Products: Sunless Tanning V. Tanning Accelerators, a
Market Review 574
Biological Tanning 576
The UV Radiation Response 576
Melanogenesis 578
Regulatory Considerations 579
Enhancing Biological Tanning 580
Artificial Tanning 581
Regulatory Considerations 582
Dihydroxyacetone 583
Formulating with DHA 586
Quality Control 586
Formulation 586
Top 10 Products Review (Ranked by 2002 Sales) 588
Tanning Accelerators 588
Sunless Tanners 591
Conclusion 594
References 595
573
574 Gonzalez and Kalafsky
INTRODUCTION
From the time a tan became symbolic of health and affluence in Western culture,
scientists the world over have been researching ways to enhance, accelerate, and
imitate the golden bronze look that consumers so deeply desire. In the dawn of
the tanning industry, reflective panels redirected the suns rays to the face while
mineral oil was slathered on the body to intensify the effects of basking in the
sun. With the 1960’s came a revolutionary new product concept, QT. This
product was the first consumer product that used dihydroxyacetone (DHA) to
provide a tanned appearance “in 3 to 5 hours without the sun”. The late 1970s
brought the tanning bed, a sarcophagus of fluorescent tubes that radiate UV to
fuel biological tanning without the sun. The first generation of tanning beds
emitted predominantly UV-A radiation. Advances in tanning beds led to quick
tan bulbs, which expanded the radiation spectrum to include UV-B and
produce a speedier bronze. As with many new mass recreational phenomena,
the increased tan population developed its own set of health related side
effects. The rise in population that tanned recreationally led to an increased popu-
lation with premature photoaging and skin cancer. Nonetheless, the market
demands for a healthy looking tanned appearance remain at an all-time high.
While the majority of this book deals with protecting us from the detrimental
effects of the sun, the authors of this chapter have chosen to investigate the
science behind the consumer demand. Advances in research are taking us ever
closer to that natural tan without the need for overexposure to harmful solar
radiation as well as an instant bronze that looks as if you have spent a week in
the Caribbean.
TANNING PRODUCTS: SUNLESS TANNING V. TANNING

ACCELERATORS, A MARKET REVIEW
Tanning products have been traditionally divided into two categories, tanning
accelerators and sunless tanners. Tanning accelerators rely on various technol-
ogies that enhance the body’s natural tanning processes to deliver a more
intense tan than exposure to the sun alone. These products typically have
exotic fragrances that provide a consumer perception of a tropical environment.
On the other hand, sunless tanners impart a tanned appearance to the skin using
colorants that can range from pigments and dyes to compounds that react with the
free amino acids on the skin to form melanin like compounds. Sunless products
that deliver an intensely colored formulation to the skin are more commonly
known as “bronzers.” Sunless tanners come in a wide array of product forms
that focus on delivering a natural looking, even tanned appearance. Regardless
of the mode of action, the consumer demand for tanning products is showing
steady growth.
In the 5 years since the last publication of this book, the market has seen a
steady increase in the consumer demand for all types of tanning products. Both
Sunless Tanning and Tanning Accelerators 575
sunless tanning and tan accelerating products have outperformed the suntan
lotion and oil segment in growth percentage of dollar sales in the time period
from 1998 until 2002. According to IRI InfoScan Reviews data of the total US
FDMX (Food, Drug and Mass excluding Walmart), the suntan lotion and oil
segment total dollar sales grew by approximately 24% from 1998 to 2002. In
1998, tanning accelerators and sunless tanning products held approximately
17% of the total dollar sales in the suntan lotion and oil segment. By 2001
these two segments managed to capture 22% of the total dollar sales in the
market. Dollar sales of tan accelerators and self-tanners grew by over 50% in
the time period from 1998 to 2002.
Tanning accelerators reached peak sales of almost $9 million in 2000, an
incredible 78% growth from the year 1998. However, by 2002 sales have
declined to just under $6 million, a net gain of 14% from the 1998 selling
year. As a result the three tanning product segments (sunless tanning products,
tanning accelerators, and tanning bed products) captured a 21% dollar share of
the total sun market in 2002. This decline may be a result of increasing public
awareness of the negative effects of natural tanning. This same phenomenon
may have led to the introduction of a new form of tanning accelerator, the
tanning bed product. Although tanning bed products had a meager sales perform-
ance of $372,000 in 1998, they have been showing steady growth in the years
since then with a peak of just over $7 million in 2002. This 18-fold dollar
sales growth successfully overtook that of the traditional tanning accelerator in
that year. Interestingly, on combining the sales of tanning bed/tanning accelera-
tor products, we get total sales of $12.8 million in 2001 and $12.9 million in
2002. This modest net growth could be indicative that consumers are leaving
the beach to tan in the assumed “safety” of the tanning bed (1).
Sunless tanners remain the dominant tanning products in the US market.
They held around 91% of the total dollar sales of the three tanning product seg-
ments in 1998 and had just over $53 million in sales or 16% of the total dollars
sold in the total suntan lotion and oil segment. Since 1998, they have shown a
moderate decrease in the tanning product segment from 91% in 1998 to 85%
in 2002. Nonetheless, sunless tanners have a net growth in dollar sales of 42%
in the years from 1998 to 2002. Sunless tanning products had peak sales of
just over $82 million in 2001. This 54% increase from the 1998 selling season
secured one-fifth of the total suntan lotion and oil sales in 2001. Incredibly,
20% of the total dollars spent on sunless tanning products in the year 2001
were on Coppertone Endless Summerw.1 With its innovative new packaging
and claims of “a natural looking tan in 30 minutes”, this product managed $16
million in US sales in 2001. One study, performed at Avon’s Center for
Consumer Sciences, showed that 58% of women who have never used a
1
Combined Stock Keeping Unit (SKU’s) 4110001623 and 4110001659.
sunless tanner are interested in trying one. This is a prime example of the
unquenched consumer demand for efficacious sunless tanning products (1).2
In recent years it has been accepted by the consumer that the preparation of
the area to be treated by sunless tanners is almost as important as the product they
choose. For example, an excess of free amino acids in the skin can lead to exces-
sively darkened spots. As a result, the majority of self-tanning products suggest
some sort of special treatment in those areas. The elbows and knees are areas that
should either be exfoliated prior to application or exposed to less product. The
demand for a natural looking sunless tan is so great that consumers are now pur-
chasing a wide array of pre-sunless tanning treatments. These products range
from presunless moisturizers to exfoliators to application gloves. The complexity
of getting the perfect artificial tan has rocketed the sunless tanning trend into the
salon. Customers are relying on the skills of aestheticians to provide a solution to
the potential streaky, uneven look provided by self-application of otherwise
excellent products. Salon services can be as simple as a cream applied by a
more experienced second party or a complex multistep preparation of the skin
followed by a machine controlled application of sunless tanning concentrate.
US Patent 6,468,508 (2) describes the following process for self-tanning at a
salon:
1) Dehydration of the skin with heat and electromagnetic radiation,
flowing heated air or chemically with alcohol or a ketone. 2) Apply-
ing a sprayed on self-tanning composition for 1 –10 minutes and
wiping off or rinsing.
Some salons now offer airbrush application of self-tanning compositions. The
airbrush allows for a fine even coverage of the skin with little need for inci-
dental contact with the palms, hair, or skin. Because this service is in its
infancy stage, the equipment used for airbrush tanning is taken directly
from the arts and crafts trade. The new atomized applications of self-
tanning formulations lead to increased risk of exposure to the mucous mem-
branes as well as inhalation of DHA. As a result, the FDA issued a statement
regarding the approved use of DHA on the skin only. In time, the equipment
used for such applications will be specialized to provide a safe and effective
airbrush tanned appearance.
BIOLOGICAL TANNING
The UV Radiation Response
Although the biological tanning process has yet to be completely described, the
scientific community has provided a broad understanding of this phenomenon to
help in producing more efficient tanning accelerators. The most basic explanation
2
Total dollar sales do not include private label manufactured products.
of the natural tanning process is as follows:

UV Insult
Stimulation of melanin Bio- Melanin synthesized in melanosomes

synthesis
+
Stimulation of melanocyte
dendricity Melanosomes migrate to dendrites
+
Increase in melanocytes
Melanosomes transfer to keratinocytes
TAN
Countless hours of research have been spent in trying to understand the role of UV
in the tanning process. Lavker and Kaidbey (3) demonstrated that 60 mJ/cm2 of
UV-B radiation in the spectrum of 280–320 nm was sufficient to induce tanning
in vivo. By observing the responses of cultures of keratinocytes and melanocytes,
Duval et al. (4) were able to demonstrate the independent effects of UV-A
(320–400 nm) and UV-B (290–320 nm) in cell culture. A dosage of 5 mJ/cm2
of UV-B radiation was sufficient to induce an increase in melanin synthesis in a
coculture of melanocytes and keratinocytes. Increasing the UV insult by an
order of magnitude was insufficient to stimulate melanogenesis in a culture of
melanocytes alone. Their work also demonstrated a dose responsive increase in
melanogenesis upon exposure to UV-A radiation in a monoculture of melanocytes.
The authors subsequently theorized that healthy keratinocytes were necessary to
elicit a tanning response to UV-B insult. However, the role of the keratinocytes
may be diminished in UV-A induced melanogenesis. These results, coupled
with the research of Tyrell (5) led to their hypothesis that UV-A induced
tanning may be a result of oxidative stress created by UV-A radiation.
Unlike its long-wave counterpart UV-A, UV-B radiation can trigger pig-
mentation in the absence of oxygen (6). However, the tanning effects that are
seen upon exposure to UV-B take significantly longer to manifest themselves
than those observed with UV-A (7). Short-wavelength environmental UV has
been shown to facilitate the release of various compounds by keratinocytes (8).
The aforementioned work of Duval et al. (4) on mono- and cocultures of epider-
mal melanin unit cells confirms the synergistic effects of both UV-A and UV-B
on the cascade of events that eventually lead to skin pigment darkening. UV-B
has also been implicated in the inhibition of neprilysin, an enzyme produced
on the surface of the melanocyte. This neutral endopeptidase was shown to down-
regulate a-melanocyte stimulating hormone and adrenocorticotropic hormone,
resulting in an inhibited production of melanin in the melanosomes (9).
UV-A induced pigmentation occurs in two steps, immediate pigment
darkening and delayed tanning. The immediate tanning effect is a product of
reactions on existing melanin and melanin reserves. It has been described as a
combination of the darkening of endogenous melanin and the migration of exist-
ing melanosomes to the dendrites of the melanocytes (10). Delayed tanning,
which requires oxygen, appears to be a systemic response to protect from
repeated or impending insults with UV-A (4,6).
Seite et al. (12) were able to show that p53 protein transactivates tyrosinase
related protein-1 (TRP-1) and tyrosinase promoters, which regulate the synthesis
of melanin. These results suggest the following model for induction of the
tanning response as a protective event (12).
Tyrosinase Melanin
UV p53
TRP-1
While investigating the protective effects of broad-spectrum sunscreens,

Nylander et al. (13) demonstrated an induction of nuclear p53 protein with UV-A
radiation from 320 to 400 nm. These data coupled with Seite’s (11) work implies
that p53 induced tanning is primarily a result of UV-A induced photodamage.
Several other researches have investigated the effects of UV photoproducts
on the induction of tanning. Eller and Gilchrest (14) describe tanning as part of
the eukaryotic response to DNA damage. By exposing melanocytes as well as
intact skin to DNA fragments, they were able to demonstrate an upregulation
of tyrosinase mRNA and protein levels. Their work showed a 7 fold increase
in melanin content of mouse melanoma cells upon exposure to pTpT. In sub-
sequent studies, Eller et al. (15) were able to further demonstrate the stimulation
of pigmentation by using other DNA fragments. The 9-mer oligonucleotide
(pGpApGpTpApTpGpApG) and 7-mer oligonucleotide (pApGpTpApTpGpA)
were able to increase melanin content in mouse melanoma cells by up to 800%
whereas the 5-mer oligonucleotide (pCpApTpApC) had no effect.
Melanogenesis
Once UV triggers the biological tanning process, a subsequent synthesis of
melanin must occur to provide a sustained pigmentation of the skin. Two types
of melanin are produced by the melanosomes, black/brown or eumelanin and
red/yellow or phaeomelanin. It is the level and ratio of these melanins that
lead to the plethora of phenotypes we see in the human species. A multiplicity
of these pigments are synthesized within organelles of melanocytes known as
melanosomes. Subsequently, various mechanisms not completely understood
will lead to morphological changes in the melanocytes causing them to become

dendritic. The melanosomes are then stored in these dendrites and eventually
transferred to keratinocytes upon insult with UV or other pigmentation enhancing
stimuli, the result of which is visible pigment darkening or tanning.
Although there have been significant accomplishments in the area of pigment
cell research, the complete map of melanogenesis has yet to be charted. Prota (16)
describes the Mason-Rapër pathway for melanogenesis as follows:
Tyrosine ! DOPA ! dopaquinone ! dopachrome !

! leucodopachrome ! dihydroxy indole ðDHIÞ !
! 5;6-indolequinone ! various oligomers polymerize to melanin ð17Þ
The key enzymes to melanogenesis are tyrosinase, tyrosinase related protein-1,

and dopachrome tautomerase (DCT), formerly TRP-2. Tyrosinase is responsible
for the conversion of tyrosine to 3,4-dihydroxyphenylalanine (DOPA) and even-
tually dopaquinone. TRP-1 and DCT are primarily involved in the production of
eumelanins that are derived from DOPA (18). Conversely, yellow and red phaeo-
melanins are produced from 5-S-cysteinyldopa (17).
Tanning has been described as an immune response (14). Therefore, many of
the same pathways the cosmetic scientist attempts to inhibit in antiaging products
are those which function to stimulate tanning. A major pathway in the irritation
response of human cells is the nitric oxide (NO) pathway. It was demonstrated
by Sakai et al. (19) that exposure of cells to the NO donor, 5-nitroso-N-acetyl-L -
arginine, led to an increased expression of tyrosinase mRNA within 2 h of
exposure. Subsequent increases in tyrosinase activity and protein levels were
observed at 24 h. Conversely, guanosine 30 ,50 -monophosphate (cGMP) inhibitors
suppressed the expression of tyrosinase mRNA. The authors concluded that cGMP
plays a key role in NO induced melanin synthesis. Other cyclic phosphates have
been indicated in the production of melanin as well. The work of Busca and
Ballotti (18) shows that the adenosine monophosphate (cAMP) pathway regulates
the production of melanin. The activation of protein kinase A and cAMP response
element binding protein (creb) transcription factor led to an upregulation of micro-
phthalmia transcription factor (MITF). MITF has been shown to activate melano-
genic gene promoters (12), thus increasing melanin synthesis. The same pathway
ultimately leads to the phosphorylation of MITF, targeting it for degradation and
eventually the downregulation of melanogenesis. Khaled et al. (20) describe the
activation of glycogen synthase kinase 3B by cAMP. The phosphorylation of
MITF facilitates its ability to bind to tyrosinase promoter genes. Lin et al. (21)
discuss how MITF regulates pigmentation by binding to TRP-1 and DCT.
Regulatory Considerations
Because tanning accelerators are intended to affect the biological process of
melanogenesis, the US FDA considers tanning accelerators to be drugs. As a
result, the legal sale of such products in the USA requires the filing of a New Drug
Application and approval by the FDA prior to marketing such products. Regard-
less of market angle or functionality, all suntan preparations that do not provide
SPF must be labeled with the following warning (22):
Warning—This product does not contain a sunscreen and does not
protect against sunburn. Repeated exposure of unprotected skin while
tanning may increase the risk of skin aging, skin cancer, and other
harmful effects to the skin even if you do not burn. (21CFR740.19)
The FDA has issued warning letters to corporations that market tanning accelera-
tors as unapproved drugs. As a result, many of today’s products make only
cosmetic claims in order to avoid further enforcement of the Food Drug and
Cosmetic Act.
Enhancing Biological Tanning

Yoon et al. (23) have demonstrated that a 3-D model of reconstituted skin can be
used as an effective screening tool for the investigation of pigmentation stimu-
lators. Such in vitro models can significantly reduce the research time required
to come up with new and novel approaches to stimulating natural pigmentation
in human subjects. Other more precise in vitro tools enable the researcher to
screen effective melanogenesis facilitators by specific mechanisms.
Tanning, being a proposed immune response (14), is most easily affected
by compounds that act on the pathways involved in the response to various
environmental insults. Oka et al. (24) demonstrate an increase in melanin
content and tyrosinase mRNA of G 361 melanoma cells by inhibition of the phos-
phatidylinositol 3-kinase (P-3K) pathway. Several P-3K inhibitors, such as the
fungal metabolite Wortmannin (25), have been described in the literature.
Another well-known immune response that has been shown to stimulate the
induction of melanogenesis is the histamine pathway. When melanocytes are
treated with histamine, they undergo morphological as well as biochemical
changes resulting in an increased dendricity and increase in tyrosinase activity.
Additionally, the cAMP content of these cells was markedly increased with
exposure to histamine and the H2 agonist Dimaprit (26). Future investigation
of H2 agonists as additives for the induction of pigmentation by topical means
may lead to new discoveries in the area of tanning accelerators. Tetradecanoyl-
phorbol-13 acetate can also stimulate dendricity and increase melanin synthesis
in neural cells as well as melanocytes (27). The compound 2-mercapto-1-( b-4-
pyridethyl) benzimidazole (MPB) has been shown to increase the dendricity of
B16 melanoma cells. In addition, MPB was able to increase tyrosinase mRNA
without affecting cAMP levels (28).
Several neurotransmitters and modulators have been implicated in melano-
genesis. The vasoconstrictive peptide endothelin-1 (ET) is secreted by melanocytes
and has been shown to stimulate pigmentation. The neutral metalloproteinase
endothelin-converting enzyme (ECE-1a) activates ET. The reaction is pH depen-

dent. Several pro-inflammatory agents have been shown to increase ECE-1a (29).
Koh shows that the 28-amino-acid neuropeptide, vasoactive intestinal peptide, has
the ability to stimulate melanogenesis in the embryonic chick’s retinal pigment epi-
thelium by stimulation of the cAMP pathway (30). Other short amino acid chains
have been shown to stimulate melanogenesis as well. Hadshiew et al. (31) found
that the effectiveness of nucleotides on the stimulation of melanin synthesis was
dependent on the presence of a 50 phosphate group. Such discoveries could lead
to synthetic compounds that are able to facilitate the synthesis of melanin
without the negative effects of pro-inflammatory agents.
Palumbo et al. (32) have shown an increase in melanin synthesis and tyro-
sinase content of the ink gland of the cuttle fish, Sepia officinalis by L -glutamate.
The authors theorize that this amino acid binds to the N-methyl aspartate recep-
tor. An aqueous extract of Astragulus membranaceus bunge successfully upregu-
lates MITF and tyrosinase activity in melanocytes (21). A hydroalcoholic extract
of mammalian tissue rich in sphingolipids was shown to induce melanogenesis in
vitro. The activity was compared to that of other sphingolipids and confirmed the
potential for sphingolipids to stimulate melanogenesis (33). Kauser et al. (34)
have shown a link between the b-endorphin/m-opiate receptor system and the
regulation of skin pigmentation. Glycyrrhizin, a triterpenoid saponin from the
licorice plant, is shown to stimulate melanogenesis in B16 murine melanoma
cell through increase in tyrosinase and DCT expression (35).
ARTIFICIAL TANNING
Although many technological breakthroughs have occurred in recent years,
science still has no answer to the instant biological tan. Therefore, consumers
have relied on basically the same sunless tanning technology for the last half
of a century. DHA reacts with amino acids in the skin to form melanin-like com-
pounds known as melanoidins. This nonenzymatic browning, known as the
Maillard reaction or glycation, is most commonly observed as the browning of
foods with cooking and is responsible for the “burnt sugar” odor found in com-
mercially available self-tanning products.
Traditionally, such reactions require significant amounts of heat energy
to take place. The ability of DHA to cause nonenzymatic browning under
ambient conditions was discovered in the early 1900s (36). Its production
from Acetobacter was described by Bernhauer (37) in 1928 was inefficient
at best. In February 1960, Green (38) filed a patent describing an optimized
process for the production of DHA. It was found surprising that by lowering
what was thought of as the optimal pH for bioconversion to 5.0 – 5.9 and
enhancing the inoculation media, Green was able to come up with a process
in which DHA could be produced in mass quantities. By 1960, the first
patent on DHA’s use as an artificial tanning agent was filed by Andreadis
and Miklean (39). US Patent 2,949,403 describes what would be the first
modern self-tanning composition:
Ethyl alcohol 50.0%

Water 45.0%
DHA 4.0%
Acetone 1.0%
Shortly thereafter, Plough would market QT by Coppertonew, which

claimed to impart a tan “in 3 to 5 hours without the sun”. The product consisted
of 8% homosalate and 3.5% DHA in a base of water, propylene glycol, sorbitan
stearate, polyoxyethylene coconut alcohol, polysorbate-60, cetyl alcohol, lanolin,
simethicone, methylparaben, citric acid, and fragrance (see Fig. 29.1).
This novel product was the first modern day self-tanner and forged a path
for the subsequent generation of self-tanners. While effective in providing color
to the skin, they were less than stellar in their ability to provide a natural look.
Resulting artificial tans were streaky and required multiple applications to even
out striations in color. The hues of these early products were closer to that of
skin stained with b-carotene than skin that had been exposed to UV. Decades
of advances have significantly improved the quality of the sunless active as
well as the commercial products that exist today. The following paragraphs
will discuss the evolution of the self-tanner as well as the potential areas for
advancement in this area.
Regulatory Considerations
The US FDA considers sunless tanning actives as color additives because they
impart color to the skin. According to 21CFR70, color additives are defined as:
a dye, pigment, or other substance . . . that, when added or applied to a
food, drug or cosmetic or to the human body or any part thereof, is
capable (alone or through reaction with another substance) of imparting
a color thereto (40).
Figure 29.1 QT, the first commercial sunless tanner with DHA.
All color additives should be labeled, without respect to concentration, fol-

lowing noncolor additives present at a concentration of less than 1%. The actives
allowed in sunless products in the USA are limited to those approved for use
as such. The following color additives are described in the Code of Federal
Regulations.
Color Additives Exempt from Certification per 21CFR73 2003 (41)
Annatto Henna Titanium dioxide

Caramel Iron oxides Aluminum powder
Carmine Ferric ammonium ferrocyanide Bronze powder
b-Carotene Ferric ferrocyanide Copper powder
Bismuth citrate Chromium oxide greens Ultramarines
Disodium EDTA copper Guanine Manganese violet
Potassium sodium copper Lead acetate Zinc oxide
Chlorophyllin
Dihydroxyacetone Pyrophyllite Luminescent zinc
Sulfide
Bismuth oxychloride Mica
Guaiazulene Silver
Color Additives per 21CFR74 2003 (42)
Citrus Red No. 2 D&C Red No. 22 D&C Yellow No. 10

D&C Blue No. 4 FD&C Blue No. 1 D&C Yellow No. 11
D&C Blue No. 6 FD&C Blue No. 2 D&C Yellow No. 7
D&C Blue No. 9 D&C Red No. 27 D&C Yellow No. 8
D&C Brown No. 1 D&C Red No. 28 Ext. D&C Violet No. 2
D&C Green No. 5 D&C Red No. 30 Ext. D&C Yellow No. 7
D&C Green No. 6 D&C Red No. 31 FD&C Red No. 3
D&C Green No. 8 D&C Red No. 33 FD&C Red No. 4
D&C Orange No. 10 D&C Red No. 34 FD&C Red No. 40
D&C Orange No. 11 D&C Red No. 36 FD&C Yellow No. 5
D&C Orange No. 4 D&C Red No. 39 FD&C Yellow No. 6
D&C Orange No. 5 D&C Red No. 6 Orange B
D&C Red No. 17 D&C Red No. 7 Phthalocyaninato
D&C Red No. 21 D&C Violet No. 2 2-Copper
Dihydroxyacetone
The formulator is limited to the aforementioned compounds to provide coloration
to the skin. Products that stain the skin (bronzers) have been marketed in the past.
However, the variable solubilities of the cosmetic dyes listed in the tables lead to
an unnatural appearance of skin when fading. Needless to say, today’s sunless
tanning products rely predominantly on one active ingredient to impart a tan
C
HOH2C CH2OH
Dihydroxyacetone
Figure 29.2 Dihydroxyacetone—the reducing sugar which produces artificial tanning

of the skin at ambient temperature.
color to the skin, DHA. Unlike tanning accelerators, the science of sunless tan-
ners relies on optimizing the performance of this active (Fig. 29.2).
DHA is a three-carbon reducing sugar produced from glycerin by the bac-
teria Acetobacter suboxydans. The nonenzymatic reaction, although not comple-
tely understood, is ubiquitous to a certain point. The initial reaction, on the skin,
involves the condensation of an amino group, usually from an amino acid, with
the keto group on the DHA molecule. The resulting compound then undergoes
dehydration to result in a Schiff base followed by a rearrangement to form a
Heyns product. This cycle then is repeated with additional amine compounds
to form high-molecular-weight chromophores. At Avon, our research indicates
that this reaction results in a consumer perceivable darkening usually within
1 –2 h of application (Fig. 29.3).
Photoacoustic spectroscopy has shown that the tanning effect takes place
between the stratum corneum and stratum granulosum. Penetration of DHA
into the skin results in an increased darkening of the skin (43). The structure
of the resulting melanoidins has not yet been completely described. Schneider
and Sprenger (44) describe the use of transaldose b to trap Schiff base intermedi-
ates for determination of their structure. Similar techniques may be useful in the
determination of the structure of the various melanoidins. Such information
would be extremely useful in explaining the variation in tonality and intensity
of sunless tanning products.
Although we do not have a complete understanding of the chemical differ-
ences between a UV induced tan and an artificial tan, some recent research has
provided insight into this phenomenon. Using a Minolta chromameter, the tonal-
ity of the natural suntan was compared to that of an artificial tan by Muizzudin
et al. (45). By measuring the change in reflectance as well as the increase in
yellow and red discoloration, the authors were able to categorize both pigmenta-
tion phenomena in a numerical format. When comparing the sunless tan to the
natural tan a clear pattern develops. DHA induced pigmentation is clearly
more yellow on the skin than a UV induced tan. This phenomenon was exagger-
ated in those with Fitzpatrick skin types I and II. Since sunless tanners increase
the yellow color of skin greater than the red color of skin it is no surprise that
H2COH HC=O
H2COH
C N R C NH R HC NH R
H2COH H2COH H2COH

Schiff base Heyns product
Figure 29.3 Non-enzymatic browning—initial reaction steps. Post condensation of

dihydroxyacetone.
those with types I and II skin would exhibit a more orange coloration than those
with skin types III and IV. The authors further describe the effects of several anti-
oxidants on DHA induced tanning. It was observed that these antioxidant com-
pounds were able to shift the color of DHA tanned skin more to the red. The
resulting combination provided a more natural looking artificial tan than
without the use of antioxidants. The authors hypothesize that the addition of anti-
oxidant compounds alters the polymerization pattern of the DHA –amino
complex to form more reddish compounds than yellow.
Even the most inexperienced of formulators is aware of the fact that self-
tanning formulations require a minimum amount of water to be effective. The
influence of water on the pigmentation reaction of DHA is more complex than
expected. Extreme hydration has been shown to inhibit DHA induced tanning
in skin. By incubating skin exposed to DHA in varying relative humidities
(RHs), Nguyen and Kochevar (46) were able to shed some light on the effects
of moisture in self-tanning systems. Minimal pigmentation was observed in
samples kept at 0% and 100% RH while a maximum effect was shown at 84%
RH. Initially, the authors expected the proteolysis of filagrin, which shows a
similar response to RH, to be the main factor in their results. However, the
authors were able to rule this out by incubating samples under optimal humidity
conditions for proteolysis to occur prior to treatment with DHA. The optimal per-
formance of DHA was shown to be independent of the presence of free amino
acids resulting from the breakdown of filagrin. Additional work with free
amino acids led them to the hypothesis that DHA induced pigmentation is a func-
tion of hydration of the skin and RH.
The utility of DHA is more than just for the sake of vanity. Dermatology is
adopting its use for treatment of various skin ailments. Suga et al. (47) have
acceptably treated vitiligo and piebald regions with a 5% solution of DHA.
The melanoidins resulting from artificial tanners have also been shown to
absorb the long-wavelength UV-A and visible light that cause photosensitivity
in patients with variegate porphyria (48). DHA induced skin coloration was
able to allow for higher doses of UV-A to be tolerated in patients receiving
PUVA treatments by protecting unaffected skin areas (49).
Formulating with DHA

Quality Control
As with any highly functional active, the formulator must take into account the
quality and chemistry of DHA when formulating. DHA exists as both a
monomer and a dimer in the crystalline state. The dimer form is not considered
effective for artificial tanning of the skin. It has been generally accepted that the
dimer readily converts to monomer when put in aqueous solution (50). However,
it was demonstrated by Forest et al. (51) that solutions made from the DHA dimer
were unable to produce a visual browning of the skin. Use of fluorescence
demonstrated that some minimal reaction did occur between amino acids and
the DHA dimer solution. The dimer of DHA can be identified by melting point
or IR analysis. The melting point of DHA varies from 608C to 908C depending
on the monomer/dimer content. A melting point in the lower end of this range
is indicative of impurities. The more accurate way to assess the quality of
DHA is by infrared spectroscopy. The carbonyl function of DHA shows a peak
at 1744 cm21, indicating the presence of monomer. The dimer form will
present a peak at 1273 cm21 due to its ether functionality. Evaluation of the
ratio of monomer to dimer will allow the formulator to accurately differentiate
the quality of DHA (36).
Formulation
Our studies show that both spray and lotion forms are deemed equally acceptable
to current sunless tanning product users. These same studies indicate that this
consumer is quite sensitive to the odor of the products they choose. This infor-
mation would lead one to believe that maintaining the functional integrity of
DHA is central to developing a successful product. Therefore, the formulator
should take every step necessary to assure that the formulation provides func-
tional levels of DHA for its suggested shelf life. Although DHA is known to
impart color to the skin at levels of ,1% to .10%, the recommended use
level for sunless tanning formulations is typically from 3% to 5% by weight.
DHA is most easily incorporated as a concentrated aqueous solution at tempera-
tures less than 408C. When developing a vehicle for DHA, the most obvious com-
ponents to avoid are amine compounds. However, amine compounds such as
EDTA do not react as strongly to DHA and may be used if necessary. The
neat raw material should be stored free from humidity at 48C to prevent break-
down of the active. Very low pH leads to the polymerization of DHA and
could result in dimer formation in finished formulations. Phosphates can facilitate
the degradation of DHA in formulation, therefore buffers containing them should
be avoided. Calcium ions complex with DHA and inhibit its ability to react
with amine compounds. Anionic emulsifiers also facilitate the breakdown of
DHA during storage. DHA is incompatible with the inorganic compounds
TiO2, ZnO, as well as iron oxides. DHA is degraded by reducing agents
such as ascorbic acid. Excessively high pH can lead to the formation of hydroxy-
acetone and methylglyoxal (36,50).
Recognizing the potential of new discoveries in the sunless tanning market,
cosmetic scientists are protecting their intellectual property in the form of
patents. The filing and enforcing of patents has become a major tool in securing
market share in the sunless tanning industry. Following is a list of granted US
Patents that claim to enhance the color and/or intensity of sunless tanning
compositions.
US Patents for Enhancing Sunless Tanning Color and Intensity
6,171,605 DHA with propolis extract (caffeic acid phenylethyl ester) to enhance
sunless tan
5,827,506 Amino acids with DHA in a two-component package
5,662,890 Self-tanning spray with DHA, water, and a penetration enhancer without
ethanol or oil
5,663,923 DHA in combination with amino acid and pH less than 4
5,503,824 Two-component self tanner with DHA in one component and an amino
silicone in the second component
6,537,528 Self-tanning composition with a flavylium salt and radical from a hydroxy
or alkoxy group
6,468,508 Conditioning skin for self-tanning by dehydration
6,406,682 Saxifragia extract and DHA for a faster, more natural tan
6,344,185 DHA with a thickener and oil-soluble polyester
6,231,837 Polyethoxyglycol with DHA, sorbitol, and polyols at pH between 3.5
and 4.5
5,801,169 5,6-dihydroxyindole polymer in combination with DHA
5,750,092 Two-component system with DHA in one component and 20 polyamines
in the other
5,705,145 DHA in combination with azole compounds to decrease coloration time
5,302,378 DHA in combination with dimethicone copolyol phosphate
4,708,865 DHA with cutch, logwood, and walnut powder
5,700,452 DHA with a cationic polymer and cationic emulsifier
5,569,460 DHA or methylglyoxal with eosin compounds
Although US federal regulations only allow for DHA as a sunless tanning

active, alternative technologies exist with the capability to impart an artificial tan
to the skin. US Patent 6,344,185 describe a skin coloring powder that consists of
formaldehyde, formic acid, and a source of sulfite ions. Uchida et al. (52)
describe the formation of advanced glycation end products via the Maillard reac-
tion mediated by methylglyoxal. Subsequent investigation into this compound
shows that it is patented under US 5,569,460 as a skin colorant. Reducing
sugars other than DHA can act as Maillard reaction intermediates, thus having
the potential for use as a sunless tanning agent as well. As a general rule, reducing
sugars have a free ketone or aldehyde functional group where the initial conden-
sation reaction of nonenzymatic browning will occur. The most commonly
known reducing sugar is glucose. Unfortunately, a large amount of heat energy is

required to trigger the glycation reaction between glucose and free amines. Such
properties render most reducing sugars useless for a self-tanning product.
As seen with methylglyoxal, corporations are aggressively pursuing new
sunless tanning technologies to remain competitive in the marketplace. The
key to uncovering new self-tanning actives is the screening of compounds that
meet the known criteria for creating glycation end products. The reducing
sugar erythrulose, which is found predominantly in the red raspberry Rubus
idaeus, has been marketed as a self-tanning enhancer for years. Potential new
sugars for use in sunless products are easily screened for their ability to act as
reducing sugars. The determination of whether or not a carbohydrate is a redu-
cing sugar must first be made. Suspect molecules may be combined with
various reagents that expose the sugar to metallic ions. The reduction of these
ions to form a colored precipitate is indicative of a reducing sugar. Subsequent
in vitro experimentation with successful candidates can determine utility in a
sunless product. Golz-Berner and Zastrow describe a method for screening
self-tanning compositions that can be evaluated in 5 s to 5 min (53). The compo-
sitions to be screened are exposed to a mixture of amino acids and purines to
determine their self-tanning ability. Another in vitro screen for self-tanning
activity involves the application of product onto a skin mimic with a controlled
level of hydration. In these systems, color development is observed within similar
timing to that of human subjects. The multitude of reducing sugars both commer-
cially available and undiscovered can provide the potential next generation of
self-tanning active. Any new actives discovered will most likely appear in
Europe and undergo several years of safe use before their adoption in the USA.
TOP 10 PRODUCTS REVIEW (RANKED BY 2002 SALES)3

Tanning Accelerators (1)
1. Hawaiian Tropic Tan Accelerator Spray $869,882
Tanning Research Labs, Inc., USA
A highly fragranced, mineral oil based single-phase spray with natural extracts.
This product claims to improve the appearance of a tan by moisturizing and nour-
ishing the skin with natural extracts, vitamins, and amino acids.
Ingredient copy: Mineral oil, Carthamus Tinctorius (Safflower) Seed Oil,
Fragrance, Beta-Carotene, Daucus Carota Sativa (Carrot) Root Extract, Aloe
Barbadensis Extract, Polybutene, Phenyl Trimethicone, Tartaric acid, L -Histidine
(Amino acid), L -Arginine (Amino acid), Isocetyl Alcohol, Propylparaben, D&C
Yellow #11, D&C Red #17, Plumeria Acutifolia Flower Extract (Plumeria),
3
Source: IRI InfoScan Review Data of the Total US Market (Food, Drug and Mass Excluding
Walmart).
Mangifera Indica Fruit Extract (Mango), Psidium Guajava (Guava), Carica

Papaya Fruit Extract (Papaya), Passiflora Incarnata Fruit Extract (Passion
Fruit), Colocasia Antiquorum Root Extract (Taro), Aleurites Moluccana Seed
Extract (Kukui Nut).
Claims: A glistening touch of Hawaiian Tropical, exotic, natural flora, fruit
and nut extracts . . . amp up with Intense Tanning Power! It is boosted with Beta-
Carotene, Carrot Extract, and natural Amino acids. This moisturizing oil actually
intensifies the quality and appearance of your dark “tan of the islands”. Moistur-
izing Forever Tanw ingredients like Aloe Vera, Plumeria, Mango, Guava,
Papaya, Passion Fruit, Taro, and Kukui Nut. Natural Amino acids help nourish
your skin. “Helps to hold your tan for weeks longer”.
2. Hawaiian Tropic Ultra Sun Formula $857,971

Tan Accelerator Spray
Tanning Research Labs, Inc. USA
A highly fragranced, mineral oil based single-phase spray with natural extracts.
This product claims to improve the appearance of a tan by moisturizing and nour-
ishing the skin with natural extracts and amino acids. The high refractive index
silicone oil, phenyl trimethicone, imparts a glossy sheen to the skin.
Ingredient copy: Mineral Oil, Fragrance, Isocetyl Alcohol, Polybutene,
Phenyl Trimethicone, Tartaric Acid, Amino acids: L -Histidine and L -Arginine,
Aloe (Aloe Barbadensis) Extract, Extracts of Plumeria, Manako (Mango),
Kuawa (Guava), Mikana (Papaya), Lilikoi (Passion Fruit), Taro, and Kukui.
Claims: A touch of Hawaiian Tropical, exotic, natural flora, fruit and nut
extracts . . . Amp up with Intense Glistening Power! Hawaiian Tropicw holds
the secret to the hottest look under the sun. Our Ultra Sunw formula actually
intensifies the quality and appearance of your dark, “tan of the islands”. Hot
tropic fragrance. Moisturizing Forever Tanw ingredients like Aloe Vera,
Plumeria, and Mango defend against peeling and “help to hold your tan for
weeks longer”. Natural amino acids help replace skin’s vital nutrients lost
during the tanning process.
3. Banana Boat Tan Accelerator Oil SPF 0 $731,793

Sun Pharmaceuticals, USA
A basic hydrophobic tan accelerator composed of triglyceride oils rather than
mineral oils. This formula utilizes essential fatty acids and vitamins A and E
to maintain the skin’s moisture barrier. The inclusion of cyclomethicone
allows this formulation to have a less greasy aesthetic than traditional tan
accelerators.
Ingredient copy: Sunflower Oil, Cyclomethicone, Sunflower Oil, Cocoa
Butter, Wheat Germ Oil, Aloe Extract, Oat Extract, Evening Primrose Oil
(Omega-6 Oil), Tocopherol (Vitamin E), Retinyl Palmitate (Vitamin A),
Fragrance.
Claims: Tan Express by Banana Boat is a unique formula that lets you tan
as fast as you can. It conditions and moisturizes your skin for the deepest, darkest
tan and beautiful smooth skin. Tan Express Dark Tanning Ultimate Oil contains
natural oils. Sunflower Oil, and Evening Primrose Oil to help keep your skin
moist and supple. This blend of exotic oils and fragrance contains vitamin A
and vitamin E. This enriched formula helps improve the skin’s elasticity and
helps protect the skin from free radical damage. Contains no mineral oil. Tan
Express for a Fast, Beautiful Tan!
4. Hawaiian Tropic Tan Amplifier Bronzing Spray $444,679

Tanning Research Labs, Inc., USA
A highly fragranced, water based spray with natural extracts. This product claims
to improve the appearance of a tan by moisturizing and nourishing the skin with
natural extracts and amino acids. Caramel is used to provide the bronzing effect.
Oil components are incorporated into the base using polysorbate 20. The formu-
lation is slightly thickened with carbomer.
Ingredient copy: Purified water, Glycerin, Polysorbate 20, Caramel, Aloe
Barbadensis Gel, Triethanolamine, DMDM Hydantoin, Carbomer, Diazolidinyl
Urea, Fragrance, Benzophenone-4, Polybutene, Phenyl Trimethicone, Amino
acids: L -Histidine and L -Arginine, Tartaric acid, Disodium EDTA, Bertholletia
Excelsa Seed Oil (Brazil Nut Oil), Phospholipids, Tocopheryl Acetate
(Vitamin E Acetate), Retinyl Palmitate (Vitamin A Palmitate), Plumeria Acuti-
folia Flower Extract (Plumeria), Magnifera Indica Fruit Extract (Mango),
Psidium Guajava (Guava), Carica Papaya Fruit Extract (Papaya), Passiflora
Incarnata Fruit Extract (Passion Fruit), Colocasia Antiquorum Root Extract
(Taro), Aluerites Moluccana Seed Extract (Kukui Nut).
Claims: A touch of Hawaiian Tropical, Exotic, Natural Flora, Fruit, and nut
extracts . . . intensify your tan with Instant Bronzing Power! Natural looking,
self-activating bronzer provides instant golden color. Our Ultra Sunw Formula
actually intensifies the quality and appearance or your dark, “tan of the
islands.” Citrus Hot Tropic Fragrance. Moisturizing Forever Tanw ingredients
like Aloe Vera, Plumeria, and Mango defend against peeling and “help to hold
your tan for weeks longer”. Natural amino acids help replace skin’s vital nutrients
lost during the tanning process.
5. Ocean Potion Australian Blend Tan Accelerator Spray Gel $421,141

Sun and Skin Care Research, Inc., Cocoa, FL, USA
An aqueous based formulation with tyrosine and riboflavin for enhancing the
tanning process. Tyrosine has been a staple active in the tanning accelerator
market for many years. It is theorized to supplement the skin’s reservoir of the
starting compound of melanin. Riboflavin is thought to synergistically enhance
the effects of tyrosine in the formula. The base is thickened with an amphiphilic
acrylates copolymer. Sorbitan oleate is used to disperse the hydrophobic com-

ponents within the external phase.
Ingredient copy: Deionized Water, Aloe Vera Gel, Sunflower Oil, Acrylics
C10-30, Alkyl Acrylate Cross-polymer, Sorbitan Oleate, Tyrosine, Vitamin A
Acetate, Ascorbic Acid (Vitamin C), Vitamin E Acetate, Riboflavin, DMDM
Hydantoin, Propylparaben, Methylparaben, Disodium EDTA, Tea Tree Oil,
Fragrance.
Claims: Dark tanning Xcellerator spray gel promotes instant tanning by
increasing the sun’s heating intensity onto the skin. This advanced gel glides
easily for quick absorption into the skin providing accelerated tanning and a
silky smooth feel. Enriched with numerous phyto effect polymers and plant
extracts such as Aloe Vera, Tea Tree, and vitamins A, C, and E to hydrate
skin cells and extend tan life.
6. Australian Gold Tan Accelerator Spray $360,669
7. Australian Gold Tan Accelerator Lotion $337,016
8. Australian Gold Tan Accelerator Spray Gel $307,883
9. Australian Gold Exotic Blend Tan Accelerator Lotion $293,398
10. Australian Gold Tan Accelerator Spray Gel SPF 4 $255,468
Sunless Tanners (1)

1. Coppertone Endless Summer $15,669,3964
Schering-Plough USA
The current market leader in sunless tanning utilizes a two-component package to

deliver color in 30 min without the use of dyes. Separate W/O emulsions in the
same package; keeps dihydroxyacetone separate from the amino silicone, oligo-
meric diaminoalkyl siloxane. When the two products combine on the skin, the
DHA reacts with the oligomer to provide faster color development. This
formula is patented under US 5,645,822 and US 5,750,092.
Ingredient copy: Water, Cyclopentasiloxane, Isohexadecane, Propylene
Glycol, PEG/PPG 20/15 Dimethicone, Polyglyceryl-4 Isostearate, Sodium
Chloride, Hexyl Laurate, Retinyl Palmitate (Vitamin A Palmitate), Avena
Sativa Kernel Extract (Oat), Cetyl PEG/PPG 10/1 Dimethicone, Lactic Acid,
Oligomeric Diaminoalkyl Siloxane, Phenoxyethanol, Butylene Glycol, Glycerin,
Isopropylparaben, Butylparaben, Isobutylparaben, Fragrance, Diazolidinyl Urea,
Dihydroxyacetone, Mica, Iron oxides.
4
Combined SKUs 4110001623 and 4110001659.
Claims: Visibly reduces fine lines and wrinkles, natural looking color in
30 min, provides just enough color to maintain a healthy, natural looking glow.
2. Neutrogena Instant Bronze Sunless Tanner/Bronzer Foam $5,483,721

Johnson & Johnson USA
This combination sunless tanner and bronzer allow the consumer to see where the
product is applied in order to avoid streaking. The natural colors caramel and
carmine provide the instant bronzing effects. This formulation contains the
additional reducing sugar erythrulose in combination with the solvents pentylene
glycol, methylpropanediol, and PPG-5-Ceteth-20. Solvents such as these are
thought to facilitate the exposure of DHA to areas where they work more efficiently.
The vehicle is a nonionic O/W emulsion stabilized with PVM/MA decadiene
crosspolymer. The formula is packaged in a nonaerosol foaming pump that provides
a rich foam for ease of application. This formula is patented under US 6,113,888.
Ingredient copy: Water, Dihydroxyacetone, Pentylene Glycol, Caramel,
PPG-5-Ceteth-20, Methyl Gluceth 20, Glycerin, PEG 100 Stearate, Erythrulose,
PVM/MA Decadiene Cross-polymer, Methylpropanediol, Decyl Glucoside,
Cetyl Hydroxyethylcellulose, Carmine, Sodium Citrate, Citric Acid, Sodium
Hydroxide, Phenoxyethanol, Methylparaben, Ethylparaben, Butylparaben, Pro-
pylparaben, Isobutylparaben, Fragrance.
Claims: Streak Free Foam. Instant hint of bronze, plus lasting sunless tan.
The sheer bronzer provides a hint of temporary, natural looking color immedi-
ately upon application and allows you to see where you have applied it to help
eliminate mistakes for flawless, streak-free, even coverage. Over a few hours,
the sunless tanner develops a natural looking tan that looks like a real tan and
fades like a real tan. Oil-free formula absorbs quickly and dries in less than 5
minutes. Light, fresh fragrance.
3. Neutrogena Instant Bronze Sunless Tanner/Bronzer Lotion $4,195,368

Johnson & Johnson USA
The lotion counterpart to the above mentioned foam, combines sunless tanner and
bronzer in one. The natural colors caramel and carmine provide the instant bronz-
ing effects. This formulation contains a sodium citrate buffer system. The solvent
Methylpropanediol is thought to facilitate the exposure of DHA to areas of the
skin where they work more efficiently. The base is a non-ionic emulsion stabil-
ized with the hydrocolloids magnesium aluminum silicate and xanthan gum.
Ingredient copy: Water, Dihydroxyacetone, Glycerin, Isopropyl Myristate,
Isopropyl Palmitate, Ethylhexyl Palmitate, Caramel, Glyceryl Stearate, PEG 100
Stearate, Magnesium Aluminum Silicate, Sorbitol, Cetyl Alcohol, Methylpropa-
nediol, BHT, Tetrasodium EDTA, Stearyl Alcohol, Xanthan Gum, Sodium
Citrate, Citric Acid, Carmine, Phenoxyethanol, Methylparaben, Ethylparaben,
Butylparaben, Propylparaben, Isobutylparaben, Fragrance.
Claims: Streak Free. Instant hint of bronze, plus lasting sunless tan. The
sheer bronzer provides a hint of temporary, natural looking color immediately
upon application and allows you to see where you have applied it to help elim-
inate mistakes for flawless, streak-free, even coverage. Over a few hours, the
sunless tanner develops a natural looking tan that looks like a real tan and
fades like a real tan. Oil-free formula absorbs quickly and dries in less than 5
minutes. Light, fresh fragrance.
4. Neutrogena Sunless Tan Nonaerosol Spray $3,606,059

This nonaerosol self-tanning spray is delivered through a pressurized bladder
system with a 3608 valve that allows for continuous even application. Dihy-
droxyacetone is delivered in an aqueous base with various solvents thought to
enhance the penetration of the active. It should be duly noted that this formulation
contains the incompatible amino-functional components diazolidinyl urea and
sodium PCA.
Ingredient copy: Water, Witch Hazel, Ethoxydiglycol, Dihydroxyacetone,
Dimethyl Isosorbide, Dipropylene Glycol, Isoceteth-20, Methyl Gluceth-20,
Glycereth-7, Sodium PCA, Citric Acid, Propylene Glycol, Diazolidinyl Urea,
Methylparaben, Propylparaben, Fragrance.
Claims: Natural-looking tan. Fast drying, oil free. Light, fresh fragrance.
Non-comedogenic. Hypo-allergenic. Get a healthy-looking glow with this safe
alternative to tanning. Oil-free formula provides a completely natural looking
tan that looks like a real tan and fades like a real tan—not orange or streaky.
Absorbs quickly and dries in less than 5 min. The one-touch continual spray
can be applied from any angle to help cover hard-to-reach areas.
5. Neutrogena Sunless Tan Foam $3,352,018

The nonaerosol mousse, counterpart to the nonaerosol spray, provides mousse-
like foam through a fine mesh pump. The foaming is provided by nonionic
sugar based surfactants and stabilized with cetyl hydroxyethylcellulose.
The formulation contains the reducing sugar erythrulose in combination with
the solvents pentylene glycol, and methylpropanediol. Solvents such as these
are thought to facilitate the exposure of DHA to areas where they work more
efficiently.
Ingredient copy: Water, Dihydroxyacetone, Pentylene Glycol, Glycerin,
Methyl Gluceth-20, PPG-5 Ceteth-20, Erythrulose, Decyl Polyglucose, Methyl-
propanediol, Cetyl Hydroxyethylcellulose, Sodium Citrate, Phenoxyethanol,
Methylparaben, Ethylparaben, Propylparaben, Butylparaben, Isobutylparaben,
Citric Acid, Fragrance.
Claims: Streak free. Natural-looking tan. Fast drying, oil free. Light, fresh
fragrance. Non-comedogenic. Get a healthy-looking glow with this safe
alternative to tanning. This light, nonsticky foam glides on smoothly to apply
easily and evenly. Absorbs quickly and dries in less than 5 min . . . provides
a completely natural-looking tan that looks like a real tan and fades like a real
tan—not orange or streaky.
6. Neutrogena Sunless Tan Lotion $3,236,605
7. Bain de Soleil Radiance Eternelle Sunless Tan Cream $2,952,754
8. Banana Boat Sunless Tan Cream $2,763,853
9. Tomas Tan Perfect Sunless Tan Waterproof Lotion Kit $2,741,219
10. Neutrogena Sunless Tan Lotion Spray $2,613,010
CONCLUSION
Given the continued research that demonstrates the harmful effects of sun
exposure, more and more people will turn to cosmetic science for that just
back from vacation look. The use of products that facilitate pigmentation of
the skin has shown steady sales growth and there are no signs of slowing. Econ-
omic gains of the market seem to have exceeded its growth in technology. The
potential gains of the discovery of a new technology in the self-tanning market
have already been demonstrated with Plough’s Endless Summerw. First-year
sales in the USA of this one product beat the entire tanning accelerator market
by more than 60%.
Consumer awareness of the negative effects of tanning has led to a sharp
decline of tanning accelerator sales. However, the tanning bed boom seems to
have saved that market for now. It is only a matter of time before the negative
effects of the suberythemal doses of UV light put forth by tanning beds will
have widespread consumer awareness. This will eventually lead to a cessation
of sales in tanning accelerators. It is not foreseen that any major corporations
will see a profitable return on investment for the research required to deliver a
breakthrough tan accelerating technology. The small size of the tanning accelera-
tor market will require true breakthroughs in technology to come from the entre-
preneurial spirit of the corporations who lead the market today.
The future of the tanning industry will lie in the hands of the self-tanner.
Although the quality of self-tanning formulations has significantly improved in
the 40 or so years they have been on the market, they are by far less than
perfect. Two major technology gaps exist to date, the speed of color development
and matching the hue of a natural tan. Perhaps a greater understanding of the
composition of melanoidins will allow the formulator to devise compositions
that can be adjusted to accommodate the natural skin tone of the end user.
Such developments could lead to a new family of products for individual skin
types. They may incorporate components of the still unknown polymer that are
devoid in a particular skin type or have additives to alter the final color imparted
by the product. We may eventually see products designed for the spectrum of
“skin that burns easily” or “for skin that rarely burns”, as opposed to today’s pro-
ducts which are marketed as light, medium, and dark.
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US Patents Referenced
6,171,605 Bevacqua A, Lahanas K, Color Access Inc., Melville, NY Self-tanning compositions containing DHA and
Muizzudin N, Vrabe N propolis extract
6,344,185 Argus L, Kambe T Shiseido Co, Ltd., Tokyo, Japan Self-tanning composition
6,036,969 Golz-Berner K, Zastrow L Coty B.V., Haarlem, NL Process for measuring cosmetic tanning and test kit
therefor
5,827,506 McShane J, Kaplan C, Meyer T Schering-Plough, Memphis, TN Sunless tanning method and apparatus
5,662,890 Punto L, Zucchino J, Lentini P Estee Lauder Inc., New York, Self-tanning cosmetic compositions and methods of
NY using the same
5,603,923 Robinson L, Tanner P Procter & Gamble Co., Artificial tanning compositions having improved
Cincinnati, OH color development
5,503,824 Lentini P, Marenus K, Skin tanning compositions
Muizzuddin N, Pelle E,
Punto L
6,537,528 Candau D, Forestier S L’Oreal S.A., Paris, France Composition comprising at least one self-tanning
agent chosen from monocarbonyl and polycarbonyl
compounds and a flavylium salt compound which
is unsubstituted in position 3, for coloring the skin,
and uses thereof
6,468,508 Laughlin T Laughlin Products, Inc., Method, apparatus, and composition for
Grapevine, TX automatically coating the human body and skin
Gonzalez and Kalafsky
preconditioning system for use therewith

6,406,682 Martin R, Belcour-Castro B, Societe L’Oreal, Paris, France Saxifraga extracts for artificially tanning human
Galup C skin
6,344,185 Argus L, Kambe T Shiseido Co. Ltd., Tokyo, Japan Self-tanning composition
6,231,837 Stroud E, Scott J Schering-Plough, Memphis, TN Self-tanning DHA formulations having improved
stability and providing enhanced delivery
5,801,169 Marrot L L’Oreal S.A., Paris, France Compounds in the form of 5,6-dihydroxyindole
polymers, their process of preparation and
compositions comprising them
5,750,092 Meyer T, Ando M, Powell J Schering-Plough, Memphis, TN Sunless tanning composition and method
5,705,145 Miklean S, Lahanas K, Vrabie N, E-L Management Corp., Skin tanning compositions and method
Pelle E, Bevacqua A New York, NY
5,302,378 Crotty B, Ziegler P Chesebrough Pond’s USA Co., Self-tanner cosmetic compositions
Greenwich, CT
4,708,865 Turner J Method and composition for artificially tanning the
Sunless Tanning and Tanning Accelerators
human epidermis
5,700,452 Deckner G, Pichardo F, Alban N, Procter & Gamble Co., Compositions for imparting an artificial tan and
Sills M Cincinnati, OH protecting the skin from UV radiation
5,569,460 Kurz T, Stossel S, Spiller A Merck Patent Gesellschaft Mit Skin-coloring preparation
Beschrankter Haftung,
Darmstadt, DE
2,948,658 Green S Baxter Labs Inc., Westfield, NJ Process for producing DHA
2,949,403 Andreadis J, Miklean S DHA compositions for tanning the human
epidermis
599
Other Actives in the Sun
Care Industry
30
Role of Antioxidants in
Sun Care Products
Ratan K. Chaudhuri
EMD Chemicals, Inc., Hawthorne, New York, USA
Introduction 604
UV-Induced Chemical and Biochemical Changes:
Causes and Consequences 605
Photosensitizer and Reactive Oxygen Species 605
Iron and Copper 605
Matrix-Degrading Metalloprotease 607
Antioxidant Defenses of the Skin 609
Antioxidant Defense Enzymes 609
Low Molecular Weight Antioxidants 610
Photoprotection of Human Skin Using Antioxidants and Other
Photoprotectants 611
Vitamin E and Its Derivatives 612
Vitamin C and Its Derivatives 614
Carotenoids 615
Plant Polyphenolics 617
Tea Polyphenols 618
Silymarin 618
Emblica Antioxidant 619

An affiliate of Merck KGaA, Darmstadt, Germany.
603
604 Chaudhuri
Combination of Antioxidants 620

Unconventional Photoprotectants 621
Selenium 622
Zinc 622
Chelating Agents 622
Compatible Solutes 623
Retinoids 623
Dihydroxyacetone 624
Commercial Products 624
Conclusions 624
References 629
INTRODUCTION
Sun is the great initiator of photochemical reactions, which provides energy
that sustains plant life and maintains human health. It warms the earth and
furnishes solar energy, and in humans, activates synthesis of vitamin D for
utilization by the body to help it absorb calcium and other minerals. As the
outermost barrier of the body, the skin is directly exposed to a pro-oxidative
environment. The effects of ultraviolet (UV) radiation from sun exposure can
induce or exacerbate oxidative attack leading to the generation of reactive
oxygen species (ROS) and other free radicals. The most severe consequence
of photodamage is skin cancer. Less severe photoaging changes result in
wrinkling, scaling, dryness, and uneven pigmentation consisting of hyper-
and hypopigmentation (1 –3).
Extended lifespan, more spare time, and excessive exposure to UV radi-
ation from sunlight or tanning devices, especially in the Western population,
has resulted in an ever increasing demand to protect human skin against the
detrimental effects of UV exposure of the skin. Sunscreens—the current
gold standard of photoprotection—are useful, but their protection is inadequate
against long-wave UV-A light because UV-A is especially efficient at generat-
ing ROS (4 –6). UV-A is being recognized increasingly as an important cause
of photoaging and skin cancer. Photoprotective products combining sunscreens
and antioxidant or antioxidant mixtures have been touted to provide increased
efficacy and safety of such products (1). This chapter is intended to focus on
three major areas: (A) major causes and consequences of UV-induced photo-
damage to skin; (B) role of endogenous antioxidant defense system; and (C)
the photoprotective potential of topically applied antioxidants. A list of com-
mercially available products containing sunscreens and antioxidants has also
been included in this chapter.
Role of Antioxidants in Sun Care Products 605
UV-INDUCED CHEMICAL AND BIOCHEMICAL CHANGES:

CAUSES AND CONSEQUENCES
Photosensitizer and Reactive Oxygen Species
Besides direct absorption of UV-B photons by DNA and subsequent structural
changes, generation of ROS following irradiation with UV-A and UV-B requires
the absorption of photons by endogenous photosensitive molecules. There are
many endogeneous chromophores in human skin, which in the presence of
UV-A radiation can generate ROS. Porphyrins (protoporphyrin, coproporphyrin,
and uroporphyrin), flavins (riboflavin), quinone (ubiquinone), and the pyrimidine
nicotinamide cofactors (nicotinamide adenine dinucleotide, NADH; and nicoti-
namide adenine dinucleotide phosphate, NADPH) are examples of common
photosentizers in mammalian cells (7). Recently, the identification of the epider-
mal UV-A absorbing chromophore trans-urocanic acid that quantitatively
accounts for the action spectrum of photo aging, has been reported (8). The
excited photosensitizer subsequently reacts with oxygen resulting in the gener-
ation of ROS including superoxide anion radical and singlet oxygen. Superoxide
anion radical and singlet oxygen are also produced by neutrophiles that are
present in increased quantities in photodamaged skin, and contribute to the
overall pro-oxidant state. Superoxide dismutase (SOD) converts superoxide
anion radical to hydrogen peroxide. Hydrogen peroxide is able to cross cell
membranes easily and, in conjunction with Fe2þ, generates highly toxic hydroxyl
radicals. Both singlet oxygen and hydroxyl radical can initiate lipid peroxidation.
Many organic sunscreens also act as triplet sensitizers that convert harmless
triplet oxygen into the highly reactive singlet oxygen (9 – 12).
As a consequence of their high reactivity, ROS react nonspecifically with
nearly every cellular target and may damage DNA, proteins, lipids, and carbo-
hydrates (13). On the upper surface of the skin, ROS are also capable of inducing
more complex responses such as the induction of genes (14). Both UV-A and
UV-B contribute to the deleterious effects on the skin, but it appears that
UV-B is more associated with autoimmune diseases than UV-A. Somewhere,
there is a balance between too much sun and melanoma risk or too little sun
and autoimmune disease.
Iron and Copper

In mammalian cells, the level of iron-storage protein is tightly controlled by the
iron-regulatory protein-1 at the posttranscriptional level. This regulation prevents
iron acting as a catalyst in reactions between ROS and biomolecules. It has been
shown that both UV-B and UV-A can cause biological damage in exposed tissues
via iron-catalyzed oxidative stress (15,16). The iron content is substantially elev-
ated over basal levels in the sun-exposed skin of healthy individuals (17). The
underlying mechanism appears to be the UV-B-induced formation of superoxide
radical anion and its attack on ferritin, resulting in the release of free iron (18).
606 Chaudhuri
Furthermore, superoxide anion radical can react with hydrogen, which again
enters the Fenton reaction (19). Iron, singlet oxygen, and hydrogen peroxide
are presently considered to be important redox active species involved in the
deleterious effects of UV-A radiation on lipids and proteins of human skin
cells (20,21). Figure 30.1 summarizes the chemistry involved in the iron- and
copper-induced formation of ROS.
When a general use of antioxidants is advocated, it is often disregarded that
these compounds not only function as antioxidants, but (intrinsically) have pro-
oxidant action as well, in the presence of transition metals. There is pro-oxidant
action even in well-known antioxidants, such as, vitamin C (ascorbate), vitamin E
(tocopherols), glutathione, and proanthocyanidins (from pine and grape). The
pro-oxidant activity of vitamin C results from the reduction of Fe3þ to Fe2þ
and its reaction with H2O2 to generate OH radical (22). Pro-oxidant effects are
not unique to vitamin C; they can be demonstrated with many reducing agents
in the presence of transition metal ions, including vitamin E, glutathione and
several plant phenolics. Thus, if vitamin C’s pro-oxidant effects are relevant,
the pro-oxidation effects of these other reductants may also be expected to
occur (23).
High concentrations of vitamin E accelerate lipid autooxidation in vitro
(24,25). Other authors also reported pro-oxidant effects in vitro for a-tocopherol
(26,27). It is quite possible that a-tocopherol can generate tocopheroxyl radical
on skin under UV radiation and may thereby act as a pro-oxidant. Indeed,
adverse biological effects of a-tocopherol are documented in skin (28).
A pro-oxidant activity of carotenoids has also been reported (29).
Presence of Iron (or Copper) and H2O2
Fe2+(or Cu+) + H2O2 → Intermediate complex (es) → Fe3+(or Cu2+) + OH. + OH-
(Very fast reaction)
Fe3+(or Cu2+) + H2O2 → Intermediate complex (es) → Fe2+(or Cu+) + O2.- + 2H+
(slow reaction)
Presence of Iron- (or Copper-) chelates and H2O2
Fe3+(or Cu2+)-EDTA + H2O2 → Fe2+(or Cu+)-EDTA + O2.- + 2H+
Presence of Iron (or copper), H2O2 & an antioxidant
Fe3+(or Cu2+) + ascorbate → Fe2+ + ascorbate.
Fe2+ + H2O2 → [intermediate complex(es)] → Fe3+ + OH. + HO-
Figure 30.1 Chemistry involved in the iron- or copper-induced formation of reactive

oxygen species.
The key question is the availability of catalytic amounts of iron and copper
in the skin (30). UV light and sweat are the two dominant sources for iron and
copper (31). Water is also a source for iron in the skin. It is also easy to see
from these data how athletes following an intensive training might become
anemic due to loss of iron. Iron-chelating agents have been shown as protectants
against UV-radiation-induced free radical production (23,30,32).
Matrix-Degrading Metalloprotease
Matrix metalloproteases (MMPs) constitute a family of structurally similar
zinc-containing metalloproteases, which are involved in the remodeling and
degradation of extracellular matrix (ECM) proteins, such as collagens, elastins,
fibronectin, and proteoglycans, both as part of normal physiological processes
and in pathological conditions. At this time over 20 different MMPs have
been identified and classified (33). Based on sequence homology and substrate
specificity, MMPs can be classified in five groups (Table 30.1). This classifi-
cation is somewhat arbitrary, since the true physiological substrates are a
matter of debate.
The ECM is the material that forms the bulk of the dermis, excluding water
and cells. Proteins and complex sugars form most of the dermal ECM and they
are arranged in an orderly network fibers and ground substances. The ECM is
not a homogeneous structure. It can include any of several classes of biomole-
cules, including structural proteins, such as collagens and elastin; adhesion
proteins, including fibronectins, laminins, and entactin; proteoglycans; and
glycosaminoglycans. This complex mixture does not simply surround cells and
hold them together, but also provides an environment in which a number of criti-
cal biological processes occur (34).
Several studies carried out by Scharffetter-Kochanek’s group using dermal
fibroblast cells show that both UV-A and UV-B cause a four- to five fold increase
in the production of MMP-1 and MMP-3 (15,34 – 36). Brennan et al. have shown
by punch biopsies of human skin after UV irradiation that MMP-1 rather than
MMP-13 as the major collagenolytic enzyme responsible for collagen damage
in photoaging (37). In contrast, the synthesis of tissue inhibitory metallopro-
tease-1 (TIMP-1), the natural inhibitor of matrix metalloprotease, increases
only marginally. This imbalance is one of the causes of severe connective
tissue damage resulting in photoaging of the skin. Although collagen content
decreases, collagen synthesis in sun-damaged skin appears to remain similar to
that of sun-protected sites (38,39). Thus, evidence suggests that the decrease
in collagen content in photodamaged skin results from increased collagen
degradation, by matrix metalloprotease, without significant changes in collagen
production (40). Recently, Fisher et al. have shown that UV irradiation increases
MMP-8 in human skin in vivo (41). Although UV irradiation induces both
MMP-1 and MMP-8, UV-induced collagen degradation is stimulated primarily
by MMP-1, with little, if any, contribution by MMP-8.
608 Chaudhuri
Table 30.1 The Matrix Metalloprotease Enzymes Relevant to Skin Care
Group Trivial name No. Principal substrate
Collagenase Interstitial MMP-1 Fibrillar collagen types I,

collagenase II, III
Neutrophil MMP-8 Fibrillar collagen types I,
collagenase II, III
Collagenase-3 MMP-13 Fibrillar collagen types I,
II, III
Collagenase-4 MMP-18
Gelatinases Gelatinase A MMP-2 Gelatins, nonfibrillar
(72 kDa) collagen types IV, V
Gelatinase B MMP-9 Gelatins, nonfibrillar
(92 kDa) collagen types IV, V
Stromelysins Stromelysin-1 MMP-3 Proteoglycans, laminin,
fibronectin, nonfibrillar
collagens
Stromelysin-2 MMP-10 Proteoglycans, laminin,
collagens
Matrilysin MMP-7 Proteoglycans, laminin,
collagens
Membrane type MT1-MMP MMP-14 Progelatinase A,
procollagenase-3
MT2-MMP MMP-15 Progelatinase A
MT3-MMP MMP-16 Progelatinase A
MT4-MMP MMP-17
MT5-MMP MMP-21
Others Stromelysin-3 MMP-11 Serine protease inhibitor
Metalloelastase MMP-12 Elastin, nonfibrillar
collagen
Enamelysin MMP-20
MMP-19
MMP-23
MMP-24
The damage caused by excessive MMP on the ECM proteins does not
appear overnight, but results from the accumulation of successive molecular
damages, especially in the case of overexposure to UV light. The skin repercus-
sion on the degradation of the ECM proteins may then be revealed in many ways
depending on age, genetic predisposition, and life-style and, of course, on the
general health status of the individual (42). The causes and consequences of
skin damages are summarized in Fig. 30.2.
UV Light
Release of Free Reactive Oxygen Release of Matrix

Iron & Copper Species Metalloprotease
Skin Damage
DNA Protein Lipids Carbohydrate

Depolymerization
Strand breakage SH oxidation Peroxidation
of hyaluronic acid
Deactivation of
Mutations
enzymes
Figure 30.2 Causes and consequences of UV-induced skin damage.
ANTIOXIDANT DEFENSES OF THE SKIN

To counteract the harmful effects of ROS, the skin is equipped with antioxidant
defense systems consisting of a variety of low molecular weight antioxidants and
antioxidant defense enzymes forming an “antioxidant network”. The antioxidant
network is responsible for maintaining the equilibrium between pro-oxidants and
antioxidants. However, the antioxidant defense can be overwhelmed by increased
exposure to exogenous sources of ROS. Such a disturbance of the pro-oxidant/
antioxidant balance may result in oxidative damage to lipids, proteins, and DNA.
The skin has developed a complex system in order to protect itself from oxidative
stress. This defense system consists of enzymes and nonenzymatic antioxidants.
Antioxidant Defense Enzymes

The discovery of SOD enzymes provided much of the basis for our current under-
standing of antioxidant defense systems, since it led to the postulation of the
superoxide theory of oxygen toxicity (43). The theory gained credibility with
the identification of the enzyme SOD by McCord and Fridovich in 1969 (44),
which provided the first compelling evidence of in vivo generation of the super-
oxide anion radical (O†2 ). Additional support came from the subsequent elucida-
tion of elaborate antioxidant defenses (45).
SOD can be divided into three types: copper- and zinc-containing isoform
(CuZn-SOD, a cytosolic enzyme), manganese-containing isoform (Mn-SOD,
a mitochrondial enzyme), and extracellular SOD (EC-SOD, a tetrameric glyco-
protein which contains Cu and Zn) (46). SOD catalyzes dismutation of superoxide
anions to hydrogen peroxide. SODs are found in all eukaryotic cells. In human,
the Cu/Zn-SOD activity seems to be five- to tenfold higher than Mn-SOD. As
compared to other body tissues, SOD activity is relatively low in skin (46).
610 Chaudhuri
Catalase is a tetrameric enzyme that is expressed in all body organs (47).

The major role of catalase is its ability to detoxify hydrogen peroxide to water
and oxygen. Mates et al. (48) reported higher catalase activity in human epider-
mis than the human dermis.
Glutathione peroxidase (GSH-Px) is a selenoenzyme consisting of four
identical subunits, each of which contains a selenocysteine residue in its active
site. GSH-Px is localized mainly in the cytosol and to a lesser extent in mito-
chondria. They convert hydrogen peroxide to water and oxygen and reduce
lipid hydroperoxides using glutathione (48). The baseline levels measured in
epidermis and dermis vary considerably and therefore do not point to a clear
preferential distribution in skin (49).
The ratio of reduced to oxidized glutathione (GSH/GSSH) in normal cells
are high so there must be a mechanism for reducing GSHG back to GSH. This is
achieved by glutathione reductase (GSH-Rx), which catalyzes the following
reaction:
GSSG þ NADPH þ Hþ ! 2GSH þ NADPþ
Enzymatic antioxidant activities in human skin are higher in epidermis than in
dermis; catalase is especially high (49). When skin fibroblasts were irradiated
with UV-A, catalase activity was destroyed, but GSH-Px and GSH-Rx were vir-
tually unchanged (48). Similar results were seen when murine skin was irradiated
with solar irradiation (50).
Low Molecular Weight Antioxidants

Low molecular weight antioxidants can be subdivided into two groups: endo-
geneous (synthesized in the body) and exogeneous (derived from the diet).
Human skin contains both lipophilic [vitamin E (tocopherols and tocotrienols),
ubiquinones (coenzyme Q) and carotenoids], and hydrophilic [(vitamin C
(ascorbate), glutathione (GSH) and uric acid (urate)] antioxidants. Vitamin E,
vitamin C, and carotenoids are derived from the diet whereas the other three
are synthesized in vivo.
On a molar basis, vitamin C is the predominant antioxidant in skin; its con-
centration is 15-fold higher than glutathione, 200-fold higher than vitamin E, and
1000-fold higher than ubiquinones (49). Concentrations of antioxidants are
higher in epidermis than dermis; six-fold for vitamin C and glutathione, and
two-fold for vitamin E and ubiquinones. Some antioxidants are also present in
the stratum corneum, such as vitamin E, which is the predominant antioxidant
in the human stratum corneum (51).
The antioxidants present in the stratum corneum are quite susceptible to
UV radiation. For example, a single suberythemal dose of UV radiation depleted
vitamin E by about 50% while dermal and epidermal vitamin E depletion
required much higher doses (51). Vitamin C seems to be present in human
stratum corneum at very low levels. Consequently, vitamin C is not available
to recycle photo-oxidized vitamin E. Ubiquinones seem to be absent in human

stratum corneum.
PHOTOPROTECTION OF HUMAN SKIN USING ANTIOXIDANTS

AND OTHER PHOTOPROTECTANTS
A large number of antioxidants have been found to exhibit protective effects
against the ROS-induced photoaging both on animals and human (1,52). A
review of the protective effects of topical antioxidants in human has recently
been published (1).
Direct application of antioxidants on to skin has the advantage over oral
administration because targeting antioxidants to the area of skin needing the
protection is easier to achieve. It seems desirable to add low molecular weight
antioxidants to the skin reservoir by applying antioxidants topically as they
protect the skin against oxidative stress.
The stratum corneum may particularly benefit from an increased anti-
oxidant capacity to topical application because cutaneous antioxidants undergo
depletion significantly under oxidative stress. To protect deeper layers of
the skin, antioxidants need to be formulated in a way that delivers them into
the skin. Antioxidants are inherently unstable compounds—hydrolytically and
photo-chemically—that is why they function in redox reactions. This also
makes it difficult to formulate a stable formulation with antioxidants. A recent
study (23) has shown that antioxidants do not have adequate aqueous and heat
stability (Fig. 30.3). However, exploiting multilevel approach of antioxidant
100
90
EMBLICA
80
% Antioxidant Activity
70 Vitamin E
60
PineAntioxidant
50
40 RosemaryAntioxid
30 ant
20 Vitamin C
10
0
0 1 2 3 6 12
Months at 45 C
Figure 30.3 Comparative stability of Emblica and other antioxidants. All antioxidant
activities were derived from optical density measurements at 517 nm in an ethanol–
water mixture using diphenylpicrylhydrazide method.
612 Chaudhuri
activity (cascading antioxidant), one can develop stable skin care and sun care
formulations having good shelf-life (53,54).
Vitamin E and Its Derivatives

The terms a-tocopherol and vitamin E are now used in the literature almost
interchangeably. This is incorrect because vitamin E is a nutritional term and
other tocopherols also have vitamin E activity. Tocopherols are a mixture of
four lipid-soluble tocopherols (a, b, g, and d) and four lipid-soluble tocotrienols
(a, b, g, and d). Tocopherols and tocotrienols differ only in their prenyl side
chain. The chromanol head of each is identical with a, b, g, and d isomers, each
containing an essential hydroxyl group necessary for antioxidant activity. Photo-
chemically, natural tocopherols are not very stable (53). The relative antioxidant
activities of tocopherols in lipid systems is a . b . g . d isomers (55). The
structures of tocopherols and tocotrienols are given in Fig. 30.4. Tocotrienols
may have higher antioxidant activities than the corresponding tocopherols (56).
Vitamin E is depleted during the oxidative stress and can not be regenerated
in the absence of a co-antioxidant. Vitamin E is important for protecting the lipid
structures of the stratum corneum proteins from oxidation. However, topically
applied a-tocopherol is rapidly depleted by UV-B radiation in a dose-dependent
manner. The photo-oxidative fate of the a-tocopherol depends on the local
environment of the vitamin E. a-Tocopherol quinone and a-tocopherol quinone
R1
HO
R2 O
CH3
Tocopherols
R1
HO
R2 O
CH3 Tocotrienols
R1 R2
α CH3 CH3
β CH3 H
γ H CH3
δ H H
Figure 30.4 Structures of tocopherols and tocotrienols.

epoxides are principal photoproducts of vitamin E that can penetrate into the
epidermal layer of the skin, whereas tocopherol dimers and trimers are formed
from a-tocopherol in a bulk phase at the skin surface. Dimer and trimer products
may participate in the prevention of UV-induced photodamage (57,58).
The photoprotective effect of Vitamin E and its esters have been studied
extensively. Topical application of vitamin E has shown significant reduction
in acute responses when applied before UV-radiation exposure, such as erythema
and edema (59,60), sunburn cell formation (61), lipid peroxidation (62,63), DNA
adduct formation (64), and immunosuppression (62,65).
Vitamin E esters, particularly vitamin E acetate, succinate, and linoleate,
were shown to be promising agents in reducing UV radiation induced skin
damage (46). Their protective effects, however, are less pronounced as compared
to vitamin E. This is quite understandable because vitamin E esters need to be
hydrolyzed during skin absorption to show antioxidant activity. It seems that
the bioconversion of vitamin E acetate to a-tocopherol is slow and occurs only
to a minor extent. Table 30.2 summarizes the photoprotective effect of topically
applied vitamin E and its esters on humans.
Table 30.2 Photoprotective Effects of Topically Applied Vitamin E and Its Derivatives
on Humans
Compound Endpoint Efficacy Remarks References
Vitamin E Mechanoelectrical Protection of — 66

properties of UVR and
skin PUVA-induced
damage
Vitamin E PUVA-induced Vitamin E No protection 67
and its erythema acetate not when applied
derivatives and changes in protective; after UVR
mechanoelectrical vitamin E exposure
property of skin and vitamin E
with shorter
chain
protective
Vitamin E Erythema (MED) Protective SPF determination 60
Vitamin E Erythema Moderate No protection 68
and its protection when applied
acetate when applied occlusively
occlusively before UVR
after UVR exposure
exposure
Vitamin E Erythema Moderate No protection 69, 70
(skin color protection when applied
and skin after UVR
blood flow) exposure;
SPF 1 (in vitro)
614 Chaudhuri
Vitamin C and Its Derivatives

L -Ascorbic acid is involved in many biological processes such as collagen
synthesis, antioxidation, intestinal absorption of iron and metabolism of some
amino acids (71). An essential function of L -ascorbic acid is to act as a cofactor
for the hydroxylation of proline and lysine residues in collagen, a major protein
component of the body. L -Ascorbic acid also increases transcription of procolla-
gen genes and stabilizes procollagen mRNA (72). Its ability to cure scurvy is
possibly due to the stimulation of collagen synthesis in connective tissues (73).
L -Ascorbic acid improves epidermal barrier function, apparently by stimulating
sphingolipid production (74).
Unfortunately, L -ascorbic acid is not stable in aqueous solutions, even at
neutral pH at room temperature (258C). Structures of ascorbic acid and its
degradation products are given in Fig. 30.5. To solve this problem, a number
of stable synthetic derivatives have been developed such as sodium (SAP) and
magnesium ascorbyl phosphate (MAP). Ascorbic acid also acts as a pro-
oxidant in the presence of transition metals (22,23). Unfortunately, SAP and
MAP have to be formulated at basic pH (.7.00) due to their instability in the
acidic system. A chelating agent needs to be included in the formulation to
prevent degradation of MAP and SAP; most commercial products do contain
EDTA as a chelating agent. Ascorbic acid has two ionizable hydroxyl groups,
and consequently has two pKa: values 4.2 ( position 3) and 11.6 (position 2).
Figure 30.5 Structures of ascorbic acid and its degradation products.

Since the mono-anion form is favored at physiological pH, the name ascorbate is
the right terminology for ascorbic acid in solution.
Topical L -ascorbic acid reduced UV-B-induced inflammation (75) and
attenuated UV-A-induced immediate pigment response in human skin (76).
Vitamin C is effective only at a high concentration in an appropriate vehicle
(77). Vitamin C is highly unstable and is only poorly absorbed into the skin, poss-
ibly explaining its poor photoprotective property when applied topically. Hence,
more lipophilic and more stable vitamin C esters, such as its palmityl, succinyl, or
phosphoryl esters might be promising derivatives providing increased photo-
protection (78). Also, a water-soluble analog of vitamin C, ascorbic acid 2-O-a-
D -glucoside (79) has been shown to have improved stability and efficacy (80).
The stability of ascorbic acid, ascorbyl palmitate, and MAP in both stan-
dard solutions and topical formulations was investigated by Austria et al. (81).
The results showed that the two vitamin C derivatives were more stable than
ascorbic acid. Esterification with palmitic acid in the 6 position did not prevent
hydrolysis of the molecule, either in solution or in emulsion; only a formulation
with highly viscoelastic properties was able to slow down the degradation of
the compound. Conversely, the introduction of the phosphoric group in the
2-position protected the molecule from the break-up of the enediol system, con-
firming MAP as a stable derivative of vitamin C.
Recently, several human clinical studies have been reported on the use of
vitamin C at high percentage levels (5%) and its beneficial effect on skin
(82,83). Topical application of 5% vitamin C cream was an effective and well-
tolerated treatment. It led to a clinically apparent improvement of the photo-
damaged skin and induced modifications of skin relief and ultrastructure,
suggesting a positive influence of topical vitamin C on parameters characteristic
for sun-induced skin aging. Table 30.3 summarizes the photoprotective effects of
vitamin C and its derivatives on humans.
Carotenoids
Carotenoids are a class of lipophilic compounds of plant origin that contain an
extended system of conjugated double bonds; b-carotene and lycopene are the
most prominent compounds. b-Carotene, a-carotene, lycopene, b-cryptox-
anthine, lutein, and zeaxanthine are major carotenoids in human skin and their
levels differ between various skin areas (86). It was demonstrated that a single
exposure to solar simulated UV light lowers the skin lycopene level by 31 –
46%, whereas the same UV dose has very little effect on the b-carotene level
(87). However, repeated exposure to UV light also depletes the b-carotene
level (88).
Carotenoids have been reported to react with virtually any radical species
likely to be encountered in a biological system (89). Carotenoids are among the
most efficient scavengers of singlet oxygen, either by physical or by chemical
quenching (90). The products of such reactions are generally short-lived
616 Chaudhuri
Table 30.3 Photoprotective Effects of Topically Applied Vitamin C and Its Derivatives
on Humans
Compound Endpoint Efficacy Remarks References
Vitamin C Cutaneous Increase in the Significant 82

biopsy after 3 skin density improvement
and 6 months and decrease
in the deep
furrows
Vitamin Cþ Cutaneous Increase grenz Statistically 84
tetrahexyldecyl biopsy after 12 zone collagen; significant
ascorbate weeks and improved improvement
evaluation of wrinkle
overall facial reduction and
improvement hydration
Vitamin C Treatment 68.4% greater Statistically 85
of mild to improvement significant
moderate vs. vehicle improvement
photodamage treated area shown by
after 3 months image
analysis
Vitamin C Erythema (skin Poor protection SPF 1 70
color and skin (in vitro)
blood flow)
Vitamin C palmitate Erythema (skin Poor protection No protection 68
color) when applied when applied
occlusively occlusively
after UVR before UVR
exposure exposure
radical species. In some cases, stable adducts can be observed, but in the majority
of interactions with radicals, carotenoids break down to degradation products in a
manner very similar to oxidative degradation processes (Fig. 30.6). It is only
recently that the biological activity of these degradation products has begun to
be investigated (89).
b-Carotene has been supplemented prior to sun exposure in order to
prevent sunburn. The protective effects are related to the antioxidant properties
of the carotenoid. The data obtained in different studies on this topic have
been reviewed by Stahl and Sies (91,92) and appear to be conflicting (91). All
the photoprotective work done on carotenoids are via oral supplementation
(91). Two recently published studies provide evidence that oral supplementation
with carotenoids alone or in combination with vitamin E increase the photopro-
tective properties of the skin and provide moderate protection against erythema
formation (93,94).
Central Cleavage Excentric Cleavage
β-apo-Carotenals
β-apo-Carotenoic acids
Retinal Retinoic acid
Figure 30.6 The central and excentric cleavage pathways of b-carotene.
There is some clinical evidence of increased skin cancer incidence in

smokers supplemented with b-carotene (95,96). Cigarette smoke is a complex
mixture of literally thousands of compounds, many of which are known or sus-
pected human carcinogens. b-Carotene oxidation products formed by smoke
may be responsible for procarcinogenic effects in human (97). It has recently
been shown that 4-nitro-b-carotene is the major product of the reaction
between nitrogen oxide in smoke and b-carotene (98).
Plant Polyphenolics
Polyphenolics comprise a wide variety of natural products of plant origin. Almost
all of them exhibit a marked antioxidant activity. Typical examples are, oligo-
meric catechols, flavonoids, monomeric and oligomeric flavan-3-ols (condensed
tannins), and gallo- and ellagitannins (hydrolyzable tannins). The tannins are
considered superior antioxidants as their eventual oxidation may lead to oligo-
merization via phenolic coupling and enlargement of the number of reactive
sites, a reaction which has never been observed with flavonoids themselves
(53,99). Many of these plant polyphenolics are consumed in the diet and are
believed to have beneficial health effect for human beings. Recently, some poly-
phenolics have been demonstrated to have significant photoprotective properties
when used topically. Administrations of different plant extracts, particularly
flavonoids, have been reported to reduce acute and chronic skin damage after
UV radiation exposure (100 – 104). Recently, Kang et al. have shown that
topical application of genistein (40 ,5,7-trihydroxyisoflavone) prevent UV-light-
induced signaling that leads to photoaging in human skin in vivo (105). Genistein
blocked UV-induction of cJun-driven enzyme, collagenase. However, genistein
had no effect on UV-induced erythema.
Polyphenolics are inherently unstable compounds due to aerial oxidation;
this allows them to function in redox reactions. In addition, many polyphenolics
618 Chaudhuri
are deeply colored, adding to the complexity of producing an acceptable esthetic

product for topical applications.
Tea Polyphenols
Tea from the Camellia sinensis is consumed by more than two-thirds of the
world’s population. Tea is the most popular beverage next to water. Tea is a
potent source of polyphenols, comprising 30– 35% of the dry weight of the
leaf. During processing, tea leaves are progressively fermented to produce
green tea, oolong tea, or black tea. Major ingredients in green tea are epigalloca-
techin-3-gallate (EGCG), epigallocatechin (EGC), epicatechin (EC), gallocate-
chin, and catechin. Black tea contains predominantly polymeric materials
(106). All these polyphenols are potent antioxidants and are capable of quenching
superoxide radical, hydroxyl radical, peroxyl radical, singlet oxygen, and hydro-
gen peroxide. Several comprehensive reviews on tea polyphenols are available in
the recent literature (1,107; this volume Chapter 31 by Elmets).
Tea polyphenols have been studied extensively for their anticarcinogenic
potential (108). EGCG is the major polyphenolic constituent present in green
tea that is responsible for this biological activity (109,110). In animal models,
extracts from green tea have been shown to be remarkably effective at reducing
the severity of adverse effects of overexposure to UV radiation (110). Topical
application of green tea polyphenols reduced UV-induced erythema and
sunburn cell formation in human skin (111). EGCG when applied topically
reduced UVB-induced inflammatory responses and infiltration of leukocytes in
human skin (112). Standardized extract of green tea polyphenols also protected
against erythema, and c-Fos and p53 induction after PUVA phototoxic injury
to human skin (113). Tea polyphenols protected human skin from UV-induced
langerhans cell depletion (111). Topical application to skin of green tea polyphe-
nols reduced UVB-induced pyrimidine dimmer formation in both epidermis and
dermis (114).
Silymarin
Silymarin is an extract of the seeds milk thistle plant (Silybum marianum), which
consists of a mixture of flavonolignans, namely, silybin, silidianin, silychristin,
and isosylibin (115,116). A standardized extract should contain 80% silymarin.
Silybin is the main component (70 –80%) and is thought to have the most biologi-
cal activity.
Silymarin has strong antioxidant effects. In animal models, silymarin has
been shown to be remarkably effective at reducing the severity of adverse
effects of overexposure to UV radiation (1,107). Topically applied silymarin
was demonstrated to have a remarkable antitumor effect (117). Silymarin
showed a protective effect against UV-induced oxidative damage by modulating
the activation of the transcription factor NF-kB in HaCaT keratinocytes (118). In
a dose-dependant manner, silymarin inhibited NF-kB activation induced by UV
radiation in human keratinocytes. NF-kB is a redox sensitive transcriptional
factor, which plays an important role in regulating the expression of various

genes that participate in many physiological processes such as inflammation,
apoptosis, and cellular proliferation.
Emblica Antioxidant
Emblica antioxidant, is a standardized extract of Phyllanthus emblica (syn.
Emblica officinalis) fruits, which is isolated using a water-based process. The
product is defined to the extent of well over 50% (typically, 60 – 75%) in terms
of its key bioactive components and has acceptable color for topical application
at about 1– 2% level. The low molecular weight (,1000) hydrolyzable tannins,
namely emblicanin A and emblicanin B, along with pedunculagin and punigluco-
nin are the key ingredients (Fig. 30.7) in the Emblica antioxidant (53,54,119). In
nature, emblicanin A and emblicanin B have only been found in P. emblica plants
(119). Emblica is a hydrolytically as well as photochemically stable antioxidant
(53,120). While most antioxidants go from an active to an inactive role, Emblica
antioxidant utilizes a multilevel cascade of antioxidant compounds resulting in a
prolongation of activities (120).
OH OH
OH OH
O O
O O
O C O C
O OH O OH
OH OH
O C O C
O O O O
O O OH O
O O OH
O
C C C C
OH OH
HO OH HO OH
HO OH OH OH HO OH
OH OH
EMBLICANIN A OH EMBLICANIN B
OH
O
OH
CO2H
O C OH
O OH H OH
O OH
OH HO H
O C
H O C
O O OH
O O OH H OH
O
C C OH
OH CH2O C
HO OH OH
O
OH
HO OH OH OH
PEDUNCULAGIN PUNIGLUCONIN
Figure 30.7 Hydrolyzable tannins of Phyllanthus emblica.

620 Chaudhuri
Emblica has an excellent free-radical and nonradical quenching ability

(53,120), strong chelating ability to iron and copper (no pro-oxidative activity)
(120), significant matrix metalloprotease (MMP-1 and MMP-3) inhibitory
activity (53). Emblica has been shown to reduce UV-induced erythema (53) to
human skin. In vitro study using human skin fibroblast cells, Chaudhuri et al.
(53) showed that Emblica antioxidant increases the synthesis of noncollagenic
proteins by about 40% over the control. An immunocolorimetric method (121)
was used for quantifying collagenic and noncollagenic proteins. Interestingly,
Emblica antioxidant had practically no effect on the synthesis of collagenic pro-
teins. Characterization of the individual noncollagenic proteins has not been
done. Human clinical trials have shown that Emblica has a strong skin lightening
or even-toning effect (54,122), which is equal or superior to hydroquinone, mag-
nesium ascorbyl phosphate (MAP), and kojic acid.
Recently, Morganti et al. (123) has published a randomized double-blind
placebo-controlled clinical study report using Emblica as a key component. In
this study, Group 1 subjects were given Emblica, melatonin, and a-lipoic acid
topically (twice a day) along with a dietary supplement consisting of ascorbic
acid, tocopherol, lutein, and a-lipoic acid (two capsules a day). The subjects in
Group 2 received only the carrier topically (placebo, twice a day) and the
dietary supplement with antioxidants (two capsules a day) and Group 3 subjects
received only the carrier topically (placebo) and orally (placebo, no anti-
oxidants). Results clearly showed statistically significant ( p , 0.005) increase in
skin hydration and skin lipids for both Groups 1 and 2 over a period of 2
months. However, Group 1 showed the highest increase both in skin hydration
(55 – 100%) and skin lipids (55 –70%) over placebo control. Moreover, oxidative
stress and consequently formation of lipid peroxides in Group 1 subjects were
also found to be lower by 30– 40% ( p , 0.005) over placebo control.
Possibly, Emblica antioxidant modulates UV/ROS initiated signal trans-
duction pathways of matrix metalloprotease induction, thereby protecting the
extracellular matrix proteins from degradation and providing photoprotective
benefits.
Combination of Antioxidants
The antioxidant network is a complex system and is interlinked (Fig. 30.8) (1).
Thus, an enhanced photoprotection can be achieved by topically applying an
appropriate combination of antioxidants. The effect of topical antioxidants
after UV irradiation is less obvious, whereas the photoprotective effect of
topical antioxidants applied before UV exposure has been well recognized (46).
Co-application of vitamins E and C provided a much more pronounced
photoprotective effect as compared to the application of a single antioxidant
(46). Even further improvement in photoprotection resulted when co-application
of melatonin together with vitamins E and C was topically done (69). Recently,
Lin et al. (83) has shown that the combination of 15% L -ascorbic acid and 1%
RO• RO
Tocopheroxyl radical
Tocopherol Ascorbate GSSG NAD(P)H
Ubiquinone
+
GSH NAD(P)
Dehydroascorbate
Ubiquinol
Figure 30.8 Interacting network of low molecular weight antioxidants. Abreviations:

NAD(P)H, nicotinamide adenine dinucleotide phosphate reduced; GSH, glutiathione;
GSSG, oxidized glutathione; NAD(P)þ, nicotinamide adenine dinucleotide phosphate—
oxidized form; NAD(P)H, nicotinamide adenine dinucleotide phosphate—reduced form;
RO., reactive oxygen free radical; RO, reduced reactive oxygen free radical.
a-tocopherol provided significant protection against erythema and sunburn cell

formation; either L -ascorbic acid or 1% a-tocopherol alone was also protective
but the combination was much superior. In addition, the combination of vitamins
C and E provided protection against thymine dimer formation.
In another clinical study, Hadshiew et al. (124) have demonstrated the
usefulness of applying a mixture of antioxidants in reducing the severity of
experimentally induced polymorphous light eruption in humans. The antioxidant
blend consists of a-glucosylrutin, ferulic acid, and tocopheryl acetate. The
reduction in experimentally induced polymorphous light erruption is observed
due to the reduction in UV-A-induced oxidative stress. A blend of vitamin E
linoleate, magnesium ascorbyl phosphate, butyl hydroxytoluene, and nordihydro-
guaradinic acid provided a significant reduction in UV radiation induced
erythema in humans (125). Oral supplementation with b-carotene or a similar
amount of mixed carotenoids also protects humans from UV-induced erythema
(92). In another clinical study, Greul et al. (126) have shown a photoprotective
effect by oral supplementation of an antioxidative combination containing
both lipid and water-soluble compounds: carotenoids (b-carotene and lycopene),
vitamins C and E, selenium, and proanthocyanidines. The primary efficacy
parameters included the reduction of UV-induced matrix metalloprotease
(MMP-1 and MMP-9) expressions.
Unconventional Photoprotectants
Apart from increasing the skin’s antioxidant capacity by topical or oral appli-
cation of antioxidants, other substances may also boost antioxidant capacity of
skin by preventing formation of reactive oxidative species, or modulating
622 Chaudhuri
complex signal transduction pathways or inhibiting matrix metalloprotease

expression and activity.
Selenium
Selenium is an essential trace mineral in the human body (127) and is an import-
ant part of antioxidant enzymes, glutathione peroxidase, and thioredoxin
reductase, which protect cells against the effects of free radicals (128,129).
The activity of selenoenzymes can be increased by selenium supplementation
(130). Selenium is also essential for normal functioning of the immune system
and thyroid gland (131). Plant foods are the major sources of selenium.
Topical L -selenomethionine protected mice against UV-induced erythema
and skin cancer (132). In human beings, topical L -selenomethionine increased the
minimal erythema dose in a dose-responsive manner (133).
Zinc
Zinc is an essential mineral that is found in almost every cell. It stimulates the
activity of over 200 metalloenzymes, which are substances that promote biochemi-
cal reactions in the body (134). Zinc supports a healthy immune system (135), is
needed for wound healing (136), helps maintain one’s sense of taste and smell
(137), and is needed for DNA synthesis (138). Zinc also supports normal growth
and development during pregnancy, childhood, and adolescence (139,140).
Zinc has an important antioxidant effect in tissues (141). All body tissues
contain zinc. In skin, it is five to six times more concentrated in the epidermis
than the dermis. Topical application of zinc, in the form of divalent zinc ions,
has been reported to provide photoprotection for skin (141). Topical applica-
tion of zinc ions has been shown to induce synthesis of metallothionein (sulfhy-
dryl-rich proteins), which may account for its photoprotective effect (142).
Alternately, zinc may replace redox active molecules, such as iron and copper,
at critical sites in cell membranes and proteins (141).
Chelating Agents
The iron content is substantially elevated over basal levels in the skin of mice
exposed to UV-B irradiation and in the skin of sun-exposed body sites of
healthy individuals (17,30). Iron participates as a catalyst in the formation of
the highly damaging hydroxyl radical. Hence, topical application of certain
iron chelators can act as photoprotectant. Thus, 2-furildioxime was shown to
be an efficient photoprotectant alone (17) or in combination with sunscreens
(30). Also, desferrioxamine, an iron-chelating agent, was examined as a photo-
protectant against UV-radiation-induced free radical production (143). Photopro-
tection was demonstrated by topically applying desferrioxamine to the human
skin by using electron paramagnetic resonance (EPR) examination. Desferrioxa-
mine reduced the 5,50 -dimethylpyrroline-1-oxide (DMPO) radical signal by
about 50% indicating that iron plays a major role in UV-induced oxidative
+
HN HN
CO2 CO2
+
H 3C N H3C N
H H H H
Figure 30.9 Structures of ectoin.
damage. Recently, Emblica antioxidant has also been shown to have excellent
transition metal chelating ability (23,54). Application of metal chelators may
be a route to prevent or reduce oxidative damage to skin.
Compatible Solutes
Compatible solutes are a group of diverse compounds; they are highly soluble in
water and have either polyhydric alcohol (such as, mannosylglycerate, mannosyl-
glyceramide diglyceryl phosphates, cyclic-2,3-bisphosphoglycerate, di-myo-ino-
sitol phosphates) or amphoteric functionalities (such as, ectoin, hydroxyectoin)
(144). The term “compatible” originally coined by Brown (145), refers to the
fact that these materials are compatible with the cells’ metabolism, even at
very high concentrations.
Recently, Bünger et al. (146,147) have shown significant photoprotective
effects of one such compatible solute, namely, ectoin (Fig. 30.9). Topically
applied ectoin was shown to reduce significantly sunburn cells formation and
destruction of langerhans cells under UV irradiation (147). Photoprotective prop-
erties of ectoin may involve inhibition of UV-A-induced expression of intercel-
lular adhesion molecule (ICAM-1) (148,149). Ectoin has also been found to have
an excellent long-term skin moisturizing ability (146).
Retinoids
Retinoids are a class of compounds consisting of four isoprenoids units joined in
a head-to-tail manner. All retinoids are derived from a monocyclic parent com-
pound containing five carbon– carbon double bonds and a functional group at
the terminus of the acyclic portion. They are vitamins, because retinol is not syn-
thesized in the body and must be derived from the diet. Vitamin A is used as the
generic descriptor encompassing retinol, retinal, and retinoic acid. The main cir-
culating form of vitamin A in the blood is retinol, and the epidermis stores it as
retinyl esters (150). The epidermis can be easily loaded with high amounts of
vitamin A by topical application of either retinol or retinal. Retinol, however,
is sensitive to light, oxygen, and heat and is difficult to formulate with (151).
Topical retinoids, namely retinoic acid (tretinoin), have been proven to
prevent and repair clinical features of photoaging; these processes are facilitated
by an ability to prevent loss of collagen from, and stimulate new collagen
624 Chaudhuri
formation in, the papillary dermis of sun-exposed skin (152). Fisher et al. (153)
have shown that pretreatment of skin with retinoic acid inhibits UV induction of
matrix metalloproteases. Several good reviews on the topical application of reti-
noids have recently been published (151,152,154 –156).
Dihydroxyacetone
Dihydroxyacetone (DHA) is a simple three-carbon sugar (157,158). It is an inter-
mediate in carbohydrate metabolism in higher plants and animals. Specifically,
this three-carbon sugar is physiological product (dihydroxyacetone monophos-
phate) of the body formed and utilized during glycolysis. In crystalline form,
DHA is a mixture of one monomer and four dimers. The monomer is formed
by heating or melting dimeric DHA or by dissolving in water.
The reaction product of DHA and the skin protein that produces the “tan”
color has been shown to provide protection against UV-A in animals and humans
(159 – 162). Experimental and clinical evidence show that skin that has been
treated topically with 3% DHA solution overnight has a sun protection factor
(SPF) of at least 3 in the UV-B region. Likewise, a photoprotection factor of
10 in the UV-A region has been observed with 15% solution of DHA. The
advantage of this DHA-treated skin pigmentation is that it cannot be removed
by perspiration, swimming, or washings. It can only be removed by desquama-
tion. Fusaro and Lynch (161) suggest using DHA tanning in conjunction with
sunscreens to reduce UV-A exposure, and thereby reduce incidence of malignant
melanoma. The combination of DHA tanning and sunscreens usage has been
shown to provide good protection against skin eruptions in a variegate porphyria
patient (163). Petersen et al. (164) have shown that sunless skin tanning with
DHA delays broad-spectrum UV photocarcinogenesis in hairless mice.
COMMERCIAL PRODUCTS
A wide range of sunscreen and skin care products containing antioxidants
(with or without photoprotectants) is available commercially (Table 30.4). Infor-
mation incorporated in the list is obtained mainly from the two well-known web-
sites (www.drugstore.com and www.dermatologistrx.com) and individual
company websites. This list is not an exhaustive one, but is an example to
show the utility of antioxidants in sunscreen and skin care products.
CONCLUSIONS
Reactive oxygen species play a major role in photoaging and induce changes in
gene expression pathways related to degradation of extracellular proteins. By
now, ample evidence exists to affirm that most cutaneous cancers and many of
the associated damages attributed to cutaneous aging, are results of exposure
to solar radiation. In dealing with this etiology, it is almost certain that preventive
modalities will continue to be the most reasonable approach to abating the
Table 30.4 Commercially Available Products Having Sunscreens and Antioxidants (and Photoprotectants): A Selected List
Antioxidants/other
Brand name Supplier SPF Sunscreens photoprotectants Selected claims
Aveeno skin Johnson & 15 Octinoxate, avobenzone Ascorbyl glucoside, Evens out skin tone and texture; brightens
brightening Johnson retinol, ascorbic acid, dull-looking skin; visibly reduces fine lines
daily treatment tocopherol
Aveeno radiant skin Johnson & 15 Octinoxate, avobenzone, Soya seed extract Improving skin texture; evening out skin tone;
daily moisturizer Johnson octisalate improving skin clarity
Almay milk plus Revlon 15 Octinoxate, oxybenozone, Retinyl palmitate, Double skin’s moisture content immediately;
nourishing facial avobenzone tocopherol acetate, improve skin’s softness and smoothness;
lotion magnesium ascorbyl reduce the appearance of fine lines and
phosphate, green tea wrinkles
and other extracts
Role of Antioxidants in Sun Care Products
Almay Revlon 15 Octinoxate, oxybenzone, Magnesium ascorbyl Increase skin smoothness and clarity; diminish
Kinetin age octisalate, avobenzone phosphate, tocopheryl the appearance of fine wrinkles; significantly
decelerating daily acetate, retinyl fade the look of brown spots and uneven skin
cream palmitate, green tea tone
and other plant
extracts
Banana boat Playtex 30 Octinoxate, oxybenzone, Tocopherol Broad-spectrum UV-A and UV-B protection;
Ultra sunblock lotion titanium dioxide aloe vera and vitamin E helps nourish skin
Bain de Soleil Schering- 30 Avobenzone, homosalate, Tocopherol, tetinyl New pro-retinol formula; ultra hydrating
Oil-free protecteur Plough octocrylene, octisalate palmitate formula for visibly smoother skin; UV-A/
faces sunscreen oxybenzone UV-B with avobenzone
lotion
(continued )
625
626

Antioxidants/other
Coppertone Schering- 15 Avobenzone, homosalate, Tocopherol, Emblica Provides broad-spectrum UV-A/UV-B sun
Endless summer Plough octisalate, octocrylene, antioxidant, sodium protection to help prevent premature skin
ultrasheer oxybenzone ascorbyl phosphate, aging, long-term skin damage and skin
sunscreen retinyl palmitate cancer; contains AO-7, an antioxidant
complex clinically proven to combat harmful
free radicals created by sun exposure
Coppertone Schering- 30 Same ingredients as above Same ingredients as Same claims as above
Endless summer Plough above
ultrasheer
sunscreen
Coppertone Schering- 45 Same ingredients as above Same ingredients as Same claims as above
Endless summer Plough above
ultrasheer
sunscreen
Coppertone Schering- 45 Avobenzone, homosalate, Tocopherol Broad-spectrum UV-A protection; helps protect
Shade sunblock Plough octocrylene, octisalate against sunburn; reduce aging and skin
lotion cancer
Coppertone Schering- 30 Avobenzone, homosalate, Tocopherol, retinyl Provides powerful protection for delicate skin;
Oil-free sunblock Plough octocrylene, octisalate, palmitate Contains a special blend of antioxidant. A
lotion for faces oxybenzone and E; Helps prevent the premature
appearance of fine lines and wrinkles
DDF DDF 15 Octinoxate, octisalate Magnesium ascorbyl Protect skin from environmental damage;
EPF moisturizer C3 phosphate, vitamin C Potent formulation that blocks free radicals
ester complex, most responsible for cell damage and aging
Chaudhuri
tocopherol of the skin

Dove Unilever 15 Octinoxate, octisalate, Tocopheryl acetate, Effectively nourish and hydrate to help make a
Face care essential avobenzone, ensulizole Retinyl palmitate, lasting difference to the health and beauty of
nutrients green tea and grape your skin; combines a broad-spectrum UV
seed extracts protection with five essential nutrients, etc.
Eucerin Beirsdorf 15 Octisalate, octctnoxate, Tocopheryl acetate, Helps prevent sun-related irritations; advanced
Daily sun defense avobenzone glucosylrutin, antioxidant complex; moisturizes as it
isoquercetin protects
L’Oreal L’Oreal 15 Octocrylene, ensulizole Tocopheryl acetate, Softer, smoother skin today; Healthier-looking
Dermo-expertise tocopherol skin in 1 week
future-e
moisturizer
L’Oreal L’Oreal 15 Octinoxate, ensulizole Tocopheryl acetate, Builds healthy, strong skin with magnesium,
Dermo-expertise ascorbyl glucoside calcium and vitamin C
hydrafresh
mineral-charged
Role of Antioxidants in Sun Care Products
moisturizer
Neostrata Neostrata 15 Octinoxate, titanium dioxide Tocopheryl acetate A highly moisturizing cream formulated with
Daytime protection broad spectrum SPF 15, which provides
cream broad spectrum sunscreen protection
Neutrogena Johnson & 15 Octinoxate ensulizole Retinol, tocopherol A retinol facial treatment with multivitamins;
Healthy skin Johnson tocopheryl acetate visibly reduces the appearance of fine lines
antiwrinkle green tea extract and wrinkles
cream
Neutrogena Johnson & 30 Titanium dioxide Tocopherol Broad-spectrum UV-A/UV-B protection;
Sunblock lotion Johnson instant protection
(continued )
627
Table 30.4 Continued 628
Antioxidants/other
Neutrogena Johnson & 45 Avobenzone, homosalate, Retinyl palmitate, UV-A/UV-B protection; waterproof,
Ultrasheer Johnson octinoxate, octisalate, ascorbyl palmitate, sweatproof, rubproof; enriched with
dry-touch oxybenzone tocopheryl acetate antioxidant vitamins A, C, and E to help fight
sunblock against environmental damage
Nivea Beirsdorf 15 Octinoxate, octisalate, Ubiquinone, tocopheryl More of skin’s own wrinkle control; Proven
Visage coenzyme oxybenzone acetate, double action wrinkle reduction
Q10 plus wrinkle
control lotion
Nivea for men Beirsdorf 15 Octinoxate, octisalate, Tocopheryl acetate, Vitamin enriched; protects every day against
vitamin enriched oxybenzone glucosylrutin, sun damage and moisturizes to relieve dry,
daily protective isoquercetin wind burned skin
lotion
Olay Procter & 15 Octisalate, avobenzone, Tocopheryl acetate, Beautifully regenerates skin’s appearance;
Regenerist Gamble ensulizole, octocrylene green tea extract broad-spectrum UV-A/UV-B sunscreen
enhancing lotion
with UV
protection
Olay Procter & 15 Octinoxate, zinc oxide Tocopheryl acetate, Gives your skin complete care, providing
Complete UV Gamble ascorbic acid everything it needs most to stay younger
defense looking and beautiful
moisture lotion
Ombrelle lotion L’Oreal 30 Octinoxate, oxybenzone, Tocopherol Helps prevent premature skin aging and
octisalate, avobenzone damage
Skin Medica Skin Medica 20 Octinoxate, zinc oxide Tocopheryl acetate, Nonoily formula includes antioxidants and
Daily sunprotection retinyl palmitate, botanical extracts that provide protection
ascorbyl palmitate from the aging effects caused by the sun,
while lightly moisturizing the skin
Chaudhuri
damages resulting from actinic insult. It would seem reasonable to assume that
sunscreens in combination with photoprotectants will continue to be the major
weapon in this preventive campaign. In order to function as photoprotective
agents, antioxidants have to be present at the right place in the right con-
centrations at the right time. Topical application of photoprotectants should
supplement the natural antioxidant protection present in skin, and provide
supplemental reserves as oxidative stress depletes antioxidant stores.
Animal studies clearly demonstrate that antioxidants have photoprotective
effects. Topical application of a single antioxidant does not take into account
the dynamic interplay of multiple antioxidants. Photoprotection involves the
synergistic interplay of several antioxidants. Thus, topical application of a
combination of antioxidants is preferred over the use of a single antioxidant.
Plant polyphenolics have been shown to have excellent photoprotective
effect. As these materials are complex mixtures of many compounds, a definite
need exists for standardization of these materials. Otherwise, quality, reproduci-
bility, and effectiveness of these materials may be compromised or questioned.
The technology (e.g., high-performance liquid chromatography, HPLC; high-
performance thin layer chromatography, HPTLC) necessary to produce truly
standardized extract exists. What is needed the standardization of these materials
(at least 50% of the constituents), keeping close to the natural compositional
balance.
The molecular pathways leading to the sunburn, photoimmunosupression,
photoaging, and photcarcinogenesis seem to be different. However, the most
studied biological end point has been the reduction of UV-induced erythema.
Selection of other biological targets is important in clinical studies. Systematic
published clinical studies combining true photostable broad-spectrum sunscreens
along with antioxidant(s) are lacking.
Certainly, there are several promising areas of human clinical research yet to
be carried out. A few examples are: (i) combination of photostable broad-spectrum
sunscreens and antioxidants; (ii) combination of photostable broad-spectrum
sunscreens with chelating agents and matrix metalloprotease inhibitors; (iii) com-
bination of photostable broad-spectrm sunscreens and unconventional photoprotec-
tants; and (iv) combination of photostable broad-spectrum sunscreens and Emblica
antioxidant as it has a broad-spectrum antioxidant activity, strong chelating prop-
erty, and excellent matrix metalloprotease inhibitory activity. Further long-term
clinical studies are warranted before a true photoprotective composition can be pro-
posed for skin protection against UV-induced damage.
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31
Photoprotection by Green
Tea Polyphenols
Craig A. Elmets, Santosh K. Katiyar, and Nabiha Yusuf

University of Alabama at Birmingham,
Birmingham, Alabama, USA
Introduction 640
Green Tea Polyphenols and Photoprotection 641
Photoprotective Effects of Green Tea Polyphenols in Skin Cancer 642
Green Tea Polyphenols and the Different Stages of Photocarcinogenesis 643
Photoprotective Effects of Green Tea Polyphenols on the Acute
UV-Induced Sunburn Response 644
Photoprotective Effects of Green Tea Polyphenols on Photoaging 645
Protective Effects of Green Tea Polyphenols in UV-Induced
Immunosuppression 646
Mechanisms of Action of Green Tea Polyphenols 647
Cellular Effects 647
Apoptosis 647
Proliferation of Keratinocytes 647
Inflammatory Cell Infiltration 647
Molecular Effects 648
DNA Damage 648
Reactive Oxygen Intermediates 648
Proteasome Activation 649
Biochemical Activities 649
Conclusions 650
Acknowledgments 651
References 651
639
640 Elmets, Katiyar, and Yusuf
INTRODUCTION
The relationship that humans have with sun exposure is delicately balanced
between the positive effects that this form of radiant energy provides and the
negative aspects that overexposure engenders. The benefits of sun exposure
include its positive psychological actions, the role it plays in vitamin D metab-
olism, and the value it has as a therapeutic agent in cutaneous and systemic
disease. The adverse consequences of overexposure include acute UV-induced
erythema (i.e., a sunburn), nonmelanoma skin cancer (cutaneous squamous cell
and basal cell carcinoma), melanoma, photoaging of the skin, and UV-induced
immunosuppression.
Lifestyle changes over the past several decades have provided individuals
with much greater amounts of time for recreational activities, and much of this
time has been spent outdoors. As a result, there has been an alarming increase in
the incidence of sunlight-related disease. In 1999, over 30% of adults in the USA
reported at least one sunburn in the prior year (1) and over 70% of youth
between 11 and 18 years of age have had at least one sunburn during their life
(2). Moreover, 1.3 million new cases of nonmelanoma were estimated to have
been diagnosed in the USA in 2000, which is equivalent to the incidence of malig-
nancies in all other organs combined (3). According to current projections, one in
five Americans will develop at least one nonmelanoma skin cancer during their life-
time. While melanomas are not as prevalent as cutaneous squamous cell and basal
cell carcinomas, they are a serious problem as well with a mortality four times that
of nonmelanoma skin cancer. There were slightly more than 50,000 new cases in the
USA in 2002 and over 7000 deaths (4). The incidence of melanoma is increasing
more rapidly than any other type of cancer. Between 1973 and 2000 in the USA,
there was .160% increase in the incidence of melanoma.
Although there are many ways in which the adverse effects of overexposure
to ultraviolet (UV) radiation can be successfully treated, a much more effective
method of handling this problem is through preventative measures. Physicians
have a responsibility to educate their patients about the adverse effects of exces-
sive exposure to UV radiation. They have an obligation to instruct individuals on
methods by which the adverse effects of UV radiation can be prevented while at
the same time allowing them to take part in the outdoor activities that they enjoy
or are part of their occupation. Current methods for the prevention of acute and
chronic photodamage include counseling patients about the adverse effects of sun
exposure, instructing them on ways in which they can reduce their outdoor activi-
ties during peak hours of UV intensity (10 a.m. to 4 p.m.), advising them to wear
hats and long-sleeved clothing, and encouraging them to apply sunscreens
regularly (5).
While not denying the importance of currently available sunscreens in
the prevention of UV injury, it should be noted that the efficacy of sunscreens
is determined by their ability to protect against sunburn under laboratory
conditions, and their value in safeguarding against photoimmunosuppression,
Photoprotection by Green Tea Polyphenols 641
photoaging, melanoma, and nonmelanoma skin cancer in humans has received

much less attention. Fortunately, the data that are available do suggest that sun-
screens are effective at preventing at least some forms of skin cancer and its
precursors. With respect to nonmelanoma skin cancer, the regular use of an
SPF 15 sunscreen over a 5-year period of time reduced the incidence of cutaneous
squamous cell carcinomas by 35% when compared to subjects who applied them
sporadically (6). The fact that regular sunscreen use did afford protection against
cutaneous squamous cell carcinomas is reassuring; unfortunately, there was no
reduction in the incidence of basal cell carcinomas in the same patients. This
illustrates that the efficacy of currently available sunscreens, as they are used
by the general public, is incomplete. In addition other issues with respect to
sunscreens include the fact that large amounts of sunscreens must be applied
to achieve the full SPF value as indicated on the label; most agents that are avail-
able in the USA at this time provide less protection against UV-A than UV-B, and
there is increasing concern about the effects that UV-A might have; none of the
currently available sunscreens has an effect on UV damage that has already
occurred. Thus, there is a well-justified interest in identifying new constituents
that can be incorporated into sunscreens which have mechanisms of action that
complement existing formulations.
GREEN TEA POLYPHENOLS AND PHOTOPROTECTION

A particularly promising group of compounds that are being evaluated as poten-
tial sunscreen additives are polyphenolic extracts from green tea (7 – 10). Tea is
used primarily as a beverage and is consumed worldwide. It is manufactured
from the leaves and buds of the plant Camellia sinensis. There are three types
of tea—black, oolong, and green—which differ from each other because of
differences in their fermentation processes. Green tea is manufactured from
fresh leaves of the plant, which are steamed and dried at elevated temperatures
with care taken to avoid oxidation and polymerization of the polyphenolic com-
pounds. Consumption rates vary among the three types, with black, oolong, and
green tea having rates of 78%, 2%, and 20%, respectively (7 – 10).
The positive health effects of green tea have been attributed to the presence
of water-soluble polyphenolic constituents termed epicatechins (7 – 10), although
there is some evidence that caffeine present in green tea contributes as well
(11 – 14). There are four major epicatechins in green tea: (2)-epicatechin (EC),
(2)-epicatechin-3-gallate (ECG), (2)-epigallocatechin (EGC), and (2)-epigallo-
catechin-3-gallate (EGCG) (Fig. 31.1). EGCG is present in the greatest amount
(10). Comparative studies have shown that, in general, EGCG has the greatest
activity followed by ECG, EGC, and EC which are less active. The polyphenols
present in green tea are also found in black tea, but in smaller amounts due to the
fermentation process. Black tea also contains theaflavins and thearubugins which
also have photoprotective activities (10,11,14,15).
Figure 31.1 Structure of the major green tea polyphenols.
Much of the stimulus for using green tea to protect against the adverse
effects of sun exposure has come from epidemiological studies suggesting that
it has chemopreventive activities in other forms of cancer (7). For example, in
areas of China with the highest esophageal cancer mortality rates, tea is infre-
quently consumed (16). Moreover, among postmenopausal women in Iowa,
daily tea consumption is associated with a .50% reduced risk of digestive
tract and urinary tract cancers (17). It is important to note that, however, other
epidemiologic studies have shown the opposite effect (7).
PHOTOPROTECTIVE EFFECTS OF GREEN TEA POLYPHENOLS

IN SKIN CANCER
Initial studies evaluating the photoprotective effects of green tea polyphenols
were conducted in animal models of skin cancer (18). When SKH-1 hairless
mice are chronically exposed to UV-B radiation they develop premalignant papil-
lomas (i.e., actinic keratoses) and cutaneous squamous cell carcinomas. When
these animals were given extracts of green tea in their drinking water (0.1%
w/v) or had green tea extracts applied to their skin before each UV treatment,
the incidence of UV-induced tumors was reduced and the latency to tumor
development was prolonged (18). The effect was dose dependent. Subsequent
experimentation in mice has shown that the EGCG component of green tea
is also highly effective at controlling UV-induced tumor formation (19). The
vehicle in which EGCG is applied is an important factor in determining the
efficacy of a given topical formulation. Incorporation of green tea polyphenols
or EGCG in hydrophilic ointment appears to be significantly more effective
than other vehicles (20).
GREEN TEA POLYPHENOLS AND THE DIFFERENT STAGES

OF PHOTOCARCINOGENESIS
Skin tumorigenesis caused by UV light has been divided into three distinct stages
(Fig. 31.2) (21). In the first stage, termed initiation, UV radiation interacts with
DNA producing 6,4-photoproducts and cyclobutane pyrimidine dimers. There
is an attempt by the body to correct this damage through activation of DNA
repair enzymes. Patients with xeroderma pigmentosum, who are predisposed
to the development of actinically induced skin cancers, have a genetic defect
in the initial stages of DNA repair (22). Although the DNA repair processes
are quite efficient, they are not completely effective, thus leaving a few persistent
mutations. Mutations in the p53 gene are particularly important for the develop-
ment of UV-induced squamous cell carcinomas (23), whereas mutations in the
PTCH gene are critical for basal cell carcinomas to occur (24).
The mutant cells produced during the initiation stage of photocarcinogen-
esis are not apparent clinically. However, with repeated UV exposure additional
biochemical changes occur during the second stage of photocarcinogenesis
termed promotion (21). The two key cellular events that occur during the
promotion stage are amplification of the inflammatory response and increased
proliferation of mutant keratinocytes. The biochemical changes that produce
these events are still being worked out (Fig. 31.3). They are thought to com-
mence, at least in part, by the generation of reactive oxygen intermediates
(25 – 27), which then activate a variety of signal transduction pathways. This
leads to the synthesis or activation of new proteins such as cyclooxygenase-2
(28) and ornithine decarboxylase (29). The end result of this stage is the devel-
opment of clinically apparent premalignant actinic keratoses.
Figure 31.2 Stages of photocarcinogenesis.

Figure 31.3 Biochemical changes occurring after UV exposure.
In the third stage, called progression, a small proportion of actinic keratoses

acquire additional genetic changes that allow them to become invasive carci-
nomas. Alterations in TGF-b1 appear to be important during this stage (30,31).
Protocols have been developed which distinguish between the effects
of UV radiation on the initiation and promotion stages of carcinogenesis.
These protocols have been employed to assess at which of the stages green tea
polyphenols act. When administered in drinking water, EGCG was able to
reduce UV-induced tumor formation when given only during the initiation or
promotion stages (32 – 34).
It is possible to assess the effects of green tea polyphenols on the pro-
gression stage by exposing SKH-1 hairless mice to UV radiation for 22 weeks.
At that point, these mice do not have tumors but are at high risk of developing
them even without further exposure to UV. When green tea was given orally
in the drinking water beginning at 22 weeks and the mice were followed for tumor
development, there was a significant reduction in the number of tumors that
occurred over the ensuing weeks (14). Even after animals had been exposed to
UV radiation for several weeks and then EGCG was applied, there was a signifi-
cant reduction in tumor development and partial regression of existing tumors
(13,15).
As was mentioned, because black tea has polyphenols, thearubigins, and
theaflavins, it, too, has been investigated for its photoprotective properties.
When black tea was given to SKH-1 mice after they had been UV irradiated for
22 weeks and had established skin tumors, subsequent tumor growth was inhibited
by 70% even though UV irradiation had stopped (13). Caffeine may have contrib-
uted to this effect, because decaffeinated black tea gave inconsistent results.
The efficacy of green tea polyphenols as chemopreventive agents for
actinic keratoses in human subjects at high risk of development of nonmelanoma
skin cancer remains to be determined. In a small clinical trial, topical application
of EGCG in an ointment base was ineffective at causing regression of existing
actinic keratoses. At this point, its role in preventing the development of new
actinic keratoses in humans has not been examined (35).

ON THE ACUTE UV-INDUCED SUNBURN RESPONSE
In humans, acute overexposure of the skin to UV radiation causes a painful
erythemal response known as the sunburn reaction (36). This is manifest as
redness, pain, and swelling, which usually peaks 6– 24 h after UV exposure, after
which it declines. Histologically, there is an acute inflammatory response with
neutrophils; within the epidermis are large numbers of dyskeratotic keratinocytes
that are undergoing apoptosis and have been termed “sunburn” cells. UV-induced
erythema is much more difficult to detect clinically in mice than it is in humans.
In this species, the edema response, measured as an increase in ear thickness after
UV compared to that prior to UV, has been employed as a quantifiable alternative
(37). In this experimental system, both topical and orally administered green
tea polyphenols reduce the UV-induced increase in ear swelling (37). This is
associated with a concomitant reduction in the number of sunburn cells detected
histologically (37) and cells in the epidermis undergoing apoptosis detected
by caspase-3 immunohistochemistry (12). The effect on apoptotic cells has
been corroborated in vitro by showing that the addition of EGCG prior to
UV irradiation of cultured keratinocytes results in a significant reduction in
apoptosis (38).
The effect of green tea polyphenols on the acute UV erythema response in
humans is similar to that in mice (39). When graded concentrations of green tea
polyphenols are applied to the skin of human volunteers prior to exposure to a
2-MED dose of solar simulated radiation, there is a dose-dependent reduction
in erythema (39), which is accompanied histologically by a decrease in
UV-induced keratinocyte hyperproliferation, a dramatic reduction in the number
of sunburn cells, and a diminution in the inflammatory cell infiltrate (40,41).
The decrease in the erythemal response is observed both in response to solar simu-
lated radiation (in which UV-B is primarily responsible for the sunburn response)
and to a UV-A radiation in which no UV-B is present (39). As with animal and
in vitro models, EGCG is the polyphenolic constituent that is most efficient at inhi-
biting erythema in humans. In human volunteers, green tea polyphenols are also
highly effective at decreasing the DNA damage and the number of cyclobutane
pyrimidine dimers that are present in UV-irradiated skin (39,42).

ON PHOTOAGING
Another major effect of chronic UV radiation overexposure is photoaging of the
skin. This manifests as coarse and fine wrinkling, increased fragility, ecchy-
moses, telangiectasias, freckling and solar lentigines. Many of these clinical
manifestations are caused by degradation of collagen through activation of
matrix metalloproteinases and by the accumulation of abnormal elastin fibers,
leading to nodular elastosis (43,44). Depletion of antioxidant enzymes, oxi-
dative modification of proteins (25) and accumulation of lipid peroxidation
and glycation products are all involved in the photoaging process (44 – 46).
Antioxidants have been shown to reverse photoaging in vitro and in vivo in
animal models (47,48). Resident cells within the skin as well as infiltrating
inflammatory leukocytes are the source of these reactive oxygen intermediates
(40,41). In matrigel skin equivalents in vitro, EGCG alone has been shown to
inhibit the expression MMP-9, MMP-2, MT1-MMP and neutrophil elastase at
concentrations that can be achieved pharmacologically (49,50). With respect
to UV radiation, recent studies have shown that administration of green tea
polyphenols in drinking water inhibits UV-induced protein oxidation, a hall-
mark of photoaging (20), and activation of matrix metalloproteinases (51) pre-
sumably through its inhibitory effects on the activity of reactive oxygen
intermediates.
PROTECTIVE EFFECTS OF GREEN TEA POLYPHENOLS IN

UV-INDUCED IMMUNOSUPPRESSION
The extent to which green tea polyphenols and their polyphenolic constituents
reverse UV-induced immune suppression has also been an active area of
investigation. UV-B-induced immune suppression is considered as a risk factor
for skin cancer development (52). It may also be a cause of reduced resistance
to selected infectious agents and of diminished immunization rates following
vaccination (53). Using murine models of contact hypersensitivity as a prototype
for cutaneous cell-mediated immune responses, it has been shown that green tea
polyphenol and EGCG treatment to mouse skin prevents UV-B-induced immune
suppression and reverses the tolerogenic effect of this form of radiant energy
(37,54). UV-induced immune suppression is mediated at least in part by an
increase in the production of IL-10 and a reduction in IL-12 levels (54).
Topical application of EGCG has been shown to change the balance between
these two cytokines, reducing IL-10 production and increasing IL-12 (54). One
of the major cellular sources of IL-10 produced in the skin following UV radi-
ation is a CD11bþ macrophage that migrates into the epidermis following
UV-B exposure (55). Application of EGCG to the skin prior to UV radiation
reduces the number of CD11bþ cells that migrate into the epidermis and inhibits
IL-10 production (54). Epidermal Langerhans cells, bone marrow-derived den-
dritic cells which are proficient at initiating cell-mediated immune responses,
are a source of IL-12 in the epidermis (56). IL-12 is a mediator and adjuvant
for cutaneous cell-mediated immune responses. The number of Langerhans
cells is reduced in UV-irradiated epidermis as is the number of IL-12-producing
cells in regional lymph nodes. Topical application of EGCG reverses the
reduction in Langerhans cells in humans (39) and has been shown to greatly
increase the production of IL-12 in draining lymph nodes compared to mice
treated with UV-B alone (54). Evidence has been presented that prostaglandin
E2 (PGE2) (57,58) and cyclobutane pyrimidine dimers (59) are responsible
for the reduction in Langerhans cells. Thus, it seems reasonable to hypothesize
that by reducing PGE2 and cyclobutane pyrimidine dimers, green tea polyphe-
nols could inhibit the reduction in Langerhans cell concentrations in skin and
in so doing could bring IL-12 levels back to normal.
MECHANISMS OF ACTION OF GREEN TEA POLYPHENOLS

A number of studies have been conducted to carefully define the cellular and mol-
ecular mechanisms by which green tea polyphenols protect against skin cancer.
Spectrophotometric analysis has shown that these agents do not absorb wavelengths
within the UV-B or UV-A and that even when administered orally they have
photoprotective effects. Thus, EGCG and green tea polyphenols do not block UV
radiation from reaching the skin indicating a photoprotective effect distinct
from that of traditional sunscreens, which block penetration of UV radiation into
the skin.
Cellular Effects
Apoptosis
The effects of EGCG on apoptosis are complex. Histologically, large numbers of
apoptotic keratinocytes, known as “sunburn cells,” can be found in skin following
acute UV overexposure. Pretreatment with EGCG limits the number of these
cells that appear both in human and in mouse skin (37,39). A very different
response occurs in skin that has been chronically UV irradiated. In murine
models, topical application of green tea polyphenols to skin that has already
been chronically exposed to UV-B and therefore is at high risk of subsequently
developing UV-induced tumors stimulates apoptosis in the malignant and pre-
malignant tissue, but not in non-tumor bearing areas of the epidermis (12).
Proliferation of Keratinocytes
One of the major cellular events that occurs following UV radiation of the skin is
increased proliferation of keratinocytes. This can be observed histologically as
hyperplasia of the epidermis. The histological abnormalities revert to normal
when green tea polyphenols are given prior to UV exposure. The epidermal
mitotic index and BrdU incorporation into epidermal DNA after UV exposure
have also been used as markers of increased epidermal proliferation. It has
been shown that the UV-induced increase in BrdUrd incorporation and the epi-
dermal mitotic index can be significantly reduced by oral administration of
green tea polyphenols in vivo (60). Caffeine has an additive effect when given
with green tea polyphenols (60).
Inflammatory Cell Infiltration

Inflammation is one of the cellular hallmarks of the sunburn response and has
been implicated in the promotion stage of UV-induced skin tumorigenesis,
UV-induced immunosuppression, and photoaging. Immunohistochemical tech-
niques have been employed to show that chronic oral feeding as well as
topical administration of green tea polyphenols to the skin of mice that were then
exposed to UV radiation significantly reduced leukocyte infiltration into the
skin (40). Similar results have been found when green tea polyphenols have
been applied to the skin of human volunteers (39). These findings are of parti-
cular interest because leukocytes may be a major source of reactive nitric
oxide and hydrogen peroxide, which are critical for biological changes that
occur following UV exposure of the skin.
Molecular Effects
DNA Damage
Direct photochemical damage to DNA, predominantly in the form of cyclo-
butane pyrimidine dimers, is one of the major effects of UV radiation (21).
It plays an important role in the initiation stage of photocarcinogenesis and con-
tributes to the induction of UV-induced immunosuppression (59). By employing
immunohistochemical techniques, green tea polyphenols have been shown to
reduce the amount of DNA damage in UV-irradiated skin in vivo (39,42).
One of the consequences of UV-induced DNA damage is the production of
mutations in the p53 gene (23). Given the fact that green tea polyphenols inhib-
ited UV-induced DNA damage, it was surprising to find that green tea poly-
phenols augment UV-B-induced increases in wildtype p53 gene (60). One of
the major effects of p53 is to initiate apoptosis in cells that have sustained
significant DNA damage (61). It has been proposed that augmentation in p53
is one mechanism by which green tea polyphenols exert their photoprotective
effects (60).
Reactive Oxygen Intermediates

Despite the fact that the skin has a sophisticated and highly effective system to
handle oxidative stress, it is not uncommon for UV radiation to overwhelm
these defenses. Substantial evidence has been presented to support the concept
that green tea and its polyphenolic constituents protect these antioxidant defenses
(8,20,62 –64). Initial studies demonstrating this effect were conducted in vitro on
murine epidermal microsomes (64). UV exposure of these subcellular organelles
enhanced lipid peroxidation, whereas the addition of green tea polyphenols
reduced this effect. In in vivo animal models, when given orally or when applied
topically prior to UV radiation, EGCG prevented UV-B-induced markers of
oxidative stress (protein oxidation, lipid peroxidation), depletion of glutathione
levels and the antioxidant enzymes catalase and glutathione peroxidase (20).
UV augments oxidative stress through both direct effects on the skin and indirect
effects through its ability to cause the recruitment of leukocytes into the skin,
which then release reactive oxygen intermediates. Green tea polyphenols and
EGCG reduce reactive oxygen intermediates produced by both mechanisms
(40). It should be noted that nitric oxide, another mediator of inflammation in
UV-irradiated skin is also inhibited by EGCG (40).
Proteasome Activation
Another molecular target for EGCG is the 20S proteasome (65). This molecule is
part of the ubiquitin –proteasome pathway that is necessary for degradation of
such proteins as p53, pRB, p21, p27Kip1, IkB-a, and Bax. Protein degradation
occurs through chymotrypsin-like, trypsin-like, and peptidyl – glutamyl peptide
hydrolyzing activities of the 20S proteasome. The chymotrypsin-like activities
of the 20S proteasome have been associated with tumor cell survival. On the
basis of similarities in the chemical structure between several of the green tea
polyphenols and other irreversible inhibitors of the 20S proteasome, in vitro
studies were undertaken to determine whether the 20S proteasome might be a
target for green tea polyphenols. Both ECG and EGCG, as well as (2)-catechin-3-
gallate and (2)-gallocatechin-3-gallate, two other tea polyphenols, were able
to inhibit the 20S proteasome in a number of different tumor cell lines, with
EGCG being the most potent. Inhibition was associated with accumulation of
p27Kip1 and IkB-a and G1 growth arrest in tumor cell lines (65). Interestingly,
SV40 transformed fibroblasts were much more susceptible to p27Kip1 accumu-
lation and G1 growth arrest than were their nontransformed counterparts.
Because many of the molecules subject to degradation by this pathway regulate
the cell cycle and cell death, it seems reasonable to hypothesize that irreversible
inhibition of the 20S proteasome is one of the key upstream events involved in the
chemopreventive actions of the green tea polyphenols (65).
Biochemical Activities
UV radiation is a potent activator of several different signal transduction path-
ways. Of particular interest has been its ability to upregulate MAP kinases,
which in turn results in activation of the AP-1 transcription factor (Fig. 31.3).
AP-1 is a nuclear transcription factor for the enzyme cyclooxygenase-2, ornithine
decarboxylase, and matrix metalloproteinases.
Cyclooxygenase-2 is an inducible enzyme which is responsible for pro-
duction of PGE2, a molecule implicated in many of the biological effects of
UV radiation. Among other actions, PGE2 has proinflammatory activities and
increases keratinocyte proliferation (66,67), it promotes angiogenesis (68,69),
and it is an inductive stimulus for the immunosuppressive cytokine IL-10
(58,70). PGE2 plays an important role in the sunburn reaction (66), in photocar-
cinogenesis (28,66,71), and in photoimmunosuppression (57,58,72). Ornithine
decarboxylase (ODC) is the rate-limiting enzyme in the polyamine biosynthetic
pathway (73). Acute UV exposure increases ODC activity and chronic exposure
augments basal ODC levels (74 – 78). The major function of MMP-1 is to degrade
collagen, and therefore it plays a critical role in selected aspects of photoaging of
the skin (44).
Green tea polyphenols interfere with many of the steps in this signal trans-
duction pathway. In vitro studies using normal human keratinocytes have shown
that EGCG interferes with UV-B-induced activation and phosphorylation of
MAP kinases (62). This effect on MAP kinases has been confirmed in in vivo
experiments in murine skin as well (20). Experiments examining PGE2 and
ODC activity in UV-irradiated skin that has been pretreated with green tea poly-
phenols have also been conducted, and it has been shown to be reduced (79). The
first demonstration that green tea polyphenols might interfere with prostaglandin
synthesis came from in vivo studies in which mice were fed green tea polyphenols
in their drinking water. PGE2 activity following UV radiation was significantly
reduced compared to controls that were UV irradiated but were not given
green tea (79). Subsequent experimentation has shown that topical application
of green tea suppresses COX-2 expression in UV-irradiated human and murine
skin (80). In mice, suppression of COX-2 was found to occur when it was
placed on the skin before or after UV irradiation (80). Mice given green tea
in their drinking water fail to develop the increase in ODC activity that is nor-
mally observed in UV irradiated mice (79). This effect of green tea polyphenols
on ODC induction is identical to that which is observed in mice whose skin
is treated with tumor promoters such as TPA (81). With respect to matrix
metalloproteinases, EGCG has been shown to inhibit MMP-3, MMP-7, and
MMP-9 when given orally or topically before acute or chronic UV radiation
exposure (51).
Another UV-induced signal transduction pathway that is modulated by
EGCG is NF-kB (82). Exposure of cultured keratinocytes to UV-B has been
shown to result in activation of the NF-kB signal transduction pathway and its
translocation into the nucleus. Incorporation of EGCG into the culture medium
caused a significant reduction in this process. EGCG did this by inhibiting acti-
vation of IKKa and degradation and phosphorylation of IkBa (82). Evidence has
been presented to indicate that this occurs through inhibition of proteasome
degradation (65). NF-kB plays a key role in the induction of UV-induced
inflammatory responses and has been shown to contribute to UV-induced tumor-
igenesis. Thus, it is reasonable to postulate that this is one mechanism by which
EGCG mediates its effect on UV-induced inflammation, cellular proliferation,
and the sunburn response through its effects on the NF-kB pathway.
CONCLUSIONS
Polyphenolic extracts of green tea and the most active polyphenolic constituent
EGCG show promise as new agents that can complement and enhance the photo-
protective effect of currently available sunscreens. These agents, which are
consumed as a beverage throughout the world, have been shown to have little,
if any, irritancy or allergenicity when applied topically. In animal models and
in preliminary studies in humans, they ameliorate many of the adverse effects
of acute and chronic overexposure to the sun. This includes photoprotection
against the sunburn response, nonmelanoma skin cancer development, photo-
aging, and UV-induced immunosuppression. They are potent antioxidants, are
anti-inflammatory, and have a broad array of other molecular and biochemical
actions. Topical formulations that include these agents are likely to lead to further
improvements in the way in which humans protect themselves from
overexposure to the sun.
ACKNOWLEDGMENTS
This work was supported by funds from the Department of Veterans Affairs
(18-103-02), NIH grants, and contracts NO1 CN-85083, R01 CA79820,
CA86172, NO1 CN1500-46, R01 CA90920, R23 ES 11421, and R23 CA94593.
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32
Botanicals in Sun Care Products
Howard Epstein
Kao Brands—The Andrew Jergens Company,
Cincinnati, Ohio, USA
Introduction 657
Botanicals of Specific Interest 659
Botanically Derived Sunscreens and SPF Boosters 659
Botanicals as Photochemoprotective Agents 660
Botanicals in Sun Care Products 661
Quality Control: Methods of Analysis 661
Recent Research Techniques: Biological Assays and
Cell Culture 665
Biological Assays of Interest for Screening Botanicals in
Sun Care Products 666
Conclusion 669
References 669
INTRODUCTION
Sun exposure has long been considered a healthy benefit of outdoor activity.
Exposure to ultraviolet radiation (UVR) can stimulate vitamin D synthesis in
the body and may promote immune tolerance toward certain antigens such as
657
658 Epstein
myelin autoantigens (1). Conversely, epidemiological data confirmed by research

of the last 20 years have shown that exposure to UVR is a major risk factor for
various skin cancers, premature aging of the skin commonly referred to as
photoaging, and alteration of the skin’s immune functions (2). More recently,
research has shown that although sunlight and oxygen are essential for life,
exposure to UVR and infrared radiation can potentially induce reactive oxygen
species (ROS) in cutaneous tissue (3 – 5). ROS are considered to be a major
factor in skin aging, cancer, and other conditions that effect the health of skin.
ROS react with proteins, DNA, and unsaturated fatty acids leading to oxidative
damage and immunosuppression.
Early studies of physiologic skin aging were “confounded” by the diffi-
culty of distinguishing between extrinsic and intrinsic aging. Intrinsic aging is
the natural biological progression of aging. Extrinsic aging is caused by external
influences such as UVR, toxins in the environment, and other damaging
environmental effects. One of the most fundamental issues for early photobiol-
ogists was to identify the molecular target for UVR in skin. UVR is arbitrarily
separated into three ranges based on wavelength: UV-A (320 – 400 nm), UV-B
(290 – 320 nm), and UV-C (200 – 290 nm). UV-C radiation is mostly absorbed
by the stratosphere ozone layer, while UV-A radiation and UV-B radiation
reach the earth and are considered the most “biologically relevant” wavelengths.
The amount of UV-A radiation reaching the earth’s surface is about 20 times
greater than that of UV-B, and it can pass through the ozone layer, clouds,
and glass with greater efficiency than UV-B radiation. Some investigators
believe that the stratum corneum can block 90% of UV-B radiation, but only
50% of UV-A, enabling UV-A radiation to penetrate to deeper layers of the
skin (6). Damage to skin from extrinsic aging serves to intensify the progression
of intrinsic aging. It is now known that the sun exerts a number of effects on
skin. One response of skin to UVR is tanning. Melanin in the skin is known
to reduce the amount of UVR that can penetrate skin through the epidermal
layers. It is a complex polymer produced by specialized cells, melanocytes
located in the epidermal layer of the skin. Melanin is capable of quenching
oxidative free radicals generated by exposure to UVR. The protective effect
of melanin is limited and one should never assume that a tan would provide
protection from the harmful effects of the sun’s radiation. Skin contains two
important chromophores, or photoreceptors, that can absorb UVR. One chromo-
phore has an affinity for UV-B and the other for UV-A. Each chromophore has
the potential to generate changes that may cause significant damage to skin.
Nuclear DNA in the lower epidermis is the major chromophore for UV-B
radiation. UVR that affects DNA can cause production of pyrimidine dimers
and other damaging photoproducts directly in the DNA. If the cellular DNA
does not repair the dimers, or undergoes cell death (apoptosis), cancer can
develop in the cell. The other important chromophore in skin is urocanic
acid. Urocanic acid can undergo photochemical reactions with DNA resulting
in photoisomerization to a molecule having immunologic effects on the body
and can generate singlet molecular oxygen. UV-A is believed to be much more
efficient than UV-B at generating oxidative stress (7,8).
BOTANICALS OF SPECIFIC INTEREST

Botanically Derived Sunscreens and SPF Boosters
Most chemical sunscreens available to the formulator of sunscreen products
provide more efficient filtering of UV-B radiation than of UV-A. Formulations
containing adequate levels of chemical and physical sunscreen agents (titanium
and zinc oxides) designed to achieve good UV-B and UV-A protection are fre-
quently perceived by the consumer as being too whitening and greasy when
applied to skin. The ideal sunscreen should protect skin from UV-A and UV-B
radiation, bind to the stratum corneum with minimal penetration into the skin,
be resistant to heat, sweating, and bathing, and have good cosmetic acceptance
by the consumer. Consumers desire innovative sun care products that continue
to provide additional benefits; health-conscious consumers are creating a
growing demand for “natural” and “functionally based” botanicals. Phytoderived
products serve various functions that include, emollients, tanning agents, and
sunscreens. Flavonoids in botanicals having active UV absorbing properties
have been identified and representative botanicals from this group have been
found to enhance the absorption of UVR. For example, at about 282 nm, the
flavones account for about 75 –98% of the absorbency; Citrus aurantium is parti-
cularly high in flavonone. To avoid issues of dermal irritation, a unique patented
process is used to extract the flavonoids of interest. Naringin, neohesperidin,
neoeriocitrin, luteolin, and rutin are among the most desirable components (9)
in galangal (Kaempferia galanga), a member of the ginger family. Galanga
root is a natural source of ethyl p-methoxycinnamate. Studies have been con-
ducted demonstrating the ability of galanga extract to “synergistically enhance
the UV absorbency of a sunscreen composition.” Further, the extract was
shown to help make a sunscreen active more “photostable in a topical sunscreen
composition,” enabling more time to pass before additional application of sun-
screen is needed for photoprotection. The synergistic effect of galanga extract with
a conventional sunscreen allows a lower percentage of conventional sunscreen to
be formulated into the sun care product (10,11). Recently, a process producing
“sunscreens from vegetable oil and plant phenols” was disclosed: a lipase-catalyzed
transesterification of a triglyceride to yield a feruyl-substituted or coumaryl-
substituted acylglycerol with properties suitable for use as a sunscreen agent.
Soybean oil is combined with ferulic acid using the enzyme lipase. Other suitable
sources of triglycerides are corn, sunflower, canola, and safflower oils. The
products of this reaction have UV absorptivity from 280 nm to 350 nm and
are claimed to be particularly effective in the range of 310– 350 nm, the
UV-A range. These products are well suited for waterproof type formulations
(12). Other botanicals with UV absorbance are found in Table 32.1 (13).
660 Epstein
Table 32.1 Botanically Derived Sunscreens and SPF Boosters
Botanical Absorption spectrum Compounds identified
Aloe (Aloe socoirina) Maximum peak at Aloin (liquid and

297 nm, with a second glycolic extracts)
peak at 360 nm
Helichrysum 275–300 nm A complex of
(Helichrysum italicum) quinonic flavonoids
Frangula 270 nm Glucofrangulin
(Rhamnus frangula) 300 nm Glycolic extract
of frangula
Camomille 250–300 nm Gylcolic extract
(Matricaria chamomilla) (oily extract had no
effective absorption)
Rhatany Shows poor Digalloyltrioleate
(Krameria triadra) absorption, tannins
produce an insoluble
complex with
proteins in skin
Source: Courtesy of R&D Systems, Inc., Minneapolis, MN.
Botanicals as Photochemoprotective Agents

Photochemoprevention is the prevention of photoaging, skin cancer, and photo-
sensitivity diseases of the skin by the use of pharmacological agents that inhibit
or reverse the photoaging process. Protection provided by sunscreens is not com-
plete and cannot repair damage to skin that has already occurred. Until recently,
the main focus of research was on UV-B radiation, it is now appreciated that
UV-A radiation also has significantly detrimental effects to the skin, such as gen-
eration of reactive oxygen species, further leading to lipidperoxidation, activation
of transcription factors, and generation of DNA strand breaks. UV-A and UV-B
exposure to skin has been shown to trigger two other major pathways leading to
photoaging: induction of matrixmetalloproteinases (MMPs), resulting in collagen
breakdown and mutation of mitochondrial DNA (mtDNA), which results in
premature aging (14 –17). Current research is investigating the potential of bota-
nicals to function as chemopreventative agents. Green tea (Camellia sinensis)
polyphenolic (GTP) compounds were among the early agents investigated and
were found to be very effective as chemoprotective and chemopreventative
agents. The primary antioxidants identified in green tea are epicatechin and epi-
gallocatechin. These antioxidants have been shown to be stronger antioxidants
than vitamin E and vitamin C (18 – 20). Studies have been conducted on
human volunteers to observe the ability of green tea polyphenols to inhibit
erythema and prevent the formation of thymine dimers, a marker for DNA
damage in skin. GTP was found to significantly reduce erythema and DNA
damage when taken orally and applied topically prior to volunteers’skin being
treated with UV-A and UV-B radiation. Other studies have indicated that mice
pretreated with GTP maintained reduced levels of ROS and reduction of inflam-
matory leukocytes, a marker for inflammation (21 – 24). Other potential natural
antioxidants to be evaluated for photochmoprotective benefits are a-tocopherol
from plant oils, apigenin from various fruits and vegetables, carotenoids,
caffeic and ferulic acids from vegetables, olives and olive oil, genistein, a phy-
toestrogen in soy, red clover, Greek oregano and Greek sage, L -ascorbic acid
from fruits and vegetables, resveratrol in grape seeds and skin, curcumin,
garlic, red clover, and milk thistle (25).
BOTANICALS IN SUN CARE PRODUCTS

The sun care industry can be divided into three categories: sunscreen and sun
blocking, sun tanning, and after-sun care products. About 80% of sun care
sales take place at mass-market counters, drug stores, and supermarkets. The
total US market for 2002 has been estimated to be in excess of $440 million,
with the majority of purchases for sunscreen and sun blocking products.
Market data indicate that about 45% of the adults in the USA use sun care
products. Prime consumers are females between the ages of 25 and 44.
Schering-Plough’s Coppertone brand is the leading product sold in the USA;
Banana Boat and Hawaiian Tropic follow. New sun care products offering
benefits beyond SPF protection are emerging as consumers are becoming more
aware of the damage to skin caused by exposure to the sun. These additional
benefits include antiaging, skin firming ingredients, and ingredients for sen-
sitive skin. Aloe remains the most common botanical used in after-sun
products, to promote soothing and rehydration of skin exposed to the sun
(Tables 32.2 and 32.3).
QUALITY CONTROL: METHODS OF ANALYSIS

Confirmation of botanical identity is the key responsibility of the botanical
supplier. The appearance and active constituents of the botanical may vary
with growing conditions and geographically diverse soil conditions. Botanicals
formulated in OTC drugs and cosmetics are not regulated and lack of quality
control/standardization is common. Adulteration of botanicals tends to
become a problem when prices are high or it is difficult to obtain a popular
botanical (26).
Botanicals should be evaluated by visual and microscopic inspection.
Appearance, color, and odor can be compared to a reference standard. An experi-
enced botanist can evaluate subtle plant structural differences under microscopic
evaluation. Sometimes stains may be used to identify a specific botanical.
662 Epstein
Table 32.2 Botanicals in Sun Care Products
Suggested purpose or
Product Botanical component claim
Nivea Sun Care Alpha flavone Antiage sun cream

Nature’s Gate Aloe Antiaging
Laboratories Oenobiol Carotene, tomato extract Antiaging
Clarins Sun Care Cream Aloe, ayapana, silver Children with
birch, camellia, shea sensitive skin
butter, mimosa, palm,
pea, quinquina, and
vanilla
Clairins Hydrating After- Aloe, chamomile, shea, After-sun use
sun Moisturizer walnut, rosemary,
Siegesbeckia orientalis,
linden, vitamins A
and E
ABRA Therapeutics, Green tea, grape seed Maximum solar
Collagen PhytoSHield, extract, vitamins C protection
SPF 15 and SPF 30 and E
Aubrey Organics, Saving Aloe vera, witch hazel, St.
Face SPF 15 John’s wort oil,
calendula oil
Bath & Body Works, Green tea extract
Suntan SPF 8
Almay Age Decelerating Kinetin (furfuryladenine), Antiaging
Daily Lotion SPF 15 salix nigra (willow)
bark extract, aloe, leaf
juice, simmondsia
chinesis seed oil,
Anthemis nobilis, salvia
sclarea, ferula
galbanifula, Camellia
sinesis, Rosmarinis
officinalis
Caudalie Grapeseed polyphenols, Antiaging and
resveratrol, passion soothing
flower, sesame, shea
butter
L’Oreal, Ambre Solarie Cactus nutriflavones Extra miniaturization
and softness to
skin
Eucerin, Onagrine line AGR, a plant flavonoid
with high antioxidant
activity
(continued )

Suggested purpose or
Product Botanical component claim
Boots, Soltan Aloe vera, watermelon, Promotes safer,

chamomile longer-lasting tans
Nivea/Beiersdorf Perfect Japanese pagoda tree Antioxidant
Protection SPF 15 extract sunscreen
protection
MOP Suncare (Modern Quinoa, horsetail extract Natural antioxidants
Organic Products) SPF with vitamins A and E to protect and
15, 30 restore skin
Kiss My Face, Sun Swat Titanium dioxide and oat (1) A natural
SPF 15 protein complex, oat sunscreen blend;
beta glucan (1) also (2) Blend of
contains citronella, bay, botanicals that
cedarwood, lavender, help repel bugs
vetivert, patchouli, and are good for
juniper, tea tree, lemon skin
peel, pennyroyal, tansy,
goldenseal (2)
Aveeno (Johnson & Soy extract A unique
Johnson)/Skin combination of
Brightening Daily naturally active
Moisturizer SPF 15 complexion
corrector
Instrumentation used to evaluate chemical constituents include infrared spec-

troscopy, thin-layer chromatography, gas and liquid chromatography (GC, LC)
and, more recently, LC/MS and GC/MS. GC/MS can selectively measure
volatile chemical constituents and nonvolatile components such as fatty acids,
phytosterols, and terpenoids. Use of instrumentation permits one to build a refer-
ence library of compounds to compare lot- to-lot submissions of botanicals. The
equipment may be used to develop what is termed a “fingerprint” or “marker
compounds,” key characteristic components of the botanical under evaluation.
The marker compounds will appear as a colored band, known as a chromatogram.
Each peak in the chromatogram represents an active constituent or component in
the botanical extract. One should be aware that while marker compounds help to
identify a specific botanical, it is frequently other components or a synergistic
interaction of components in the botanical that are responsible for its activity.
In cases where one wishes to evaluate a botanical or combination of botanicals
for a synergistic effect, a biological assay may be the preferred method of
quality control.
664 Epstein
Table 32.3 US Patent Technology
Botanical or active in
Patent number botanical Application
5,665,367 Flavonoid: naringen Treatment of

and/or quercetin photodamaged skin,
wrinkles
US Patent application Olive plant extract (Olea Skin beautification,
number 20020176903 europaea L.) antiaging via an
antioxidant effect
6,121,243 Alpha-glucosyl rutin and Antiaging, antioxidant
one or more flavonoids
and their glycosides,
cinnamic/ferulic acid
derivatives (obtained
from beet crops latex
from umbelliferous
plants such as Ferula
asafetida)
6,251,878 Tamarind seed Inhibition of UV-
induced immune
suppression and
interleukin-10
production
5,861,415 Curcumoids (curcumin, Antioxidant, anti-
demethoxy curcumin, inflammatory,
bis-demethoxy antimutagen
curcumin)—extracted
from the roots of
tumeric
5,824,659 Aloe oligosaccharide Prevents damage to the
skin immune system
by UVR
6,248,341 Green tea— When combined with
epigallocatechin, tyrosinase inhibitors
epicatechin gallate is useful for
treatment or
prevention of dark
circles,
melanization, anti-
irritant
6,531,165 Fagus crenata Collagen production
promotor, repair of
collagen damaged
from UV exposure
(continued )

Botanical or active in
Patent number botanical Application
6,596,761 Various flavonoids in Antioxidant, helps to

combination with protect skin against
cinnamic acid UVB and UVA
derivatives radiation
6,592,911 (2)-Olivil from Antioxidant,
Stereospermum comparable to
personatum tocopherol
6,589,514 Morinda citrifolia (Indian Antiaging serum,
mulberry plant) repair skin damaged
by UVR
To ensure safety, botanical shipments should be certified to be free of pes-

ticides, heavy metals, and microbial contamination. Documentation should state
the correct Latin name, part of the plant used, season and method of harvest,
method of storage, and extraction method used including solvents that may
have been removed prior to shipment.
Recent Research Techniques: Biological Assays and

Cell Culture
Currently, common industry practice is to standardize botanicals to “marker”
compounds. Biological assays (bioassays) enable one to standardize botanical
products that have been mixed or contain several components that are responsible
for the activity of the plant. Botanicals are considered to have “holistic, func-
tional benefits that are beneficial for more than one body site.” For this reason,
a biological assay would be considered a preferable approach to standardizing
a botanical for a desired activity. Bioassays are desirable when chromatography
is unable to separate a compound effectively or chemical analysis does not yield
satisfactory results. As the human genome project comes to completion, the
herbal industry has benefited by the availability of techniques and instrumenta-
tion capable of determining “receptor binding, enzyme inhibition, DNA
nicking,” and antioxidant activity. Biological assays offer the advantage of
rapidly screening large numbers of samples for a specific desired activity.
Cells of the body react to the external environment and each other through a
series of complex signaling networks. These networks contain feedback loops
with various isolated pathways that have begun to be understood only in recent
years. Signal transduction is the process of conversion of “external signals,
such as hormones, growth factors, neurotransmitters, and cytokines to a specific
666 Epstein
internal cellular response, such as gene expression, cell division, or even cell
suicide” (27). There are five basic routes for external cell signaling (28):
1. Diffusion of hydrophobic molecules across lipid bilayers of cell
membranes
2. Cell surface signaling enzymes located on the interior of cell
membranes, for example, tyrosine kinases and Ras proteins; these
molecules trigger a signaling cascade while anchored to the plasma
membrane
3. Ion channels are specific membrane proteins that permit specific ions
to pass through a cell membrane
4. Receptor binding on the cell surface, found on the exterior of the
membrane; examples are tumor necrosis factors or cytokines
5. G protein-coupled receptors are seven-transmembrane proteins com-
posed of subunits in triplicate; these molecules traverse both sides of
the cell membrane.
Signal transduction initiates at the cell membrane where the release of a
chemical signal or other external stimulus stimulates a cascade of enzymatic reac-
tions inside the cell. These reactions eventually cause changes in cell function or
identity of the cell through protein interactions. Signal transduction pathways
contain “go-no go” control points that, when activated by environmental stresses
such as UVR, lead to photoaging, immunological compromise, and possibly skin
cancer. Biological signaling is the result of interacting signaling molecules that
are mostly protein in nature. SWISS-PROT, an online molecular biology database,
lists approximately 1551 human signal proteins and a total of 2986 signal proteins in
humans (SWISS-PROT protein database, public release Number 36). Signaling net-
works exist on several levels of complexity. Hormones and other molecules carried
by the circulatory system control activities of organs and tissues; other messenger
molecules such as amino acids, peptides, proteins, fatty acids, lipids, nucleosides,
and nucleotides act as second messengers to relay signals to other body parts. Ulti-
mately, gene expression is regulated in the process. Cell signaling and detection of
the messengers and changes in gene expression through protein interactions are the
basis of contemporary drug discovery programs. “Genes control all cellular func-
tions responsible for maintaining human health by serving as blueprints for the pro-
duction of protein in cells.” Gene regulating enzymes are frequently kinases and
phosphatases involved in intracellular signaling. Normally, there is a balance
between the promoters, activators, and inhibitors in the cascade system that
maintains the cells in an optimal state.
Biological Assays of Interest for Screening Botanicals in

Sun Care Products
Biochemical assays have been traditionally used to study the enzyme mechanism
and in identification of enzyme inhibitors or activators (Table 32.4). Cell-based
Table 32.4 Examples of Biochemical Assays—Measure Enzymatic Reactions or

Biological Responses Induced by Immunologic Interactions
Assay Concept Comments
Matrix MMPs (e.g., Prolonged exposure to Visual immunofluorescence,

MMP 1, 2, 3, 9,12) UV-A and UV-B immunuhistochemistry
(family of radiation stimulates assay using antibody to
endoproteases) expression of MMP
collagenases, degrades Protease activity can be
collagen and elastin in measured by colorimetric
dermal layer of skin activity
Fibroblast cell cultures can be
used with enzyme-linked
immnosorbent assay to
measure release of MMP
Elastase inhibition Elastin is broken down by Dermal fibroblast cells can be
the enzyme elastase, used as a source of elastase;
which is produced by botanical extract can be
photodamaged skin screened for elastase
inhibition as measured by
colorimetric activity
Nitric oxide synthase, Nitric oxide is a free Western blot analysis
inducible (iNOS) radical that is a Immuncohistochemistry with
biological mediator in appropriate antibodies
many organs of the
body
Cyclooxygenase-2 COX-2 is elevated in cells Effect on enzymatic activity,
(COX-2) when inflammation a colorimetric assay
exists Expression of COX-2 activity
on mRNA
p38 A series of gene regulating Antibodies react with
pathways that include standards and samples
mitogen-activating from cell lysates to form a
protein kinases, colorimetric reaction
extracellular signal-
regulated kinase, c-Jun
N-terminal kinase;
these regulating family
members are believed
to be involved in the
control of cell
proliferation,
differientiation,
inflammationand
apoptosis (cell death) in
response to UVR.
668 Epstein
Table 32.5 Cell Culture Based Biological Assays—Measure Biochemical or

Physiological Response at the Cellular Level
Assay Concept Comments
Interleukin 10, 12 Interleukins are Keratinocyte cell cultures

pharmacologically active have been shown to
proteins that regulate cell show an immunologic
functions such as response upon exposure
inflammatory and to UVR
immune response
Nuclear factor-kappa A signal transduction Protein is found in the cell
beta protein responsible for nucleus
immunity, inflammation
and cell death
Apoptosis Apoptosis is involved in the Sunburn cells are believed
(programmed cell development and growth to be apoptotic cells
death) of the epidermis
Programmed cell death
occurs in late stages of
keratinocyte
differentiation; UV-B
radiation is known to
induce apoptosis
DNA damage UV radiation damages cell Various methods are
by fragmenting sections available
of the cell’s DNA, these DNA damage can lead
fragments will migrate to apoptosis
out of damaged cells
under influence of an
electric potential
Phosphorylation assays Many functions of cell These cellular signals are
Mitogen-activated biology are controlled involved in cellular
protein kinases, by a reversible aging associated with
extracellular signal- phosphorylation of UVR and other disease
regulated kinases, protein targets by kinases pathogenesis
c-Jun N-terminal Involved in oxidative stress
kinase of cell, cell proliferation,
differentiation, and
apoptosis
assays can be used to evaluate signal transduction events when a cell is stimulated
as previously described. Cell-based assays have traditionally been used to evalu-
ate the efficacy and potency of inhibitors that have been previously screened by
biochemical assays. Cell-based assays are now becoming more commonly used
as the primary screening assay (Table 32.5). Some assays cannot be performed
with a biochemical assay. A cell-based assay is necessary for ion channel assay,
signal transduction assay, and transporter assay. For these tests, live cells are
required to measure the end points (29).
CONCLUSION
It is now acknowledged that cellular damage from UVR and the resulting inflam-
mation contributes to the appearance of aging skin. Furthermore, while it is
known that excessive exposure to the sun’s radiation is a cause of many forms
of skin cancer, the incidence of skin cancer continues to increase dramatically.
Sunscreens are designed to protect against sunburning, which is believed to be
directly related to skin cancer development. Sunscreens that provide adequate
protection against sunburn may not be as effective in providing protection
against the immunosuppression caused by UV-A exposure. Some investigators
speculate that this may explain why some skin cancers develop on skin in
places with little exposure to UVR (30). Research techniques developed during
the era of the human genome project have advanced the understanding of cell sig-
naling and normal cellular functioning. Cell signaling serves to regulate gene
expression and other cellular functions in response to external stimuli in the
environment. Cell signaling and gene regulation are controlled at the molecular
level through the formation of protein– protein interactions. Protein –protein and
other molecular interactions have enabled molecular biologists to evaluate the
ability of botanicals to repair or prevent cell damage from occurring. The
study of cell signaling pathways and gene expression resulting in protein inter-
actions connected to the genetic expression is becoming an integral part of an
emerging field known as “systems biology.” Systems biology is an integrative
approach that measures the various biological responses of an entire organism
involving genomics, proteonomics, and metabolomics from an interactive
“systems” perspective (31). The ability to apply this emerging science to the
study of botanical interaction will provide future opportunities to formulate
sun care products with “functional” botanicals.
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135:867– 875.
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scavengers on protection of human skin against UVB, UVA and IR irradiation.
Skin Res Technol 1999; 5:260– 265.
4. Vayalill PK, Elmets CA, Katiyar SK. Treatment of green tea polyphenols in hydrophi-
lic cream prevents UVB induced oxidation of lipids and proteins, depletion of
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33
Antiaging Actives in Sunscreens
Karl Lintner
Sederma, Paris, France
Introduction 673
Strategies of Antiaging Actives in Sunscreens 677
Prevention of Damage (“Slowing Down the Aging Process”) 677
Vitamins 677
Botanicals 680
Enzymes 681
Miscellaneous 683
Treatment of UV-Induced Age Symptoms 684
Barrier Repair 685
Tissue Repair 686
Conclusions 689
References 689
INTRODUCTION
The first and second editions of Sunscreens did not contain a chapter equivalent
to the present one. Including “antiaging actives” in the present book reflects some
of the changes occurring in cosmetic formulations and marketing strategies. As in
so many other domains, we see a blurring of frontiers, a mixing of categories, and
a (deliberate?) gradual disappearance of clear distinctions and definitions.
673
674 Lintner
Although the title of Sunscreens has not changed and certainly suggests
to most readers the general category of “cosmetic products used on the skin
during extensive sun exposure in order to protect the skin against the deleteri-
ous effects of direct sunlight,” the apparent simplicity of this description is decep-
tive. Even more ambiguity is contained in the title of this chapter, with the two
powerful, but vague, concepts of “antiaging” and “actives” (or “cosmeceuticals,”
as these ingredients are sometimes, erroneously, called). It appears therefore necess-
ary to start with a few definitions of our own, that we will use within the scope of this
chapter, without prejudice to different meanings in other parts of the book.
Let us call “sunscreens” the finished cosmetic consumer product that bears
a clear message of “protection against solar radiation” such as the prevention of
erythema, sunburns, sometimes even cancer. This would include in most cases
“suntan lotions,” “sun care products,” “sunblocks,” and the like. Generally, it
would not include “after-sun lotions” and “self-tanning products.” Although
the word “sunscreen” is sometimes also used to designate the chemical entity
that blocks the sunlight from reaching the skin, these chemicals contained in
“sunscreens” should be called ultraviolet (UV) filters or UV reflectors.
Difficulties in nomenclature also arise because of different legislations in
different parts of the world (cf. the section on regulatory aspects) and because
of technical and marketing considerations: a “sunscreen” of today contains,
more and more often, specific skin and/or body care active ingredients, accom-
panied by a corresponding claim (this is the reason for this chapter); on the other
hand, an increasing number of classic “skin care” (i.e., face care, lip care,
makeup, body care, and even hair care) products boast sun protection factors
(SPFs) in the 5– 15 range. These products have primary skin care claims
(moisturizing, antiwrinkle, firming, . . .) and offer the sun protection as an
additional benefit. So where is the borderline between the two? A “sunscreen”
of SPF 15 with an additional antiwrinkle claim is a “sunscreen” (e.g., Biotherm’s
recent launch with exactly that name: “Antiwrinkle Suncare”) because the
marketeer positions the product as such (advertising, point of sale, timing of
promotional activity), whereas Yves-Saint Laurent’s spring launch of Age
Expert (“age-defying cream”) has an SPF15 but is clearly not positioned as a
“sunscreen”. It claims to contain DHEA-like actives and lycopene as a free
radical scavenger and is a “classical” face care product.
In any case, the New Zealand Society of Dermatology proposes on its website
that “sunscreens should be applied daily, more often when outdoors.” While this
makes sense, it is certainly not the daily routine of the general population.
How about “actives”? My opinion and arguments for it can be found in the
proceedings of the PCIE conference (1). Briefly, any cosmetic ingredient that has
(i) demonstrated cosmetic activity on human skin (or its appendages), (ii) a sub-
stantiated claim, and (iii) a plausible “story” to go with it can be considered an
active: this encompasses then the wide field of ingredients (such as found in
the CTFA/INCI dictionary) from botanicals (various types of plant extracts) to
pure chemical entities that possess a function that is clearly different from the
Antiaging Actives in Sunscreens 675
galenic purpose (emulsifiers, texturizers, thickeners, preservatives, fragrances

etc.). Again, it may occur that an ingredient functions as an “active” in one
product (positioned as such by the marketeer) and as a basic ingredient in
another product (glycerin, lecithin, and lanolin come to mind). In the main body
of this chapter, we shall concentrate on “actives” that are particularly suited or are
already in use in the general category of “sunscreens,” “actives” that make sense
in the context of sun care and skin protection/treatment.
We can therefore now drop the quotation marks from the word active.
Finally, “antiaging” (again with quotation marks): the term is catchy,
seductive, but very vague. Some countries have regulations forbidding the use
of this “claim” in cosmetic advertising or on the packaging.
As usual, there are two aspects to the concept: prevention and treatment.
Antiage prevention implies that a consumer product helps “reduce the speed of
the appearance of the clinical signs of (cutaneous) aging,” based on the protective
active contained in the product. Antiage treatment promises to reverse (some of )
the visible signs of skin aging (such as wrinkle reduction, firmness improvement,
moisturization of dry skin, etc.), based on actives that “restore, regenerate,
repair, . . .” skin items such as “barrier, extracellular matrix, collagen fibers,
hydrolipid balance” and the like.
If one really wants to get a more global perspective of the antiaging field in
general, books like Pharmacological Intervention in Aging and Age-Associated
Disorder (2) are a good place to start. Yu and Yang introduce the discussion
there with a “critical evaluation of the Free Radical Theory of Aging” (see in
following text, the impact of free radicals and antioxidant strategies). Many
articles and references therein are useful for finding ideas in “antiaging”.
In the following sections we consider both types of “antiaging” actives and
their respective merits in sunscreens.
I apologize for the lengthy introduction and the many quotation marks and
hope the reader has thus a clear picture of where this chapter is headed and what
the various terms are meant to convey.
In view of the many detailed chapter headings before and after this one in
the present book, it would be redundant to repeat much that is described about the
dangers of the sun to our skin, about the photobiology, the physics of filters, the
differences between chronological aging and photoaging. If modern UV filters
are so well suited to protect us against the sun’s dangerous rays, for what
reason (other than a marketing and/or label claim) should the formulator of a
modern sunscreen add antiaging actives to his product?
For one, and most importantly, UV filters are not absolute: even an SPF 60
(not allowed as a claim everywhere) will wear off with time, or may not be
applied in sufficient amount from the beginning, or the exposure of the person
wearing it continues beyond the period of protection. Any well-chosen additional
active in the product will help decrease the damages that are not prevented by the
UV filter. For instance, this seems to be particularly true for the combination
of UV-A filters with antioxidant protective molecules. The presently available
676 Lintner
UV-A filters are rarely (not?) able to block out all of the UVA radiation such as to
prevent all free radical generation in the deeper layers of the skin.
Second, the trend in all cosmetic formulas and products goes that way:
makeup mascaras, foundations, lip sticks, powders, also cleansers, body care,
and scalp care SKUs all contain actives for additional benefits. True skin care
needs a global, and continuous, approach. We need the sunlight for the synthesis
of vitamin D and for our psychic well-being (“healthy tan”), and we desire silky,
youthful skin: for this we need the optimum combination of sunscreen and skin
care actives.
Before reviewing the traditional actives used and useful in sunscreens and
presenting a few new ideas in the final section, Table 33.1 summarizes the ration-
ale for the different types of actives that might make sense in sunscreens,
Table 33.1 Rationale for Adding Different Types of Actives to Sunscreens
Type of danger/ Type of active Increased

damage proposed “Cause” sophistication
Dryness Moisturizer/humectant IR, UV-A, UV-B

Dryness Barrier repair: ceramides UV-B
Skin sagging Firming, elasticity UV-A, UV-B
enhancing
Wrinkles Tissue repair: ECM, UV-A, UV-B
collagen stimulation,
cell metabolism,
skin tighteners
Skin thinning Tissue repair: ECM, UV-A, UV-B
collagen stimulation,
cell metabolism, skin
tighteners
Roughness Smoothing, emollients UV-B
Inflammation Anti-inflammatories, UV-A, UV-B
(redness) soothing actives
Melasma, age Skin “whitening” UV-A
spots
Yellowing, Elastase inhibitors UV-A, UV-B
elastosis
Telangiectasis Anticouperose, veinotonic UV-B
Blackheads, Antiacne UV-B
whiteheads
Free radical Radical scavengers UV-A
damage
Lipoperoxidation Antioxidants UV-A
Enzyme damage Enzymes, pseudoenzymes UV-A, UV-B
DNA damage DNA repair UV-B
Apoptosis Cell repair UV-B P
although some appear far-fetched. Very roughly, one can partition these actives
along the following lines.
UV-B rays generate actinic damages that need antiage treatment (long-term),
UV-A radiation needs to be addressed with actives more immediately: to prevent
oxidation, to scavenge the radicals, to reduce local inflammation and thus avoid
long-term damages of molecular nature to accumulate (antiage Prevention).
STRATEGIES OF ANTIAGING ACTIVES IN SUNSCREENS

Prevention of Damage (“Slowing Down the Aging Process”)
Vitamins
One of the first and most widely used categories of actives formulated in sun-
screens is the one comprising the vitamins C and E, sometimes A (retinoids)
or a few of the B group.
The literature on the effects of vitamins C and E as photoprotective agents
in cell cultures (in vitro) and on animals is impressively large. Although general
consensus is expressed that the protective effect afforded by these molecules
“might be beneficial” to human skin, there is astonishingly little documentation
of the benefits of vitamin uses in cosmetic finished products, especially sun-
screens, on human skin (in vivo). Pehr and Forsey concluded in 1993, that
“after 44 years of research there is still scant proof of vitamin E’s effectiveness
[. . .]; it is of no use in [. . .] skin damage induced by ultraviolet light” (3). It is not
the purpose of this chapter to present an exhaustive review of this topic, as
antioxidants will also be discussed in a separate chapter. Such a review can be
found, for instance, in Pinnell (4) in the form of a lecture, followed by a quiz.
A rapid overview of the literature however shows that research into the
effects of topical vitamin application continues, many papers focusing on combi-
nations of vitamins, such as E and C, E and A.
Vitamin E (a-tocopherol) is a ubiquitous, liposoluble molecule, the major
activity of which is as an antioxidant. Although more powerful antioxidants can
be found in nature, vitamin E is most accessible, by synthesis or extraction, is
colorless and well documented as being toxicologically safe. Ritter et al. (5)
show the beneficial effects of tocopherol application before UV irradiation on
mice. They note an increase in epidermal thickness, which might contribute to
the decrease in the number of sunburn cells. The concentration of tocopherol in
the vehicle (50% in ethanol) is however quite unrealistic in cosmetic and sunscreen
applications. Saral et al. (6) studied vitamin E acetate (the more stable ester form of
vitamin E that is preferentially employed in sunscreens) by applying it topically for
3 weeks on guinea pigs before a single UV-B dose. Measuring lipid peroxide levels
and enzyme scavenging activity (cf. also following text) these authors find
that tocopherol acetate did prevent the UV-B-induced effects. Trevithick et al.
(7) studied the application of tocopherol acetate immediately after UV-B irradia-
tion on mice and found decreases in sunburn cell number, inflammatory infiltration,
678 Lintner
and edematous swelling. Even delayed application (8 h after irradiation) afforded

some protection, again however at high concentrations (5%).
Another interesting study was carried out on the antioxidant activity of
a-tocotrienol in topical application (8). Although it did not address UV
irradiation, the oxidant damages were induced by benzylperoxide (10%).
Application of a 5% w/v preparation of a-tocotrienol for 7 days reduced the
BPO-induced lipid peroxidation significantly. For cosmetic purposes, 5%
vitamin E again appears unrealistically high.
Vitamin C has several properties, which make it attractive to the formulator
of sunscreens. Not only does the molecule possess antioxidant (reducing)
activity, but it also stimulates the synthesis of collagen (in vitro) and contributes
to the hydroxylation and the correct lay-down of collagen fibers in skin tissue. Its
cosmetic use is found particularly in “antiwrinkle” creams (based on the collagen
stimulation claim) and in “skin whitening” products (based on the inhibition of
melanogenesis).
Darr et al. (9) investigated the topical use of vitamin C on pigskin and
found protection against UV-B damages as measured by erythema and sunburn
cell formation. As innate vitamin C concentrations decrease as a result of UV
irradiation, topical supplementation is a potential strategy to counter this deleter-
ious effect of sunlight. Follow-up studies later confirmed the protective effect of
vitamin C, when formulated together with a UV filter (oxybenzone) (10).
An even more broad-spectrum protection is achieved with the combination of
vitamin C, vitamin E and the sun-filter, as vitamin C affords particular protection
against the UV-A-mediated phototoxicity in this animal model.
Some more recent studies suggest benefits to using vitamin C together with
vitamin E in topical products such as sunscreens. Moison et al. (11) describe a
synergistic effect between the two molecules in protecting the lipids, also on
pigskin; moreover, the inherent vitamin C and E content of the skin is maintained
at its levels, against depletion by UV-B radiation. Steenvorden and Beijersbergen
(12) investigated vitamins C and E independently and conjointly: topical appli-
cation on mice before UV-B irradiation led to reduced immunosuppression. In
their model, no synergy was found, however. Both studies cited showed that
vitamin C concentration needed to be about 500 – 1000 times higher than
vitamin E to obtain comparable efficacy.
Human in vivo studies were carried out by Dreher et al. (13) using
three antioxidant molecules, alone or in combination: vitamin C, vitamin E,
and melatonin. Slight synergistic results are obtained by combining the ingredi-
ents two by two or in a threesome and applying them in a vehicle 30 min
before UV exposure. Skin color and skin blood flow were used as markers for
UV-induced damage.
The same authors then studied the effects of these combinations when
applied 30 min, 1 h, and 2 h after UVR exposure, using the same end-points
(14). As no protective effect whatsoever was noted, the authors concluded that
UVR-induced skin damage is rapid; antioxidants can alleviate or prevent
damages only when present before or during sun exposure. Melatonin is of course
used in oral supplementation against jet lag, but Reiter et al. (15) describe in
much detail its antioxidant, radical scavenging activity, and life span pro-
longation! Lin et al. (16) tried a further combination of 15% vitamin C and 1%
vitamin E on pig skin and found that repeated application of this cocktail
reduced erythema, sunburn cells, as well as thymidin dimers (DNA damage)
generated by repeated UV irradiation with a solar simulator. While the protection
against this latter aspect is of importance in the prevention of mutations and their
consequences, the sunscreen formulator may again have difficulties in incorpor-
ating these levels of ingredients in the finished product.
And what about vitamin A and its derivatives? Kligman (17) in 1987 rec-
ommended the use of retinoic acid to replenish the inherent pool of this molecule
in the skin after its depletion by UV light. Together with Schwartz (18) he also
demonstrated that post-UV irradiation treatment with 0.05% retinoic acid stimu-
lated collagen synthesis in vivo in albino hairless mice. Ho et al. (19) showed in
1992 that retinoic acid augments UV-induced melanogenesis, an interesting side
effect to all other activities known for retinoids. The study was carried out on a
specific mouse strain and confirmed on two human volunteers. As retinoic acid is
considered a prescription drug in most countries, the cosmetic industry became
interested in retinol, retinol esters, and retinaldehyde. Thus, more recently,
Boisnic et al. (20) published a study with a retinaldehyde cream, applied to an
ex vivo human skin model. Eighteen days of regular UV-A exposure simulated
photoaging; this was followed by application of the retinaldehyde cream for
2 weeks. The UV-A-induced alterations of collagen and elastic fibers were
reversed by the retinaldehyde, and collagen synthesis rates were restored to the
levels of unexposed skin. Sorg and colleagues (21,22) have interested themselves
in the combination effects of retinoids and vitamin E; they find certain specific
benefits, depending on the type of irradiation (UV-A, UV-B), the time of appli-
cation (before or after exposure), and other parameters.
More data on human volunteers in studies on retinoids in conjunction with
UV radiation can be found in Kang et al. (23). One opposing opinion is, however,
expressed in Ref. (24) under the aggressive title: “Tretinoin and cutaneous
photoaging: new preparation. Guaranteed adverse effects!”
Knowing that the skin contains various antioxidants all together, a more
holistic approach was taken by Greul et al. (25) where a combination of
b-carotene, lycopene, vitamin C, vitamin E, selenium, and proanthocyanidins
was tested in a double-blind placebo-controlled human study involving UV
irradiation and skin analysis. Findings concerned significant differences in
MMP 1 and MMP 9 expression and a slowdown in the development and grade
of UV-induced erythema. This reference is given tongue in cheek (excuse
the pun), as the study did not use the antioxidant mixture topically, but orally.
Somewhat similar results were obtained in the SUVIMAX study (26).
In summary, “vitamins are good for you.” Their use in sunscreens is wide-
spread; based on the numerous studies, even if most of them are animal or in vitro
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studies, their claim to “antiaging” activity is not far-fetched. Vitamins C and E

would be considered more of the “preventive” type (antioxidant, to be used
before or during sun exposure), vitamin A and derivatives are more the
“repair” type, undoing some of the UV-caused damages. Their main drawback
is the difficulty in formulating stable vehicles, such that the right amount of effi-
cacious vitamins can be guaranteed for sufficient shelf life.
Botanicals
Like the antioxidants, botanicals, also called plant extracts, are also discussed in
another chapter in the present book. Nevertheless, they merit a short mention
here, as an increasing number of ingredients of plant origin are offered and
used that are tested and positioned as “antiaging” actives, and thus used or
useful in sunscreens.
Plant extracts cover the spectrum from hydroglycolic solutions of analyti-
cally ill-defined nature to pure, isolated, chemically identified molecules, and all
products that present intermediate stages of purification. The reputation of the
plant kingdom is one of almost unlimited source of potential healing activities,
thousands of substances yet undiscovered.
A closer look reveals, however, that with some notable exceptions, a few
broad categories suffice to describe the benefits obtained from plant extracts
for cosmetic claims: we find antioxidant activity (polyphenols, vitamins, flavo-
noids), anti-inflammatory properties (nonsteroidal enzyme inhibitors), tissue
repair molecules (di- and triterpenes). All of these activities can be employed
for “antiage” claims, all of them make sense in the context of sunscreen formu-
lation. A few references gleaned from the peer-reviewed literature shall illustrate
this concept. It is of course impossible to list here all the commercially available
plant-derived cosmetic ingredients (cf. CTFA dictionary) that are claimed to be
antiaging based on some or another in vitro, ex vivo, or even in vivo test with or
without UV irradiation included in the test protocol.
Green tea is a favorite among the botanicals with well-known reputation.
In vitro scavenging of hydrogen peroxide and prevention of UV-induced
oxidative damages on skin cells in culture by various fractions of green and
black teas, including purified epigallocatechin gallate (EGCG) were described
by Wei et al. (27). The pure molecule enhanced the observed activity and is con-
sidered the major active substance in these preparations. An in vivo study by
Vayalil et al. (28) on hairless mice confirmed the prevention of UV-induced
lipid peroxidation by green tea polyphenols, such as EGCG. Interestingly, the
authors also quantified the amount of inherent antioxidant enzymes (catalase,
glutathione peroxidase): whereas UV irradiation depleted these enzymes in
the skin, EGCG application before single UV-B doses prevented this loss by
50 –90% (see also following text).
Less well known botanical extracts such as those obtained from methanolic
maceration of Capparis spinosa L. buds (29), crude ethanol extracts from Culci-
tium reflexum H.B.K. (30), or Chromolaena odorata (31), to cite just a few exotic
ones, all contain flavonoids, phenolic acids, coumarins and the like. They all
show in vitro antioxidant activity that can be used for antiage claims in sun-
screens. Prunus persica Batsch extracts rich in kampferol glycoside derivatives
(32) also showed inhibition of UV-induced edema on mouse ear and tumor
prevention (33) in UV-B- and UV-C-irradiated mice.
A further aspect, not yet widely recognized or mentioned in this context of
sunscreen protection by antiaging products is discussed by Okano et al. (34). It is
known that with advancing age, proteins and sugar molecules react, unspecifi-
cally, in a process called glycation to give what has been aptly termed, advanced
glycation endproducts (AGEs). Okano et al. describe that AGEs are not
only inherently a sign of aging skin (less elasticity of the glycated proteins)
but also contribute actively to aging by reducing fibroblast proliferation,
matrix synthesis, and by generating reactive oxygen species (ROS) during
UV exposure! He then describes that unspecified extracts of Paenia suffruticosa
and Sanguisorba officinalis inhibit AGE formation and scavenges hydrogen
peroxide at the same time.
A review of photochemoprevention by botanical antioxidants in view of
their use in sunscreens is given in Ref. (35).
A typical example of anti-inflammatory activity of a botanical extract
useful in a suncare product is described by Hughes-Formella et al. (36). UV-B
irradiation, provoking erythema on the back of 30 volunteers was followed by
application of a Hamamelis virginiana lotion 7, 24, and 48 h after irradiation.
Significant differences in erythema values (chromameter, visual scoring) were
observed with respect to the vehicle lotion. This type of use is, however, better
suited for after-sun products than for the sunscreen itself and we shall not
dwell on these applications.
Enzymes
We have cited earlier two studies (6,28) that mentioned antioxidant enzymes of
the skin. This aspect has received less attention in the sunscreen and protection
field; two reasons may account for this. Technical difficulties in analyzing enzyme
activities on human skin, and the inherent instability of enzymes which
make them hard to formulate and stabilize in finished cosmetic sunscreens.
Nevertheless, basic research into the innate enzyme defense system of the skin
has progressed, and a number of in vitro, animal and human in vivo studies
point to the delicate balance that is required between the various enzymes in
the skin.
We shall first review the salient facts about cutaneous defense enzymes and
then discuss the possibility of using antiaging actives within this scope.
Once again, the problem turns around the free radicals, lipoperoxidation,
and other oxidative damages. ROS such as superoxide anion, hydroxyl radical,
singlet oxygen, and hydrogen peroxide cause numerous deleterious effects on
structural and functional (enzyme) proteins, lipid membranes, tissue polysacchar-
ides, and genetic material (DNA). The molecules present in the skin that are
682 Lintner
supposed to protect us against these damages are the vitamins (see preceding
text), a few other antioxidants (melanin, urocanic acid, glutathione, and ubiqui-
none) and specific enzymes: essentially superoxide dismutase (SOD), glutathione
peroxidase (GPO), and catalase.
It now has become evident that these inherent antioxidant defense systems
of the skin are rapidly overwhelmed by the amount of sun exposure we stress
them with in today’s lifestyle. Not only are vitamins C and E depleted in the
skin by UV irradiation, but the same also occurs with the enzymes. Miyachi
et al. (37) describe the decrease of SOD activity in mice after a single dose of
UV light, Pence and Naylor (38) confirm this observation in hairless mice and
add that catalase activity also was significantly depressed. Punnonen et al. (39)
extended this observation to human epidermis. A quantitative analysis of the
localization of these enzymes (and nonenzymatic antioxidants) in murine skin
and their decrease after UV exposure is presented by Shindo et al. (40). These
acute effects are in opposition to long-term irradiation, as Okada et al. (41)
show: after 36 weeks of regular UV exposure, SOD activity increased with
UV-B, but not with UV-A; catalase activity however was strongly depressed
by UV-A. Although catalase, which detoxifies hydrogen peroxide into water
and molecular oxygen is the enzyme most frequently cited as being necessary
in conjunction with SOD, which transforms the superoxide anion into hydrogen
peroxide (itself a cytotoxic molecule), the two enzymes do not react in similar
ways to long-term UV exposure. A few, more pointed investigations into the
details can be found in Shindo and Hashimoto (42), Filipe et al. (43), Aricioglu
(44), and Naderi-Hachtroudi et al. (45) and references therein.
A thorough investigation on humans, carried out over winter and summer
season, confirms this fact: catalase is easily destroyed by UV-A light in summer,
more active in winter (oh, the logic of nature!), whereas SOD is much more resi-
lient (46). This then leads to a potential buildup of hydrogen peroxide in the skin,
not necessarily the best thing to occur. The need for a balanced antioxidant
enzyme system thus becomes apparent.
Two approaches are possible: (a) to stimulate and/or protect the innate
enzyme system, so that even under UV exposure, it retains its efficacy, and (b) to
supply the lacking enzymes by topical application, for instance, within a sun-
screen, as well as presun or postsun products.
Hoppe and colleagues (47), as well as Maes and coworkers (48) presented
examples of the first strategy: they show that molecules such as salicin in skin
fibroblasts (Hoppe) and vitamin D derivatives or betulinic acid in keratinocytes
(Maes) are able to stimulate the synthesis of heat shock proteins which are
able to protect the catalase against UV-induced degradation. These molecules
could therefore be used advantageously in sunscreens as antiaging actives in as
much as they induce protection of our own antiaging defense systems. Other
molecules that induce heat shock could be worthwhile looking for. A more con-
troversial proposal is put forward by Inal et al. (49) who show that treatment of
rats with quercetin (a plant-derived molecule) reduces the UV induced damages
to SOD, catalase, GPO significantly. Quercetin is often described as mutagenic

(based on Ames tests) and its behavior under UV light (photostability) would
need investigation.
Once more it may be instructive to refer to orally administered substances
such as deprenyl, a monoamine oxidase B inhibitor which upregulates SOD
activity and has shown to prolong the “remaining life span of old rats” (50).
Antiaging concepts may be found in many strange places.
Strategy (b) has a few limitations. Usually available enzymes such as SOD
and catalase (extracted from yeast or other biotech sources) are not easy to stabil-
ize in cosmetic formulas, to say the least. Complicated packaging stratagems or
encapsulation techniques may overcome the problem; it is, however, well known
that enzymes—relatively large proteins—are inherently unstable in aqueous
environments, and also heat and UV sensitive. Furthermore, SOD alone on the
skin would lead, at least theoretically, to a buildup of hydrogen peroxide,
already described by Maes and colleagues (46) as being the “natural” problem
of seasonal variations of these enzyme activities. Adding the fragile catalase is
not only difficult, it is also not possible for any formula sold in Europe
because of an archaic prohibition of catalase use in cosmetic products (51).
A neat solution to this problem is afforded by antioxidant enzymes originat-
ing from organisms that live and thrive under extreme conditions of heat: the
“extremophiles.” Discovered a little more than a decade ago, these bacteria
live close to the hydrothermal vents at the bottom of the ocean, at temperatures
that can reach 80 –1008C. It is possible today to cultivate these organisms at sea
level, in industrial fermenters, and to extract heat-stable antioxidant enzymes that
mimic the skin’s SOD, catalase and GPO activity. Further, the enzymes are the
more active, the hotter it gets, up to 1008C (which is unrealistic from a cosmetic
point of view anyway). They are thus ideal for incorporation into sunscreens
where the exposure to UV and to the sun’s heat will not only not destroy the
defensive activity afforded by them, but also even increase it with increasing
outside temperature of irradiation. An active ingredient based on this concept
is described by Lintner et al. (52,53). Thermus thermophilus bacteria, harvested
6000 ft below the California coast, are fermented at 758C, then extracted and con-
centrated to yield a high potency solution containing superoxide anion dismutat-
ing (SOD), hydrogen peroxide converting, and GPO mimicking activity. In vitro
tests carried out on this cosmetic ingredient include protection of human
fibroblasts in culture, lipoperoxidation inhibition, protection of DNA against
the formation of 8-oxo-guanidine, collagen contraction. Studies on human
volunteers show the persistence of cutaneous catalase against UV-A irradiation
and a decrease in in vivo lipoperoxidation of the stratum corneum.
Miscellaneous
A few more (nonexhaustive!) ingredients of diverse nature that might be of inter-
est in photoprotection can be found in the literature. Pinnell and coworkers have
reviewed the evidence supporting the antioxidant role of zinc in UV protection
684 Lintner
(54), Mitani et al. (55), on the other hand, reminds us that iron is bad for the skin
and that Kojic acid treatment prior to sun exposure may help reduce UV-induced
wrinkling (in hairless mice).
A complex but very promising concept is presented by Maes and coworkers
(56): they found that creatine, the precursor molecule to phosphocreatine (PCr),
protects cells from UV damage either by pretreatment or after UV irradiation.
The story involves cellular energy, as creatine is neither a filter, nor an antioxi-
dant, but a key molecule in the chemical energy management (ATP, PCr) of
the cells. The additional energy reserves afforded by supplementation in the
culture medium with creatine allow the repair mechanisms (thymidine dimer
excision, for instance) to function more efficiently, thus protecting the cells
against apoptosis and further damage. These authors confirm the beneficial
effects of creatine in a clinical study where they show that the number of UV-
induced sunburnt cells is diminished by topical application of creatine.
An intriguing study from back in 1978 shows that caffeine and theophylline
protect mice ears from UV-induced tumors (57). Knowing that these molecules
stimulate the pool of cyclic AMP (an essential ingredient in the cellular processes
of both melanogenesis and lipolysis), their use in sunscreens has been promoted
in Sun Active Body Refiner (SPF 8) by Lancaster/Coty in a recent launch.
Treatment of UV-Induced Age Symptoms

As mentioned in the introduction, “reversing” some of the signs of aging is of
course also considered “antiage” activity. Is it realistic? Can anything but retinoic
acid reduce some of the wrinkles, the sagging skin, the dryness, and loss of tonus
that comes with (photo)aging?
And even if so, does it make sense to include these antiaging actives in
sunscreens? Apart from price considerations in the highly competitive market,
the relatively seasonal aspect of sunscreen use and the relatively short contact
times (when compared with “standard” skin care products) would cast doubt
on the proposition.
Whatever the theoretical considerations say, the market has already acted
and begun to introduce sunscreens that contain various actives with some type
of antiage and repair claims. It is not for us to judge the scientific validity, but
to describe possible concepts and ideas that may be useful to the marketeer, if
sufficiently documented by experimental evidence.
Once more, it is not possible to review here the enormous mass of antiage
and wrinkle repair ingredients of synthetic, marine, botanical, or biotechnological
origin proposed on the market, which all might be considered, based on their
merit, for inclusion in sunscreens.
We shall examine two major aspects—barrier repair of the skin surface and
tissue repair in the deeper layers—and discuss some actives that appear to have
clearly perceivable, demonstrated benefits. Contrary to the “prevention type”
products discussed above, the interaction between the repair active and the
sunscreen and/or the UV irradiation is not compulsory. We shall simply review

the “repair” aspect as a possibility to boost sunscreen marketing appeal, an added,
but logical, benefit to the use of these products.
Barrier Repair
Scanning the literature on the relationship between skin barrier and UV
irradiation, one realizes quickly that the subject is more complex than expected.
First: definitions. For our purpose here, we limit the terms barrier, barrier
function, and barrier repair to the epidermis, essentially to the stratum corneum
(SC) where ceramides, cholesterol, and corneocytes constitute the cutaneous
barrier. Although this is purely arbitrary—and not necessarily consistent with
my general view of barrier repair—it is convenient and simple for the purpose
at hand.
On one hand, UV-B irradiation stimulates barrier synthesis: the epidermis
thickens, ceramide synthesis is increased, involucrine (a distinct marker protein
of cell differentiation and cornification) increases (58 –60). On the other hand,
this seems to be a transient effect, an immediate reaction of the skin to the
danger of UV rays. Long-term effects of UV exposure clearly lead, especially
in old age, to a diminished barrier function (61,62); all systems of the skin
suffer through photoaging, and so does the capacity to repair the important struc-
ture that is called stratum corneum: enzymes necessary for the process are
fewer in number and less active, lipids are peroxidized, the skin is thinner, and
the normal desquamation process is altered.
When should barrier enhancement actives be used in a sunscreen? Only for
“mature” skin? Starting when? Or as a preventive (again?) measure, right from
the start, even on young skin? Too few in vivo studies are available to form a
clear prescription. A few ideas may help in making one’s own decision on the
type of “barrier function antiage” active to use in sunscreens.
Hydroxy acids: Lactic acid, one of the most widely used actives in skin
care, is known to stimulate many processes in skin, in particular the proliferation
of keratinocytes and barrier repair. A 4-week in vivo study by Rawlings et al. (63)
showed that L -lactic acid increases ceramide synthesis by 38% over baseline.
This is confirmed by a similar study using TEWL as a measure of barrier
repair. Rendl et al. (64) investigated more immediate effects in a model of
human skin (reconstituted epidermis) and found that lactic acid in a cream
increased growth factors (VEGF), and decreased angiogenin secretion. They
conclude that the regulation of keratinocyte growth factors and cytokines by
AHA may explain some of the therapeutic effects observed in treating photoaged
skin with lactic acid. Scott (65) reviewed a large number of AHA and BHA
containing preparations and found only a few of them active on photoaged
skin. Glycolic acid, found in fruit and milk sugars is described as a cosmetic
ingredient with photoprotective activity. Hong et al. (66) describe its inhibition
of UV-induced skin tumorigenesis in hairless mice and investigate some of the
686 Lintner
complex mechanisms involved. However, a more recent study of 2003 by

Kaidbey et al. (67) suggests that AHAs can increase the sensitivity of the
skin to UV light. After pretreatment for 4 weeks (24 applications of a 10%
glycolic acid product or placebo on the back of 29 Caucasian subjects) the
skin was irradiated with 1.5 MED. They observed increased sunburn-cell induc-
tion and lowered MEDs and conclude that 10% glycolic acid sensitizes the skin to
the damaging effects of UV light. Thus, clearly more systematic studies are
needed to determine the benefits of hydroxy acids in sunscreens for antiaging
purposes.
Ceramides: The large family of complex lipids called ceramides needs

no review here. They are the essential element in the cement of cell cohesion
of the stratum corneum; long-chain lipids, highly insoluble, ceramides are not
so much “biologically active” as structurally important. There is thus less pos-
sible controversy about their use in sunscreens. In view of the outdoor activities
that go with the use of sunscreens, the abrasion, frequent bathing and the sun
exposure, it seems reasonable to use ceramides or ceramide promoting actives
in the formula. Any barrier repair contribution will be beneficial to the skin.
The improvement of barrier function by ceramides in general has been described
in numerous papers (68 and references therein), rarely though in conjunction
with UV irradiation. Various studies report the effects of substances that stimu-
late keratinocyte differentiation and ceramide synthesis: niacinamide (vitamin
B3) (69,70), avocadofuran (71), vitamin C (72), calcium (73), mevalonic acid
(74), ursolic acid liposomes (75), and others.
The T. thermophilus ferment described in the previous section (52,53) has
one additional antiaging benefit. Not only does it contain the heat-stable
anti-oxidant SOD and catalase-like enzymes to protect the skin against the
heat and the free radicals, it also turns out to stimulate keratinocyte differen-
tiation, involucrin synthesis, and barrier repair by increased ceramide and choles-
terol production. In vivo, this translates to greater resistance of the skin barrier
against aggression and to better moisture retention, both important antiage
concepts (76).
Tissue Repair
The most important antiage activity, from a cosmetic point of view, is to reduce
wrinkles. Wrinkles are of course, as we have said at the outset, a major, visible,
consequence of the actinic damages sunlight, rather excessive sunlight, generates
in the skin. Does it therefore make biological, physiological, scientific sense, to
include antiwrinkle actives in sunscreens? Similar arguments as those used for
barrier repair actives in sunscreens hold here, too. Sunscreens, if properly used,
are in contact with the exposed skin for quite some time. During the outdoor
activities that incite the consumer to use a sunscreen, she or he will hardly use
other skin care products. But the benefits of truly active tissue repair, antiage
molecules lie in extended use, regular exposure to their action, and constancy.
In the way a good modern skin care (face care) product should offer at least some
SPF—even if not positioned as a sunscreen (cf. Introduction), in the same way a
sunscreen may offer tissue repair ingredients to bridge the periods between
morning face preparation and the night cream.
Two major categories of antiage ingredients are presently of great interest,
that follow the wave of hydroxy acids and retinoids discussed earlier: the isofla-
vones (phytohormones), which are proposed as plant-derived “(pseudo)substi-
tutes” of estrogen, for mature (i.e., postmenopausal) skin, and the matrikines,
natural protein fragments with specific, tissue repairing activity which are
wound healing research inspired new cosmetic ingredients. We shall limit our
discussion mainly to those two fields.
Isoflavones: Although there appears to be an impressive amount of lit-
erature on the benefits of isoflavones (genistein, daidzein, puerarin, biochanin A,
and others), more of it is again concentrated on demonstrating the antioxidant
(and thus protective) effects of these molecules (extracted most often from soy,
sometimes from red clover or more exotic plants) than on their wound-healing
and tissue repair activities. At least, this is true with respect to peer-reviewed pub-
lished studies. But hundreds of references to the stimulating and repair activating
properties of these molecules—in pure form or presented as enriched extracts—
are nevertheless found on websites and in promotional documents. Two recent
publications by Widyarini et al. (77) and Kang et al. (78) describe the protective
effect of isoflavones against UV-induced inflammation and photoaging. More in
the spirit of the present section and of significant interest is the study by Myazaki
et al. (79), which shows that topical genistein and daidzein stimulate hyaluronic
acid production in human keratinocyte culture and in hairless mice. This is tissue
repair of a type that antiaging claims require. Schmid and Zülli (80) have gone
further and measured the skin thickness increase by topical application of soy
isoflavones in a human, placebo-controlled trial. The most recent document on
soy isoflavone activity in human skin is by Kawai (81), demonstrating the
ability of these extracts to stimulate collagen synthesis in the skin.
Cosmetic research has most certainly produced many more examples and
data about the skin repair benefits of isoflavone (“phytoestrogens”); for reasons
of intellectual property and fierce competition, only a small portion of this
research sees publications in peer-reviewed journals. It can thus only be surmised
that the use of these ingredients in sunscreens helps keep the skin in better
(i.e., more youthful) condition.
Matrikines: A whole new concept in tissue repair, and thus in antiaging
strategy, is offered by the discovery of matrikines. The term was coined by
Macquart (82) to designate protein fragments (peptides) of small size, which
are generated by the gradual hydrolysis of natural, structural proteins in the
connective tissue. But not just any breakdown product of proteins will be a
matrikine. During wound healing and/or inflammation, proteolytic enzymes
break down collagen, elastin, fibronectin, and other structure proteins into smaller
688 Lintner
pieces. Certain peptide sequences, thus released, possess mediator (“kinin”) or

messenger (ormon1 ¼ “hormone”) function: they act on nearby cells (fibro-
blasts) to stimulate them into neosynthesis of tissue macromolecules, or to
attract them to the damaged tissue site (chemotaxis). Like all mediators or
signal molecules, these peptides of specific amino acid sequence, act at very
low (nano- to micromolar) concentration, but achieve dramatic effects in the
rapid regeneration of tissue.
These peptides, derived from the natural sequence of the damaged proteins,
are usually in the tri- to hexamer range.
Some of these matrikines have found cosmetic use, for which it was neces-
sary to attach a lipophilic, fatty acid chain in order to assure skin diffusion and
bioavailability (83). It has thus been shown that a few parts per million of the tri-
peptide palmitoyl-Gly-His-Lys (a serum protein fragment) is able to stimulate
collagen and GAG synthesis in vitro, which translates into skin thickening and
antwrinkle effects in vivo. Equally low concentrations of palmitoyl-Val-Gly-
Val-Ala-Pro-Gly (a fragment of elastin) or palmitoyl-Gly-Gln-Arg-Pro (a fragment
of Immunoglobulin IgG) have potent skin repair activities (84,85) that may be
used in antiaging compositions.
As a concrete example of cosmetic use of this concept, the matrikine
peptide palmitoyl-Lys-Thr-Thr-Lys-Ser shall be presented in more detail in the
following.
Discovered by Katayama et al. (86) during wound healing related research
on lung cells, it was investigated for skin applications (87) first in in vitro studies
on normal human fibroblasts which demonstrate the extracellular matrix (ECM)
stimulation by the palmitoylated peptide: collagen I and GAG are increased
over baseline by amounts varying between 50% and 250%. This is confirmed
on full thickness skin tissue where 2 ppm of Pal-KTTKS achieve the same
result as 1000 ppm of vitamin C and in clinical, vehicle, or benchmark
(retinol, moisturizer) controlled studies using the Pal-KTTKS peptide in topical
antiwrinkle creams (87 – 89). The use of 3 – 5 ppm of Pal-KTTKS in a topical
formula leads to significant, measurable, and consumer perceivable benefits
in reducing wrinkle volume, depth, density, and to overall improvement of the
facial skin when used for up to 6 months. Skin biopsies that were taken during
one of the panel studies (88) on both the Pal-KTTKS treated group and the
placebo group, at time points T ¼ 0, T ¼ 2 months, and T ¼ 4 months show
that the treated skin has improved collagen IV and elastin fiber assemblies
whereas the control group showed no notable changes in the skin samples.
Matrikines such as Pal-KTTKS are thus ideal candidates for cosmetic tissue
repair.
Nothing in the nature, activity, or mechanism of action of these molecules
with true antiaging properties prevents them from being used in sunscreens. They
are compatible with any kind of formulation, they are stable, their mode of action
is unperturbed by UV and outdoors. They are clearly an additional benefit to
sunscreens, as they demonstrably can repair some of the actinic photodamage.
CONCLUSIONS
Some aspects of this chapter may appear somewhat polemic and/or tongue in
cheek. Whereas UV absorbing molecules are clearly designated as sun filters
and constitute a well-defined category of chemicals, the notion of “antiage”
actives (cosmeceuticals?) is much less well characterized, whence the occasional
asides.
We have tried to demonstrate that the notion of antiaging actives in
sunscreens opens many possibilities to the formulator to improve the basic
sunscreen products, to add real benefits and to allow for variety in claims and
marketing positioning.
Prevention of sun damages on the skin can be reinforced by some of the
antioxidant and photoprotective agents; treatment of sun damage during or
immediately after sun exposure with repair actives is also justified. Teaching
the consumer on how to “manage” the sunlight (prevention goes beyond using
sunscreens and includes wearing adequate clothes, avoiding the hottest hours
of the day, etc.) has become part of the marketeer’s obligation.
Depending on the country, however, from the USA to Europe to East Asia,
the legislations on sunscreens, claims, and formulations, are quite different and
complex. Adding antiage actives to these sunscreens makes the legal situation
even more complex with respect to advertised claims. Other chapters in this
book address the regulatory aspects of sunscreens per se: the notion of which
actives can legally be called “actives” varies even more. From my understanding,
in the USA, a “cosmetic antiaging active” is an oxymoron [if it is physiologically
active, it is a drug and not a cosmetic (90)], in Europe, neither sunscreens nor
cosmetic actives are specifically regulated other than by the general European
directive and its seven amendments (the notion of active is used in the industry,
but not in legal texts), in Korea, certain actives (for wrinkle reduction, thus
antiage) have become “functional ingredients,” that is, quasidrugs, similar to
the eponymous Japanese category.
Harmonization seems a far way off in the future. Careful wording of any
antiaging claims in sunscreen is thus recommended, no matter how many
studies one cites in support of this added benefit.
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Production and Quality Control
34
The Manufacture of Suncare Products
Timothy Meadows
Farpoint, Inc., Dallas, Texas, USA
Introduction 700
Product Types 700
Oil-in-Water Emulsions 700
Water-in-Oil Emulsions 703
Spray Emulsions 703
Heavy Creams 705
Hydroalcoholic Products 705
Scale Up 707
Mass 707
Mixing 707
Cooling 707
Production Methods 708
Raw Material Handling 709
Quality Control of Sunscreens 710
Stability Testing 712
Analysis by Nonscanning UV Analysis 713
Contract Manufacturing of Suncare Products 716
Conclusions 718
References 718
699
700 Meadows
INTRODUCTION
For the average private label, contract, or name brand manufacturer, suntan/
sunscreen products usually represent between 16% and 35% of their production.
With so much production devoted to this category, it is especially important to be
aware of any processing techniques that would enable one to bring the production
from the initial preweigh to filling as quickly and as efficiently as possible.
Most sunscreen items are considered a seasonal product by the retailers,
with the unsold product to be returned at the end of the season. It is very import-
ant to have as little overhead in that product as possible. To further complicate
this, sunscreens are considered OTC products which require expiration date
unless the manufacturer can provide the required long-term stability data.
Although these are primarily marketing concerns, if the product is not man-
ufactured efficiently and according to specifications, both quality and marketing
problems may arise.
PRODUCT TYPES
Based on the physical form of a product the method of manufacture may be
drastically different. Different viscosities, emulsion types, pHs usually require
different manufacturing techniques.
Since a product’s SPF value is an efficacy rating and not simply a quanti-
tative measure of a product’s UV absorber level, a sunscreen product’s physical
form is very important. Very often the manufacturing procedure is directly
responsible for a sunscreen’s efficacy. The same level of UV absorbers in two
different bases can produce two very different SPF values. Besides the
formula, the method of addition, mixing temperatures, homogenization, etc.,
can be a major factor in determining the SPF value or whether a product is
water resistant or not.
Sunscreen products come in all forms and emulsion types depending on
the type of delivery system that the marketer desires. The following are some
of the basic categories.
Oil-in-Water Emulsions
This the most basic type of emulsion system. The traditional method of manufac-
ture is to add the oil phase to the water phase at about 808C. Mix until 458C, then
add the fragrance, vitamins, and any other heat sensitive materials. The usual pro-
cedure in making waterproof oil-in-water (o/w) emulsion is to add an oil-soluble
film former to the oil phase. The selection of materials is covered in another section
of this book, but whatever materials are used, it should be added to the rest of the
oil phase from the beginning. Many o/w emulsions use water-soluble thickeners
such as the carbomers. These are best dispersed in pure water at room temperature
before the rest of the water phase is added. Depending on the formulation, the
water phase is neutralized either first, before the addition of the oil phase, or
Manufacture of Suncare Products 701
last, after the phases are combined. There are some formulations where the water-
proofing ability is totally dependent on when the carbomer is neutralized.
Formulas 1 and 2 show two formulations that use water-soluble polymers
for external thickening and emulsification. Formula 1 is neutralized after the
Formula 1 SPF 30 Lotion (Final neutralization)
Percentage Material
Phase A
50.85 Water
0.20 Carbomer 934
0.10 Carbomer 941
Phase B
0.30 Methylparaben
0.1 Propylparaben
0.05 Disodium EDTA
1.00 Proplyene glycol
10.00 Aloe vera gel
0.05 Alpha bisabalol
Phase C
5.00 Octinoxate
4.00 Oxybenzone
5.00 Octocrylene
0.50 Silicon fluid 200, 350 CS
5.00 Octisalate
4.00 Stearic acid
5.00 Sorbitan isostearate
0.10 Tocopheryl acetate
2.00 Crodaphos CESa
Phase D
0.50 Triethanolamine
Phase E
QS Fragrance
100.00
a
Croda Chemical Company.
Manufacturing procedure:
1. Disperse the ingredients in cold water in phase A.
2. When fully dispersed add phase B to phase A.
3. Begin heating A/B to 808C.
4. Heat phase C to 808C.
5. At 808C add oil to water with good agitation.
6. Mix for 15 min.
7. Add phase D.
8. Mix and cool to 458C.
9. Add fragrance.
702 Meadows
Formula 2 SPF 15 Sunscreen Lotion (Water phase neutralized first)
Percentage Material
Phase A
69.30 Water
0.20 Carbomer 934
Phase B
2.50 Glycerin
0.05 Verseen NA
1.00 Disodium EDTA
0.30 Methylparaben
0.10 Propylparaben
0.20 Aloe concentrate (10)
Phase C
0.40 Triethanolamine
Phase D
3.50 Stearic acid
7.50 Octinoxate
40 Oxybenzone
0.30 Silicon 200
1.00 Hydrogenated vegatable oil
1.50 Glyceryl stearate, SE
2.25 Sorbitan stearate
3.00 Octyl palmitate
2.00 Lexoraz 200a
Phase E
QS Fragrance
100.00
a
Inolex Chemicals
1. Disperse the carbomer in cold water. Mix until fully dispersed.
2. Heat phase A to 808C. Add phase B.
3. At 808C neutralize with phase C.
4. Heat phase D to 808C.
5. With both phases at 808C. Add phase D to A/B/C
7. Add phase E
phase addition, and in Formula 2 the water phase is neutralized first. Both are
water resistant, but Formula 1 requires the addition of the oil-soluble film former.
When manufacturing high-SPF products the oil phase can exceed 40%.
This leaves little room for the hydration of water-soluble polymers or gums.
Often the small water phase will get too thick, even when unneutralized to
heat evenly. The traditional answer to this problem is to add a very small amount
of a mineral acid to the water phase (1). This will thin out the solution immedi-
ately. However, the appearance of an acid like hydrochloric acid on the label may
not be acceptable. There may also be other reactions with some of the other
ingredients. In this case the addition of certain botanicals will help. Aloe vera
is mildly acidic and as little as 3% in the water phase will thin out the slurry
to an acceptable viscosity. Most sunscreen products use aloe in any case. One
must be sure that the aloe material used is in fact real aloe vera and not a
diluted extract, otherwise it will not thin out the unneutralized carbomer
solution (2). Formula 2 uses this technique.
Carbopol 1342TM is often used in waterproof formulations. It is less soluble
in water that than other carbomers and is slightly oil soluble, thus making it more
difficult to wash off. Dispersing the 1342 in the water can be a problem though. It
has a tendency to foam and thicken, even when unneutralized in low percentages.
For this reason the addition of 1342 into the heated oil phase is often done. It is
important to keep the oil phase mixing during addition to the water phase, other-
wise the 1342 will settle to the bottom of the oil tank. Once the phases are blended
the 1342 will migrate into the water phase. The batch can then be neutralized. In
the case of Formula 3, PEG-8 is used to neutralize the batch. This allows the
hydrogen bonding to occur and permits the 1342 to gel, while not creating the
salt which is more water soluble and thus less water resistant.
Water-in-Oil Emulsions
Any water-in-oil (W/O) emulsion is usually much more difficult to manufacture
than the basic O/W type. Most W/O formulations require some degree of hom-
ogenization, which adds to the time and expense of manufacture. The continuous
phase (oil) is usually small, often under 50%, making it difficult to heat and
mix in a large processing tank.
Spray Emulsions
These types of products have been very popular in Europe for many years,
and now here in the USA we are beginning to see more sunscreen products in
this form. Since almost all beach and pool suncare products are expected to be
waterproof, this is an expected feature for a spray emulsion product as well.
Without the physical support of the viscosity of a cream or lotion a high
emulsifier level is usually employed in the formula to obtain product stability.
However a high level of emulsifiers often results in a sticky or tacky feel.
Therefore, emulsification is best achieved by mechanical means.
There are many types of homogenizers available, and most are very
expensive. One of the best techniques is to pass the product backward through
a centrifugal pump with perforated impellers. The degree of shear can be
determined by adjusting the flow rate of the pump (positive displacement
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Formula 3 SPF 30 Sunblock Lotion
Percentage Material
Phase A
71.60 Water
0.30 Methylparaben
0.10 Propylparaben
0.05 Disodium EDTA
1.00 Aloe vera gel
Phase B
7.50 Octinoxate
5.00 Oxybenzone
4.00 C12– 15 alkyl benzoate
5.00 Octisalate
Phase C
1.00 DEA cetyl phosphate
Phase D
0.40 Acrylates/C10– 30 alkyl
acrylate cross-polymer
Phase E
4.00 PEG-8
Phase F
QS Fragrance
100.00
1. Heat phase A to 808C.
2. Heat phase B to 908C.
3. Once phase B is at temperature add phase C to it with mixing.
4. Mix at 908C until phase C is completely melted.
5. Add phase D to B/C with agitation.
6. As soon as phase D is dispersed, combine the phases (oil to water).
7. Mix until smooth, add phase E.
9. Add phase F.
type), which is feeding the centrifugal pump. With this method the pump can be
used on various tanks, thus making it far less expensive than the traditional
in-tank homogenization. It also cuts down on processing time because the
product can be pumped directly from the processing tank into the portable tank
or whatever vessel is used to hold the product for filling. Figure 34.1 shows
the basic setup of this system.
Formula 4 is an SPF 30 spray product. After initial neutralization and
emulsification citric acid is added to disrupt the gel structure of the Carbopol
Inline Homogenization System
Production Tank
Batch Tank
P osit ive Centrifugal pump Holding Tank

displacement w/ perforated
pump impeller
Pumping against flow
Figure 34.1 Inline homogenization system.
1342. In order to stabilize the product now, it is passed through a homogenization

system.
Heavy Creams
Sunscreen creams can be very luxurious and go well in a tube application;
however, they are often difficult to produce and fill. Therefore, it is often
necessary to cease manufacturing and begin filling the cream at higher
temperatures than normal. Since most sunscreen creams derive their high
viscosity from an external thickening system such as carbomers, keeping the
product warm only slightly reduces its viscosity.
Hydroalcoholic Products
The general perception of the public is that products that are alcohol based are
drying to the skin. Even so, there are some great advantages to sunscreen products
containing alcohol since most UV absorbers are oil soluble and dissolving them
in alcohol permits a more uniform film upon spreading onto the skin.
Obtaining a clear gel or solution is often difficult. In many cases the
addition of even the smallest amount of water will cloud the system. Selecting
the correct ratio of different UV absorbers is critical here. Each UV absorber
has different hydroalcoholic solubility but with all the formulation challenges
this class of products offer many advantages. They dry quickly on the skin,
feel cool, and are usually waterproof without the use of a film former.
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Formula 4 SPF 30 Spray Emulsion
Percentage Material
Phase A
69.00 Water
0.05 Disodium EDTA
1.00 Aloe vera gel
Phase B
7.50 Octinoxate
5.00 Oxybenzone
4.00 C12– 15 Alkyl benzoate
5.00 Octisalate
0.10 Cocoa butter
1.00 Sorbitan isostearate
Phase C
1.00 DEA cetyl phosphate
Phase D
0.40 Acrylates/C10 – 30
alkyl acrylate cross-polymer
Phase E
4.00 PEG-8
Phase F
0.80 Propylene glycol, methylparaben,
propylparaben, and
diazolidinyl urea
1.10 Citric acid
Phase G
QS Fragrance
100.00
2. Heat phase B to 908C.
3. With rapid agitation, add phase C to phase B.
4. When the phase C is melted, quickly add phase D to phase B.
5. As soon as phase D is dispersed, immediately add phase B to
phase A.
6. After the phases are combined, mix for 15 min.
7. With good agitation, add phase E to batch.
9. Slowly add phase F to batch.
10. Lower agitation as batch thins out.
11. Cool to 458C. Add phase G.
12. Cool to 358C. Run product out through homogenizer.
Obviously, the products flammability is a major consideration during

manufacture. All motors must be explosion proof, both in compounding and in
filling rooms.
SCALE UP
Many formulations, which work very successfully in the laboratory, do not
translate well into full-scale production. There are several factors that come
into play when manufacturing a large production batch which are not present
in the laboratory.
Mass
When making 500 or 1000 g of a product in the laboratory, the effects of the mass
of the product itself or the emulsification and mixing are negligible. But when
dealing with thousands of kilograms of a product, it then becomes a factor to con-
sider. Often the shear weight of the product is enough to squeeze out the internal
phase of the emulsion resulting in either oiling or watering out of the product.
Since many high-SPF formulations have a high internal oil phase the external
pressure of the batch can simply push it out. Making the batch size smaller can
help to prevent this. This is a trial and error procedure. Continue to decrease
the batch size until you achieve the desired results. The maximum batch size
will depend on your equipment.
Mixing
High-SPF sunscreens usually have specific gravities greater than 1.00. The
mixers should be of sufficient horsepower to be able to move the product in
the processing tank. Both side sweep and propeller agitation are required for
complete mixing. If the batch is not mixed thoroughly, then proper emulsification
cannot occur. There may be a batch size limitation for some types of products.
There are many emulsions that simply will not mix together properly at
volumes greater than 750 gal. When larger batches of these types of formulas
are made, they tend to exhibit some oiling out. The solution is able to mix the
product more thoroughly. This is achieved by decreasing the batch size or
modifying the equipment.
Cooling
The cooling rate of a batch is just as critical as the mixing efficiency. The rate at
which an emulsion is cooled can determine its stability and physical charac-
teristics. Care must be taken not to cool the batch too quickly. The emulsion stab-
ility is often dependent on the formation of wax or fat crystallization. If this
crystallization process is disrupted, an unstable emulsion may be the result.
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This in turn not only will affect the aesthetics of the product but the function as
well, such as its water resistance.
Many “very water resistant” lotions are of the water in oil type. These
emulsions present a different type of cooling problem. Since the water is in the
internal phase, and since water has a higher heat capacity than oil, it requires
more cooling time than oil. But since the external phase is the more easily
cooled oil part, the initial temperature drop is quick. Then as the internal heat
of the water phase comes through, the product begins to heat up again. If the
emulsion is cooled down too quickly and pumped out of the tank it can reheat
itself, and without the continued mixing, destabilize. Therefore, a slow cooling
while mixing is the best way to insure that the product will remain stable after
manufacture.
PRODUCTION METHODS
As previously mentioned O/W emulsions are the most common type. They
usually have the best feel and have greater stability that W/O emulsions. Most
of these emulsions require a water-soluble thickener or film former for stability
and water resistance. If the selected thickener or film former requires neutraliz-
ation, then, there are two ways to do so, either before or after the phases are
combined.
By combining the phases as usual at 76 –808C and immediately adding the
neutralizing agent, the neutralization will be “shared” between the thickener and
any other material in the oil phase like stearic acid. This may create a stable,
good-feel product, but if a soap is created (e.g., tea-stearate), then it is unlikely
that the emulsion will be waterproof.
By neutralizing the water phase first and allowing it to thicken and then
adding the oil phase you can usually create a transitional emulsion, that is, an
emulsion that feels like an oil –water type, but upon rubbing it on the skin acts
like a water – oil type. Since the W/O type has the best chance of being water
resistant, this method of neutralizing is often the best (Formula 2).
If the thickener has no or little emulsification capabilities, however, then
the decision of when to add the neutralization agent is not as important.
We have previously touched upon the subject of where and how to
incorporate different thickeners or film formers.
In the laboratory, you have all the time you want and a very large ratio of
mixing to product volume. It is easy to disperse almost any polymer, but in a
1000 gal tank it may be another story. Foaming is probably the biggest
problem in dispersing carbomers, especially Carbopol 1342. It is often easier
to add the Carbopol 1342 to the oil phase after it is at emulsifying temperature
and the heat is off. Once the Carbopol 1342 is dispersed, the oil phase should
immediately be pumped over to the water phase. It should then be neutralized
as soon as the phases are combined (Formula 3).
RAW MATERIAL HANDLING

Most of the ingredients used in the formulation of sunscreens are also used
in many other types of skin care products. The obvious exception would be the
active ingredients, the UV absorbers. Most are oil soluble, a few are water
soluble, and two are dispersions of specialized physical pigments. The oil-
soluble ones can be treated like any other ingredient in the oil phase. These
products are all very stable at high temperatures and pose no special handling
problems. The water-soluble materials usually have to be neutralized first in
cold water before any of the other ingredients are added. Once they are in solution
you can proceed with the batch as usual. Remember though that these are salts
and therefore may be incompatible with systems that are salt intolerant.
The most difficult UV absorbing materials are the dispersions on titanium
dioxide and zinc oxide. When these dispersions first appeared they were very
difficult to work with. They would separate in their drum after only a small
amount of time and therefore needed to be mixed up before use. Even with
mixing, the powder would settle on the bottom and cake up, not being usable
at all. Since then, there are many solvents to choose from as the dispersant and
the dispersion itself is far more stable.
It is best to add the oil dispersions to the oil phase after the phase is all
melted and at emulsifying temperature. Also, the heating should be over. The
dispersion can “burn” and coagulate at the bottom of the vessel. This also
holds true for W/O emulsions. The addition of the dispersion into the continuous
phase should be handled in the same manner.
Since sunscreen products are OTC drugs, the handling of these raw
materials (including labels, bottles, etc.) must be documented in a procedural
company handbook for FDA inspection. Form 1 is an example of a procedure
used by a manufacturer for handling raw material.
FORM 1
Raw Material Sampling and Approval Procedure

. The warehouse receiving manager informs Quality Control (QC) when
a shipment of chemicals or compentry arrives.
. If it is a chemical raw material the following procedure is used:
. The warehouse receiving department notifies QC that a shipment
has arrived and brings to the laboratory a copy of all relevant
paperwork.
. QC collects one sample from each lot of material, stickering the
containers from which the sample is taken. The materials, item
number, identity, lot number, and date received are entered into
the QC Raw Material Log Book.
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. Each container is then labeled with the materials item number,

lot number, and date received. The sample is analyzed in the
laboratory against the manufacturer’s certificate of analysis sheet.
. A sample of the material is labeled and stored.
. If the material passes the laboratory analysis, the warehouse is
notified and the material is put into inventory.
. If the material is a package component, the following procedure is
used:
. A representative sample is brought to the laboratory for identifi-
cation.
. A capacity test, weight check, and general inspection are
performed on the component.
. If the component passes the tests, the warehouse is notified and
the material is transferred to the general warehouse.
. If the material is labels, then the following procedure is used:
. Warehouse receiving notifies QC that labels have arrived.
. QC collects samples of both front and back labels from each lot.
. The labels are visually compared to a standard for text, color, etc.
. The labels are then attached to a piece of paper and retained in a
QC standard file.
. If the labels are approved, the warehouse is notified and they are
placed in the inventory.
QUALITY CONTROL OF SUNSCREENS

As dictated by FDA regulations each production facility needs to have a “Master
Batch Control Record.” This outlines each step of operations of an OTC
manufacturing facility (3). The following is an example of the 10 sections of
such a record:
1. Master formula including the manufacturing procedure of the product
2. Quality control analysis and release form
3. Tote or portable tank sanitizing report/procedure
4. Filling machine cleaning and sanitizing report/procedure (this docu-
ments that the fill machine has been properly cleaned in preparation
for the run, and the person responsible)
5. Production setup checklist (this list insures that all the components
are available for the fill run and are correct)
6. Daily fill report (it should include work times, fill weight checks,
yield analysis, etc.)
7. Daily production quality control report (this is usually the hourly
checklist performed by the line inspector, who monitors the fill
level, the label placement, and the general appearance of the package)
8. Label check report (at the end of a run, all labels must be accounted
for, even the waste)
9. Machine time logs
10. Used tote or portable tank tags (the original tag should be included
with the complete batch report).
This Master Batch Control Record not only outlines for any FDA inspector
how the company operates, but shows them at a glance the entire process.
Forms 2– 4 are some examples of these documents.
To summarize, Form 5 represents the steps in the process from incoming
raw materials to product release.
FORM 2
Finished Product Sampling and Approval Procedure

. Batch approval
. When the batch is complete two samples are brought to the
laboratory along with the batch sheet, one for evaluation, and
one for microtesting.
. The product specification sheet is pulled out and the appropriate
tests are performed on the product. If the product passes the
tests, verbal approval is given to compounding and the product
is transferred into totes for filling.
. A bulk sample of the batch is labeled and retained for a period of
1 year.
. Tote tags containing the batch information are issued to
compounding. These tags are placed on the filled totes.
. The filled totes then are put into the racks until ready for filling
into bottles.
. The QC report is attached to the Batch report and goes into a yield
packet.
. Filling approval
. A start-up sample is taken from the tote and given to QC for
inspection and microtesting.
. QC checks the tote tag against the yield packet to verify that the
correct product is being filled.
. Random filled samples are removed from the line for micro-
testing during the beginning, middle, and end of the fill run.
. Random samples are also pulled from the line for weight checks
and specific gravity measurements.
. The product may be released from quarantine if it tests clean
after 3 days. All plates are held for 5 days before being
discarded.
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FORM 3
Finished Product Filling Sampling and Approval Procedure

. A start-up sample is taken from the tote and given to QC for inspection
and microtesting.
. QC checks the tote tag against the yield packet to verify that the
correct product is being filled.
. Random filled samples are removed from the line for microtest-
ing during the beginning, middle, and end of the fill run.
. Random samples are also pulled from the line for weight checks
and specific gravity measurements.
. The product may be released from quarantine if it tests clean after
3 days. All plates are held for 5 days before being discarded.
FORM 4
Finished Product Filling Procedure

. Once QC has given approval to begin filling, the following procedure is
performed:
. A QC inspector completes the “production set-up list” to insure
that all the correct components are present. A separate “label
check” is also performed.
. Throughout the filling process the “machine time log”, and the
“Daily production QC report” are filled in.
. The “Daily filling report” is completed in order to keep track of
the exact number of bottles filled, fill weights, waste, and final
yield.
. When the fill run is completed all the information is put together
in the yield packet.
Stability Testing
Once a batch is manufactured and a sample is submitted to quality control the
usual tests should be performed on the batch.
The batch sample should be cooled to room temperature with mixing. Once
cooled, the usual tests should be performed. These include viscosity, pH, specific
gravity, and general appearance. Since sunscreen products are classified as
OTC drug products, chemical analysis of the active ingredients is also required.
The overall assay of the UV absorbance using a UV spectrophotometer is a good
in-process test for the testing of active ingredients, but the individual assay of the
various actives is preferred by the FDA. At this point many other countries
FORM 5
Product Flow Diagram
Receipt for raw materials

#
Quality control analysis of chemicals and packaging
# #
Approval of materials Rejected materials
#
Reweigh chemicals for compounding
#
Manufacture of product
# #
Quality control approval of batch Batch rejected ! Destroyed
# #
Filling of product Batch corrected
#
Quality control during filling
#
5-day microhold on finished product ! Rejected
# #
Product released from quarantine Destroyed
#
Product shipped
require individual analysis of the actives by HPLC or equivalent analysis. Form 6

is an example of a stability worksheet that should be followed on a production
batch. It is recommended that even after the 3-year stability testing is complete
you randomly choose a product to test each year.
Analysis by Nonscanning UV Analysis

This method is a good, quick way to check that the total amount of UV absorbers
are present in your batch. It does not determine the percentages of each of the UV
absorbers, but it will determine if the overall UV absorbance of the product
matches your laboratory standard.
Your laboratory sample is scanned at a specific wavelength to determine
the degree of absorbance of the product. The ratio between the absorbance at a
specific wavelength and the sample size is calculated. This can then be compared
to the batch sample. By using a simple ratio and proportion calculation, you can
determine the total percentage of UV absorbers in a product.
The procedure and calculation is shown in Form 7 (4).
Once the lab has determined that the batch sample is equivalent to the
standard, it can be submitted for the more detailed and specific HPLC analysis.
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FORM 6
Annual Product Stability Testing Report
Product:
Formula number:
Manufacture date:
Room Temperature
Test Specification Int. results 30 days 90 days 6 months 1 year

Appearance
Odor
Viscosity
pH
% Actives
Sp. gravity
Challenge test
Other
Oven (458C)
Test Specification Int. results 30 days 60 days

Appearance
Odor
Viscosity
pH
% Actives
Sp. gravity
Challenge test
Other
Freeze– Thaw Cycles
Test Specification Int. results Three cycles
Appearance
Odor
Viscosity
pH
% Actives
Sp. gravity
Challenge test
Other
FORM 7
Simple Test for Percent Sunscreen in a Product
EQUIPMENT:
1. Analytical balance
2. UV spectrophotometer
3. 100 mL volumetric flask (two per sample)
4. Quartz glass cuvette
5. 10 mL volumetric flasks
6. 1.0 mL graduated volumetric pipettes
7. 5.0 mL volumetric pipettes
8. Ultrasonic cleaner (for samples)
REAGENTS:
1. Isopropyl alcohol (IPA) (spectrophotometric grade)
2. Sunscreen(s) used in products to be tested
STANDARD PREPARATION:
A. Standard preparation:
1. Make the standard solution by preparing a solution of IPA and
the exact percentage of each sunscreen. For example, for a sun-
screen product that has 7.5% octinoxate and 4.0% oxybenzone
you would prepare the following solution:
Octinoxate 7.5%
Oxybenzone 4.0%
IPA 88.5%
2. Take exactly 0.1 mL of the stand solution and dilute to 100 mL
in a volumetric flask. Then, take exactly 1.0 mL of this solution
and dilute to 10 mL in a 10 mL volumetric flask. This concen-
tration should give an absorbance in the range of 0.4 –1.7.
B. Product analysis:
Prepare the sample for analysis in the same manner. Run the absor-
bance at 310 nm for the standard and sample.
C. Calculation and results:
By using a simple ratio and proportion method you can calculate the
total percent sunscreen in a finished product. The equation is as follows:
Std abs: sample abs
¼
% sunscreen X
where X ¼ total percent sunscreen in the product.
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Although the UV spectrophotometric method is presumptive, it is able to

determine if the total sunscreen percentage in the batch matches the laboratory
standard.
Analysis of sunscreens with physical sunscreens is more difficult. Unlike
organic UV absorbers, the UV protection of products that utilize physical
absorbers is totally dependent on the dispersion of the pigment. No matter
how small the particle size of the starting material is, if it agglomerates in the
emulsion, its UV absorption qualities will be negligible. Therefore, an analysis
that can determine the actual protectiveness of the product is necessary.
Simply determining the amount of titanium dioxide or zinc oxide is not suffi-
cient (5).
The Optometrics MPF scanning spectrophotometer can asses the UV
absorbance characteristics of the actual product, and not just determine the
amount of UV absorbers in the product. UV light is passed through the
product, which is spread on a special tape, which simulates skin (6). A detector
on the other side of the tape records the level of absorbance at each wavelength.
The manufacturing procedures for products containing pigment dispersions
are sometimes very different from those for typical emulsions. The addition of the
pigment slurry or powder can be a very tricky maneuver.
If the pigment is dispersed in an oil-soluble material, it should be added to
the oil phase after the phase has come to temperature while under good agitation.
The dispersion should not be allowed to settle on the bottom of the tank otherwise
it has a tendency to agglomerate. If agglomeration still occurs, the addition of the
slurry after the phases are combined may work.
There are also aqueous dispersions of these micronized pigments. Since it
is the water phase that would contain any acids, bases, or salts, the addition of an
aqueous pigment dispersion has to be carefully considered. Like an oil dispersion
if agglomeration occurs the dispersion should be added after the phases are
together. Formula 5 represents a typical SPF 15 O/W emulsion using a 40%
TiO2 oil dispersion (7).
With both forms of dispersions it is important to continually mix while
cooling. The batch should be completely cooled before it is pumped out of the
tank.
CONTRACT MANUFACTURING OF SUNCARE PRODUCTS

More and more of the suncare products on the market are controlled or store
brand products. That is, they are products made specifically for the retailer,
with their name on them. Almost all of the them are national brand equivalent
(NBE) products, products that match the popular name brand products. With
more and more consumers reading the back labels of products they are comparing
what is inside the bottle to the price, and not what is printed on the outside, like
label design.
Formula 5 SPF 15 O/W Lotion
Percentage Material
Phase A
2.00 Stearyl alcohol
5.00 Octyl palmitate
5.00 Triethylhexanoin
2.00 Polysorbate 60
7.50 Isohexadecane
Phase B
15.00 Solaveil CT-100a
Phase C
54.80 Water
2.50 Arlatone 2121a
0.20 Rewoderm S1333b
Phase D
0.80 Veegum Ultrac
0.20 Xanthan GUM
1.00 Germaben IId
4.00 Propylene glycol
100.00
a
Uniqema.
b
Witco.
c
R T Vanderbilt.
d
ISP.
2. At 808C add phase B while mixing.
3. Heat phase C to 808C.
4. Premix the ingredients of phase D and add them to phase C.
5. Adjust both phases to 808C.
6. With good agitation add the oil to the water phase.
7. Homogenize for an appropiate time.
8. Cool to 358C.
Formulation- and manufacture-wise, this is a reverse engineering exercise.

The product must be first formulated to match the physical characteristics of the
national brand, using the same ingredients, then it should go through all the safety
and performance testing required by the FDA for an OTC drug product. When all
this is completed and the product stability is complete, the manufacturer has a
product to sell to the store.
The term NBE is used to describe a product that has been reverse engin-
eered to match a national brand. The qualification is usually preformed by an
outside testing laboratory which specializes in NBE qualifications.
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CONCLUSIONS
The manufacturing of sunscreen products encompasses the worst of both worlds.
Being OTC products, they must be made under strict FDA guidelines. This
includes detailed product analysis, stability studies, process validation, etc. But
they must be manufactured at a low enough cost to be able to compete in
a world of close-out/discount stores. As with all cosmetic manufacturing,
technique is as much a part of success as science. Knowing the limitations of
your equipment and formulas is of paramount importance.
REFERENCES
1. Carbopol Resins Handbook. Cleveland, OH: Noveon Inc.
2. Product Bulletin. Ormond Beach, FL: Concentrated Aloe Corporation.
3. Code of Federal Regulations (CFR), sec. 21, part 211.
4. Analytical Procedure #4A. Ormond Beach, FL: Concentrated Aloe Corporation.
5. Tioveil Product Guide. Unichema Inc. TVI/1.
6. Product Bulletin. Ayer, MA: Optometrics USA Inc.
7. True transparency for Solaveil. Uniqema Product bulletin.
35
Quality Control of Finished
Sunscreen Products
Henry T. Kalinoski
L’Oréal USA Products, Inc., Clark, New Jersey, USA
Introduction 719
Product Forms 721
Sampling 721
Physical Methods 722
Chemical Methods 725
Spectroscopy 726
Chromatography 727
Validation 728
Microbiology 729
Efficacy 730
Stability 730
Summary 730
References 731
INTRODUCTION
Any description of the techniques for product quality control should start with an
agreed definition of the term. The description almost requires that the question
719
720 Kalinoski
“Why do quality control at all?” be asked. In the modern times of Good

Manufacturing Practices (GMP) (1,2), speed to market, just-in-time processes,
and government mandated development and production, quality control of the
finished product is almost an expensive complication delaying the release of
finished products. The reality is that even with the best systems in place, with
all of the supplier qualifications completed, with a regular auditing process,
and with government oversight, there is still a need to ensure that material
produced will meet the expectations of the final consumer. One could probably
find many definitions of quality and a number of systems to ensure product
quality. For the purposes of this chapter, quality is defined as meeting the custo-
mer’s expectations every time. Such an approach is described, for example, by
Juran and Godfrey (3), who indicate two aspects of quality. The first definition
covers the features of products that meet customer needs and thereby provide
customer satisfaction. The second is the freedom from deficiencies, which
could result in the need for rework or lead to product failure and therefore
customer dissatisfaction. This latter aspect has, for the most part, been addressed
through conformance to specifications. This grew from a belief that if something
meets specifications, it will satisfy the customer. Newer approaches with greater
emphasis on customer focus require that a broader view be taken, that quality is
not always captured only in specifications. From such a view grows the definition
of quality control as a universal managerial process for conducting operations so
as to provide stability—to prevent adverse change and to maintain the status quo.
The quality control process maintains this stability by evaluating actual perform-
ance, comparing actual performance to goals and acting on differences found (3).
This chapter does not pretend to cover all of the aspects one must understand,
address and control to have a quality system or even a quality control system.
It also does not cover quality assurance (defined as verification that control is
being maintained), quality improvement, “total quality management,” or other
extensions of these concepts and philosophies. This is an ever-evolving area
and today’s definitions are likely to change again in the future. Many volumes
have been written on that. Quality control is a program with the steps taken by
the developer and manufacturer to support delivery to the customer’s expec-
tation. Quality control focuses on control during operations and meeting the
goals for operations. Quality assurance is involved at later steps and interacts
with a broader range of functions involved in the product life cycle.
For a finished consumer product, quality control begins with an understand-
ing of the customer’s expectations. The product marketer wants to demonstrate or
be assured that material produced and packaged for sale to and use by the final
consumer is equivalent to the material originally developed in the product devel-
opment process. Further, there is a need to ensure that this material is produced
consistently through the life of the product. Taking these views requires that
quality control is much more than an after-the-fact inspection. Any quality
control testing depends heavily on an appropriate set of product specifications
being set and agreed to during the product development process. This reduces
Quality Control of Finished Sunscreen Products 721
the important characteristics of a product to a series of numbers that can be

evaluated with an accepted set of test methods. This results in a series of objec-
tive standards and tests that can be used and replicated at any point along the
product’s life cycle. The range of accepted values is determined during the
product development process and evaluated during the product life cycle.
Characteristics and their associated methods can be grouped into release criteria
and other characteristics, those important to know but not essential to meet to
allow product to be released to the final consumer. There will be times when
certain key characteristics cannot be reduced to a number. These subjective
tests require the development and acceptance of suitable standards for each
product or formulation. Training of the quality control testing staff is critical to
ensure that subjective criteria are met consistently. All of this is coupled with
input from the target consumer.
This chapter really focuses more on evaluation of the finished product and
does not really address in-process control (inspection, sampling, etc.). Similar
tests, characteristics and approaches could be taken but in-process control is a
topic all to itself (4). Also, this chapter does not go into the intricacies of the stat-
istical aspects of the quality control process. Such aspects have led to detailed
developments in statistical process control (SPC). These areas are topics of
great interest in and of themselves (4).
This chapter describes the characteristics of finished sunscreen products
that are most often evaluated in the quality control process. This is a general
outline and there may be some specific products where a property or performance
is key for that particular product but is not included here. Included here are the
typical methods used to evaluate these characteristics and some of the parameters
that should be controlled or established for proper use of these techniques.
PRODUCT FORMS
The various forms for sunscreen products, oils, lotions, sticks and balms, sprays
(alcohol or aqueous, aerosol or pump) are described in some detail elsewhere
(this volume, chapter by SaNogueira). It is important to consider that form and
associated ingredients may influence the type or range of characteristics of
importance for quality evaluation. Techniques or characteristics appropriate for
one product form, a lotion, for example, would not necessarily be of much
importance for another form such as a stick. Other parameters, such as actives
content, would be of importance for all forms. Specific testing or modifications
to address particular product forms are not addressed in this chapter.
SAMPLING
Any effort at finished product quality control must include a consideration of the
sampling plan (3 – 5). It must be determined what constitutes a characteristic
representation of the total production of a given product. The approaches to
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the development of a sampling plan are covered in considerable detail in a

number of texts (3 –5) and requirements are detailed in guidance documents or
individual monographs (5,6). In general, a sampling plan should be based on
the amount of material produced and it should include sampling from the bulk
product as well as product in final packaging. Whether a product is produced
in a batch or continuous process will determine some aspects of the sampling
plan. The plan should also require sampling from the top, middle, and bottom
portions of a tank, drum, tote, or final package and samples from the early,
middle, and late parts of a filling run. All these steps are required to ensure repre-
sentative sampling as well as to gauge whether changes are occurring during pro-
duction processes. Each step in manufacturing, filling, storage, and transportation
can have effects on the “quality” of a product and the sampling plan should be
robust enough to acknowledge and address these (7). The time intervals
between samplings and after filling but before shipping should be considered
in a sampling plan. Sampling should ensure that material tested for quality
control purposes is characteristic of the formula and representative of the material
to be used by the consumer. If sampling for quality control purposes reveals
inconsistencies in product properties (separation, gelling, solidification, liqui-
fication), that information must be included in any reporting of quality control
results.
PHYSICAL METHODS
These are methods that evaluate the physical, rather than chemical or compo-
sitional, characteristics of the finished products. This section does not include
the methods used to ensure proper product delivery from the final package
(such as spray rate, etc.), although that should be addressed during the product
development and manufacturing process. These methods deal with the character-
ization of the “juice” in the package. Color, odor, appearance, refractive index,
specific gravity, viscosity, or more generally rheology, flash point, melting
point, particle size analysis (useful for any emulsion product, some application
to sunscreen lotions), and perhaps others relate to the properties of the complete
product. Some of these physical attributes are influenced by the actives but many
are not.
The three initial characteristics (color, odor, and appearance; COA) are
most appropriately evaluated in comparison to an accepted standard. This
accepted standard is usually production material that is agreed by developers
to be “characteristic” of the desired end product. A general product description
may be included in the finished product specifications (e.g., thick, creamy-
smooth white lotion with no visible oil separation, sandiness or grittiness, with
a mild citrus fragrance). It is even better if this comparison standard is from
the same batch or lot that has been used for consumer acceptance testing. This
practice ensures that production material closely matches material already
deemed acceptable by the final consumer. This is a key area of distinction
from the characterization or quality control of raw materials or determinations by

other test methods. For those other materials, intrinsic properties of the chemicals
define these appearance factors. With the final product, the product developer
uses the input from the consumer to define what these acceptance criteria will
be. For the raw materials, specific values are determined based on raw material
or product performance. Acceptable COA parameters for final products are
based heavily on consumer acceptance. Hedonics are strong factors in consumer
preference for a particular product and the quality control of COA can ensure that
consumer preference, established in testing during development, is consistently
met by final production material.
In addition to matching a standard, color can also be evaluated using stan-
dard colorimetric techniques (7 – 9). In such evaluations, a representative aliquot
of a product is introduced to a colorimeter or spectrophotometer and the color
values read directly from the instrument. The instruments function based on
the absorption or reflection of light, usually a defined, full-spectrum white
light. Color values are a complex combination of the primary colors (blue, red,
and yellow) along with light intensity and contributions from reflectance
(gloss), transmittance or opacity. This allows for an objective representation of
the color of a product. There are a number of accepted, industry-standard
approaches to color measurements (7 – 9) that might be relevant to quality
control of sunscreen products. The colorimetric methods would be guided by
the accepted product standard agreed to during product development.
Another physical property, refractive index, is also related to how a product
interacts with light. Refractive index is a measure of how a material interferes
with the transmission of light or, more specifically, the ratio of the velocity of
light in air to the velocity of light in the substance (10). The refractive index is
related to and can influence both the color and appearance of a product. A
measure of refractive index is an objective means to evaluate the more subjective
aspects of product appearance. The refractive index of a product is directly deter-
mined by the ingredients in the formula but cannot be predicted simply by
knowing the product formula. Refractive index is typically measured at 258C
and any quality control testing should specify and record the temperature at
which refractive index measurements are made.
Specific gravity [a ratio of the weight of a volume of a liquid relative to an
equal volume of pure water, at 258C, (11)] is also a function of the ingredients
that are combined to produce the final product. As the value of specific gravity
is dependent on the formula, its measure during a quality control process can
give some evaluation that the correct formula has been followed and that proces-
sing conditions were appropriate. This value is also related to how the final
consumer interacts with the product although the consumer would have no
easy means to define that relationship. The specific gravity would have some
relationship with the viscosity and overall rheology of a finished product. Specific
gravity is a function of temperature and the temperature at which a specific
gravity measurement is made should be specified.
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Viscosity is probably the most complex physical property of a finished

sunscreen product. In the simplest definition, it is a measure of how a material
will flow. Many things can affect viscosity and its measurement offers a “snap-
shot” of a product’s life or history. One can take a rather simple (get a number
that indicates a sample’s “quality”) out through a very detailed (know and
define every aspect of a product’s behavior) view of this characteristic. From
the quality control point of view, for product release, it is usually sufficient to
obtain a number under a specified set of conditions.
Viscosity is a subset of the more complex area of rheology. A dictionary
definition of viscosity is the internal friction of a fluid that makes it resist a ten-
dency to flow. By definition, rheology is the study of change in form and the
flow of matter. Viscosity is the measure of the amount of force required to
move a layer (shear) of a product (or more correctly, a fluid) relative to the
rate at which a stress is applied. The result is that high-viscosity fluids (those
having more internal friction) require more force to move than low-viscosity
fluids. The viscometer is a tool to measure this internal friction and viscosity
can be measured or reported as absolute or apparent viscosity. The behavior
of a material under shear conditions is related to properties and composition
of the material and allows for classification based on observed properties.
These properties will impact how a product can be formulated, processed,
packaged, and finally experienced by a consumer. As there is a range of
product forms, properties of sunscreen products run the gamut through the
range of rheological systems. Products can be solutions in water or mineral
oil that will likely exhibit Newtonian properties (12,13). Such systems will
show no change in viscosity with added shear with the result being an easy
pouring, easy to process, and easy to apply product. More complex rheology
runs the range out through pseudoplastic and thixotropic, where the more
stress that is encountered, the more the product will change (12,13). Some of
these non-Newtonian fluids will change and not return to the original properties
after stress is released. The understanding of the rheological behavior of a
product is required to ensure straightforward (and economical) processing and
consumer-acceptable final product attributes.
For some products, a simple measure of apparent viscosity at a defined
stress and shear rate will suffice to define a product for quality control release.
More complex rheological measurements of stress/rate relationships, yield
curves, and flow curves are more appropriately performed during product devel-
opment to ensure an acceptable range of product properties will be consistently
produced using the given formula under the intended production, processing,
filling and application processes. Even the simple apparent viscosity measure-
ment can be influenced by temperature and product “history.” Temperature
should be controlled and any sample history should be recorded for the quality
control record.
These three physical characteristics (refractive index, specific gravity, vis-
cosity) are often used as release parameters as they are easily measured and relate
to both formula and function of the finished product. There is no way to calculate
or determine beforehand the final values of any of these properties for any given
product. They are intrinsic to a particular product, are usually determined during
the development of a particular formula and relate closely to how a product is
perceived by a consumer. Control and monitoring of these properties should
ensure ongoing acceptance of the final product by the consumer.
Physical values such as melting point, boiling point, or flash point might be
critical parameters in the identification and characterization of a pure compound
or raw material. They are less relevant to the quality control of a finished product.
As the finished product is such a complex mixture of ingredients, these measure-
ments do not necessarily yield much useful quality control information on the
product. For certain product forms, such as a stick, it might be important to
know and control the melting point to ensure performance and stability. For
alcohol or oil products, a flash point might be required for packaging or transpor-
tation. These determinations should be made during product development and
then checked during process validation.
CHEMICAL METHODS
As with some of the physical tests described in the previous section, most
chemical tests specified for individual actives (acid value, saponification value,
metal content) are not relevant to the finished product. The control and testing
of incoming raw materials would limit undesirable impurities such as metals in
the finished product. Again the complex nature of finished products limits the
utility of many chemical tests.
The pH of a product is a measure of the free hydrogen ion content and can
be a very important chemical characteristic. The value of pH is dependent on the
materials used in the formulation and their interactions. The pH can affect the use
properties of the product as well as the stability of the actives and stability of the
overall formula. The pH might be taken directly on the completed formula or on a
solution of known concentration of the product in water. In either case, the
conditions under which the pH is obtained, including the temperature of the
sample, should be monitored and recorded. For some product forms, such as
oils, a pH measurement is meaningless.
Water content of a finished product can be critical to long-term stability,
actives stability, product use properties, physical properties, and the suscepti-
bility to microbial growth (14). There are generally two techniques to determine
the water content of a product. One method, the titrimetric or Karl Fischer
method, specifically determines water through a chemical reaction. This is a
fairly well defined reaction but it can be complicated if systems and the environ-
ment in which the method is conducted are not kept scrupulously dry. The second
method is the gravimetric or loss on drying approach (15). This method may be
simpler to perform but may include other materials in addition to water in the
final value. Any material volatile at the temperature of the determination will
726 Kalinoski
evaporate in the test and be reported as part of the loss. This approach is only
appropriate for a product where water is known to be the only volatile material
in the formula. Water content or loss on drying might be used as a release
criterion for a finished product. If the gravimetric approach is used, the tempera-
ture and time used for the determination should be recorded.
SPECTROSCOPY
Bulk spectroscopic methods, such as ultraviolet (UV) or infrared (IR) spectro-
scopy (16 –18), are not used as much for finished products as they would be
for raw materials. Finished products are quite complex mixtures, the spectro-
scopic methods are fairly general and it would be difficult to associate specific
features, characteristics, or changes to specific product issues or problems. The
techniques may be used to evaluate some individual component in a formula,
such as a preservative, as some ingredients likely have unique absorbances that
could be distinguished in a complex spectrum. This measurement would probably
not be a release criterion and release would rely more on microbiological
evaluation.
One technique amenable to quality control is near-IR spectroscopy (18).
This approach uses only a part of the IR spectrum to characterize a sample. In
contrast to full spectrum approach, the near-IR technique uses a portion of the
spectrum characteristic of interactions between materials. This allows for a
better evaluation of mixtures. More importantly, when coupled with a computer
data system and appropriate spectral evaluation software, the technique can yield
some simple good/bad, yes/no, or pass/fail determinations. The spectral evalu-
ation and chemometric (19,20) software required for such determinations rely on
the development of a data set of spectra of acceptable and unacceptable samples.
Once such a comparison data set is produced, the technique is reduced to
appropriate sample preparation and introduction. This preparation is usually
not complicated and near-IR systems can be installed and used in both the
quality control laboratory as well as directly in the production area. This
approach permits a much greater in-process control of materials and products.
Spectroscopic techniques are also used for elemental analysis and, as some
inorganic actives are used in sunscreen products, atomic absorption (AA) or
inductively coupled plasma (ICP) spectroscopy (18) might be used in quality
control. The inorganic actives titanium dioxide and zinc oxide are best addressed
using one of these techniques. The techniques involve introducing solution
samples into a flame or plasma to excite the elements present and then detecting
the light absorbed or emitted by the excited elements. The amount of light
absorbed or emitted is directly proportional to the amount of an element
present. The techniques both require the inorganic material to be present in the
elemental form. As both sunscreen actives are used as oxides of the metal, and
are present in complex matrices of organic materials in finished products,
sample preparation involves digestion of the product and isolation of the
inorganic components. This is a harsh procedure that could be hazardous due to

the nature of the reagents and conditions used (strong acids, high temperatures).
Care must be taken to ensure product samples are thoroughly digested to obtain
dependable results without interferences and without getting equipment exces-
sively “dirty.” As it is an absorbance technique, AA is usually performed
one element at a time using individual wavelengths of light characteristic of
the element of interest. The ICP technique relies on light emitted from excited
elements and can be conducted for both elements (Ti and Zn) simultaneously.
ICP spectroscopy yields better sensitivity but this level of sensitivity is not
usually necessary based on the concentrations of sunscreen actives typically
employed. The greater sensitivity can allow for the evaluation of a much
smaller size sample in ICP, requiring less sample preparation, lower hazard,
and less waste disposal. Determination of inorganic actives would be required
before product could be released for distribution.
Mass spectrometry (21) would usually be used coupled with chromato-
graphy (gas or liquid) to simplify sample preparation or introduction. This
technique is most useful for determining the presence or, more specifically, the
identity of an unknown material. As it is not likely that unknowns will routinely
appear in production materials, and process steps are taken to limit likely
occurrences, mass spectrometry is not typically used as a quality control tool.
CHROMATOGRAPHY
Chromatographic separation techniques (22,23) are quite amenable for the quan-
titation of the actives in finished sunscreen products. Chromatography allows for
efficient separation of ingredients in complex formulations followed by selective
or sensitive detection of the components of interest. Of the two most widely used
chromatographic techniques, gas chromatography (GC) and liquid chromato-
graphy (LC), the physical requirements for GC render it less useful for finished
product analysis. The technique requires samples be in the gas phase for analysis
and many complex sunscreen product formulations contain a variety of low vola-
tility or thermally labile materials. The technique may be more compatible with
some product forms (oils or alcohol-based) and it could be used for determination
of alcohol content, if that is a critical parameter. GC may be used coupled with
headspace sampling for odor analysis or fragrance characterization of finished
products. This approach would not likely be used as a release criterion but
might be a follow-up if a sample fails a subjective odor analysis.
LC is more likely to be used due to compatibility between the physical
properties of samples and the requirements of the technique. In general,
reverse phase LC is used, with mobile phase solvents being water-based and
modified siloxane based stationary phases used. Many sunscreen product formu-
lations can be readily prepared as solutions in solvents appropriate for LC. As
such, sample preparation can be kept as simple as possible (dilute and shoot)
and it would be easy to incorporate an appropriate internal standard into a
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sample solution for precise quantitation. The chemical nature of sunscreen

actives also allow for very selective and sensitive detection in LC. This selective
detection following separation typically uses UV or diode-array UV absorption,
permitting sensitive detection of actives in the presence of a great variety of other
formula ingredients. The most critical application of LC would be for organic
actives determinations, as most actives are readily amenable to LC and show
characteristic UV absorption. It is also possible that preservatives could be
quantified using an LC procedure. Determination of actives level would
absolutely be a product release test.
Although sunscreen actives and finished products formulations are readily
addressed using LC techniques, the process of method development in LC can be
quite complicated. The method development process should lead to conditions
that give baseline separation of all active components in a formulated product,
with good chromatographic peak shape, in a relatively short period of time.
The resulting quality control method should also have selective detection of
the actives, with a wide concentration range for detection. Finally, the method
should be free from interferences from other components in the mixture or in
the chromatographic mobile phase. There are a variety of stationary phases avail-
able for LC and it is often best to start with a generally applicable phase such an
octadecyl-modified (C18) siloxane coating on silica. The primary mobile phase
component is water with various organic solvents as mobile phase modifiers.
Methanol and acetonitrile are among the solvents often employed. Further
mobile phase modification may come from the use of organic acids (such as
acetic acid) to adjust the pH of the mobile phase.
VALIDATION
Validation is now required for the methods used to characterize over-the-counter
(OTC) products such as sunscreen formulas. Validation is the process of demon-
strating and documenting that the described method is appropriate for producing
the information used for making a quality decision and applicable to the parti-
cular product being evaluated. Requirements for validation are described in
a number of national and international regulations and guidance documents
(24 – 29). In general, validation of a method includes documentation that the
method is specific, linear, accurate, and precise. The appropriate range of these
parameters must be defined and it must include the expected target concentration
of the sunscreen active. In addition, the technique or method must be able to be
performed under a range of defined conditions that may vary from the original
development conditions and it must be able to be performed by different oper-
ators in different laboratories or settings. The equipment used to practice a
method must also be documented to be appropriate for the method (qualified)
and must be in proper working order prior to obtaining any sample characteriz-
ation or quality release information. This final step is achieved in a process
known as system suitability. Many of the details and requirements for validation
developed from the evaluation of chromatographic techniques. Some techniques

would not require full validation, as they are compendial methods, and proven
through wide use to be appropriate. Any chromatographic techniques, however,
would need to be validated for the specific formulations and active ingredients in
any particular finished sunscreen product.
MICROBIOLOGY
In addition to the physical and chemical characteristics, the impact of biological
processes on finished products must also be evaluated. Product integrity, perform-
ance, functionality, and safety are all aspects of product quality and are reliant on a
product being impervious to microbiological contamination. Consequences of a
contaminated or improperly preserved product range from undesirable aesthetics
(off-color, odor, separation) through loss of production batches to potential physical
harm and illness to consumers. Two tests in microbiology are generally performed,
one is appropriate for quality control of finished goods. First there is a need to
perform a microbial content test (30–32) to ensure microbial “purity” of produced
and packed product. Although sunscreen products are controlled OTC drugs pro-
duced under defined GMP conditions, a producer cannot simply rely on GMP regu-
lations to ensure product safety and quality. Product developers may rely on the
determination of the presence of preservatives and earlier development work on
the establishment of appropriate preservative system to create a robust product.
The microbial content test ensures that any given production batch is free from con-
tamination. Microbiology tests can be time-consuming, requiring the growth of
living organisms. This time requirement may necessitate establishment of a
“micro hold” on material to allow completion of the microbiology tests before a
product can be released for distribution. The microbial content test is simply an
incubation of a specifically prepared sample of a product in a medium to
promote the growth of microorganisms. After a specified time to allow for
growth, the sample is evaluated for the presence or absence of organisms. The
quality control specification may stipulate that levels for all organisms be under a
certain level or that certain extremely hazardous organisms be absent from the pro-
duction material. Certain product forms by their chemical nature are resistant to
microbial infection and may be exempted from microbiological specifications.
The second microbiology test is not standard for every batch. A preservative
efficacy or challenge test (33–37) is used to evaluate whether a finished formulation
can withstand a microbial insult. The test requires a product to be dosed with a
known level of specific microorganisms and the dosed product is observed to deter-
mine whether the organisms will grow. Growth of microbes in a dosed system indi-
cates the preservative system is inadequate to control microbiological infection of
the product. This type of evaluation is usually performed during product develop-
ment but may also be checked following first production or during production
validation. The long-term efficacy of the preservative system would be a critical
730 Kalinoski
component of overall product stability. The preservative challenge test would then
be a part of the life cycle stability program for the sunscreen product.
EFFICACY
Efficacy of a sunscreen product would be tested using the sun protection factor
(SPF) test, as defined in the Food and Drug Administration (FDA) sunscreen
monograph (38 – 40). This is an in vivo test using a number of live subjects.
This testing would be performed during product development and would not
be appropriate as a quality control test. There are also in vitro SPF test procedures
(41,42) that are likely performed during product development. This combination
of tests would have led to a formulation with an appropriate active level to deliver
desired product performance. It would be desirable to evaluate the SPF of pro-
duction material to ensure that production conditions are not, in some unforeseen
manner, influencing the final efficacy of the product. This would be done primar-
ily using the in vitro method, comparing results from production batches to those
obtained during product development. Efficacy testing, while valuable to ensure
that the final product meets the customer’s expectations, would not be used as a
release criterion for production.
STABILITY
Overall product stability, either real-time or accelerated, is also performed as part
of product development. It is useful to perform an accelerated test of production
material to verify information on product stability gained during product
development. Results from production material, most importantly from initial
production and process validation, would be compared to results for materials
produced during product development. Again, results of this testing would not
be used as release criteria.
SUMMARY
To conduct appropriate quality control, it is important to start with a quality defi-
nition that relates to consumer acceptance of the finished sunscreen product. This
definition leads to a series of criteria or measurements used to judge the pro-
duction of a finished formula. The criteria require use or development of accepted
methods that can be for product release or to understand other characteristics of
the products. All quality parameters and product specifications are based on use
and maintenance of acceptable product standards. Quality parameters can be
objective (numbers based) or subjective and the training of staff is key to consist-
ently evaluate products certain to meet the customer’s expectations.
The key subjective criteria used for finished sunscreen products are color,
odor, and appearance. Key physical parameters include specific gravity, refrac-
tive index and viscosity. Among the key chemical parameters are water, pH
(as appropriate), and actives content. Depending on the types used in a product,
actives can be determined by spectroscopy (AA or ICP) for inorganics and liquid
chromatography for organic materials. Testing for microbiological content is a
critical release parameter for most product formulations. The efficacy and
stability of a formula are important to know but are product development, not
quality control, determinations.
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copeial Convention, Rockville, MD, 2002.
32. Bacteriological Analytical Manual. 8th ed. Gaithersburg, MD: AOAC International,
1995.
ation Technical Guidelines—Microbiology Guidelines, Section 13. Washington, DC:
Cosmetic, Toiletry and Fragrance Association, 2001.
ation Technical Guidelines—Microbiology Guidelines, Section M-3. Washington,
DC: Cosmetic, Toiletry and Fragrance Association, 2001.
ation Technical Guidelines—Microbiology Guidelines, Section 10. Washington, DC:
Cosmetic, Toiletry and Fragrance Association, 2001.
36. United States Pharmacopeia, Twenty-Sixth Revision, [51], The United States Pharma-
copeial Convention, Rockville, MD, 2002.
37. Horowitz W (ed.). Official Methods of Analysis of the AOAC International. 17th ed.
Gaithersburg, MD: AOAC International, 2003.
38. Code of Federal Regulations 21CFR352.72, General Test Procedures, 281 – 282,
April 2001.
39. Code of Federal Regulations 21CFR352.73, Determination of SPF Values, 282 – 284,
April 2001.
40. Code of Federal Regulations 21CFR352.76, Determination if a Product is Water
Resistant or Very Water Resistant, 284– 285, April 2001.
41. Diffey BL, Robson J. J Soc Cosmet Chem, 1989; 40:127 – 133.
42. Spruce SR, Hewitt JP. Euro Cosmetics June 1995, 14 – 20.
36
Quality Control of Ultraviolet Filters
Nadim A. Shaath
Introduction 736
FDA Approved Category I UV Filters 736
Quality Control Procedures 737
Physical Analyses 737
Odor 737
Color 737
Physical Appearance 738
Melting Point 738
Refractive Index 738
Specific Gravity 738
Optical Rotation 738
Solubility 739
Moisture Determination 739
Viscosity 739
pH Determination 739
Flash Point 739
Chemical Analyses 739
Saponification Value 739
Acid Value 740
Functional Group Analysis 740
Metal Contents 740
Chromatographic Techniques 740
Gas Chromatography 740
735
736 Shaath
High-Performance Liquid Chromatography 741

Spectroscopic Techniques 742
Ultraviolet Spectroscopy 742
Nuclear Magnetic Resonance Spectroscopy 744
Infrared Spectroscopy 745
Mass Spectrometry 746
Atomic Absorption and Emission Spectroscopy 747
Inductively Coupled Plasma 747
Conclusions 748
References 748
INTRODUCTION
The recent rapid growth of the sunscreen market reflects increased consumer
awareness concerning the protection against excessive exposure to the sun’s
damaging ultraviolet (UV) rays (this volume, chapters by Nelson and Diffey).
This large-scale introduction of UV filters into a multitude of cosmetic and
toiletry products has complicated the task of the quality control chemist.
UV filters are analyzed in their pure form by ingredient suppliers and also
by cosmetic companies that purchase those filters for incorporation into their fin-
ished products. Once these UV filters are included into cosmetic finished products
they also need to be analyzed for both quality control and regulatory compliance.
This chapter deals primarily with the analysis of the UV filters as the pure
chemical ingredients supplied by their manufacturers. The analysis of the fin-
ished sunscreen products is dealt with in the chapter by Kalinoski (this book)
and also in the chapter by Shaath and Flores (this book) dealing with modern
analytical techniques in the sunscreen industry.
FDA APPROVED CATEGORY I UV FILTERS

The final monograph (1) published on May 21, 1999 lists 16 UV filters as
Category I ingredients as shown:
i. Inorganic particulates
1. Titanium dioxide
2. Zinc oxide
ii. Organic filters
UV-A filters UV-B filters
1. Avobenzone 1. PABA
2. Oxybenzone 2. Cinoxate
Quality Control of Ultraviolet Filters 737
ii. Organic filters

3. Sulisobenzone 3. Octocrylene
4. Dioxybenzone 4. Ocinoxate
5. Meradimate 5. Octisalate
6. Padimate-O
7. Homosalate
8. Ensulizole
9. Trolamine Salicylate
Of the 14 organic chemical UV absorbers, four are ketones namely avobenzone,

oxybenzone, dioxybenzone, and sulisobenzone, and the rest are acids, their salts
or esters. These compounds can be easily analyzed using standard physical,
chemical, chromatographic, and spectroscopic techniques.
QUALITY CONTROL PROCEDURES

The quality control procedures for all UV filters includes the following:
1. Physical analyses
2. Chemical analyses
3. Chromatographic techniques
4. Spectroscopic techniques.
Listed next are all the possible tests that will verify the purity of a UV filter (2).
The analysts should consult the UV filter ingredient supplier for the appropriate
battery of tests to undertake to determine the purity of the ingredient in question.
Physical Analyses
Odor
Sunscreen chemicals generally exhibit little or no odor. They should be compared
with a standard that is kept in a cool dry place, in an amber bottle free of head-
space, and away from heat and light. Request a new standard from your sunscreen
supplier every 6– 9 months. Odors should be smelled on blotters and not directly
from the containers. The sunscreen chemical should not be stored next to a highly
odoriferous material to avoid cross contamination of sunscreens that are other-
wise odorless, especially if they are viscous liquids or solids.
Color
The color of the sunscreen should be noted on the specifications sheet. Care is to
be exercised when comparing the color of the new batch with a sample stored
over a period of time. The color of the standard may have changed on standing
for more than six months. The chemistry of the sunscreen may be indicative of
a potential color problem. For example, cinnamates and PABA derivatives
738 Shaath
may darken on standing due to air oxidation. Phenolic derivatives, such as

salicylates, interact with iron contaminants and form pinkish colorations.
Generally, unlined metal drums should be avoided. Restoration of original
colors may be possible in some sunscreen liquids through simple chemical treat-
ments, distillations, or otherwise. Sunscreen suppliers should be aware of such
procedures and will recommend the most appropriate remedy.
Physical Appearance
Without resorting to any instrumentation, recording the physical appearance
alone may be a critical factor in acceptance or rejection of the sunscreen chemi-
cal. Observe the nature of the product as to whether it is a solid or liquid, clear or
cloudy, viscous or free flowing. Check for particulates, sediments, or foreign
substances in the product.
Melting Point
This property is applicable to solid sunscreens such as the benzophenones,
avobenzone, ensulizole, and PABA. Record the temperature and melting range
in degrees Celsius. Observe the behavior during the melting process. Report
any swelling, sweating, charring, or other melting characteristics. This may reveal
information on the purity of the sunscreen raw material. The dimer of dihydroxy
acetone (DHA) is identified via its melting point.
Refractive Index
The refractive index ([n]D at 208C) is the change in direction of a light ray passing
from one medium to another of different density. The index of refraction of the
substance may also be expressed as the ratio of the velocity of light in vacuum to
its velocity in the substance. It varies with the wavelength of the incident light,
temperature, and pressure. The usual light source is the D line of sodium and
the standard temperature is 208C. This method applies to liquid sunscreens that
are not too viscous to analyze.
Specific Gravity
The specific gravity is the ratio of the density of a substance to the density of a
reference substance (water). The temperature should be specified at all times.
In the absence of a gas chromatograph, this property is helpful in determining
the purity of the sunscreen chemical.
Optical Rotation
The optical rotation (a at 208C) is the change in direction of the plane of polar-
ized light either to the right or to the left as it passes through a molecule contain-
ing one or more asymmetric (chiral) carbon atoms. The optical rotation is
measured by the use of a polarimeter. This method applies only to sunscreens
that are optically active.
Solubility
The supplier should recommend a procedure for monitoring the solubility beha-
vior of the sunscreen in various solvents. Depending on the application, the
sunscreen may be tested at several concentrations in different solvents of
various polarities. Usually, a 5% solution of the sunscreen is tested in water,
ethanol, mineral oil, isopropyl myristate, corn oil, acetone, isopropyl palmitate,
or glycerin.
Moisture Determination
The presence of moisture in the sunscreen product may be detrimental to certain
applications. A Karl Fisher titration (manual or automatic) for the determination
of moisture content should be performed if it is suspected that the product con-
tains over 0.5% water.
Viscosity
This is a measure of the resistance of fluid sunscreen to flow, expressed in dyne
second per square cm or poises. Centipoises, which are 0.01 poises, are also used
in the industry.
pH Determination
The pH is a value that represents the acidity or alkalinity of an aqueous solution.
It is defined as the logarithm of the reciprocal of the hydrogen ion concentration
of a solution pH equals: pH ¼ ln 1/Hþ. The pH of a number of sunscreen acids
and their salts should be routinely determined in the quality control laboratory
especially ensulizole, trolamine salicylate, PABA, and sulisobenzone.
Flash Point
A closed cup flash point determination in degrees Fahrenheit of the sunscreen is
required by the Department of Transportation (DOT) whenever the chemical is to
be transported outside of the laboratory facilities. A flashpoint below 1408F is
considered to be flammable and possibly combustible.
Chemical Analyses
Saponification Value
This procedure is applicable to the analysis of sunscreen chemicals that are esters.
Esters can be converted to carboxylic acids and alcohols by alkaline hydrolysis.
The acids can be detected and quantitatively determined by neutralization. The
saponification value is defined as the number of milligrams of KOH required
for the Saponification of the ester and neutralization of free acids in 1 g of
sample (3). Typical values range from 160 to 240.
740 Shaath
Acid Value
Some sunscreen products contain carboxylic acids that may be present as
unreacted products from the synthesis of the sunscreen (e.g., esterification), as
degradation products (e.g., aldehydes), or as part of the compound (e.g.,
PABA). The amount of acid president is determined by titrating with a standar-
dized base. If the acid value is performed to determine impurity, values lower
than 5 should be observed. Some products require a percentage acid as
opposed to an acid value.
Functional Group Analysis

In the absence of chromatographic and spectroscopic techniques, many sun-
screens containing functional groups may be analyzed with conventional chemi-
cal methods. Acetals, acids, aldehydes, esters, ketones, or phenols are analyzed
both quantitatively and qualitatively through functional group analyses. For
example, hydroxylamine hydrochloride will react with the carbonyl group
in ketones, forming oxides and liberating HCl. The amount of ketone can be
determined from the amount of HCl liberated (4).
Metal Contents
Zinc oxide and titanium dioxide as well as metal contaminants, such as iron or
chromium are analyzed by atomic absorption spectroscopy (5), by ion chromato-
graphic procedures (6) or inductively coupled plasma (7).
Chromatographic Techniques
Chromatography may be defined as the science of separation techniques invol-
ving a mobile phase [the solvent in thin layer chromatography (TLC) and
high-performance liquid chromatograph (HPLC), or the helium/nitrogen gas in
gas liquid chromatography (GC)] passing through a stationary phase (alumina
or silica in TLC, C-18 packing in HPLC, silicones or carbowax in GC) (8).
The ability to separate various components in a mixture of sunscreen chemicals
(owing to the presence of impurities or isomers) is based on selective and
preferential partitioning of these components between the mobile phase and
the stationary phase. Two advanced automated techniques that are used routinely
for the analysis of UV filters are GC and HPLC.
Gas Chromatography
The last 20 years have witnessed an explosion in the use of gas liquid chromato-
graphy [also known as gas chromatography (GC) or vapor phase chromatography
(VPC)] in the analysis of sufficiently volatile and fairly stable organic chemicals.
The supplier should recommend suitable conditions for the analysis by GC.
The equipment available, however, maybe the determining factor. The following
parameters are crucial in any GC sunscreen analysis (9).
1. Column: The type of column (packed or capillary), the packing

material (polar or nonpolar) and the length and diameter of the
columns must be specified.
2. Temperature conditions: The injector, detector, and oven temperature
should be noted. Any variations could lead to erroneous results. If
temperature programming is available, record the initial and final
temperature, as well as the temperature ramp.
3. Detector: From the many detectors commercially available, thermo-
conductivity detectors (TCDs) and flame ionization detectors (FIDs)
are adequate for most analyses.
Other factors that may be important are the carrier gas, flow rate, split ratio,
and undercoating of columns. However, as long as the standard and the new batch
are analyzed back-to-back, any condition mentioned in the foregoing may be
adequate for the analysis. Caution must be exercised in comparing data run
on two different machines or on two different days without ensuring that the
conditions are identical. The use of internal or external GC standards may be
helpful in those circumstances.
A typical set of GC conditions for the analysis of sunscreen chemicals
follows:
Sample size 0.1 mL

Oven temp 65– 2508C
Program rate 48C/min
Injection port temperature 2108C
Detector FID
Carrier flow 1 mL/min
Split ratio 200 : 1
Attenuation 0
Threshold 0
Detector temperature 2508C
Carrier gas Helium
High-Performance Liquid Chromatography

Liquid chromatography is quite similar to GC except that the mobile phase is a
liquid instead of a gas (10). Many laboratories are currently equipped with
HPLC machines and are routinely analyzing their products with this procedure.
The following conditions have to be specified:
1. Solvent: State whether the analysis requires gradient elution or iso-

cratic conditions. If gradient elution is used, the mixing ratio of
the binary or ternary solvents must be specified. The use of ultra
pure-grade solvents is highly recommended.
742 Shaath
2. Column: Other than the length and width, the most important factor is
the type of packing in the column. Specify whether it is a reverse phase
column or a normal phase column.
3. Detector: The use of either a UV or refractive index detector is
recommended. If a UV detector is used, the exact wavelength should
be specified. Other detectors such as conductivity, fluorescence, or
electrochemical maybe suitable for particular application.
Unlike GC, HPLC may require extensive preworkup, the use of pure
reagents, and generally longer analysis time. However, it is the method of
choice if the sunscreen is either thermally unstable or is insufficiently volatile
(e.g., PABA or sunscreen salts).
Spectroscopic Techniques
Spectroscopic methods of analysis are excellent methods for the identification of
sunscreen chemicals and for the elucidation of their molecular structure (11).
This is accomplished by recording the energy absorbed or emitted by the sun-
screen chemical in any of the wavelengths of the electromagnetic spectrum in
response to excitation by an external energy source.
Ultraviolet Spectroscopy
UV spectroscopy is used in the characterization of sunscreen chemicals which, by
definition, are UV radiation absorbers. UV spectroscopy involves the absorption
behavior of the chemical and can be either qualitative or quantitative. The quali-
tative application of absorption spectroscopy depends on the fact that a given
molecular species absorbs light in a specific region of the spectrum. Such a
display is called an absorption spectrum and serves as a fingerprint for identifi-
cation purposes. In quantitative applications, the unknown concentration of a
given species is determined.
Several useful data may be extracted from the UV spectrum to aid in the
identification and characterization of sunscreen active chemicals, namely the
UV pattern, the lmax , the molar absorptivity (1), the K-value, and % purity.
1. UV pattern: Pattern recognition of the UV spectrum may provide infor-
mation for the identification of sunscreen chemicals. Care must be
exercised in selecting the appropriate solvent for the analysis at an
extremely high purity (ultrapure or spectroscopy-grade solvents).
The concentration and dilution techniques have to be carried out
carefully since the UV pattern is directly affected by the concentration,
as shown in the Beer – Lambert law (12), which governs the UV
absorption:
AM
1¼
bc
where 1 is the molar absorptivity in moles per cm (mol/cm) gram and

is a constant, characteristic of the solute. The molar of absorptivity is
directly proportional to the chemicals ability to absorb UV radiation.
Therefore, the greater the absorptivity, the more UV radiation the
chemical absorbs; A is the absorbance at the wavelength maximum;
M is the molecular weight of the solute in moles per cubic centimeter
(mol/cm3); b is the cell width in centimeters; and c is the concentration
of the solute in grams per cubic centimeter (g/cm3).
2. lmax: The wavelength of maximum absorption, lmax is a characteristic
of the sunscreen chemical under investigation, provided that the
solvent is clearly defined. The lmax , the extinction coefficient (1) in
ethanol and the percent allowed for the 16 sunscreen chemicals used
in the USA are as follows:
FDA-OTC Panel Category I Sunscreens

Extinction
coefficient (1)
Sunscreen Approved % lmax (ethanol) (ethanol)
A. Organic absorbers
UV-A absorbers
Avobenzone 3 357 30,500
Oxybenzone 6 325 9400
Sulisobenzone 10 324 8400
Dioxybenzone 3 327 10,440
Meradimate 5 336 5600
UV-B absorbers
PABA 15 283 15,300
Cinoxate 3 305 9000
Octocrylene 10 303 12,600
Ocinoxate 7.5 311 23,300
Octisalate 5 307 4900
Homosalate 15 306 4300
Padimate O 8 311 27,300
Ensulizole 4 310 28,250
Trolamine Salicylate 12 298 3000
B. Inorganic particulates
Zinc oxide 25 Broad spectrum
Titanium dioxide 25 Broad spectrum
3. Molar absorptivity (1): The molar absorptivity (1), or molar extinction

coefficient, is a measure of the radiation’s attenuation in an absorbant
medium. It is characteristic of the sunscreen chemical and dependent
on the wavelength of light, nature of the solvent, concentration and
744 Shaath
the temperature. See Shaath (13) for the procedure is used to determine
molar absorptivity (1).
4. K-value: The K-value is used in the sunscreen industry to rate the effec-
tiveness of the sunscreen chemical. It is the ratio of its maximum
absorbance to its concentration in g/L measured in a cell of 1 cm
path length.
UV absorbance
K-value ¼
Concentration of sunscreen (g=L)
See Shaath (13) for the procedure used to determine K-value.

5. Percentage purity: Although GC is the best method to determine the
purity of a sunscreen chemical, UV spectroscopy could also be used
for that purpose provided accurate weighings are performed on an
analytical balance and a reference material of known purity is available
to calculate molar absorptivity. The UV spectrum of Oxybenzone is
shown in Fig. 36.1.
See Shaath (13) for the procedure to calculate the percentage purity.
Figure 36.1 Oxybenzone ultraviolet spectrum.
Nuclear Magnetic Resonance Spectroscopy

Nuclear magnetic resonance (NMR) spectroscopy is a powerful technique used to
examine the environment of the nuclei of the atoms which make up the sunscreen
chemical (14). The nuclear environment depends strongly on the nature of the
chemical bonds that hold the atoms together in the molecule and is also depen-
dent on the number of types of other atomic nuclei in the immediate vicinity.
Thus, in the NMR experiment the hydrogens (protons) are “seen” and their
environment characterized. Figure 36.2 illustrates the NMR spectrum of
oxybenzone.
Figure 36.2 Oxybenzone NMR spectrum.
Infrared Spectroscopy
When the sunscreen chemical interacts with infrared (IR) radiation, portions of
the incident radiation are absorbed at particular wavelengths. This absorbed
energy causes the atoms in the chemical to undergo a series of twisting,
bending, rotational, and vibrational motions. These motions, occurring simul-
taneously, produce a highly complex absorption spectrum that is uniquely
characteristic of the functional groups (e.g., carbonyl group, phenolic group)
present in the sunscreen molecule and of the overall configuration of the atoms
as well. The use of the IR spectrum as a “fingerprint” for the sunscreen chemical
provides the analyst with an extremely powerful technique for identification and
characterization (15). The IR spectrum of oxybenzone is shown in Fig. 36.3
IR spectroscopy has been used to analyze for the purity of the artificial
tanning ingredient, dihydroxy acetone (DHA). The carbonyl group DHA has a
peak at 1744 cm21 indicative of the presence of the monomer form of the
ingredient. The dimer form has an absorption peak at 1273 cm21 representing
the ether bonding. Evaluation of the ratio of the monomer to the dimer will
Figure 36.3 Oxybenzone infrared spectrum.

746 Shaath
allow the chemist to accurately decipher the exact quality and purity of
DHA (16).
Mass Spectrometry
The main advantage of mass spectrometry (MS) is its increased sensitivity over
other analytical techniques and its specificity in identifying unknowns and for
confirming the presence or absence of suspected compounds (17). The excellent
specificity results from characteristic fragmentation patterns, which can give
information about molecular weight and molecular structure. The mass spectrum
of oxybenzone is shown in Fig. 36.4.
The following table lists typical GC/MS conditions utilizing a quadruple
instrument.
GC/MS conditions Parameter

Sample Size 0.1 mL
Oven temperature 55–2508C
Oven ramp rate 28C/min
Injection port temperature 2508C
Detector Total ion chromatogram
Carrier flow 1 mL/min
Split ratio 100 : 1
Peak threshold 30
MS ionization voltage 70 eV
Scan time 108.3 amu/s
Scan start delay 0s
Start, stop delay 35–400
Electron multiplier voltage 1800 eV
The interfacing of two powerful analytical techniques, namely the separation

technique of capillary GC and the identification technique of MS has produced
the single most powerful analytical tool to date: the GC/MS. The automation
Figure 36.4 Oxybenzone mass spectrum.

and the computerization currently available in the state-of-the-art instrumenta-

tion of GC/MS has had a major effect on the flavor and fragrance industry, the
food industry, the petroleum industry, the cosmetic and toiletries, sunscreen,
and household products industries (18). With the use of a selective ion monitoring
(SIM) technique in GC/MS, for example, subparts per million of an impurity
can be detected in sunscreen chemicals (19). However, the importance as to
the absence or presence of these low-level impurities in the cosmetic and
toiletry product is currently considered insignificant and is not measured.
Nevertheless, the use of this advanced technique, if available, facilitates the
analysis tremendously and decreases the time needed to complete even the
most complicated tasks.
For more details see chapter by Shaath and Flores on Modern Analytical
Techniques in this book.
Atomic Absorption and Emission Spectroscopy
Atomic absorption (AA) and emission spectroscopy deals with the measurement
of the absorption and or emission of electromagnetic radiation by atoms. The
wavelength at which electromagnetic radiation is absorbed or emitted is exclu-
sive for a particular element such as titanium or zinc. This amount of light
absorbed by a chemical is proportional to the concentration of the mineral
element being analyzed as governed by the Beer – Lambert law. This technique
is considered to be one of the simplest and best quantitative method for the
analysis of metals.
A new addition to the GC’s arsenal has been the availability of the atomic
emission detector (AED). The strength of the AED lies in the detector’s ability
to simultaneously determine the atomic emissions of many of the elements in
analytes that elute from a GC capillary column.
Inductively Coupled Plasma
Inductively coupled plasma (ICP) is a more advanced technique used to deter-
mine the elemental compositions (zinc and titanium) in sunscreens.
An ICP works by injecting a mist from a sample into the center of an argon
plasma. The plasma is created from a flow of gas within a high-energy field,
which ionizes the gas and causes intense heating. When the mist of the sample
enters the plasma field, the intense heat causes the dissociation of most chemical
compounds. The energy that the component atoms absorb causes them to undergo
excitation and ionization energy transitions which then produce spectral emis-
sions characteristic of the elements being excited. The spectra produced by the
plasma is broken down into individual spectral lines by the ICP’s spectrometer,
and the ICP software translates the spectral lines into concentrations for a
specified suite of elements.
For more information on atomic spectroscopy, the reader is urged
to read the many references available on this topic (this book, chapter by
Shaath and Flores).
748 Shaath
CONCLUSIONS
With the rapid growth of the sunscreen industry in both its sales and the number
of new product introductions, UV filters are incorporated into a multitude of pro-
ducts used in our daily lives. It has thus become necessary for the quality control
chemist to know much more about analytical procedures, the chemical structure
of sunscreens and their potential interaction with solvents, impurities, the
environment (heat, light, oxygen, or other), and other UV filters. The procedures
outlined in this chapter are meant to provide the analyst with the general methods
for the analysis of sunscreen chemicals. Sunscreen suppliers should be consulted
for the selection of tests appropriate to the ultraviolet filters they offer. The
analytical chemist should also research and develop new techniques that can
identify impurities, isomers, and other ingredients more accurately.
A new challenge has also been introduced with the incorporation of new
forms of zinc oxide and titanium dioxide filters. These ingredients are sold
either in their pure form or coated (with silica, dimethicone, aluminum salts,
etc.) or are predispersed with a variety of emollients for ease of handling, dis-
persion, and nonconglomeration of the particles. Thus, the analytical chemist
needs to be aware of the properties and impurities of these new forms of inorganic
dispersions used in the newer sun care products.
Finally, essential oils, biologically active ingredients, and functional bota-
nical extracts are being incorporated in many new sun and skin care products.
This poses a serious challenge to the quality control chemist who has to
acquire both the additional skills and techniques as well as the advanced instru-
mentation to properly analyze the multitude of active and functional ingredients
present in the new sun care products.
This increased activity in the sunscreen industry will only increase the
burden on the analytical, research, and quality control chemists to meet the
new challenges of purity, consistency, accuracy, and, more importantly, claims
substantiation.
REFERENCES
2. Shaath NA. The analysis of sunscreen chemicals. Part 1. Quality control procedures
for sunscreen chemicals. Cosmet Toilet 1987; 3:69 –81.
3. Association of Official Analytical Chemists. Official Methods of Analysis. Procedure
28.028, 1984.
4. Shriner R, Fuson R, Curtin D, Morrill T. The Systematic Identification of Organic
Compounds. New York: John Wiley & Sons, 1980.
5. Willard H, Merrit L, Dean J, Settle F. Instrumental Methods of Analysis. Belmont,
CA: Wadsworth Publishing, 1981.
6. Freiser H. Ion Selective Electrodes in Analytical Chemistry. New York: Plenum Press,
1980.
7. http://ral.coafes.umn.edu/icp.htm
8. Poole C, Schuette S. Contemporary Practice of Chromatography. New York: Elsevier,

1984.
9. Jennings W. Gas Chromatography with Glass Capillary Columns. New York:
10. Snyder L, Krkland J. Introduction to Modern Liquid Chromatography. New York:
11. Silverstein R, Bassler GC, Morill T. Spectrometric Identification of Organic Com-
pounds. New York: John Wiley & Sons, 1963.
12. Jaffe H, Orchin M. Theory and Application of Ultraviolet Spectroscopy. New York:
13. Shaath NA. Quality control of sunscreens. In: Lowe NJ, Shaath NA, Pathak MA, eds.
14. Casy AF. PMR Spectroscopy in Medicinal and Biological Chemistry. New York:
15. Colthup NB, Daly LH, Wilberley SE. Introduction to Infared and Raman Spec-
troscopy. New York: Academic Press, 1974.
16. Soliance ARD. Dihydroxyacetone Technical File, Soliance Pomacle Fr, 27 – 42.
17. Jennings W, Shibamoto T. Qualitative Analysis of Flavor and Fragrance Volatiles by
Glass Capillary Chromatography. New York: Academic Press, 1980.
18. Chapman J. Computers in Mass Spectrometry. New York: Academic Press, 1978.
19. Agilent 5973N GC/MS System Users Manual 2003.
37
Modern Analytical Techniques in
the Sunscreen Industry
Nadim A. Shaath
Alpha Research & Development Ltd., White Plains, New York, USA
Frederick Flores
International Flavors and Fragrances, New York, New York, USA
Introduction 752
Separation Techniques 753
Physicochemical Methods 753
Extractions 753
Distillations 754
Sublimations 754
Chromatographic Methods 754
Gas Chromatography 754
High-Performance Liquid Chromatography 755
Headspace (Purge and Trap) 755
Ion Chromatography 755
Identification Techniques 755
Chemical Methods 755
Chromatographic Methods 756
Gas Chromatography/Retention Time 756
Gas Chromatography/Mass Spectrometry/Data System 756
High-Performance Liquid Chromatography/Retention Time 756
Headspace/Gas Chromatography/Retention Time 756
751
752 Shaath and Flores
Spectroscopic Methods 756

Mass Spectrometry 756
Infrared Spectroscopy 757
Ultraviolet Spectroscopy 757
Nuclear Magnetic Resonance Spectroscopy 757
In Vitro Sun Protection Factor Analyzers 758
New Analytical Techniques 758
GC and GC/MS Ancillary Methods 760
Fast GC 760
GC Racer 760
Retention Time Locking 760
Programmable Temperature Vaporizing Inlet 761
Simplified 2-D GC 761
Solid Phase Microextraction 761
Gerstel Twister and Thermodesorption 762
Mass Spectrometer—Selective Ion Monitoring 762
Atomic Emission Detector 762
HPLC Ancillary Methods 763
Fast HPLC 763
Liquid Chromatography/Mass Spectrometry 763
Other Methods 763
Supercritical Fluid Extraction 763
Inductively Coupled Plasma 763
X-Ray Photoelectron Spectroscopy 764
X-Ray Fluorescence Spectroscopy (Auger Electron) 764
Conclusions 764
References 765
INTRODUCTION
Excessive exposure to the harmful ultraviolet (UV) rays of the sun leads to pre-
mature aging of the skin, photoallergies, and ultimately, malignant melanoma
and skin cancer (this volume, chapters by Nelson and Diffey). The increased
use of UV filters for protection has become of paramount importance in our
daily lives. Scientists have been busy during the last two decades researching
novel ingredients and techniques to reduce the spiraling statistics in the prolifer-
ation of skin cancer, estimated today to top 1.5 million new cases annually in
the USA alone. Primary to this research effort has been the development of
new ultraviolet filters. Both organic sunscreens and inorganic sunscreens have
Modern Analytical Techniques in the Sunscreen Industry 753
been developed and incorporated into a variety of cosmetic formulations contain-

ing a plethora of other ingredients to enhance and boost protection.
The sunscreen industry in particular has benefited from the introduction of
many new technologically advanced analytical techniques. This chapter will
attempt to highlight those developments and also review the classical analytical
techniques utilized in the analysis, identification, and quantitation of new and
improved ingredients and formulations for the sun care industry (1).
Modern analytical techniques are employed to analyze UV filters and
formulations incorporating those sunscreens and a multitude of other cosmetic
ingredients. Advanced instrumentation is used for quality control purposes, for
research and development purposes and ultimately for regulatory compliance,
monitoring, and enforcement. This chapter will first tackle separation techniques
followed by identification procedures highlighting both accepted current
methodology as well as newer more advanced research techniques.
SEPARATION TECHNIQUES
Cosmetic formulations are by their nature highly sophisticated mixtures of a mul-
titude of ingredients engineered to effectively deliver the UV active components
to the skin (this volume, chapter by Klein and Palefski). The UV filters are the
ultimate ingredients in a cosmetic preparation that prevent the penetration of
the harmful rays of the sun into the skin. Biologically active ingredients have
been recently introduced in sun care and skin care formulations to combat
other important potential damages of the UV rays (this volume, chapters by
Lintner, The Aveda group, Epstein, Chaudhauri and Elmets). These include:
. Moisturizers, humectants, and barrier repair ingredients for dryness,
scaling, and chapping.
. Firming, elasticity enhancing, tissue repair, and collagen stimulation
ingredients for wrinkles and skin sagging.
. Emollients, anti-inflammatory, and soothing agents for inflammation.
. Radical scavengers, botanicals, and antioxidants for free radical
damage and lipoperoxidation.
. Ultimately, DNA and cell repair agents for DNA damage and cell
apoptosis.
For the analysis of each of the aforementioned type of ingredients, consult your
raw material supplier, specific reference manuals, and Section VII in this book.
Physicochemical Methods
Extractions
The goal of an extraction procedure is to isolate the original ultraviolet filter from
the matrix it is incorporated in for analysis and identification (2). This matrix may
be hydroalcoholic, oil-based, emulsion, mousse, gel, or shampoo base. The
proper selection of solvents is crucial in ensuring the appropriate and complete

extraction.
Advanced extraction techniques that have become automated are:
. Sep pack extractions
. Soxhlet extractions
. Supercritical fluid extractions.
For details see section on New Analytical Techniques in this chapter.
Distillations
This is a separation process in which a liquid is converted to vapor, depending
on the boiling point of each component (3). The vapor then condenses and
each component in the mixture is individually collected. The purpose of distilla-
tion is purification, concentration, or separation of the components of a mixture.
Procedures are termed either simple or fractional distillations depending upon the
presence or absence of a packed column. Other distillation techniques are steam
distillation and molecular distillation.
Sublimations
This is the direct passage of the substance from its solid state to its vapor state
without passing through the intermediate (liquid) state (4). This method is used
in the isolation and purification of select sunscreens in certain emulsions.
Chromatographic Methods
Chromatography may be defined as the science of separation techniques
involving a mobile phase passing through a stationary phase. The ability to sep-
arate various components of a mixture of organic compounds is based on
selective partitioning of these components between the mobile phase and the
stationary phase (5).
The sunscreen industry uses all classes of chromatographic procedures,
including column chromatography, thin layer chromatography and some
techniques described in the following text.
Gas Chromatography
Gas chromatography (GC) is useful for relatively volatile and normally stable
organic compounds. This method involves a gaseous mobile phase (helium or
nitrogen) and a liquid stationary phase. The sample to be analyzed is injected
at a temperature sufficient to vaporize it. The gaseous sample is then partitioned
between the stationary liquid phase and the mobile phase causing the separation
of the components in the mixture. The separation is a function of both the polarity
and volatility of the components of the sample (6).
High-Performance Liquid Chromatography

Liquid chromatography is quite similar to GC, except that the mobile phase is a
liquid instead of a gas. Pumps delivering thousands of pounds per square inch
push the mobile phase through columns of very fine particles. High-performance
liquid chromatography (HPLC) offers advantages of high speed, reusable
columns, automatic and continuous solvent addition, reproducible-programmed
gradients of solvents, automatic and continuous monitoring of the samples
eluted. As the chemicals separate, either a refractive index detector or a UV
absorption detector is used for identification. HPLC is primarily used when
samples contain components not volatile enough to be detected by GC (7).
Headspace (Purge and Trap)

This method is used when the volatile components to be analyzed are incorpor-
ated into a matrix of nonvolatile components. The volatile components are sep-
arated from the nonvolatile matrix by purging with helium, collecting this
“headspace” fraction of gas on Tenax traps followed by eluting the traps onto
the GC for analysis. This method can be employed to separate volatile materials
from both liquid and solid matrices, such as purging sunscreens from a plastic
packaging matrix (8).
Ion Chromatography
With the advent of the modern ion chromatographs, separations of highly ionic
compounds, such as salts, anions, cations, sugars, and phenols, has become
routine in instrumentation laboratories. The ion chromatographs use several
types of highly sophisticated detectors, such as the suppressed ion conductivity
and the pulsed amperometric detectors, which are especially suited for the
detection of ionic polar compounds (9).
IDENTIFICATION TECHNIQUES
After a satisfactory separation is achieved, the following identification methods
are employed. Most sunscreen chemicals are readily identified by chemical, chro-
matographic, and spectroscopic techniques that are used in research laboratories.
Chemical Methods
Various chemical tests can be extremely helpful in fully characterizing all the
components being investigated. Details of many of the procedures can be
found by consulting the many monographs on the subject. The procedures
include: alcohol analysis, ester, aldehyde or ketone content, acid value, saponifi-
cation number, analysis of phenols, derivative formation, and identification (10).
Chromatographic Methods
Gas Chromatography/Retention Time
GC is used as an identification technique. A wealth of information has been accu-
mulated that allows the identification of chemicals by using a relative retention
time (RT) library. Information is best when used on the state-of-the-art GC
capillary columns (12).
Gas Chromatography/Mass Spectrometry/Data System
The GC interface with the mass spectrometer (MS) data system (DS) is the
primary instrument involved in sunscreen identification. A capillary GC
column is employed to separate the components of the sample then detected
and analyzed by the mass spectrometer. The GC/MS data are automatically
stored in the data system computer. After the run is completed, the computer is
programmed to search for identifications in the MS library. Libraries are avail-
able or can be assembled that contain all available information on sunscreen
active chemicals.
High-Performance Liquid Chromatography/Retention Time
HPLC is generally a separation technique, but with an appropriate library it can
be an effective identification technique. Initially, a standard is run and the RT is
measured. Comparing its chromatogram with that of the standard allows for the
identification of the unknown compound.
Headspace/Gas Chromatography/Retention Time
The coupling of two separation techniques, namely, headspace (HS) and GC,
permits the analysis of complex matrices from which the volatiles are difficult
to extract for direct GC analysis. With the use of a retention index (RT) library
of chemicals, identification of sunscreens in normally difficult to analyze
products is readily accomplished.
Spectroscopic Methods
Spectroscopy is a branch of analytical chemistry devoted to the identification of
elements and the elucidation of atomic and molecular structure. This is
accomplished by measurement of the radiant energy absorbed or emitted by a
substance in any of the wavelengths of the electromagnetic spectrum in response
to excitation by an external energy source (11).
Mass Spectrometry
The mass spectrometer produces charged particles consisting of the parent ion and
ionic fragments of the original molecule and sorts these ions according to their
mass/charge ratio (10). The mass spectrum is a record of the number of different
kinds of ions; the relative numbers of each are characteristic for every compound,
including isomers. The main advantages of mass spectrometry as an analytical tech-

nique are its increased sensitivity over other analytical procedures and its specificity
in identifying unknowns or for confirming the presence of suspected compounds.
The excellent specificity results from characteristic fragmentation patterns, which
can give information about molecular weight and molecular structure. The
tandem technique of MS/MS offers further refinements and improvements in sen-
sitivity and specificity over conventional GC/MS. Also HPLC/MS has increased
the sophistication of the separation/identifying technique. Finally, the ratio of
the isotopes of carbon, C-12/C-13, can be accurately measured revealing subtle
differences as to the biological origin of material.
Infrared Spectroscopy
Infrared (IR) spectroscopy involves the twisting, bending, rotational, and
vibrational motions of atoms in a molecule (13). On interaction with IR radiation,
portions of the incident radiation are absorbed at particular wavelengths. The
multiplicity of vibrations occurring simultaneously produces a highly complex
absorption spectrum that is uniquely characteristic of the functional groups that
compose the molecule and the overall configuration of the atoms as well.
Routinely, chemicals can be separated and collected from cosmetic bases and
an IR spectral measurement is performed to assist in the identification of the
unknown. With the advent of the more, modern GC/FT-IR (Fourier transform)
instruments, separation of a complex mixture followed by rapid infrared analysis
can be accomplished in minutes with extremely small (nano- or milligram)
samples.
Ultraviolet Spectroscopy
Ultraviolet (UV) spectroscopy involves the absorption behavior of substances
and can be either qualitative or quantitative (14). The qualitative application of
absorption spectrometry depends on the fact that a given molecular species
absorbs light in a specific region of the spectrum indicative of that particular
sample. Such a display is called an absorption spectrum of that molecular
species, and serves as a fingerprint for identification purposes. The quantitative
application is for determining an unknown concentration of a given species.
The data derived from a UV spectrum include the lmax (maximum wavelength
of absorption), the extinction coefficient (1), and the K value.
Nuclear Magnetic Resonance Spectroscopy
Nuclear magnetic resonance (NMR) can be used to examine the environment of
the nuclei of the atoms that make up a molecule (15). A given nuclear environment
depends strongly on the nature of the chemical bonds that hold the atoms together
and is also dependent on the number of types of other atomic nuclei in the immedi-
ate vicinity. Proton or hydrogen magnetic resonance (PMR), is the most common
NMR technique. Other nuclei such as phosphorous and 13C NMR are also uti-
lized. In PMR experiments, the hydrogens in the molecule are “seen” and their
environment characterized. A powerful diagnosis of molecular structure can, there-

fore, be obtained from an NMR experiment. The coupling of this technique with
powerful computer manipulations (Fourier transform) permits the analysis of extre-
mely small quantities of chemicals. As the power of the magnets increases, these
days exceeding 600 MHz, the H/D ratios can be accurately measured revealing
extremely subtle differences as to the biological origin of materials.
The reader is referred to the procedures outlined in an earlier publication
for the identification of UV filters in complex cosmetic formulations utilizing
an HPLC and GC procedure (1).
IN VITRO SUN PROTECTION FACTOR ANALYZERS

In Vivo sun protection factor (SPF) testing on 20 subjects is a requirement for
the FDA’s Final Rule (16). UV spectroscopic analyses utilizing dilute solutions
in quartz cuvettes of sunscreen formulations suffer from deviations in the Beers –
Lambert law (17). They generally provide unreliable data but are currently used
to reveal trends for preliminary research purposes. Recently, In vitro SPF tests
have been developed to provide fast, inexpensive, and reliable data that correlate
reasonably well with current in vivo techniques on human subjects.
Diffey and Robinson (18) developed, in 1988, a procedure utilizing a
surgical tape from 3M Corp., called Transpore tape, as a substrate for in vitro
SPF measurements. This has now become the basis of a number of commercial
instruments, including the Optometrics (19), Lab sphere (20), and the CIBA (this
volume, chapter by Herzog) in vitro SPF analyzers. A number of improvements
have been proposed including the Vitro – skinw by Sottery (21) and the human
stratum corneum by Pearse and Edwards (22).
The instruments utilize a continuous UV –Vis source, color compensating
filters, diffusion plates, a grating monochromator, and a photomultiplier detector.
The quantity of UV-A and UV-B radiation transmitted from a 75-W xenon arc
lamp is transmitted through the substrate, with and without sunscreen applied,
and the monochromatic protection factor (MPF) is determined automatically
by recording photocurrent in 5-nm steps from 290 to 400 nm. Computer calcu-
lations are performed to determine the SPF, the UV-A/UV-B ratio as well as
the critical wavelength of a cosmetic formulation with ultraviolet filters.
Diffey, in 1994, proposed a critical wavelength of 370 nm for all formulations
with a significant level of broad-spectrum protection (23).
The in vitro SPF analyzers are most capable of analyzing the SPF and
critical wavelength as well as the photo stability of an ingredient or a cosmetic
formulation (this volume, chapter by Stanfield).
NEW ANALYTICAL TECHNIQUES

There are several specialized techniques that offer the analyst additional insights
into any analytical problem on hand. It is beyond the scope of this chapter to
describe the details of the procedures beyond the brief description below. The
reader, however, should consult the many excellent monographs cited in this
chapter.
The specialized chromatographic techniques can be subdivided into three
categories:
Use of special detectors in GC (24):

. Thermal conductivity (TC)
. Flame ionization detector (FID)
. Nitrogen phosphorus detector (NPD)
. Mass selective detector (MSD)
. Electron capture detector (ECD)
. Infrared detector (IR)
. Flame photometric detector (FPD)
. Halls detector.
Specialized detectors in HPLC and ion chromatography (25):
. Mass spectrometer detector
. Fluorescence detector
. Coulometric detector
. Suppressed conductivity detector
. Pulse amperometric detector.
Supplementary chromatographic techniques (5):
. Heart cutting
. Trapping
. Headspace—purge and trap
. Split –splitless techniques
. On-column injection
. Dual capillary channels
. New column technology
. Precolumn derivatization
. Postcolumn derivatization.
Recently, new advanced analytical techniques have been commercialized.

These include:
1. GC and GC/MS ancillary methods:
A. Fast GC
B. Racer GC system
C. Retention time locking
D. PTV inlet injection
E. Simplified 2-D GC
F. SPME
G. Gerstel twister and thermodesorption system (TDS)
H. Mass spectrometer—selective ion monitoring (SIM)
I. Atomic emission detector (AED)
2. HPLC ancillary methods

A. Fast HPLC
B. LC/MS (Electrospray LC)
3. Other methods
A. Supercritical fluid extractors (SFE)
B. Inductively coupled plasma (ICP)
C. X-ray photoelectron spectroscopy (XPS)
D. X-ray fluorescence spectroscopy (XRF) (Auger)
A brief description of each of these methods follows. The reader is encour-
aged to seek details of these procedures from equipment suppliers and specialized
references.
GC and GC/MS Ancillary Methods

Fast GC
Fast GC is now becoming the norm in the GC field due to the great advantages it
offers. Results can be obtained up to 10 times faster than the standard GC without
losing the accuracy and consistency compared to a traditional GC run. Savings on
operating cost is dramatic. There is less equipment to buy and maintain, therefore
maintenance can be done with fewer operators. GC analysts have more time to do
interpretation work and quicker results allow them more timely decisions. Other
operating cost savings includes the use of less carrier gas, less electricity, and less
expensive columns (26).
Fast GC analysis is achieved using small diameter and shorter columns, fast
oven temperature ramps, high inlet pressure, and the use of hydrogen as the
carrier gas.
GC Racer
GC racer is manufactured and patented by Restek and Zip Scientific (27). It is
mainly an auxiliary heating unit controlled by the GC to achieve a rapid oven
temperature programming. It offers similar advantages as the fast GC in a less
expensive way. With the GC racer unit, it will maintain a temperature program
rate of 708C/min up to 3508C, or a rate of 608C/min to temperatures as high
as 4508C.
Retention Time Locking

Retention time locking (RTL) is a GC software that electronically makes auto-
matic adjustments on the pneumatic pressure controls of the GC, locks a
method by making a single injection and enters the retention time locking com-
pound into the software to produce virtually identical chromatograms regardless
of the inlet, detector, operator, or location (26). Some of the benefits of RTL
are reproducible chromatograms, faster and very accurate identification of
compounds once a retention time library is developed, as well as fast and easy
comparison of results. It is excellent for routine GC analysis.
Programmable Temperature Vaporizing Inlet

Products such as sunscreen lotions contain minor volatile compounds in this
complex matrix. Identification of the volatile compounds generally requires
sample preparation and extraction by solvents. Concentration of the extract is
often required to detect and quantify the ingredients of importance. A gas chro-
matograph with programmable temperature vaporizing (PTV) inlet eliminates
these time consuming and costly steps. PTV allows you to inject large volume
injection of the solvent diluted complex sample to detect analytes at parts per
billion or even parts per trillion levels. Other significant advantages of PTV injec-
tion over conventional split –splitless or on-column injection are as follows.
(a) Avoiding evaporation from the syringe needle, eliminates an important
source of discrimination of higher boiling components. (b) Nonvolatiles from
the sample injected are retained in the vaporization chamber. This avoids a poss-
ible degradation of the column performance due to by-product accumulation (26).
Simplified 2-D GC
This is a GC separation technique which is a simplified Deans switch heart-
cutting device for the analysis of complex samples. Peaks of interest from one
column are “cut” onto another column having a different stationary phase. As
a result, compounds that might co-elute with analytes on the first column are
separated from analytes on the second column (26).
Solid Phase Microextraction

Solid phase microextraction (SPME) is an alternative to liquid – liquid extraction
or Soxhlet extraction. It has become the technique of choice for separating and
concentrating complex matrices in the laboratory. SPME is currently used in a
wide variety of applications in the food and flavor, fragrance, environmental,
sunscreen, pharmaceutical, and clinical industry.
In SPME a fused silica fibre, coated with a stationary phase is immersed
into the sample solution for several minutes. The analytes adsorb onto the station-
ary phase, which is subsequently pushed into a hot GC injector to rapidly desorb
the sample for separation and analysis.
SPME is a sample preparation and introduction method in which analytes
partition from the sample into a polymer, coated on a fused silica rod of typically
1 cm length by 100 nm diameter. The fiber is fastened into the end of a fine
stainless steel tube contained in a syringe-like device, and protected by an
outer stainless steel needle. The device’s plunger is depressed to expose the
fiber to the sample matrix, retracted at the end of the sampling time, and then
depressed again to expose the fiber to a desorption interface for analysis, typically
by GC or HPLC (28).
Gerstel Twister and Thermodesorption

The Gerstel twister is a small magnetic stir bar coated with polydimethylsiloxane
(PDMS), which is used to analyze organic constituents from aqueous matrices by
GC without sample preparation. This technique is also called stir bar sorptive
extraction or SBSE. Twister practically came from the SPME technology,
therefore it has similar advantages such as total reduction of time, solvents,
costly preparation steps, ease of use and lower detection limits. However, it
has a sensitivity of up to 1000 times more than SPME (29). The twister is
dropped in the aqueous mixture and stirred using a common magnetic stir
plate for a short period of time. While stirring, the PDMS coating absorbs
the organic constituents. The stir bar can then be soaked in a small amount of
extraction solvent such as methylene chloride to extract the analytes or can be
directly transferred to a thermodesorption system (TDS).
The TDS is a unit mounted directly to the GC and it is used to trap volatile
and semivolatile substances on an adsorbent and for direct thermal extraction of
volatile constituents from solids without sample preparation (30).
Mass Spectrometer—Selective Ion Monitoring

A quadruple mass filter can be operated in a scan mode or select ion monitoring
(SIM) mode. SIM sets the mass selective detector to repeatedly scan a few
selected ions rather than the full range spectrum (scan mode, 40 to 500 amu).
This provides the greatest sensitivity and is used for quantitative applications.
The analyst has to have a prior knowledge of what ions to expect to use this
method. With this procedure, components in the parts per billion concentration
range may be detected and quantified.
Atomic Emission Detector

Atomic emission detector (AED) is one of the newest additions to the gas chro-
matographer’s analytical tools. This detector is more expensive than other GC
detectors but it is a very powerful alternative.
The AED detects nearly all elements within any volatized compound at
very low sensitivities (picogram level). It also has a much wider applicability
because it is based on the detection of atomic emissions. The strength of the
AED lies in the detector’s ability to simultaneously determine the atomic emis-
sions of many of the elements in analytes that elute from a GC capillary column.
As the eluants come off the capillary column, they are fed into a microwave
powered plasma (or discharge) cavity where the compounds are destroyed and
atoms are excited by the energy of the plasma. The light that is emitted by the
excited particles is separated into individual lines via a photodiode array detector.
The associated computer then sorts out the individual emission lines and can
produce chromatograms made up of peaks from eluants that contain only a
specific element (31).
HPLC Ancillary Methods

Fast HPLC
Fast HPLC has very similar technical and cost savings advantages as fast GC. It
has a setup that typically uses shorter columns with smaller particle size packing
and the highest flow rate possible. In addition to length, column inner diameter is
the other variable to consider. Optimizing fast separations requires an under-
standing of the interrelationships of these variables and the compromises
involved.
Liquid Chromatography/Mass Spectrometry
An LC/MS is an HPLC system with a mass spectrometer detector. The HPLC
separates chemicals by conventional liquid chromatography on a column.
Usually the method will be reverse phase chromatography, were the metabolite
binds to the column by hydrophobic interactions in the presence of a hydrophilic
solvent (e.g., water) and is diluted off by a more hydrophobic solvent (methanol
or acetonitrile). As the metabolites appear from the end of the column they enter
the mass detector, where the solvent is removed and the metabolites are ionized.
The metabolites must be ionized because the detector can only work with ions,
not neutral molecules. Ions only fly through very good vacuum, so removal of
the solvent is a vital first step. The mass detector then scans the molecules it
sees by mass and produces a full high-resolution spectrum, separating all ions
that have different masses (32).
Other Methods
Supercritical Fluid Extraction
Supercritical fluid extraction (SFE) is used to extract organics from samples using
carbon dioxide (CO2) as the extracting solvent. It extracts the analytes faster and
is more environmentally friendly than typical organic solvents. Another major
advantage in using supercritical carbon dioxide fluid extraction is that a small
reduction in temperature, or slightly larger reduction in pressure, will result in
almost all the solute precipitating out as the supercritical conditions are
changed or made subcritical (33). This allows for more efficient separations
and extraction of component from complex matrices. Supercritical fluids can
produce a product with no solvent residues.
Inductively Coupled Plasma
This is a more advanced technique than atomic absorption spectroscopy and is
used to determine the elemental compositions (Zn/Ti) in sunscreen compo-
sitions. An inductively coupled plasma (ICP) works by injecting a mist from a
liquid into the center of an Argon plasma. A plasma is created from a flow of
gas within a high-energy field, which ionizes the gas and causes intense
heating. When the mist of the sample enters the plasma, the intense heat
causes the dissociation of most chemical compounds, and the energy that the
component atoms absorb causes them to undergo excitation and ionization
energy transitions. These transitions produce spectral emissions characteristic
of the elements being excited. The spectra produced by the plasma is broken
down into individual spectral lines by the ICP’s spectrometer, and the ICP’s com-
puter translates the spectral lines into concentrations for a specified suite of
elements (34).
X-Ray Photoelectron Spectroscopy
This is a surface-sensitive chemical analysis technique that provides straight-
forward data interpretation and chemical bonding information. This can also
be used in the elemental analysis (Zn/Ti) of sunscreen formulations (35).
X-Ray Fluorescence Spectroscopy (Auger Electron)
This highly advanced technique is used to measure the elemental composition of
sunscreen preparations containing inorganic particulates (Zn/Ti). When a
primary X-ray excitation source from an X-ray tube or radioactive source strikes
a sample, the X-ray can either be absorbed by the atom or scattered through the
material. The process in which an X-ray is absorbed by the atom by transferring
all of its energy to an innermost electron is called the “photoelectric effect.”
During this process, if the primary X-ray had sufficient energy, electrons are
ejected from the inner shells, creating vacancies. These vacancies present an
unstable condition for the atom. As the atom returns to its stable condition, electrons
from the outer shells are transferred to the inner shells and in the process give off a
characteristic X-ray whose energy is the difference between the two binding ener-
gies of the corresponding shells. Because each element has a unique set of energy
levels, each element produces X-rays at a unique set of energies, allowing one to
non destructively measure the elemental composition of a sample. The process of
emissions of characteristic X-rays is called “X-ray fluorescence,” or XRF. Analysis
using XRF is called “X-ray fluorescence spectroscopy.” In most cases, the inner-
most K and L shells are involved in XRF detection. A typical X-ray spectrum
from an irradiating sample will display multiple peaks of different intensities.
Depending on the application, XRF can be produced by using not only
X-rays, but also other primary excitation sources like alpha particles, protons,
or high-energy electron beams. Sometimes, as the atom returns to its stable
condition, instead of emitting a characteristic X-ray it transfers the excitation
energy directly to one of the outer electrons, causing it to be ejected from the
atom. The ejected electron is called an “Auger” electron. This process is a
competing process to XRF (36).
CONCLUSIONS
The improvements made to the standard chromatographic and spectrophoto-
metric techniques utilized in the sunscreen industry have been outstanding.
Advanced instrumental techniques today have become routine, inexpensive, fast,

and reliable. Trace components in the parts per million or even the parts per
billion level can now be identified as tell-tale signs of the purity of formulations.
Complex mixtures can be isolated more efficiently by SPME and Gerstel twister
techniques allowing for a more accurate identification and quantitation of the
sunscreen active ingredients.
With the rapid expansion of the new inorganic and organic particulates into
the sunscreen formulations of today, more reliable analytical tools need to be
investigated and developed. In addition to the standard atomic absorption tech-
niques for the identification of inorganic elements, we have presented a
number of novel and advanced methods for the accurate assay of these UV par-
ticulates. These methods, which include ICP, XPS, AED, and XRF techniques,
will hopefully be developed into fast, reliable, and inexpensive methods for the
successful assay of future cosmetic formulations with particulate sunscreen
filters.
Modern analytical advanced instrumentation has kept pace with the recent
developments and growth of the sun care industry. Their use bodes well for the
introduction of more sophisticated and efficient cosmetic formulations that are
sorely needed to stem the rise in skin cancer incidence observed today.
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31. www.shsu.edu/chemistry/AED/AED.html
32. http://www.jic.bbsrc.ac.uk/SERVICES/metabolomics/lcms/why.htm
33. http://www.faqs.org/faqs/sci/chem-faq/part5/section-5.html
34. http://ral.coafes.umn.edu/icp.htm
35. http://www.analytical.org/xps2.html
36. http://www.amptek.com/xrf.html
Analytical Testing Procedures
38
US FDA Protocol for Determining
Sun Protection Factor
Toni F. Miller
Essex Testing Clinic, Verona, New Jersey, USA
Background of FDA Sunscreen Guidelines 770

Sun Protection Factor Determination (64 FR 27666) 770
Light Source: Solar Simulators 770
Standard Sunscreen 770
Testing Procedure 771
Selection of Panel Subjects 771
Informed Consent 771
Skin Test Sites 771
Application of Test Materials 772
Evaluation of Response 772
Determination of the MED for Unprotected Skin 772
Rejection of Test Data 772
Determination of the SPF Value 773
Determination of Individual Subject SPF Values 773
Determination of the Test Product’s SPF Value and Product
Category Designation 773
Determination of a Water Resistant or Very Water Resistant
Product 774
Test Modifications 775
US vs. the International SPF Testing Method 775
References 778
769
770 Miller
BACKGROUND OF FDA SUNSCREEN GUIDELINES

The US Food and Drug Administration (FDA) published the “Final” Monograph
(1) for sunscreen drug products for over-the-counter human use on May 21, 1999
(64 FR 27666). This Monograph outlined the testing requirements for deter-
mining a sun protection factor (SPF) for product labeling. On December 31,
2001 (66 FR 67485) (2) FDA issued a partial stay to 21 CFR Part 352, including
Subpart D—Testing Procedures, the part of the Monograph that outlines the
testing requirements for establishment of an SPF value.
The anticipated new effective date for FDA’s issuance of the SPF test-
ing methodology is 2005 or later. The FDA has proposed that the amended
Part 352 will address formulation, labeling, and testing requirements for both
ultraviolet-A (UV-A) and ultraviolet-B (UV-B) radiation protection.
Given this regulatory situation, the most recently proposed testing
protocols for SPF determination (64 FD 27666) will be addressed, with the
knowledge, that these may change when the final monograph is indeed issued.
SUN PROTECTION FACTOR DETERMINATION (64 FR 27666)

The sun protection factor is defined as:
Minimal erythema dose on protected skin
SPF value ¼
Minimal erythema dose on unprotected skin
The minimal erythema dose (MED) is defined as the quantity of erythema-
effective energy (expressed as joules per square meter) required to produce
the first perceptible, redness reaction with clearly defined borders.
Light Source: Solar Simulators

The solar simulator used for SPF determination must provide:
. Continuous emission spectrum from 290 to 400 nm similar to sunlight
at sea level with the sun at a zenith angle of 108.
. Less than 1% total energy output from wavelengths shorter than 290 nm.
. Not more than 5% of total energy output from wavelengths longer than
400 nm.
. No significant time-related fluctuations in output after an appropriate
warmup time.
. Beam uniformity within 10%.
. Output measured periodically with a calibrated spectroradiometer or
equivalent instrument.
Standard Sunscreen
The standard sunscreen will be an 8% homosalate preparation with a mean SPF
value of 4.47 (S.D. + 1.279). The 95% confidence interval for the mean SPF
US FDA Protocol for Determining SPF 771
must contain the value 4. Directions for the preparation of the standard appear in
the Final Rule (1) and in Steinberg’s chapter.
Testing Procedure
Selection of Panel Subjects
Not more than 25 subjects will be chosen to participate on a panel. The number
of subjects will be fixed in advance by the study investigator. From this panel, at
least 20 subjects must produce valid data for analysis.
Only fair-skin male and female subjects with skin types I, II, and III may be
used. Skin type is defined by the response of an individual to the first 30 – 45 min
of sun exposure after a winter season of no sun exposure:
Type I Always burns easily; never tans (sensitive)
Type II Always burns easily; tans mimimally (sensitive)
Type III Burns moderately; tans gradually (light brown) (normal)
Type IV Burns minimally; always tans well (moderate brown)
(normal)
Type V Never burns; deeply pigmented (insensitive).
The subjects should be in general good health, especially for any skin con-
ditions; should not be taking any medications (topical or systemic) that are known
to produce abnormal sunlight response; and should not have any history or known
abnormal sunlight responses such as phototoxic or photoallergic reactions.
Subjects should be examined for physical indications of the presence of
sunburn, suntan, scars, active dermal lesions, and uneven skin tones on the
areas of the back proposed for test sites. The presence of nevi, blemishes, or
moles may be acceptable if in the physician’s judgment they will not interfere
with the study results. If an individual has excess hair, clipping or shaving
may have to be undertaken to provide for an acceptable test site.
Informed Consent
Legally effective written informed consent is required for all test subjects.
Skin Test Sites
The skin test site area used for MED determination shall be:
. Located on the back between the beltline and the shoulder blade and
lateral to the midline.
. A minimum of 50 cm2 in area (e.g., 5 cm 10 cm), outlined with ink,
drawn with the subject in the test position, for example, upright or supine.
Each skin site area shall be:
. Divided into at least three test subsite areas that are at least 1 cm2.
Usually four or five subsites are used for each test.
772 Miller
Application of Test Materials

Both the test sunscreen product(s) and the standard suncreen shall be applied as:
. Two milligrams per square centimeter
. Spread using a finger cot
. Applied in a blinded, randomized manner
. A period of at least 15 min is required after application and before UV
exposure
. If only one sunscreen drug product is being tested, UV radiation doses
will be applied in a randomized manner.
Evaluation of Response
The evaluator must be a different person than the person who applied the test
products or administered the UV radiation.
The following evaluations must be recorded:
. All immediate responses (e.g., an immediate darkening or tanning;
immediate reddening; immediate heat response such as a heat rash).
. The smallest dose that produces erythema reaching the borders of the
exposure site at 22 – 24 h after UV exposure.
Erythema response should be evaluated with:
. Either a tungsten light bulb or a warm white fluorescent light bulb
that provides a level of illumination at the test site within the range
of 450 –550 lux.
. Subjects positioned similarly to when the test site was irradiated.
The goal of the exposure evaluation is to observe some exposures that produce
absolutely no effect, and some exposures that produce an effect, with the maximal
exposure being no more than twice the total energy of the minimal exposure.
Determination of the MED for Unprotected Skin
. The MED for unprotected skin is determined by administering a
geometric series of five exposures represented by (1.25)n for
example, 6, 8, 10, 13, and 16 s.
. Usually a preliminary MED series is administered on the day before
the SPF test and the result determines the doses administered to
unprotected and sunscreen-protected skin which are used to calculate
the SPF.
Rejection of Test Data

The following reasons warrant rejection of the test data:
. An MED response is not elicited on either the treated or unprotected
treated skin sites.
. The responses on the treated test sites are randomly absent (indicating
that the test substance was not spread evenly).
. The subject(s) were noncompliant (e.g., the subject withdrew from the
test due to illness or work conflicts, or the subject did not shield the
exposed testing sites from further UV radiation until the MED was
read).
Determination of the SPF Value

The erythema action spectrum used to calculate the erythema effective exposure
of a solar simulator are:
Vi (l) ¼ 1:0 (250 , l , 298 nm)
Vi (l) ¼ 1:00:094(298l) (298 , l , 328 nm)
Vi (l) ¼ 1:00:015(139l) (328 , l , 400 nm):
Determination of Individual Subject SPF Values

. A series of seven doses is administered to the sunscreen-protected sites.
Doses will be determined by the preliminary MED and the expected
SPF of the product.
. For products with an expected SPF ,8, the exposures will be the
preliminary MED of unprotected skin times: 0.64X, 0.80X, 0.90X,
1.00X, 1.10X, 1.25X, and 1.56X, where X equals the expected SPF of
the test product.
. For products with an expected SPF between 8 and 15, the exposures
will be the MED of unprotected skin times: 0.69X, 0.83X, 0.91X,
1.00X, 1.09X, 1.20X, and 1.44X, where X equals the expected SPF of
the test product.
. For products with an expected SPF .15, the exposures will be the
MED of unprotected skin times: 0.76X, 0.87X, 0.93X, 1.00X, 1.07X,
1.15X, and 1.32X, where X equals the expected SPF.
. The SPF value of the test sunscreen is then calculated as the ratio
of the MED of sunscreen-protected skin to the MED of unprotected
skin.
Determination of the Test Product’s SPF Value and Product

Category Designation
. Use SPF values from at least 20 test subjects.
. Compute the SPF value for each subject.
. Compute the mean SPF value, x, and the standard deviation, s.
. Find the upper 5% point from the t distribution table with n21 degrees
of freedom (this is “t”).
p
. Compute A ¼ ts/ n
774 Miller
. The label SPF equals the largest whole number less than (x 2 A).
(Typically, a product with a mean SPF of 15 would be labeled 13, by
this approach).
. Determine the Product Category designation according to the following
chart:
Product category
Mean SPF value Label SPF value designation
X , (2 þ A) ,2 Not a sunscreen
(2 þ A) , X , (12 þ A) 2 – 11 Minimal
(12 þ A) , X , (30 þ A) 12 – 30 Moderate
X . (30 þ A) 30(plus/þ) High
Determination of a Water Resistant or Very Water Resistant Product

The general testing procedure used for SPF testing is used except modified in the
following way:
. An indoor pool, whirlpool, or jacuzzi maintained at 23– 328C is used
during the testing procedure. The pool and air temperature and the
relative humidity are recorded.
For a water-resistant claim, the label SPF shall be the label SPF value
determined after 40 min of water immersion according to the following
procedure:
. Apply the sunscreen test product (followed by the waiting period
indicated on the product labeling).
. Subjects maintain a moderate activity in the water for 20 min.
. Subjects maintain a 20-min rest period (without towel drying the test sites).
. Subjects maintain moderate activity in the water for 20 min.
. Air dry test sites without toweling.
. Conduct solar simulator exposure to test site areas.
For a very water resistant claim, the label SPF shall be the label SPF value
determined after 80 min of water immersion according to the following
procedure:
. Apply the sunscreen test product (followed by the waiting period
indicated on the product labeling).
. Allow a 20-min rest period (without towel drying the test sites).
. Subjects maintain moderate activity in the water for 20 min.
. Air dry test sites without toweling.

. Conduct solar simulator exposure to test site areas.
Test Modifications
The US FDA allows alternative testing methods (including automated or in vitro
procedures) if a formulation or mode of administration of certain products
requires testing methodology modification. Any proposed modification or
alternative procedure must be submitted to the US FDA as a petition that contains
data supporting the modification or data demonstrating that the alternative
procedure provides results of equivalent accuracy.
US VS . THE INTERNATIONAL SPF TESTING METHOD

Several countries have SPF determination methods that vary from the USA. An
effort to “harmonize” several of these methods was undertaken by The European
Cosmetic Toiletry and Perfumery Association, the Cosmetic Toiletry &
Fragrance Association of South Africa, and the Japan Cosmetic Industry Associ-
ation (3). This International testing guideline was issued in 2003. It should be
noted that the JCIA has a revised SPF Test Method for SPF determination of
products with expected SPFs .30 that is not discussed here. A comparison of
the major parameters of the US and International SPF testing methodologies is
presented.
International Sun Protection

US (21 CFR Part 352) Factor (SPF)
Parameter (1999) Test Method (2003)
1. Selection of test Medical history of general Recommended interview
subjects good health without any by health professional;
abnormal responses to no sun exposure for at
sunlight. Test site free least 4 weeks prior to
of any interfering skin testing
conditions.
2. Exclusion criteria – Recommended interview
by health professional;
no sun exposure for at
least 4 weeks prior to
testing
3. Skin phototypes I, II, III I, II, III
4. Test area Back between scapulae Back (between scapulae
and lateral to midline line and waist)
5. Age limitation – No children
6. Frequency interval – Not less than 2 months
between tests between tests and the
site is clear
776 Miller

7. Number of test Not more than 25 subjects 10 – 20 subjects (10
subjects with the number fixed in subjects sufficient if
advance (at least 20 95% CI of the mean is
subjects must produce within +17% of the
valid data) mean; if not, subjects
are increased until
met; if not met
after 20 of 25, test
is rejected)
8. Reference standard 8% HMS (An SPF 15 Low SPF standard High
control formulation SPF standard (if high
has been proposed and SPF standard is used,
may be adopted in the no need to include
next monograph low SPF standard)
publication)
9. Acceptance limits for SPF value of 4.47 + 2 . SPF . 20
standard 1.279 and the 95% Choose P1 DIN
CI must contain 4 low or HS (SPF ¼ 4)
or P2 (SPF ¼ 12)
or P3 (SPF ¼ 15)
If SPF .30 use P3
(SPF ¼ 15)
10. Quantity applied 2 mg/cm2 2 mg/cm2 + 2.5%
(balance sensitivity at
least 0.0001 g)
11. Mode of delivery Volumetrically Syringe/pipette or other
quantified means with
spreading time of
20 – 50 s.
12. Test site (subsite) At least 1 cm2 0.5 cm2
13. Drying time after At least 15 min before 15 – 30 min
application exposure
14. Solar simulator Specific type not Xenon arc simulator
specified
15. Solar simulator Periodically with a Once a year and when
monitoring calibrated physical component
spectroradiometer or is changed; Before
equivalent instrument each UV site exposure,
UV shall be checked
with a radiometer.
16. UV quality Continuous emission ,290 must not exceed 0.1%
spectrum from 290 to 290 – 310 ¼ 49 – 65%
400 nm similar to 290 – 320 ¼ 85 – 90%

sunlight at sea level with 290 – 330 ¼ 91.5 – 95.5%
the sun at a zenith angle 290 – 340 ¼ 94 – 97%
of 108 ,1% total energy 290 – 350 ¼ 95.5 – 98.5%
output ,290 nm. ,5% 290 – 400 ¼ 100%
total energy output and total UVA II
.400 nm. No significant (320 – 340) must equal
time-related fluctuations or exceed 20% of total
in output after an UV (290 – 400 nm) and
appropriate warm-up time. UVA I (340 –400 nm)
Beam uniformity +10%. must equal or exceed
60%of the total UV
17. Number of exposure 5 for Control; 5
sites 7 for Test Product
18. Progression SPF , 8 ¼ MED x 0.64X, 1.12 or 1.25 (1.12 if
of doses 0.80X, 0.90X, 1.00X, expected SPF is .25)
1.10X, 1.25X, 1.56X
SPF ¼ 8 –15 ¼ MED x
0.69X, 0.83X, 0.91X,
1.00X, 1.09X, 1.2X, 1.44X
SPF . 15 ¼ MED x
0.76X, 0.87X, 0.93X,
1.00X, 1.07X, 1.15X,
1.32X
19. Exposure site size At least 50 cm2 Minimum 30 cm2 to
maximum 60 cm2
20. Skin response First perceptible Minimum erythema
unambiguous with defined borders
redness reaction
with clearly
defined borders
21. Observation time post Immediate and 16 – 24 h after exposure
exposure 22– 24 h after
exposure
22. MED determi- Blind Blind; simultaneous
nation MEDu and MEDp
23. Individual test See Section B.10 95% CI with 17% of
response mean SPF or
SEM 7.5%(n ¼ 10)
24. SPF definition for See Section B.11 Arithmetical mean x of
labeling purposes SPFi; lower integral
number
778 Miller

25. Rejection Criteria No erythemal response No erythemal response on
on all subsites all subsites
Erythemal response Erythemal response absent
absent within an within an exposure series
exposure series All subsites show an
Subject noncompliant erythemal response
(If data on five subjects
rejected, test is rejected)
REFERENCES
1. Sunscreen drug products for over-the-counter human use. Final Monograph. Fed Reg
1999; 64:27666.
2. Sunscreen drug products for over-the-counter human use. Final Monograph Partial Stay
Final Rule. Fed Reg 2001; 66:67485.
3. International Sun Protection Factor (SPF) Test Method. Cosmetic, Toiletry &
Fragrance Association of South Africa, The European Cosmetic Toiletry and
Perfumery Association (Colipa), and Japan Cosmetic Industry Association. February
2003.
39
SPF Testing in Europe
The International SPF Test Method
Mike Brown
The Boots Company plc, Nottingham, UK
Introduction 779
The International SPF Test Method 782
The UV Light Source 784
Volunteer Selection 790
Product Application Procedure 791
Use of Standard Products 792
UV Exposure Procedure 793
Minimum Erythemal Dose Definition and Determination 794
SPF Calculation and Statistical Acceptance/Rejection Criteria 795
Comparison of the International SPF Test
Method and the US FDA SPF Method 798
SPF Labeling Guidelines 798
Water Resistance Testing and UV-A Measurement 803
Acknowledgments 805
References 805
INTRODUCTION
Sun products have been a way of life for many years with some leading brands
dating back as far as the 1940s, 1930s, or even the 1920s. However, products
779
780 Brown
from this era provided somewhat limited sunburn protection and were rarely
labeled with any reliable measure of their protective efficacy.
The first attempts to realistically describe the protective performance of a
sunscreen were made by Ellinger in 1934 (1). Ellinger described an ultraviolet-
protective quotient system, which decreased in value as protection increased.
However, the system was not particularly attractive as a marketing tool for
suncare products since lower performing products achieved higher quotient
values. Ellinger’s “inverted” quotient was not revised until 1956 when
Rudolf Schulze described a method for determining the level of protection pro-
vided by a sun product (2). The “Schulze” method, as it became known, described
a sunscreen’s protection level simply by using the reciprocal of Ellinger’s
quotient.
The Schulze method was the test method of choice for many European pro-
ducts for several years, but it was not until 1974 that the term “sun protection
factor ” (SPF) was first introduced by Greiter (3) to describe the outcome of
this testing. What is more, it was not until 1977 – 1978 that a SPF number first
appeared on a bottle of a European brand (Piz Buin) of suncare products.
Greiter’s new SPF rating was simply an alternative application of the method
of Schulze but it has since become both widely used and universally recognised
as the measure of a sunscreen product’s ability to prevent sunburn.
The universal adoption of Greiter’s SPF measure was quickly followed by a
plethora of attempts to standardise the test procedure. The resulting glut of test
methods lead to the situation where SPF numbers in some countries were often
significantly different from SPF numbers in other countries, despite the fact
that the SPF test was theoretically the same worldwide. Table 39.1 shows a
chronological history of worldwide SPF test methodologies and their subsequent
revisions which evolved between the 1970s and the present day.
Many European countries initially conducted SPF testing according to the
Deutsches Institut für Normung (DIN) method first published in 1985 (4). This
method differed in many significant ways from the established test method
described in the US FDA’s proposed sunscreen monograph, previously published
in 1978 (5). A major difference between the two methods was the amount of test
product applied to the skin. The DIN method specified an application rate of
1.5 mg/cm2 whilst the FDA method required application at 2.0 mg/cm2. This
fundamental procedural difference inevitably gave rise to large differences in
the measured SPF. In addition to this, the two methods used quite different
sources of artificial sunlight (solar simulator), which again had a significant
impact on the SPF measured and consequently the SPF labeled.
Because of the incompatibility between the German (DIN) SPF method and
that of the US FDA, many Europeans “defected” to the FDA SPF test method,
whilst others continued to follow the DIN method. This created an untenable situ-
ation in Europe and so the European Trade Association for the Cosmetics and
Toiletries Industry (COLIPA) decided to develop a common SPF guideline for
all European Union countries. The resulting 1994 COLIPA SPF test method (6)
SPF Testing in Europe 781
Table 39.1 A Chronological History of Major Worldwide Methodologies for Sun

Protection Factor (SPF) Testing
Year Issuing authority Territory
1978 Food and Drug Administration (FDA) USA

1983 Standards Association of Australia (SAA) Australia
1985 Deutsches Institut für Normung (DIN) Germany
1986 Standards Association of Australia Australia
(SAA) (revised)
1991 Commission Internationale De L’Eclairage (CIE) International
1992 Japanese Cosmetic Industry Association (JCIA) Japan
1992 South African Bureau of Standards (SABS) South Africa
1993 Food and Drug Administration (FDA) (revised) USA
1993 Standards Association of Australia (SAA) (revised) Australia
1994 The European Cosmetic and Toiletries Europe
Trade Association (COLIPA)
1996 Deutsches Institut für Normung (DIN) (revised) Germany
1997 Standards Australia/Standards New Zealand Australia and
(AS/NZS) (revised) New Zealand
1998 Korean Pharmaceutical Affairs Committee Korea
1998 Standards Australia/Standards New Zealand Australia and
(AS/NZS) (revised) New Zealand
1999 Ó´ Norm Austria
1999 Japanese Cosmetic Industry Association Japan
(JCIA) (revised)
1999 Food and Drug Administration (FDA) (revised) USA
2002 South African Bureau of Standards South Africa
(SABS) (revised)
2003 COLIPA/JCIA/SABS—International Method South Africa, Japan,
and Europe
introduced many revisions to the procedures in common use in Europe in order to

“move closer” to the newly revised sunscreen tentative final monograph pub-
lished by the FDA in 1993 (7). The method also proposed a number of advance-
ments and improvements in the test procedure, which were to become standard
practice throughout Europe for nearly a decade.
However, even after careful design, the 1994 COLIPA SPF test method still
differed sufficiently from other national SPF test methods (specifically the 1993
US FDA tentative final monograph and the various revisions to the Standards
Australia/Standards New Zealand SPF Test Method). Consequently, European
SPF numbers were still not completely comparable with SPF numbers in other
major international markets.
The first steps to address this international incompatibility have now been
taken. The European SPF Test Method (1994 COLIPA method) has been comple-
tely revised and harmonized with the Japanese Cosmetic Industry Association
782 Brown
(JCIA) SPF Method (8) and the South African Bureau of Standards (SABS) SPF
Method (9). The result is a new and improved international SPF test method,
which is considerably more compatible with both the final (1999) FDA Sunscreen
Monograph (10) and the most recent Standards Australia/Standards New
Zealand (AS/NZS) SPF Test Method (11).
THE INTERNATIONAL SPF TEST METHOD

The International SPF Test Method is now the method of choice throughout
Europe. In the UK in particular, there is a growing expectation amongst law enfor-
cement authorities that sunscreen products should be labeled according to the
“European” method. One of the main objectives of the new method was to help
facilitate an eventual complete harmonization with other national SPF methods
and so it was designed to be as similar as possible to the US FDA sunscreen mono-
graph. As a consequence, it should now be possible to conduct a single SPF test that
would satisfy not only local requirements for SPF testing (e.g. FDA monograph
requirements in the USA) but also the requirements of Europe, Japan, and South
Africa as laid out in The International SPF Test Method.
The International SPF Test Method has all the main elements of other SPF
test methods throughout the world. The procedure requires that the skin of a
number of human volunteers be exposed to increasing doses of sunlight simulated
ultraviolet radiation, sufficient to elicit minimal erythemal (redness) responses
when observed between 16 and 24 h after exposure. For each individual volun-
teer, a SPF is determined as the ratio of the dose of sunlight simulated ultraviolet
(UV) radiation required to produce the first (minimal) erythemal reaction in skin
protected by sunscreen product, to the dose of sunlight simulated UV radiation
required to produce the first (minimal) erythemal reaction in unprotected skin.
The test product’s SPF is then simply the mean of all individual SPFs measured.
The general outline of the test is as follows:
The SPF test begins with the selection of a panel of suitable human volun-
teers previously screened against medical, photobiological, and physical exclu-
sion criteria. Investigative work by the European, Japanese, and South African
cosmetic and toiletries industry associations (COLIPA, JCIA, and CTFA-SA)
suggested that different SPF numbers might be measured on the skin of volun-
teers with different levels of underlying pigmentation. Fitzpatrick has previously
described six generic “skin types” based on natural genotypic pigmentation levels
(12). The higher the level of natural skin pigmentation, the more likely this is to
interfere with the SPF test. Consequently volunteer selection is restricted to pale
skin types (Fitzpatrick types I –III).
A minimum of ten and up to a maximum of 20 volunteers of skin types
I– III must complete the study with valid data. The proportions of skin types I,
II, and III should reflect a “normal” population to avoid any possible bias
toward higher SPF which is thought may occur with lower skin types. Each
volunteer is then subjected to the same procedure.
UV light from an artificial source of sunlight simulated ultraviolet radiation

is directed onto a number of unprotected 1 cm square sites on the volunteer’s back.
Both the quality and the intensity of the source of UV light are critical to the accu-
rate measurement of SPF and so these are strictly defined in the International SPF
Test Method. Each individual 1 cm square receives an incrementally larger dose
of UV light than the previous square, such that a progression of increasing UV
exposures is achieved. The intensity of the UV source is usually some 20–50
times the intensity of natural sunlight ultraviolet light, so exposure times are typi-
cally within the range of 20 s to 3 min depending on choice of light source. Since
UV-induced erythema is a dose-dependent response (13) and not flux dependent
(within certain practical limits) the exact UV intensity of the light source is not
normally critical, however a close match to “natural” sunlight spectrum is crucial.
The starting dose for the series of irradiation exposures is defined by the volunteer’s
“Fitzpatrick” skin type, their previous exposure history or colorimetric measure-
ment of their resting level of pigmentation.
Sixteen to twenty-four hours after exposure to the incremental doses of
simulated sunlight, each of the irradiated sites is visually assessed in order
to determine the exposure dose (joules/m2) that initiated the first perceptible,
unambiguous erythema with defined borders appearing over most of the field
of exposure. This dose, known as the minimum erythemal dose (MED) acts as
reference for the individual’s sensitivity to UV light (in unprotected skin). It
will be unique for that individual and a function of their skin type and genotype.
Having determined the MED for unprotected skin (MEDu ), sun product is
applied at the precise application rate of 2.0 mg/cm2 to an adjacent area of the
same volunteer’s back. Product application is a major potential source of variability
in SPF measurement and so many parameters in the product application procedure
are very precisely defined and controlled in the International SPF Test Method.
After application, the product is left to dry for a minimum of 15 min and a
maximum of 30 min. Once the product has dried, UV light from the solar
simulator is again directed onto a series of at least five 1 cm2 areas of product-
protected skin. As with the unprotected exposures, an incremental progression
in UV dose is delivered so that a second series of UV exposure doses is achieved.
However, these doses will be considerably greater than those delivered to unpro-
tected skin since the skin should now be protected from burning by the applied
sunscreen product. The exact doses delivered are dependent on the previously
measured MEDu and the expected SPF of the test product. For example, an
SPF10 product should protect the skin 10-fold from UV-induced erythema and
so the middle dose in the protected skin incremental exposure series is typically
10 times the unprotected MED.
Sixteen to twenty-four hours after irradiation of the product-protected skin,
each exposure site is visually assessed for erythemal response in the same manner
as the unprotected MED. The dose of UV light, which initiated the first per-
ceptible unambiguous erythema with defined borders appearing over most of
the field of UV exposure, is the MED for product-protected skin (MEDp).
784 Brown
The sun protection factor for each individual volunteer (SPFi) is then calculated
as the ratio:
MED on product protected skin MEDp
SPFi ¼ ¼
MED on unprotected skin MEDu
When sufficient volunteers have completed the study with valid SPFi data,
the final SPF for the product is calculated as the arithmetic mean of all valid
individual SPFi values, that is
Pn
SPFi
Mean SPF ¼ 1
n
where SPFi denotes the individual SPF and n is the total number of individuals
with valid data.
The exact number of individual volunteers tested is defined by statistical
criteria which address data variability and confidence, but will be between 10
and 25 subjects with between 10 and 20 yielding valid data.
The basic procedure for SPF testing as described above is fundamentally
very simple. However, there can be several possible sources of variation at
each step in the procedure which when compounded, may lead to significant
error in determining a realistic or “correct” SPF number. With any SPF test
method, it tends to be the detail which is included in an attempt to control
these possible sources of error, that ironically gives rise to the differences
between methods.
In Europe, the SPF test method of choice is the International SPF Test
Method, a single method shared by industry throughout Europe, Japan, and
South Africa. This method is considerably more aligned with other existing
national SPF test methods than was the COLIPA (1994) SPF Test Method, but
it also retains the strengths of the historical methods of Europe, Japan, and
South Africa. However, the International SPF Test Method is not simply a regur-
gitation of the US FDA final sunscreen monograph, nor is it just a “revamp” of
the old COLIPA method. Instead, it addresses what were considered to be the
major potential sources of experimental variation in the SPF procedure. The
main areas of possible variation identified and addressed were; the definition
of the UV-light source, volunteer selection, product application procedure, use
of appropriate standard SPF products, UV exposure procedure, MED definition
and determination and finally, SPF calculation and statistical acceptance/
exclusion criteria.
The UV Light Source

The UV light source, or solar simulator, used to measure a sun product’s SPF is
critical to the whole test procedure. This arises from the fact that different wave-
lengths of sunlight have different capacities for inducing erythema in human skin.
Consequently, solar simulators that emit different spectra or distributions of
UV wavelengths will have different potentials for causing erythema. This effect
is exaggerated when we introduce the filtering effect of a sunscreen product.
When the output spectrum of a solar simulator matches the absorption spectrum
of the sunscreen, then the sunscreen will be very good at “blocking” the UV light
from the solar simulator and it will deliver a high SPF. However, if the solar
simulator output spectrum is not aligned to the absorbance spectrum of the sun-
screen, then the sunscreen will be less effective and will not be able to block
that portion of UV light which falls outside its absorbance range. This will
result in a much lower SPF for the same product. This effect is illustrated in
Fig. 39.1. The solid curve represents the protection profile of a sunscreen
product with its peak UV absorption at approximately 305 nm, typical of a
UV-B sunscreen. The dotted curve shows the output spectrum of the UV-B-
rich solar simulator by wavelength, expressed in terms of its ability to cause
erythema in human skin. This solar simulator produces a peak burning potential
at approximately 305 nm, which is matched to the peak of the protection spec-
trum for the sunscreen. Consequently, the sunscreen will be very effective at
reducing the peak burning wavelengths of the solar simulator and the product
will measure as having a high SPF.
When we consider the case of the UV-B-depleted solar simulator (hatched
curve), we see that it delivers its peak burning effect at a wavelength of approxi-
mately 315 nm. Whilst this is only a 10 nm shift, it can be seen that the
1.4
1.2
Relative Erythemal Intensity
1.0
0.8
0.6
0.4
0.2
0
290 300 310 320 330 340 350 360 370 380 390 400
Wavelength (nm)
Figure 39.1 Graph to show the importance of solar simulator output spectrum on
protective ability of sunscreen product and hence SPF. Solid curve ¼ protection profile
of sunscreen product. Dotted curve ¼ UV-B-rich solar simulator erythemal output.
Hatched curve ¼ UV-B-depleted solar simulator output.
786 Brown
peak burning wavelength now falls outside of the protective “umbrella” of the
sunscreen, that is, the sunscreen product has begun to lose protective performance
at the wavelengths where the solar simulator is emitting its most burning
radiation. Consequently, the same product will not be able to offer as good
protection from this UV-B-depleted solar simulator and hence the product will
return a lower SPF in the test.
Because SPF measurement is critically dependent on the output spectrum
of the UV light source, the International SPF Test Method defines strict limits
of compliance for any light source used in the test. These limits are defined by
a parameter known as the relative cumulative erythemal effectiveness (RCEE)
of the source. The RCEE is a measure of the spectral distribution of the light
source in terms of its capacity to generate erythema and informs which wave-
lengths of light are contributing what proportion of the total erythemal response.
RCEE is described in terms of cumulative erythemal effectiveness by successive
wavelength bands from 290 to 400 nm (i.e., all terrestrial UV wavelengths). The
erythemal effectiveness for each band of wavelengths is expressed as a percen-
tage of the total erythemal effectiveness of all wavelengths from 290 to 400 nm.
For example, a light source might have a spectrum of emission which con-
tained amounts of UV light in the range 290 –300 nm that would contribute, say
10% to the total erythemal response that would result from exposure of skin to
this lamp. The source would then be said to have a %RCEE value of 10% for
wavelengths 290 –300 nm. If a further 30% of total erythema was then contrib-
uted by wavelengths between 300 and 310 nm, then the cumulative effect is
that the source has a relative cumulative erythemal effectiveness percentage
(%RCEE) of 40% for wavelengths in the range 290– 310 nm.
The accumulation is continued from 290 to 400 nm until the full 100% UV
contribution is achieved. Once all %RCEE values have been calculated for any
UV source, they are compared with the maximum and minimum limits for
each wavelength band. These are defined within the International SPF Test
Method. The limits are based on the practical measurement of the outputs of
numerous suitable light sources and on the %RCEE values for known “standard”
sunlight spectra, particularly that for Australian sunlight (14). The maximum
(upper) and minimum (lower) permitted %RCEE limits for any UV source are
shown in Table 39.2, along with representative %RCEE values for a typical
solar simulator. As an example, it can be seen that the %RCEE limits for wave-
lengths of light between 290 and 320 nm (i.e., the UV-B wavelengths) are 85.0%
(lower) and 90.0% (upper). This means that a minimum of 85% of any erythema
resulting from exposure to a qualifying UV source must have been initiated by
wavelengths between 290 and 320 nm and that the maximum contribution to
the erythemal response from these wavelengths should be 90%. The “typical”
solar simulator shown in the table is a xenon arc source filtered with 1-mm
thick Schottw WG320 and UG11 filters. A total of 87.4% of the erythema
resulting from exposure to this source is initiated by the wavelengths from
290 to 320 nm.
Table 39.2 Maximum and Minimum Percentage Relative Cumulative Erythemal

Effectiveness (%RCEE) Limits for Ultraviolet Light Sources Used in SPF Testing
%RCEE
Spectral range (nm) Lower limit Upper limit Typical solar simulator
,290 – 0.1 0.0

290 – 300 2.0 8.0 4.0
290 – 310 49.0 65.0 56.7
290 – 320 85.0 90.0 87.4
290 – 330 91.5 95.5 93.3
290 – 340 94.0 97.0 95.3
290 – 350 95.5 98.5 97.2
290 – 400 100.0 100.0 100.0
To illustrate the importance of controlling the UV source spectrum,

Table 39.3 shows the potential effect of the solar simulator spectrum on the
SPF measured. The effect of eight different spectra, each being possible
outputs from commercially available solar simulators, is illustrated. The different
spectra are identified by their %RCEE value for the wavelength range
290 –320 nm. The predicted SPFs shown are calculated from a model incorpor-
ating a real SPF35 sunscreen product absorption profile (Fig. 39.2), the solar
simulator output spectra corresponding to the various %RCEE values and the
CIE (1987) erythemal effectiveness spectrum (15). From Table 39.3 it can be
seen that the predicted SPF which is likely to be measured for the SPF35
Table 39.3 Potential Effect of Various Solar

Simulator Output Spectra, Described by the Percen-
tage Relative Cumulative Erythemal Effectiveness
(%RCEE) Parameter, on the SPF of a Sun Product
as Predicted by a Model Incorporating the CIE
(1987) Erythemal Effectiveness Spectrum, and the
Absorbance Spectrum of the Sunscreen Product
Shown in Fig. 39.2
%RCEE (290 – 320 nm) Predicted SPF
80 25.8
82 28.0
84 30.0
85 31.4
87 34.6
89 38.5
90 41.0
91 44.4
788 Brown
3.0
2.5
2.0
Absorbance
1.5
1.0
0.5
0.0
290 300 310 320 330 340 350 360 370 380 390 400
Wavelength [nm]
Figure 39.2 Absorbance profile of a commercially available SPF35 sunscreen product,

used in the predictive calculation of the effect of UV spectrum on SPF, shown in
Table 39.3.
sunscreen product shown in Fig. 39.2 can vary from as low as SPF25.8 and up to
as high as SPF44.4. If we were to add to this model calculation, the biological
variation that is inherent in any human volunteer study, then the actual SPF
range that might be measured could potentially be even larger.
The examples shown are calculated from outputs of real solar simula-
tors (albeit extreme examples) and so they do represent real possibilities for
variability. By limiting the acceptable range for solar simulator output to a
minimum %RCEE (290 –320 nm) of 85.0% and a maximum of 90.0%, we effec-
tively limit the theoretical SPF range for a SPF35 product to SPF31.4 – 41.0.
In reality, the light source that most readily complies with the limit require-
ments set out in the International SPF Test Method is the xenon arc lamp.
In addition to this, the best way to conform to the additional requirement
that wavelengths .400 nm be limited as much as possible is to incorporate a
glass cut-off filter such as a Schottw UG11 filter (or similar) which transmits
minimal visible or infrared radiation. The standardised use of a visible cut-off
filter such as the Schottw UG11 also has the additional benefit of ensuring that
all solar simulators have a similar spectral distribution in the UV-A region of
the sunlight spectrum. This is important since studies conducted by COLIPA
member companies have shown that the UV-A component of a lamp spectrum
can have a surprising effect on the determination of the SPF of a sun product.
Even though the UV-A wavelengths only contribute about 12.5% of all erythema
in unprotected skin, the UV-A contribution to erythema can become quite
significant when a sunscreen product is applied to the skin. This effect was
demonstrated in a ring-test in which the same solar simulator in each laboratory
was first filtered with a Schottw UG5 cut-off filter and then with a UG11. These
filters have little impact on the UV-B emission of the solar simulator but can dra-
matically reshape the UV-A emission without taking the solar simulator outside
the permitted %RCEE limits. In the ring-test, the two different filtration systems
were used to determine the SPF of several sun protection products and in many
cases, different SPF numbers were returned for the UG11 and UG5 filtration. In
several instances these differences were significant, although not always large.
Consequently, the exclusive use of a Schottw UG11/1 mm filter (or similar) is
strongly advised when conducting SPF testing in Europe and xenon arc lamps
are the only permitted sources.
Figure 39.3 shows actual emission spectra for two solar simulators,
filtered with a Schottw UG11 filter, which comply with the upper and lower
spectral limits for lamp output according to the International SPF Test Method.
As can be seen from the graph, the permissible variation in light source quality
is small.
One final requirement of any light source used in SPF testing in Europe
is that the total output intensity (energy) of the source used, should be
restricted to that which would not cause an excessive feeling of heat in the
skin. As a guide, total irradiance of 120 mW/cm2 appears not to produce exces-
sive heating and so this would be considered a suitable intensity for total solar
simulator output.
16000
Spectral Irradiance ( mW/nm/m2 )
14000
12000
10000
8000
6000
4000
2000
0
290 300 310 320 330 340 350 360 370 380 390 400
Wavelength [nm]
Figure 39.3 Graph to show two typical solar simulator output spectra complying with
the upper (dotted curve) and lower (hatched curve) lamp output limits, defined by the
International SPF Test Method.
790 Brown
Volunteer Selection
Several laboratories engaged in SPF testing across the world have reported that
the SPF measured on dark or tanned skin can often be marginally lower than
the SPF for a product tested on white, nontanned skin. For this reason, volunteers
who participate in a SPF test in Europe are restricted to those with skin types I, II,
or III according to the Fitzpatrick classification (12). In addition to this, the
International SPF Test Method also includes an optional selection technique
based on reflectance colorimetry. This procedure may be used to exclude
deeply tanned type III individuals where an existing tan might threaten to inter-
fere with the measurement of SPF.
A minimum of 10 volunteers and a maximum of 20 volunteers must com-
plete an SPF test with fully valid data. There is provision for rejection of data on
the grounds of volunteer noncompliance or incomplete data but rejections are
limited to a maximum of five volunteers and must be justified on scientific
grounds. Consequently, the maximum number of volunteers which may be
tested is 25 and since a maximum of five volunteers may be rejected, the
minimum number of volunteers required to produce valid data increases with
the total number of volunteers tested according to Table 39.4.
Table 39.4 Minimum Number of Volunteers that

Must Produce Valid Data for Varying Numbers of Vol-
unteers Tested in an SPF Test. The Maximum Number
of Volunteers That May be Tested is 25 and the
Minimum is 10 Provided All Return Valid Data
Minimum number of
Number of volunteers required to
volunteers tested produce valid data
10 10
11 10
12 10
13 10
14 10
15 10
16 11
17 12
18 13
19 14
20 15
21 16
22 17
23 18
24 19
25 20
The actual number of volunteers required to complete a test, with valid

data, is determined by certain statistical criteria (described later). These criteria
govern the acceptable level of variability on the data. If these criteria are satisfied
by valid data from 10 volunteers, then the test may end at this point and the SPF
is calculated as the mean from these 10 volunteers. However, if the statistical
criteria are not achieved after 10 volunteers then testing must continue on
additional volunteers until such time as the statistical criteria are met, or until
20 volunteers have returned valid data. Should the criteria not be met after
testing the maximum number of 25 volunteers, then the whole test is rejected
and the investigator must examine their test procedures for sources of error or
noncompliance with methodology.
Product Application Procedure

Product application should be a straightforward and easily controllable parameter
in the SPF test, but in fact it is one of the largest, if not the largest, potential source
of error. This is because the SPF number measured is extremely dependent on
the way in which the sunscreen product is distributed on the surface of the
skin. There are two factors which affect surface distribution. These are appli-
cation rate and spreading technique. The higher the application rate, the higher
the SPF that will be measured. This relationship is pseudologarithmic so that
the SPF increases approximately logarithmically with increasing application
rate. Because of this, it is critical that the amount of product applied to the
skin is very accurately controlled. The International SPF Test Method requires
that product is applied accurately, at an application rate of 2.0 mg of product
per square centimetre of skin. The technique for weighing out the product and
transferring it to the skin is strictly defined to ensure that all weighed product
is transferred to the skin. All weighing must be carried out to an accuracy of
2.5% on a balance capable of weighing to a sensitivity of 0.1 mg. Whilst this
might appear excessive, the reality is that the previously mentioned logarithmic
relationship between application amount and SPF, means that overweighing by as
little as 2.5% would theoretically lead to a SPF40 product testing as SPF44, that
is, a 10% error.
But application rate is not the whole story here. As part of the development
of the International SPF Test Method, several laboratories studied the effect of
product spreading technique. Two parameters were investigated: spreading
time and spreading pressure. Both were found to be possible sources of signifi-
cant variation in the SPF measured, under certain circumstances. In the spreading-
time study, two products were SPF tested following the same procedure but with
different product spreading times of 20 s and 40 s. For one of the two products, a
significantly higher SPF was measured with the 20 s spreading time than the 40 s
spreading time. This is thought to suggest that rubbing some products for too long
a time, can transfer too much product into the recesses of the skin’s topography,
leaving the ridges unprotected and hence leading to a lower measured SPF.
792 Brown
In the spreading-pressure study, two products were SPF tested after spread-
ing with two different forces (300 and 50 g). Results for one of the two
products showed a significantly higher SPF for the product spread with low pres-
sure (mean SPF ¼ 20.6) compared with that spread with high pressure (mean
SPF ¼ 14.7). These results are again consistent with high pressure resulting
in more product being transferred to the recesses in the skin’s topography,
leaving the ridges unprotected.
These studies lead to the introduction of much more explicit guidelines on
product application technique in order to ensure that product is applied and
spread consistently. Two key stages to the product application technique were
defined. The first is the application of the product using a “weighing by loss”
technique, which accurately dispenses the correct amount of product.
A syringe or micropipette is weighed after filling with the test product and is
then weighed again after dispensing the product directly on to the skin in a
series of small droplets distributed over the whole product application site. The
difference in weights gives the exact amount of product dispensed onto the
volunteer’s back. The area of skin to which the product is applied must be no
less than 30 cm2 and no more than 60 cm2. This area was defined from practical
experience, which suggested that areas ,30 cm2 required product application
volumes which were too small to weigh accurately, whilst areas .60 cm2
required the applied product to be spread over too large an area of skin to be
able to achieve a sufficiently uniform distribution. The second stage of product
application requires the product to be rubbed into the skin using “light” pressure
for a period of between 20 s and 50 s using either the bare finger or a “finger cot.”
The product is then left to dry for at least 15 min but no more than 30 min.
The procedures described above, apply to the majority of sun- or UV-
protective products that is, those in cream, lotion, milk, oil or gel format.
However, it was recognized that a unique product application technique was
needed for products in powder format. Therefore, the International SPF Test
Method also defines a specific procedure for application of powder products.
Because of the complexity of the product application technique and the dif-
ficulty to describe it adequately using only the written word, the International
SPF Test Method is accompanied by a CD-ROM based video which illustrates
visually, the correct application procedure.
Use of Standard Products

Most SPF test methods incorporate at least one standard product which is
included in every SPF study as an internal control to ensure that procedures
have been correctly followed. The International SPF Test Method is no excep-
tion. It requires one standard product to be tested as part of any SPF test.
However the SPF of the products being tested governs the choice of standard.
If the products under test are all of expected SPF below SPF20 then any one
of four named SPF standards may be used (P1 “DIN Standard”—SPF4; P7
“FDA 8% HMS Standard”—SPF4; P2 “CTFA/JCIA High SPF Standard”—

SPF13; or P3 “COLIPA High SPF Standard”—SPF15). However, if any
product in the test has an expected SPF of 20 or above, then one of the two
high SPF standards (P2 or P3) must be chosen.
The expected mean SPF values for each of the standard products were
derived by combining ring-tests carried out by the European Trade Association
(COLIPA) during 1993 with an International SPF ring-test conducted in 1996
and are shown in Table 39.5. Since these data are somewhat dated and were
obtained following methodologies which preceded the International SPF
Test Method, it is the intention of the International Harmonisation Committee
to redetermine the SPF values for the standard products in a new ring test
likely to be conducted during 2004.
UV Exposure Procedure
The SPF test requires that the back of a human volunteer is exposed to incremen-
tally increasing doses of UV light in order to determine the minimum dose of
sunlight simulated light which will induce the first perceptible redness (erythema)
response, 16 –24 h after exposure. Volunteers may be exposed to the doses of UV
radiation in either the seated or the prone position, however, the same position
must be maintained for all exposures as well as for the subsequent assessment
of erythemal responses.
The minimum area of skin to be exposed to the solar simulated light source
is 0.5 cm2. However, an area of at least 1.0 cm2 is highly recommended. Each
area of exposure should be separated from its adjacent area of exposure by a
distance of at least 1.0 cm and each area of skin exposed to the incremental
doses of simulated sunlight must be of the same size. In practice, most European
laboratories will expose an area of skin equivalent to 1.0 cm2 to each incremental
dose of radiation.
When determining the unprotected MED, a minimum of five sites on the
unprotected skin of the volunteer must be exposed to geometrically increasing
doses of simulated sunlight UV light, with the increment between the doses
Table 39.5 Expected SPF Values for Standard Products with Indication of Expected
Variability According to Historical Ring-Tests Conducted in 1993 and 1996 (To Be
Revised)
Nominal Measured SPF Standard SPF Range

Standard product SPF (mean) deviation (+1.65 S.D.)
P1: Low SPF standard 4 4.2 0.2 3.8– 4.5

P7: Low SPF standard 4 4.2 0.3 3.8– 4.7
P2: High SPF standard 13 12.7 1.2 10.7– 14.8
P3: High SPF standard 15 15.3 1.3 13.2– 17.4
794 Brown
being either 1.12 or 1.25 times. On product protected sites, a minimum of five
separate areas of skin on an adjacent region of the back, must be exposed to
geometrically increasing incremental doses of simulated sunlight with the size
of the increment being dependent on the expected SPF of the product under
test. For products where the expected SPF is less than or equal to SPF25, an
increment of no more than 1.25 times should be used. For products where the
expected SPF is greater than SPF25, the increment between successive doses
of simulated sunlight exposure should be no more than 1.12 times. Smaller
increments may be used for any protected MED determination, but the increment
must be consistent throughout the whole irradiation sequence.
The requirement for a smaller maximum increment of exposure for high
SPF products is intended to increase the sensitivity of the test, whilst also safe-
guarding the volunteer from exposure to unnecessarily high doses of ultraviolet
light (albeit with protection from the test product).
Minimum Erythemal Dose Definition and Determination

A major difference between the new International SPF Test Method and the 1994
COLIPA SPF Test Method, which it will replace, lies in the definition and the
determination of the MED. The new definition of an MED is much more akin
to that of the US FDA final sunscreen monograph definition and it is the same
for both the MED on unprotected skin (MEDu) and for the MED on skin protected
by the test product (MEDp). It is defined as “The lowest ultraviolet light dose that
produces the first perceptible, unambiguous erythema with defined borders
appearing over most of the field of UV-exposure 16 to 24 hours after exposure.”
There is no longer a requirement for color-matching between the MEDu and
MEDp (as was required by the 1994 COLIPA test method) nor for interpolation
between two adjacent erythemal responses in order to achieve a color match.
All MED determinations are by visual assessment of the sites exposed to
UV radiation, by a trained assessor who has been checked for normal colour
vision. The visual assessment is made between 16 and 24 h after exposure,
by an assessor who has had no previous involvement in the application of
product, delivery of UV exposures or other test design (e.g., randomization of
test sites) on that particular volunteer. A minimum of 500 lux illumination is
required for the MED assessment, which must be recorded either as the total
energy dose delivered to the site (J/m2 or mJ/cm2) or the time (in seconds)
for which the irradiation was delivered, provided that the solar simulator has
been demonstrated to emit a constant output flux.
The International SPF Test Method has introduced specific circumstances
under which MED data must be rejected. These are shown in Table 39.6. Some
circumstances will lead to the rejection of all data from all test products tested on
a single individual whilst in other circumstances some of the data may be
salvaged. However, if data has to be rejected on more than five different
Table 39.6 Criteria Under Which MED Determinations Are Invalid and Must Be
Rejected
Standard product Test product

Rejection criterion Unprotected skin protected skin protected skin
The exposure series Reject all data for Reject all data for Reject all data for
on a subject fails all products all products the test product
to elicit any affected
erythemal
response on any
site, 20 + 4 h
after exposure
Erythemal Reject all data for Reject all data for Reject all data for
responses within all products all products the test product
an exposure affected
series on a
subject are
randomly absent,
20 + 4 h after
exposure
All subsites in the Reject all data for Reject all data for Reject all data for
exposure series all products all products the test product
on a subject show affected
an erythemal
response,
20 + 4 h after
exposure
Note: When multiple products are Tested on one individual and the rejection criterion applies only to
the product protected MED for a single product (column 4), then only the data for the affected product
are rejected.
individuals, then the whole test is invalid and must be repeated on a completely
new panel of 10– 25 volunteers.
SPF Calculation and Statistical Acceptance/Rejection Criteria

The International SPF test is similar to other SPF test methods throughout the
world in that it requires the outcome of the test to be described by way of an
arithmetical mean SPF, calculated from each of the individual SPFi values
measured on every volunteer.
Where the method differs from other methods is in its reliance on a statisti-
cal assessment of the variability of the SPF data to define the exact number of
individual SPFi values (from the individual volunteers) from which the mean
SPF may be calculated. Another difference lies in the fact that statistical criteria
796 Brown
are also used to define a maximum limit of variability that is acceptable on the
mean SPF.
The test is initially conducted on 10– 15 volunteers in order to generate a
minimum of 10 valid individual SPF results after rejection of a maximum of
five invalid results. A provisional mean SPF for these first data is calculated
together with a 95% confidence interval (95% CI) for the mean. The 95% CI
is a statistical estimate of the range within which the population mean SPF
might reasonably be expected to fall. Put another way, it represents the range
of SPF values within which one might be 95% confident of finding the “true”
mean SPF. If the 95% CI for the first 10 valid results falls within a range of
+17% of the measured mean SPF, then the test may be declared valid and
complete. However, should the 95% CI exceed +17% of the mean SPF, then
the test must continue by adding further volunteers to reduce variability, until
the statistical acceptance criterion (95% CI 17% of mean SPF) is achieved.
The number of additional volunteers that should be included can be estimated
statistically.
After successfully testing the additional volunteers, a new provisional
mean SPF is then calculated with its 95% CI. If this new 95% CI now falls
within +17% of the new provisional mean SPF then the test is valid and may
end. If the 95% CI is still greater than +17% of the new provisional mean
SPF then further volunteers are added until a maximum of 20 valid individual
SPF results have been determined. If the statistical criterion is still not achieved
after 20 volunteers have returned valid data, then the entire test must be rejected
and a repeat test will have to be conducted on a new panel of volunteers. Under
these circumstances, a full review of experimental technique and equipment
would be advisable.
This procedure is best illustrated by example. Table 39.7 shows data from a
hypothetical SPF test. Eleven volunteers were required in order to obtain the initial
10 valid individual SPF values. These data are shown in plain font. Each individual
SPF was calculated as the ratio of MEDp:MEDu. The mean SPF for these first 10
valid results was SPF20.3 with a standard deviation of 5.8. The calculated 95% CI
was SPF16.2–24.5 indicating that there is a 95% probability that the “true” popu-
lation mean lies somewhere within this range. At its extremes, the range represents
a +20.4% variation on the mean SPF for the first 10 valid results. This does not
meet the acceptance criterion for data variability (i.e., within +17% of mean)
and so testing continued on additional volunteers.
Using the standard deviation from the first ten valid results, the t-statistic
and the +17% variation target, it was possible to predict that an additional
four volunteers were likely to be needed to achieve the acceptance criterion.
Four more volunteers were tested (data shown in italic) and individual SPFs
were calculated. These were added to the original ten SPF values and a new
mean SPF of 20.1 was calculated from all fourteen volunteers who produced
valid data, along with a new 95% CI of 17.3 –22.9. The extremes of this new
95% CI represent a +14.1% deviation from the mean SPF and hence were
Table 39.7 SPF Data from a Hypothetical SPF Test Showing Individual MED Doses, Calculated Individual SPF Values, and 95% Confidence
Intervals
Pass or
Vol. Skin MEDu MEDp Individual Mean SD on Test 95% Target 95% CI fail 95%
no. type (mJ/cm2) (mJ/cm2) SPFi SPF mean SPF CI (mean +17%) CI criterion
1 I 10.2 163.2 16.0 – – – – –

2 II 20.0 564.0 28.2 – – – – –
3 III 31.3 626.0 20.0 – – – – –
4 II 25.0 400.0 16.0 – – – – –
5 II 16.0 400.0 25.0 – – – – –
6 III 31.3 500.0 16.0 – – – – –
7 I 12.8 164.0 12.8 – – – – –
8 II 16.0 No result – Invalid result—data rejected
9 II 20.0 564.0 28.2 – – – – –
10 III 25.0 400.0 16.0 – – – – –
11 III 31.3 783.0 25.0 20.3 5.8 16.2– 24.5 16.8 –23.8 Fail
12 II 16.0 288.0 18.0 – – – – –
13 II 20.0 450.0 22.5 – – – – –
14 III 31.3 563.0 18.0 – – – – –
15 II 20.0 400.0 20.0 20.1 4.9 17.3– 22.9 16.7 –23.5 Pass
Note: The mean SPF and 95% CI were initially calculated after the first 10 valid results obtained from the first 11 volunteers tested (plain font). Since the test 95% CI
was outside the target 95% CI, then the acceptance criterion was not achieved and a further four volunteers were added (italics). This additional number of volunteers
was predicted statistically. A new mean SPF and 95% CI was calculated after the completion of the 15th volunteer and the new 95% CI was found to lie within the
new target 95% CI calculated from the revised mean SPF.
797
798 Brown
within the +17% target (i.e. SPF16.7– 23.5). Consequently, no further testing
was required and a mean SPF of 20.1 was reported.
COMPARISON OF THE INTERNATIONAL SPF TEST

METHOD AND THE US FDA SPF METHOD
Sunscreen manufacturers in the USA, Europe, or other parts of the world who
produce international brands, have historically been seriously encumbered by the
fact that the 1994 COLIPA SPF Test Method and the SPF test method described
by the US FDA sunscreen monograph were significantly different. This lead to
the inevitable situation that products intended for sale in both Europe and the
USA, for example, had to be tested twice to comply with local legislation or custom.
The International SPF Test Method has been designed not only as an
improvement on preceding methodologies in use in Europe, Japan, and South
Africa, but also as an attempt to move closer to common practice elsewhere in
the world. The result is that The International SPF Test Method has moved
considerably closer to the US FDA and other national SPF methods, whilst
still maintaining a certain uniqueness, evidenced by the many small differences
that remain. Fortunately, these remaining differences are surmountable and
with care, a single SPF test can now be designed, which would comply with
both the requirements of the FDA and with European methodology. The data gen-
erated from such a test, would still require some degree of different handling and
different calculation processes, however, the underlying techniques, procedures,
and data generated are now fundamentally compatible.
Table 39.8 summarizes the major elements of any SPF test method and
compares the International SPF Test Method with the FDA method described
by the 1999 final sunscreen monograph (10). The last column in this table high-
lights the areas of caution that should be observed, or areas of difficulty that might
be encountered by any laboratory attempting to conduct a single SPF test which
was intended to comply with both methods.
As a consequence of the introduction of the International SPF Test
Method, European SPF testing is now much the same as that elsewhere in
the world. The small differences that remain are thought to represent enhance-
ments to the existing procedures of other methodologies and if followed
these enhancements would not compromise compliance with other methods
but would contribute positively to the accuracy of those existing procedures.
In moving closer to the US FDA SPF test methodology and to other
leading international SPF test methods, it is hoped that European SPF testing
has taken its first step toward full-scale worldwide harmonization of SPF testing.
SPF LABELING GUIDELINES

The International SPF Test Method does not offer any guidance on sun product
labeling. The method is purely a technical procedure for determining the mean
Table 39.8 Comparison of the Major Elements of the 2003 International SPF Test Method and the US FDA 1999 Final Sunscreen Monograph
SPF Test Method with Particular Attention to the Areas Where Caution Must Be Exercised in Order to Comply with Both Methods When
Conducting a Single, Combined Test
Test parameter International SPF test US FDA test Dual compliance guidance
UV Source † Xenon arc lamp with UG11 type † Continuous, stable, uniform It is possible to design a system
filtration. Output must be (within 10%) emission spectrum comprising a xenon arc lamp that
continuous, stable, uniform and from 290 to 400 nm similar to complies with both specifications
comply with erythemal effectiveness sea-level sunlight at 108 zenith for output. Sea-level sunlight at
limits between 290 and 400 nm angle 108 zenith angle (FDA) would
† ,0.1% of output below 290 nm † , 1% of output below 290 nm have a spectrum which fell within
† Output above 400 nm restricted † , 5% of output above 400 nm the erythemal effectiveness limits
† Need to avoid excessive heating by of the international method
restricting total irradiance Measurement of exact output
(120 mW/cm2) spectrum is critical to comply
† Periodic measurement with † Periodic measurement with with international method
accurately calibrated accurately calibrated
spectroradiometer spectroradiometer
Test subjects † Skin types I, II, or III † Skin types I, II, or III To satisfy both methods, 20– 25
† Minimum number ¼ 10 † Minimum number ¼ 20 volunteers must be recruited. All
† Maximum number ¼ 20 † Maximum number ¼ 25 are used for the FDA test but only
† Actual number variable between † Actual Number variable those that are needed (in
10 and 20 according to between 20 and 25 chronological order) to achieve
statistical criteria the minimum International
† Maximum of five rejections † Maximum of five rejections method acceptance criteria are
† Specific criteria for rejection † Specific criteria for rejection recorded. Note that data
(volunteer) rejection criteria are
different
799
(continued )
800

Test site † The back between scapula line and † The back between beltline and Compliance with both methods
the waist shoulder blade, lateral to the requires a test site of between 50
midline and 60 cm2.
† Minimum area ¼ 30 cm2 † Minimum area ¼ 50 cm2
† Maximum area ¼ 60 cm2
Definition of † The lowest UV dose that produces † The quantity of erythema- This is the same response worded
minimum the first perceptible unambiguous effective energy (expressed as slightly differently
erythemal dose erythema with defined borders joules per cm2) required to
(MED) appearing over most of the field of produce the first perceptible,
UV exposure, 16– 24 hours after redness reaction with clearly
UV exposure. defined borders
Unprotected MED † Minimum of five exposures † Exactly five exposures Only five exposure subsites of 1 cm2
determination † Minimum of 0.5 cm2 of skin † Minimum of 1.0 cm2 of skin with 1.25X geometric progression
exposed to UV (recommended exposed to UV between doses in order to comply
1 cm2) with both methods. Erythemal
† 1.12 or 1.25 times geometric † 1.25 times geometric responses must be read by an
progression between irradiation progression between irradiation independent assessor at
doses doses 23 h + 1 h under tungsten or
† Read after 16– 24 h under at least † Read after 22 – 24 h under warm white fluorescent light
500 lux illumination tungsten or warm white within the range of 500–550 lux
fluorescent light within the
range of 450 – 550 lux
Brown
† Independent assessor † Independent assessor

Test product † 2.0 mg/cm2 + 0.05 mg † 2.0 mg/cm2 With the appropriate technique and
quantity and † Application area ¼ 30– 60 cm2 † Application area 50 cm2 application procedure, product
application † Apply in 15– 30 droplets can be applied to an area of
technique † Rub-in with light pressure for a † Rub-in with a finger cot between 50 and 60 cm2 and left to
period of 20– 30 s using dry for 15–30 min. In this way
finger-cot or bare finger both methods are complied with
† Drying time 15– 30 min † Minimum drying time 15 min
Standard † P1 Low SPF (SPF4) † 8% HMS Standard (SPF 4.47) International SPF Standard P7 is the
sunscreen † P7 Low SPF (SPF4) FDA 8% HMS Standard so this
products † P2 High SPF (SPF 13) product may be used alone in tests
† P3 High SPF (SPF15) where the test products’ SPFs are
† Select one standard from all four if all less than SPF20. For SPFs 20
test product SPF ,20 or from P2 or then the 8% HMS standard and
P3 if SPF 20 either P2 or P3 must be tested in
order to comply with both
methods
Protected † Minimum of 0.5 cm2 of skin † Minimum of 1.0 cm2 of skin For SPFs 25 the FDA procedure
MED exposed to UV (recommended exposed to UV should be followed, ensuring that
determination 1 cm2) erythemal assessments are made
† Minimum of five exposures † Exactly seven exposures under 500–550 lux illumination.
† Maximum 1.25X geometric † Fixed dose progressions of: This will comply with the
progression between doses for 1.25X for SPFs ,8 International method
expected SPFs 25 1.20X for SPF 8 – 15 For SPFs .25, it is not possible to
† Maximum 1.12X geometric 1.15X for SPFs .15 use a single irradiation series and
progression between doses for for irradiation doses 1, 2, 4, 6, and a hybrid series comprising of the
expected SPFs .25 7. Irradiation doses 3 and 5 to be International progression of 1.12X
the midpoint between adjacent and the FDA progression of 1.15X
doses will need to be used. This is likely
801
(continued )
802
† Read after 16– 24 h under at least † Read after 22 – 24 h under to require the exposure of 11
500 lux illumination tungsten or warm white subsites to UV light, when testing
fluorescent light within the SPFs .25
range of 450 – 550 lux
† Independent assessor † Independent assessor
SPF calculation and † Total number of volunteers † Total number of volunteers Both tests make essentially the same
statistical (n) ¼ 10– 20 (n) ¼ 20 –25 calculations. The FDA test has no
acceptance † Calculate arithmetic mean SPF † Calculate arithmetic mean SPF limitation on variability (although
† Calculate the standard deviation on † Calculate standard deviation on this will affect labelled SPF).
the mean SPF the mean SPF Therefore a joint test must comply
† Calculate 95% CI and check test † Calculate the lower limit of the only with the International test
validity ie 95% CI is less than 95% CI for the SPF data variability requirement, that is
+17% of mean SPF that the 95% CI must be less than
+17% of mean SPF
Brown
SPF value for a sunscreen product. However, COLIPA has published an SPF
labeling guideline (16) for its European members and the majority of European
sunscreen manufacturers do adhere to this guideline.
This guideline is not complex and is summarized below:
. The sun product’s SPF must be determined according to the latest SPF
test method recognized or issued by COLIPA. The result of the test is
reported as the mean SPF with its 95% CI.
. The labeled SPF is the nearest recognized SPF number below the
measured mean SPF. COLIPA recommendation number 11 (16) only
recognizes certain SPF numbers for product labelling in an attempt to
reduce the proliferation of different SPF numbers on sun products.
The recognised SPF numbers are SPF 2, 4, 6, 8, 10, 12, 15, 20, 25,
30, 40, 50, and 50þ. Only these numbers may be used for labeling
the SPF of a sun product. As an example, a product that tested with a
mean SPF of 11.8 would be labeled as SPF10 as this is the first recog-
nized SPF number below 11.8.
. The maximum SPF that may be labeled is SPF50þ. Products labeled as
SPF50þ must have returned a mean SPF of at least SPF 60.
. Product protection category descriptors are optional however if used,
then only the following descriptors will be used: “low” (SPFs 2 –6);
“medium” (SPFs 8 –12); “high” (SPFs 15 – 25); “very high” (SPFs
30 – 50); and “Ultra” (SPF 50þ). The term sunblock will not be used
under any circumstances.
WATER RESISTANCE TESTING AND UV-A MEASUREMENT

The International SPF Test Method describes the technique for measuring the
static sun protection factor of a sunscreen product only. There are currently no
internationally harmonized guidelines or guidelines specific to Europe, which
outline how to measure either the water resistance of a sunscreen product or its
UV-A protection level.
Of course, European sun products do make claims regarding their water
resistance and also their ability to protect against the UV-A component of sun-
light ultraviolet light. However, the tests conducted to support these claims are
not defined either by legislation or by trade association guidelines.
Most laboratories in Europe now adopt a procedure for water resistance
testing which is very similar to that described in the US FDA (1999) sunscreen
final monograph; although water resistance labeling of European products can
be somewhat different to that in the USA and other territories of the world.
It is usual for the water resistance test to be conducted in a spa-pool. The
volunteers are immersed for two separate 20-min immersions in the spa, with
each immersion separated by a 10 – 20-min drying period (no towelling) with
the volunteer removed from the spa. At the end of the immersion procedure,
the SPF of the product is determined following the International SPF Test
804 Brown
Method to establish the post-immersion SPF number. Unlike the USA and
Australia, the labeled SPF for a European water resistance product is the static
SPF and not the SPF value after water immersion. When the term water resistance
is used in Europe, it is usually considered that the SPF after two 20-min immer-
sions will continue to be at least 50% of the labeled SPF. If the term “extra water
resistant” is used, then this usually implies that the product will retain at least
75% of its SPF after water immersion.
COLIPA, the trade association for the cosmetic and toiletries industry in
Europe, is currently developing guidelines on water resistant testing which
should be completed in the very near future. These guidelines are likely to be
extremely similar to that described in the US FDA sunscreen final monograph
although the method of labeling of water resistant sunscreen products may not
necessarily be the same.
UV-A labeling in Europe is a much more difficult matter. There is no single
agreed test method for UV-A measurement in Europe, but UV-A protection is a
major area of interest and concern in Europe. Consequently, COLIPA has been
trying for many, many years to find a consensus amongst its members, for a
UV-A protection measurement technique. One of the major hindrances to pro-
gress has been the debate over the appropriateness of in vitro techniques versus
in vivo techniques although there is now some hope that agreement on this issue
may be close at hand. COLIPA continues to persevere in its attempt to establish a
European guideline on UV-A measurement.
Meanwhile, manufacturers have used their own initiative with UV-A
claims in Europe. Consequently, many product UV-A claims are supported by
different UV-A test methodologies. The most popular in vivo method has been
the persistent pigment darkening (PPD) technique, described by Moyal et al.
(17,18). This test is essentially the same procedure as the SPF test but utilises
a solar simulator, which emits only UV-A light as the irradiation source and
the immediate pigmentation response that occurs in pigmented skin after
exposure to large doses of UV-A light as the measurement parameter. The
method has been adopted by the Japanese Cosmetics Industry Association as
their recommended method for UV-A measurement.
In addition to the in vivo PPD method, in vitro techniques for UV-A
measurement are also very popular. In Germany, it is now common practice to
test products for UV-A protection level according to the in vitro method
described in the Australia/New Zealand Standards Association’s standard AS/
NZS 2604 (11). Products are often labeled as conforming to this standard for
UV-A protection. Elsewhere, many investigators rely on techniques based on
the in vitro transmission method described by Diffey and Robson in 1989 (19).
Many variations of this technique are used in Europe, primarily for screening new
formulations but in the UK the technique has been adopted with a few adaptations
into a UV-A measurement and labeling system, which has been in widespread use
for more than a decade. This system, launched by The Boots Company, uses a
simple UV-A logo depicting five levels of UV-A performance by means of a
series of stars. Each level of performance is determined by the ratio of the sun-
screen product’s UV-A absorbance to its UV-B absorbance and so, strictly speak-
ing, it is a measure of how “balanced” a product’s UV-A absorbance is, compared
to its UV-B absorbance. Whilst use of this system is purely voluntary (although
under licence) it has become almost universally used in the UK. Any manufac-
turer who intended to market a sunscreen product in this region of Europe
would be well advised to familiarise themselves with the system.
COLIPA continues to seek a consensus on UV-A labeling, which might
lead to a single UV-A test procedure for Europe. There is widespread desire in
the European cosmetics industry that an in vitro UV-A technique be adopted,
which would remove the need to subject human volunteers to yet more exposure
to ultraviolet light. Progress has recently been good and it is hoped that a
COLIPA UV-A test might become a reality in the near future. How similar
this test might be to other legislative or advisory UV-A test methods elsewhere
in the world is yet to be seen, but it is likely that a harmonization effort in this
area may well be needed in the future. But for now, at least we do have an
SPF test method that is harmonized across a large proportion of the world and
which is similar enough to the other SPF methods of the world to enable a
single test to be conducted, which satisfies all national requirements.
ACKNOWLEDGMENTS
The author would like to acknowledge the considerable efforts of friends and
colleagues who make up the International SPF Harmonisation Committee and
the individual trade associations of Japan (JCIA), South Africa (CTFA-SA),
Europe (COLIPA), and the USA (CTFA). Without their hard work and
commitment, the International SPF Test Method would never have been possible.
Sadly, one person who was highly instrumental in the early European effort never
witnessed the completion of the work. This chapter is dedicated to the memory of
the late Jack Dupuis.
REFERENCES
1. Henne W. In vivo determination of the sunscreen factor of cosmetic preparations,
history and the present state of the art. Parf Kosm 1983; 64:415 – 423.
2. Schulze R. Einige versuche und bemerkungen zum problem der handelsublichen
lichtschutzmittel. Parf Kosm 1956; 37:310 – 315.
3. Greiter F. Sun protection factor—development methods. Parf Kosm 1974; 55:70– 75.
4. Deutches Institut für Normung. Experimentelle dermatologische bewertung des
erythemschutzes von externen sonnenschutzmittein für die menschliche haut. DIN
Standard (1985); 67.501:1-9 and DIN Standard 1996; 67.501.
use. Proposed safety, effective and labeling conditions. Federal Register (August 25,
1978 Part II); 43 (No. 166):38205 – 38269.
806 Brown
6. COLIPA Sun Protection Factor Test Method. COLIPA Publication 94/289

(1994):October 1994.
use; tentative final monograph; proposed rule. Federal Register (May 12, 1993);
58(No. 90):28194 – 28302.
8. Japanese Cosmetics Industry Association. Standard sun protection factor test method,
1999. Available from JCIA.
9. South African Bureau of Standards. Sunscreen Products. SABS Standard 1557 (1992);
May 1992.
use; final monograph. Federal Register (May 21, 1999); 64(No. 98):27666 – 27693.
11. Standards Australia/Standards New Zealand. Sunscreen products—evaluation and
classification. AS/NZS 2604 (1998):1– 32.
12. Wolff K, Gschnait F, Honigsmann H, Konrad K, Parrish JA, Fitzpatrick TB. Photo-
testing and dosimetry for photochemotherapy. Br J Dermatol 1977; 96:110– 122.
13. Sayre RM, Kaidbey KH. Reciprocity for solar simulators used in sunscreen testing.
Photodermatol Photoimmunol Photomed 1990; 7:198– 201.
14. Bernhard G, Mayer B, Seckmeyer B, Moise A. Measurement of spectral solar UV
irradiance in tropical Australia. J Geophys Res 1997; 102(D/7):8719– 8730.
15. Commission Internationale De L’Eclairage (CIE). A reference action spectrum for
ultraviolet induced erythema in human skin. CIE Research Note 6 (1987).
16. COLIPA. Colipa Recommendation No. 11—SPF Classification/upper limit. COLIPA
Document Reference 02/068-AF (June 2002).
17. Moyal D, Chardon A, Kollias N. Determination of UV-A protection factors using the
method. Photodermatol Photoimmunol Photomed 2000; 16(6):245 – 249.
18. Moyal D, Chardon A, Kollias N. UV-A protection efficacy of sunscreens can be deter-
mined by the persistent pigment darkening (PPD) method. Part 2. Photodermatol
Photoimmunol Photomed 2000; 16(6):250 –255.
19. Diffey BL, Robson J. A new substrate to measure sunscreen protection factors
throughout the ultraviolet spectrum. J Soc Cosmet Chem 1989; 40:127 – 133.
40
Balancing UV-A and UV-B Protection
in Sunscreen Products: Proportionality,
Quantitative Measurement of Efficacy,
and Clear Communication to Consumers
Patricia P. Agin
Schering-Plough HealthCare Products Inc.,
Memphis, Tennessee, USA
Curtis A. Cole
Johnson & Johnson Consumer Products Worldwide,
Skillman, New Jersey, USA
Christopher Corbett and Cheryl M. Sanzare
L’Oréal USA Products, Inc., Clark, New Jersey, USA
Kenneth Marenus
Estee Lauder Companies, Melville, New York, USA
John P. Tedeschi
Bath & Body Works, Reynoldsburg, Ohio, USA
Carolyn B. Wills
Mary Kay Inc., Dallas, Texas, USA
Introduction 808
Background on the Requirements for UV-A/UV-B Proportionality 809
Protection Minimums for Proportional UV-A/UV-B Protection 811
Beyond the Minimum Balance Requirements: Extra UV-A Protection 813
807
808 Agin et al.
Identification and Communication of Two Distinct Levels of

UV-A Protection 813
The Need to Measure Both Breadth and Quantity of Protection 815
Testing Formulations to Evaluate the Reproducibility of the PFA and
Persistent Pigment Darkening UV-A Test Methods, with Additional
Assessment of Broadness 816
Results 817
Discussion 818
Conclusions and Recommendations 823
References 824
INTRODUCTION
In 1996, industry submitted to Food and Drug Administration (FDA) for
consideration an in vitro UV-A test method called Critical Wavelength (1).
That method measured the broadness of the protection provided by a sunscreen
product, but did not address either the magnitude of protection or the issue of
the appropriate proportionality of UV-A to UV-B protection. The importance
of assessing the quantity of UV-A protection provided by sunscreen products
was highlighted by the FDA in correspondence relating to the approval of the
combination of avobenzone with certain other active ingredients (2,3). In that
correspondence, the Agency asked for additional clinical UV-A protection data
beyond Critical Wavelength to support the UV-A efficacy of those ingredient
combinations. The data that the Agency requested was to be based on the in
vivo Protection Factor A (PFA) test method (4).
The importance of proportionality between UV-A protection and the SPF
was raised at a 1999 feedback meeting between The Cosmetic, Toiletry and
Fragrance Association (CTFA) and FDA. At that meeting, FDA asked industry
to comment on the requirement for proportionality between the SPF and UV-A
protection. The request for information on this point was made again in an
FDA letter to CTFA in March 2000. In addition, the importance of the
proportionality of UV-A to UV-B was addressed by the American Academy of
Dermatology (5) in their April 2000 press statement on UV-A:
The AAD recommends that an increase in the SPF of a sunscreen must
be accompanied by a proportional increase in the UV-A protection
value. These “proportional” values should be determined jointly by
the FDA and the industry.
The importance of both the measurement of the quantity of UV-A protec-
tion in a formulation and the proportionality of UV-A protection to the SPF is
Balancing UV-A and UV-B Protection in Sunscreen Products 809
clear. However, a final element to consider is the clear communication of both

SPF and UV-A protection information to consumers. The American Academy
of Dermatology has wisely recommended maintaining the SPF as the primary
indicator of overall sunscreen performance. In 1996, CTFA submitted market
research to the FDA (6) that showed that the best way to communicate UV-A
protection to the consumer was in the form of simple text descriptors, as
opposed to utilizing additional numbers or graphics on the package label. This
finding continues to be important, and is consistent with the concept of maintain-
ing the SPF as the primary indicator of the protection provided by the sunscreen
product, while providing an opportunity to expand label information about
product performance.
Another benefit of the adoption of our approach is that voluntary
professional labeling information could be provided to physicians, giving
details beyond those needed for consumer labeling concerning the quantity and
broadness of the UV-A protection offered by a product. This information
would allow physicians to recommend sunscreen products for specific needs
and conditions, based on individual evaluation of their patients. However, such
professional labeling cannot take the place of simple, clear, and comprehensible
information on the label for consumers.
The approach presented in this document offers a way to create a compre-
hensive approach to sun protection which assures not only proportionality of
UV-A to UV-B protection levels but also ensures breadth of absorbance for pro-
ducts making UV-A protection claims. More importantly, in the light of concerns
expressed by the FDA that high-SPF products may increase sun exposure and
consequently UV-A exposure, this proposal also ensures that high-SPF products
contain proportionally increased levels of UV-A protection, coinciding with the
views expressed by the American Academy of Dermatology. This system also
supports communication of the level of UV-A protection in a simple, integrated
format consistent with existing SPF labeling.
BACKGROUND ON THE REQUIREMENTS FOR UV-A/UV-B

PROPORTIONALITY
The primary use of sunscreen products is to prevent sunburn and other forms of
UV damage to skin. According to Urbach (7), the ratio of damage from the UV-B
and UV-A components in sunlight over a day is 80% from UV-B and 20% from
UV-A. Of the 20% due to UV-A (320 – 400 nm), 62% of the damage risk has been
ascribed to the shorter UV-A II wavelengths (320 –340 nm). Diffey (8) and Cole
and Van Fossen (9) have described a similar relationship of UV-B to UV-A
(4B:1A ratio) for UV-induced biological effects on the skin. Therefore, to
provide proportional protection against both UV-A and UV-B, a sunscreen
must protect against the 80:20 ratio of UV-B and UV-A in incident sunlight.
The overall SPF is a composite of the UV protection provided by the sunscreen
product in both UV-B and UV-A. The biological response of the skin to sunlight
810 Agin et al.
can be expressed as MED ¼ MEDB þ MEDA, where one minimal erythemal dose
(MED) is composed of the contribution to sunburn from both the UV-B and the
UV-A wavelengths present in sunlight at any point in time. Using the 4 : 1 UV-B:
UV-A relationship above, we can calculate the minimum UV-A blockage needed to
provide UV-A/UV-B protection for any SPF level. Table 40.1 describes the number
of MEDs resulting from UV-B radiation and UV-A radiation reflecting that relation-
ship. This table also illustrates the corresponding UV-A blockage needed at each SPF
to provide minimum protection in the UV-A against sunburn and other forms of
UV-A-induced damage based on the 4B:1A ratio of incident sunlight.
While there are .30 sunburning MEDs per day possible for Fitzpatrick
(10) skin type I in the USA, a liberal estimate of the total UV-A MEDs available
per day is 4 – 6 UV-A MEDs, delivered at a fairly constant rate of 12 MED per
hour in summer (11,12). However, it is shortsighted to consider only the acute
effects of either UV-A or UV-B. Suberythemal doses and chronic doses of
UV-A as well as UV-B have been shown to produce measurable damage in the
skin. Therefore, considering only the total number of UV-A MEDs available
per day may underestimate the ability of UV-A to contribute to and exacerbate
long-term UV-B-induced skin damage, including skin cancer and photoaging.
Action spectra for UV damage to skin are also key elements to be con-
sidered in determining a method for confirming the UV-A protection provided
by sunscreens. If the action spectra for other known forms of damage are com-
pared to the action spectrum for sunburn (Fig. 40.1), it is easy to see why a
test method for assessing UV-A protection must include the effects of the
shorter-wave UV-A as well as the longer-wave UV-A. In vivo responses to
UV-A radiation, which can be measured in clinical tests using light sources
that include only UV-A wavelengths (320 –400 nm), can be used to substantiate
protection across the UV-A spectrum [Fig. 40.2(A) and (B)].
Table 40.1 At Each SPF, What Is Required for Proportional Protection?
MEDs SPF UVA UV-B Minimum PFA

incident required MEDs MEDs required
2 2 0.4 1.6 1
4 4 0.8 3.2 1
8 8 1.6 6.4 1.6
12 12 2.4 9.6 2.4
15 15 3 12 3
20 20 4 16 4
25 25 5 20 5
30 30 6 24 6
35 35 7 28 7
40 40 8 32 8
50 50 10 40 10
UVB UVA
Anders (Erythema) 1995

Cole (Carcinogenesis) 1986
Elmets (Photoimmune Suppression)
Parrish (Erythema) 1982
DNA
Carcinogensis
Figure 40.1 On the basis of the comparison of the action spectrum for sunburn to the
action spectra for the other known forms of UV damage shown, it is important to
include the effects of the shorter-wave UV-A as well as the longer-wave UV-A in any
assessment of sunscreen UV-A protection.
Protection Minimums for Proportional UV-A/UV-B Protection

Based on Table 40.1, a PFA 2 in the UV-A is needed at incident levels of 10
MEDs of sunlight and above. At levels below 10 MEDs, there is no requirement
for a PFA of 2 to prevent erythema from UV-A, as the UV-A component of
erythema is one MED or less at those levels. Nevertheless, it is desirable to incor-
porate measurable UV-A protection at all SPF levels; therefore, a minimum PFA
of 2 should be a requirement even at low SPF levels for products that claim to
protect against UV-A as well as UV-B.
The UV-A wavelengths from 320 to 340 nm have been recognized as
wavelengths that can contribute significantly to the development of skin
cancer. Studies by Kelfkens et al. (13) have shown that short-wave UV-A
(,340 nm) is five times more efficient in producing skin cancer than the
longer-wavelength UV-A. This is important in light of suggestions that the
measurement of sunscreen UV-A effectiveness be limited only to a description
of its longwave UV-A protection (i.e., to only its broadness) or that only one
“pass – fail” level of UV-A protection be recognized.
812 Agin et al.
(A) Xenon Arc Solar Simulator

(3mm WG335 and 1mm UG11 filters)
0.05
UVB UVAI
Relative Intensity
UVAII
0.04
0.03
0.02
0.01
0
290 300 310 320 330 340 350 360 370 380 390 400
Wa velength (nm)
(B) PFA and PPD Biological Response: Primarily UVA I

(Xenon arc simulator with 3m WG335 filter)
UVAII UVAI
Relative Effectiveness
5 Ery
4 Tan
3
2
1 30% (Ery) 70% (Ery)
20% (Tan) 80% (Tan)
0
320 330 340 350 360 370 380 390 400
Wavelength (nm)
Figure 40.2 (A) Spectral distribution of the UV-A source used in both the PFA and the
PPD test methods. Less than 2% of the biological response results from the UV-B con-
tained in the source. (B) The action spectra for erythema (Ery, V) (CIE) and PPD (Tan, A),
when cross-multiplied with the WG335 3 mm filtered xenon arc solar simulator, clearly
show that the predominant biological response is due to the UV-A I portion of the spec-
trum (340 –400 nm). This illustrates that the proposed in vivo test methods do not solely
test UV-A II and therefore are not redundant with SPF test results.
From an active ingredient perspective, to block the UV-A contribution to

sunburn and skin cancer, the absorbance of products of SPF 10 and above must
extend beyond the UV-A II region (320–340 nm) to be effective. This is often
achieved through the inclusion of oxybenzone or other UV-A absorbers. For
higher-SPF products, the UV-A absorbance must extend into the UV-A I region
360 nm, to achieve the UV-A/UV-B balance needed at those SPF levels. This
can be achieved by including combinations of UV-A absorbers or by increasing
the content of one or more active ingredients as needed. Products which provide
proportional UV-A/UV-B protection should be readily identifiable to consumers,

along with those products that include “extra” UV-A protection.
Beyond the Minimum Balance Requirements: Extra UV-A Protection

Based on today’s technologies, products can be created such that more UV-A
protection is provided at any SPF level than is required from a sunburn protection
standpoint. This can be done either to provide extra protection against other
forms of potential UV-A damage beyond sunburn or as a consequence of extend-
ing the spectrum of absorbance through the inclusion of certain active ingredients
which absorb well into the UV-A I (i.e., .360 nm). While the action spectrum
for photoaging effects appears to be very similar to the action spectrum for
sunburn for some biological end points such as dermal elastosis (14,15), there
have been other studies which have shown that long-wave UV-A (.340 nm)
may contribute in different ways to premature skin aging. Studies by Lowe
et al. (16) and Lavker et al. (17) suggest that repeated exposure to suberythemal
doses of UV-A may result in long-term damage, resulting in increased photo-
aging of the skin. The regular use of sunscreens with effective UV-A and UV-B
protection may help to protect against these cumulative, long-term forms of skin
damage, as well as the more acute effects.
Honigsmann (18) has suggested that a PFA of 3 (67% UV-A blocked) be
incorporated into every sunscreen product above SPF 10. However, it appears
from Table 40.1 that if only one protection factor was to be set for all UV-A
claims purposes, it would mandate more UV-A protection than is scientifically or
medically justifiable in lower-SPF products (SPF 2–8), while allowing less UV-A
protection than is actually needed for adequate UV-A protection at SPFs of 12
and above. We propose that the minimum requirement for products that provide
“extra UV-A protection” should be a PFA of 3. From there, UV-A protection that
increases as SPF increases can be incorporated into products based on UV-A protec-
tion factors determined in vivo, in combination with broadness of protection. Broad-
ness of absorbance alone does not guarantee proportionality of UV-A to UV-B.
Identification and Communication of Two Distinct Levels of

UV-A Protection
Based on specific ratios of UV-A to SPF, categories of UV-A protection can be
defined to recognize products which provide a basic, proportional UV-A/UV-B
protection, and those providing “extra UV-A protection”. Breadth of absorbance
(i.e., the product has absorbance 360 nm1) could also be determined to ensure
that the broadness of protection was appropriate to support a UV-A protection
claim at any SPF level. This could be measured using the critical wavelength
method (1) or by a spectrophotometric assessment of the absorbance spectrum.
1
According to the 1999 Final Monograph (19), p. 27672.
814 Agin et al.
The means to ensure UV-B/UV-A proportionality as SPF rises is shown in

Table 40.2. To determine the level of UV-A protection needed at any SPF, the
SPF would be multiplied by 0.20. For example, an SPF 20 product would
require a PFA of 4 to qualify as a sunscreen providing proportional UV-A/
UV-B protection. Table 40.2 also illustrates the increased UV-A protection
that would be required for formulations that would qualify for “extra UV-A
protection” in comparison to the level of UV-A protection present in formulas
that exhibit basic, proportional UV-A/UV-B protection. To qualify for the
higher level of claim, a PFA to SPF factor of 0.25 must be reached. An SPF
40 product would require a PFA of 8 for proportional UV-A/UV-B protection,
and a PFA of 10 or more to qualify for extra UV-A protection labeling. The
ratio of the UV-A protection factor to the SPF can be thought of as the “UV-A
index” and readily provides the UV-A labeling category.
Using the UV-B to UV-A relationships shown in Table 40.2, a product
could qualify as providing proportional UV-A/UV-B protection, or could
qualify for the “extra UV-A protection” claim (e.g., for products which include
avobenzone). This method of assessing and communicating protection would
serve (along with SPF as the primary indicator of product efficacy) to easily
identify products which provide a higher level of protection from UV-A and
UV-B, for the most sun sensitive consumers and for dermatology recommen-
dations. It would also serve to allow those who prefer a lower-SPF product to
identify and select a product based on their skin type or needs. Not every consu-
mer will want or need only products with extra UV-A protection. A selection of
affordable, balanced UV-A/UV-B protection products will continue to remain
important, and there should be a readily identifiable UV-A claim for the
proportional protection that they provide. This proposal would recognize the
basic UV-A protection provided by products which do not choose to utilize
Table 40.2 Providing Proportional Protection: Examples of UV-A Protection Values at

Increasing SPFs
UV-A Protection Extra UV-A Protection

PFA:SPF factor ¼ 0.20 PFA:SPF factor ¼ 0.25
SPF %UV-A blocked Minimum PFA % UV-A blocked Minimum PFA
,12 50 2 66 3
12 60 2.4 66 3
15 66 3 75 4
25 80 5 84 6.25
30 83 6 87 7.5
40 88 8 90 10
45 89 9 91 11.25
50 90 10 92 12.5
avobenzone or zinc oxide, but which do exhibit good UV-A protection

nonetheless.
The existence of two distinct levels of UV-A protection will not only allow
consumer choice, but will also challenge industry to strive to meet the higher cat-
egory by developing new technologies and new types of formulations. The “extra
UV-A protection” category would present true formulation challenges within the
limitations of the active ingredient combinations currently allowed, especially at
high SPFs. As future technologies are identified and our knowledge of the effects
of UV-A progresses, this strategy also provides the flexibility to consider higher
levels of sun protection, without altering the familiar labeling that consumers will
have come to expect on sunscreen products.
THE NEED TO MEASURE BOTH BREADTH AND QUANTITY

OF PROTECTION
Critical Wavelength and similar in vitro methods primarily measure the broad-
ness of UV-A absorbance. They do not quantitatively measure the magnitude
of protection. This has been illustrated in previous submissions to the docket
that showed that two sunscreens with similar critical wavelengths could have
very different UV-A absorbance curves and thus provide different protection
for consumers. The following figure and table [from Ref. (20)] demonstrate
that two formulations with the same SPF can have different absorption curves
and very different levels of UV-A protection. Similar findings from a recently
conducted study confirm these observations and will be discussed later. To
have a complete understanding of the UV-A protection provided by a sunscreen
product, both broadness of absorbance and magnitude of UV-A protection must
be assessed.
17 Formulation 4-A
15 Formulation 4-B
13
11
mPF
1
290 300 310 320 330 340 350 360 370 380 390 400
Wavelength (nm)
Monochromatic protection factor curves of two prototype formulations.

816 Agin et al.
Product code SPF (in vivo) lc (nm) UV-AePF

4-A 7.5 379 10.2
4-B 7.4 372 5.2
From this discussion the following important points can be made:

1. A minimum 50% UV-A efficacy (a PFA of 2) is appropriate for products
below SPF 12 that wish to make basic UV-A protection claims. Higher-
SPF products should contain correspondingly higher UV-A protection
levels to provide proportional UV-A/UV-B protection.
2. A sliding scale of minimum UV-A efficacies can be proposed so that
commensurate UV-A protection is guaranteed at each SPF based on
the PFA:SPF ratio of 0.20 (i.e., ensuring that a product provides pro-
portionally balanced protection at every SPF).
3. In addition, a higher category of protection based on a higher ratio
(PFA:SPF ¼ 0.25) would ensure that products which claim extra UV-A
protection on their labeling deliver that benefit from the perspective of
both the magnitude of UV-A protection and the breadth of absorbance.
For that higher classification, a minimum PFA of 3 would be required at
SPFs below 12, with UV-A protection rising with SPF.
4. Broadness of absorbance can be guaranteed for both the “basic” and
the “extra” levels of UV-A protection through the requirement that
all products that make UV-A claims must demonstrate absorbance
360 nm.
TESTING FORMULATIONS TO EVALUATE THE REPRODUCIBILITY

OF THE PFA AND PERSISTENT PIGMENT DARKENING UV-A TEST
METHODS, WITH ADDITIONAL ASSESSMENT OF BROADNESS
CTFA sponsored a study in which seven prototype products representing a wide
variety of sunscreen formulation vehicles and active ingredients were used to
test the reproducibility of the PFA (4) and persistent pigment darkening (PPD)
(21,22) in vivo UV-A test methods between laboratories. This test also served
to compare the results obtained by using these methods to determine if the two
methods could be used interchangeably to measure UV-A protection. In addition,
the formulas were evaluated to determine if they met the sunscreen monograph
criterion of absorbance 360 nm. The in vitro method used to assess the broad-
ness of absorbance was the CTFA method previously submitted to the FDA in
RPT 9 (1).
The protocols for the PFA and PPD [Japan Cosmetic Industry Association
(JCIA)] tests have become standard methods (4,22). In the PFA method,
erythema from UV-A is evaluated at 16 – 24 h post-exposure. In the PPD
(JCIA) method, persistent pigment darkening is assessed 2 – 4 h post-exposure.
Both methods utilize a xenon-arc solar simulator, filtered with a 3 mm WG335

filter, which includes both the UV-A II (320 –340 nm) and the UV-A I (340 –
400 nm) [Fig. 40.2(A)]. The main difference in the two test methods (other than
the post-exposure results reading time) lies in the skin types of the subjects
tested. Skin types I, II, and III are used for PFA; skin types II, III, and IV are
used for PPD. The biological response spectra for the in vivo test end points
(erythema or pigment darkening/tanning) when tested with this light source
are shown in Fig. 40.2(B). Two laboratories conducted both the PFA and the
PPD test procedures to determine the in vivo UV-A protection provided by
each of the seven prototype formulations. One laboratory included an evaluation
of the PPD results at 2, 3, and 4 h postexposure.
Two laboratories also assessed the broadness of absorbance using the Criti-
cal Wavelength method as submitted by CTFA in 1996 (1). One laboratory pro-
vided data on the critical wavelength both before and after sample preirradiation.
The other laboratory provided data based both on the labeled SPF of the samples
and on the mean (average) SPF of the formulations (however, no differences in
critical wavelengths were observed).
RESULTS
The data summary in Table 40.3 shows that for each sunscreen tested, the UV-A
protection values determined by the two in vivo test methods (PFA and PPD)
were comparable, which confirms the results of earlier studies (11,23). These
data also demonstrate that clinical test methods for assessing UV-A protection
can be used to obtain reliable, reproducible results. Similar conclusions were
made based on the multicenter study published on the PFA method by Cole
(4). Comparison of the PFA results and the PPD results from the two laboratories
is shown in Fig. 40.3(A) and (B). A comparison of the PPD results obtained at 2,
3, and 4 h post-exposure to the PFA data from the same laboratory is shown in
Fig. 40.4 and Table 40.4. The correlation of the PPD and PFA results for the
seven products is shown in Fig. 40.5.
Six of the seven products met the “broadness” criterion (i.e., absorbance
360 nm); however, they exhibited a wide range of protection levels in vivo,
as determined by the PFA and PPD methods. Only formula E, which contained
7% octyl methoxycinnamate with no added UV-A absorber, did not provide a
minimum UV-A protection value of 2. Additionally, formula E did not exhibit
absorption 360 nm. These results are shown in Table 40.3 and Fig. 40.6(A)
and (B).
Based on the data provided, we suggest that the formulation for product A be
used as a control formulation for UV-A testing. This formulation is the same SPF 15
formulation submitted by CTFA as a “high-SPF” control formulation for SPF
testing (for which SPF data and methods validation have already been provided
to FDA by CTFA November 17, 1992 on and March 6, 2000, respectively).
818 Agin et al.
Table 40.3 Test Value Comparisons
Critical
PPD PFA Wavelength (nm)
Sample—testing (JCIA, (Cole, (CTFA method,
laboratory Active ingredients, SPF Ref. 20) Ref. 4) Ref. 1)
J—TKL 10% octocrylene, 14.07 13.00

J—CPT 6% oxybenzone, 10.80 12.19 379.6
5% octyl salicylate,
3% avobenzone
J—IMSI SPF 30 380
A—TKL 7% Padimate O, 3.18 3.23
A—CPT 3% oxybenzone 3.24 3.70 360
A—IMSI SPF 15 362
I—TKL 6% Octyl methoxycin- 2.18 2.59
I—CPTs namate, 4% zinc oxide 2.27 2.36 370.4
I—IMSI SPF 12 374
G—TKL 7% Octyl methoxycin- 4.65 4.4
G—CPT namate, 3% avobenzone 3.88 4.73 376.8
G—IMSI SPF 12 379
F—TKL 5% Oxybenzone 2.95 3.43
F—CPT SPF 9 3.23 3.66 360
F—IMSI 362
E—TKL 7% Octyl methoxycin- 1.58 1.79
E—CPT namate 1.72 1.75 336
E—IMSI SPF 8 355
H—TKL 20% Zinc oxide 3.57 4.01
H—CPT SPF 4 3.98 4.34 380
H—IMSI 381
DISCUSSION
Six of the seven formulas would qualify for UV-A labeling based on the criterion
of absorbance 360 nm, based on the proposed UV-A protection classification
system described in this document. Formula E did not qualify for UV-A labeling
based on the criterion of absorbance 360 nm, nor did it meet the minimum UV-
A protection level (PFA or PPD) needed to fulfill the proportionality requirement
for basic balanced protection, and thus would not qualify for any UV-A labeling
under the proposed plan.
Formula A (SPF 15) would qualify as a product providing basic, pro-
portional UV-A protection, based on meeting the requirements of a PFA:SPF
factor of 0.20, with absorbance 360 nm. This formulation had a PFA or PPD
value of 3 and absorbance 360 nm.
Formula I (SPF 12) appears to be borderline. While its absorbance is
.360 nm, the PFA values just barely meet the requirements (PFA of 2.4) for
(A) 14
PFA-Lab1
12 PFA-Lab2
10
8
6
4
2
0
A E F G H I J
(B) 16
PPD-Lab 1
14
PPD-Lab 2
12
10
8
6
4
2
0
A E F G H I J
Figure 40.3 (A) Comparison of mean PFA results from two laboratories. (B) Compari-
son of mean PPD results from two laboratories.
14
2-HOUR PPD
12
3-HOUR PPD
10 4-HOUR PPD
16-24 HR PFA
8
6
4
2
0
A E F G H I J
Figure 40.4 Comparison of mean PPD and PFA values from one laboratory.
820 Agin et al.
Table 40.4 Comparison of Mean PPD and PFA Values from One Laboratory
Product 2 h PPD result 3 h PPD result 4 h PPD result 16– 24 h PFA result
A 3.24 3.16 .3.16a 3.61

E 1.72 1.60 1.64 ,1.64a
F 3.23 3.06 3.06 3.66
G 3.88 3.78 3.86 4.73
H 3.98 4.35 4.43 4.34
I 2.27 2.27 2.31 2.36
J 10.8 10.8 10.57 12.2
a
Data sets include one to two inexact values.
the basic level of UV-A protection. The PPD results for this formula would not
meet the requirement.
Formulas F, G, H, and J would qualify as formulas that provide extra UV-A
protection at their SPF level based on the required PFA:SPF ratio of at least 0.25,
as well as exhibiting absorbance 360 nm.
The results (Fig. 40.4) from the study on PPD (PPD/JCIA) which included
reading of results at 2, 3, and 4 h postexposure show that the biological response
is constant over that time period. While the standard time for reading PPD results
is 2– 4 h postexposure, the data show that this response appears to be very stable,
14
12
R2 = 0.999
10
8
PFA
0
0 2 4 6 8 10 12 14
PPD
Figure 40.5 For each sunscreen tested, the PPD and PFA in vivo tests provided compar-
able results. These two in vivo methods can be used interchangeably to produce reliable
data to measure the “quantity” of UV-A protection.
{ } - CTFA Product Designation

(A) 14
{J}
12
10
8
PPD
6
{G}
4 {A}
{F} {I} {H}
{E}
2
0
340 345 350 355 360 365 370 375 380 385
Critical Wavelength (nm)
{ } -CTFA Product Designation

(B) 14
{J}
12
10
8
PFA
6
{G}
4 {F}
{I} {H}
{E} {A}
2
0
340 345 350 355 360 365 370 375 380 385
Critical Wavelength (nm)
Figure 40.6 Broadness of absorbance alone (as measured by critical wavelength) does
not measure the quantity of UV-A protection or fully describe sunscreen product perform-
ance in the UV-A.
and that PFA and PPD results are comparable. The data shown in Fig. 40.3(A)
and (B) illustrate that the differences between the two laboratories for each end
point were also small, for both PFA and PPD.
A comparison of the in vivo UV-A protection values to the in vitro broad-
ness of absorbance (critical wavelength) shows that it is possible to create
formulas with a range of SPFs which can provide significant amounts of UV-A
protection as measured by the magnitude of protection (PFA or PPD) and by
the broadness of absorbance. However, the data also show that it is not possible
822 Agin et al.
to predict the magnitude of UV-A protection from either the SPF or the broadness
of absorbance (critical wavelength) at a specific SPF. As shown in Fig. 40.7(A)
and (B), when comparing formula I and formula G (both SPF 12 formulations),
we can see that formula G has a PFA or PPD value of 4 (blocks 75% of the UV-A
damage risk), while formula I has a PFA or PPD value of just over 2, which
would block just over 50% of the UV-A risk. Despite its zinc oxide content,
formula I falls slightly short in the PPD test for the minimum protection
needed to provide proportional UV-A/UV-B protection at that SPF (i.e., it did
not reach the required PPD:SPF ratio of 0.20).
{ } - CTFA Product Designation

(A) 14
{J}
12
10
8
PPD
6
{G}
4 {H}
{F}
{A}
2 {I}
{E}
0
0 5 10 15 20 25 30 35
SPF
{ } -CTFA Product Designation

(B) 14
{J}
12
10
8
PFA
6
{G}
{H}
4 {F}
{A}
2
{E} {I}
0
0 5 10 15 20 25 30 35
SPF
Figure 40.7 Sunscreens with the same SPF can exhibit different levels of UV-A protec-
tion. Therefore, the argument that PFA or PPD results are redundant with the information
provided by the SPF is not correct.
The data are also relevant to questions raised about the need to assess both the
magnitude and the broadness of UV-A protection. As shown earlier and in
Table 40.3, it is apparent that two sunscreens with the same SPF can exhibit differ-
ent levels of UV-A protection. Therefore, the argument that PFA or PPD results are
redundant with the information provided by the SPF is not accurate. This is also
highlighted by Fig. 2(B), which shows that the predominant biological response
of these in vivo test methods is due to the UV-A I portion of the spectrum (340–
400 nm). This again illustrates that the proposed in vivo test methods do not
solely test UV-A II and therefore are not redundant with the SPF test results.
It is not possible to predict the level of UV-A protection from the SPF
alone, or to predict the quantity of UV-A protection solely from the broadness
of the protection (see results for product I, earlier, and in Table 40.3). Comparing
the level of protection using the results of either the PFA or the PPD test method
to the broadness of absorbance (as measured by critical wavelength) documents
the absence of a correlation between broadness and magnitude of protection as
both the SPF and the critical wavelength values increase. This finding supports
the recommendation of the American Academy of Dermatology, which con-
cluded that measuring broadness alone is not sufficient to accurately describe
product performance in the UV-A.
CONCLUSIONS AND RECOMMENDATIONS

1. SPF should retain pre-eminence on the principal display panel, and
should continue to be the primary driver of consumer product selec-
tion. UV-A labeling should also be displayed on the principal
display panel in terms of simple text descriptors, using wording that
will allow consumers to identify and select the sunscreen product
with the level of SPF and UV-A protection that suits their skin types
and sun protection needs.
2. UV-A protection claims should be allowed for sunscreen products with
SPFs of 4 and higher. UV-A protection should increase proportionally
with higher SPFs, which can be ensured through the use of defined
ratios of SPF to PFA or PPD (see Table 40.2). A minimum PFA of 2
(blocks 50% of the UV-A) should be a requirement even at low SPF
levels (SPF ,12) for products that claim to protect against UV-A as
well as UV-B.
3. Sunscreen products can be formulated to provide proportional UV-A/
UV-B protection at each SPF level, or to exceed that requirement to
provide increased UV-A protection for those who want or need extra
UV-A protection. Therefore, two distinct categories of UV-A protec-
tion are warranted.
4. Broadness of absorbance alone does not fully measure UV-A protec-
tion or describe product performance in the UV-A. A measure of the
824 Agin et al.
“quantity” of UV-A protection provided by a product is needed in

addition to an assessment of broadness of absorbance.
5. The PPD and PFA in vivo tests provide comparable results. Either
method can produce reliable, reproducible data to measure the quantity
of UV-A protection. For practical purposes, having the option avail-
able of conducting testing for which the results can be read at 2 – 4 h
(PPD) or at 16– 24 h (PFA) may be important. For each product, the
test method would be selected in advance; all testing for that formu-
lation would be conducted using one method only. An advantage of
the PFA method (4) is that it allows inclusion of skin type I subjects,
who are those most in need of sun protection and who produce sunburn
when exposed to UV-A, whereas the PPD method can only be con-
ducted on darker skin types, who produce pigmentation. The PPD
test, however, may be convenient for some laboratories and with its
acceptance as the JCIA method, may support ongoing efforts for
global harmonization.
6. Voluntary professional labeling can be provided to physicians that will
allow them to select or recommend sunscreen products for their
patients’ needs, based on more detailed information describing the
quantity (protection factor) and the broadness of protection.
REFERENCES
1. CTFA/NDMA. CTFA/NDMA Taskforce Report on Critical Wavelength Determi-
nation for the Evaluation of the UVA Efficacy of Sunscreen Products. FDA Docket
78N-0038, RPT 9, April 9, 1996.
2. Food and Drug Administration. Letter 167, FDA Docket 78N-0038 to T.S. Elliott,
April 8, 1999.
3. Food and Drug Administration. Letter 169, FDA Docket 78N-0038 to T.S. Elliott,
November 2, 1999.
4. Cole C. Multicenter evaluation of sunscreen UVA protectiveness with the Protection
Factor A test method. J Am Acad Dermatol 1994; 30:729– 736.
5. American Academy of Dermatology, Press Release April 20, 2000. Available at
“http://www.aad.org/PressReleases/futuresunscreen.html”.
6. CTFA/NDMA. Sunscreen UVA Labeling, Market Research Study Report. FDA
Docket 78N-0038, February 6, 1996.
7. Urbach F. Ultraviolet A transmission by modern sunscreens: is there a real risk?
8. Diffey B. Human exposure to ultraviolet radiation. Semin Dermatol 1990; 9:2 –10.
9. Cole CA, Van Fossen R. Testing UVA protective agents in man. In: Urbach F, ed.
Biological Responses to Ultraviolet A Radiation. Overland Park, KS: Valdenmar
Publishing Co., 1992:335 – 345.
10. Fitzpatrick T. The validity and practicality of sun-reactive skin types I through IV.
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ultraviolet A in vivo. J Am Acad Dermatol 1987; 16:346– 353.
12. Sayre RM, Agin PP. A method for the determination of UVA protection in normal
skin. J Am Acad Dermatol 1990; 23:429 – 440.
13. Kelfkens G, de Gruijl FR, van der Leun JC. Tumorigenesis by short-wave ultraviolet
A. Carcinogenesis 1991; 12:1377 – 1382.
14. Kligman LH, Sayre RM. An action spectrum for ultraviolet induced elastosis in hair-
less mice: quantification of elastosis by image analysis. Photochem Photobiol 1991;
53:237– 242.
15. Wulf HC, Poulsen T, Davies RE, Urbach F. Narrow band UV radiation and induction
of dermal elastosis and skin cancer. Photodermatology 1989; 6:44 – 51.
16. Lowe NJ, Meyers DP, Wieder JM, Luftman D, Bourget T, Lehman MD, Johnson AW,
Scott IA. Low doses of repetitive UVA induce morphological changes in human skin.
J Invest Dermatol 1995; 105:739– 743.
17. Lavker RM, Gerberick GF, Veres D, Irwin CJ, Kaidbey KH. Cumulative effects from
repeated exposures to suberythemal doses of UVB and UVA in human skin. J Am
Acad Dermatol 1995; 32:53– 62.
18. Honigsmann H. UVA and human skin. J Photochem Photobiol B 1989; 4:229.
19. Food and Drug Administration. Sunscreen products for over the counter human use;
Final Monograph. Fed Reg 1999; 64(98):27666– 27693.
20. L’Oreal Research/Cosmair Cosmetics Corp. Comment C545. FDA Docket 78N-
0038, May 15, 1998.
21. Chardon A, Moyal D, Hourseau C. Persistent pigment darkening response as a method
for evaluation of ultraviolet A protection assays. In: Lowe NJ, Shaath NA, Pathak
MA, eds. Sunscreens: Development, Evaluation, and Regulatory Aspects. 2nd ed.
22. Japan Cosmetic Industry Association. Measurement Standards for UVA Protection
Efficacy, 1998.
23. Stanfield JW, Edmonds SH, Agin PP. An evaluation of methods for measuring sun-
screen UVA protection factors. In: Lowe NJ, Shaath NA, Pathak MA, eds. Sunscreens:
Development, Evaluation, and Regulatory Aspects. 2nd ed. New York: Marcel
Dekker, 1997:537 –557.
41
Dosimetry of Ultraviolet Radiation:
An Update
B. L. Diffey
Newcastle General Hospital, Newcastle, UK
Nature of Ultraviolet Radiation 828

Quantities and Units 829
Radiometric Calculations 829
The Standard Erythema Dose 830
Detection of UV Radiation 830
Dosimetry of UV Radiation 831
Spectroradiometry 831
Components of a Spectroradiometer 832
Input Optics 832
Monochromator 832
Detector 833
Calibration 833
Sources of Error in Spectroradiometry 833
Commercial Spectroradiometers 833
Broad-Band Radiometry 834
Spectral Sensitivity 834
Angular Response 834
Radiometers That Simulate Biological Action Spectra 835
Wavelength-Independent Radiometry 835
Radiometer Stability 835
827
828 Diffey
Measuring Personal Exposure to UV Radiation 836

Physical Dosimeters 836
Chemical Dosimeters 836
Biological Dosimeters 836
Simulated Sources of Sunlight 837
Xenon Arc Lamps 837
Fluorescent Lamps 837
References 840
NATURE OF ULTRAVIOLET RADIATION

Ultraviolet (UV) radiation covers a small part of the electromagnetic spectrum.
Other regions of this spectrum include radiowaves, microwaves, infrared radiation
(heat), visible light, X-rays, and gamma radiation. The feature that characterizes
the properties of any particular region of the spectrum is the wavelength of the
radiation. UV radiation spans the wavelength region from 400 to 100 nanometers
(abbreviated to nm). Even in the UV portion of the spectrum the biological effects
of the radiation vary enormously with wavelength and for this reason the UV spec-
trum is further subdivided into three regions. The notion to divide the UV spectrum
into different spectral regions was first put forward at the Copenhagen meeting
of the Second International Congress on Light held during August 1932. It was
recommended that three spectral regions be defined as follows:
UV-A: 400– 315 nm
UV-B: 315– 280 nm
UV-C: 280– 100 nm
The subdivisions are arbitrary and differ somewhat depending on the discipline
involved. Environmental and dermatological photobiologists normally define
the wavelength regions as:
UV-A: 400– 320 nm
UV-B: 320– 290 nm
UV-C: 290– 200 nm
The division between UV-B and UV-C is chosen as 290 nm since UV radiation at
shorter wavelengths is unlikely to be present in terrestrial sunlight, except at high
altitudes. The choice of 320 nm as the division between UV-B and UV-A is
perhaps more arbitrary. Although radiation at wavelengths shorter than 320 nm
is generally more photobiologically active than longer wavelength UV, advances
in molecular photobiology indicate that a subdivision at 330– 340 nm may be
more appropriate and for this reason the UV-A region has, more recently, been
divided into UV-AI (340 –400 nm) and UV-AII (320 –340 nm).
Dosimetry of Ultraviolet Radiation 829
QUANTITIES AND UNITS

Quantities of UV radiation are expressed using the radiometric terminology given
in the following table:
Term Unit Symbol

Wavelength nm l
Radiant energy J Q
Radiant flux W F
Radiant intensity W sr21 I
Radiance W m22 sr21 L
Irradiance W m22 E
Radiant exposure J m22 H
Terms relating to a beam of radiation passing through space are the radiant
energy and radiant flux. Terms relating to a source of radiation are the radiation
intensity and the radiance. The term irradiance, which is the most commonly
used term in photobiology, relates to the object (e.g., patient) struck by the radi-
ation. These radiometric quantities may also be expressed in terms of wavelength
by adding the prefix spectral. The time integral of the irradiance is strictly termed
the radiant exposure, but is sometimes expressed as exposure dose, or even more
loosely as dose.
Whilst radiometric terminology is widely used in photobiology, the units
chosen vary throughout the literature. For example, exposure doses may be
quoted in mJ cm22 or kJ m22. Examples of the equivalence of these units are:
To convert from To Multiply by

J cm22 mJ cm22 103
J cm22 J m22 104
J m22 mJ cm22 107
kJ m22 J cm22 107
kJ m22 mJ cm22 1010
Radiometric Calculations
The most frequent radiometric calculation is to determine the time for which a
patient (or other object), who is prescribed a certain dose (in J cm22), should
be exposed when the radiometer indicates irradiance in mW cm22. The relation-
ship between these three quantities (time, dose, and irradiance) is simply:
1000 Prescribed dose (J cm2 )
Exposure time (minutes) ¼ :
60 Measured irradiance (mW cm2 )
830 Diffey
The Standard Erythema Dose

The problem of dosimetry in skin photobiology lies in the fact that the ability of
UV radiation to elicit erythema in human skin depends strongly on wavelength,
encompassing a range of four orders of magnitude between 250 and 400 nm.
Thus a statement that a subject received an exposure dose of 1 J cm22 of UV
radiation conveys nothing about the consequences of that exposure in terms of
erythema. If the radiation source were a UV-A lamp, no erythemal response
would be seen apart from in people exhibiting severe, abnormal pathological
photosensitivity. The same dose delivered from an unfiltered xenon arc lamp
or fluorescent sunlamp would result in marked erythema in most white skinned
individuals. Consequently, there is often a need to express the exposure as an
erythemally weighted quantity.
It has been common practice for many years to use the term minimal
erythema dose (MED) as a “measure” of erythemal radiation. This is absurd
because the MED is not a standard measure of anything but, on the contrary,
encompasses the variable nature of individual sensitivity to UV radiation.
To avoid further confusing abuse of the term MED, it has been proposed (1)
that this term be reserved solely for observational studies in humans and other
animals. The term Standard Erythema Dose (SED) should be used to refer to
erythemal effective radiant exposures from natural and artificial sources of UV
radiation. One SED is equivalent to an erythemal effective radiant exposure of
100 J m22 (2). Examples of how the SED can be used are:
. The ambient diurnal exposure on a clear sky summer day in Europe is
approximately 30 –40 SED
. An exposure dose of 4 SED would be expected to produce moderate
erythema on unacclimatized white skin, but minimal or no erythema
on previously exposed skin.
DETECTION OF UV RADIATION
Techniques for the measurement of UV radiation fall into three classes: phys-
ical, chemical, and biological. In general, physical devices measure power,
whilst chemical and biological systems measure energy. The use of chemical
and biological methods usually forms the basis of integrating personal ultra-
violet dosimeters (see section titled “Measuring Personal Exposure to UV
Radiation”).
A physical UV radiation detector consists of an element that absorbs the
radiation and a means of measuring the resulting change in some property of
the element. There are two basic physical types: thermal and photon.
Thermal detectors respond to heat or power and have a broad spectral
response with near-uniform sensitivity from the ultraviolet to the infrared, the
most common example being the thermopile.
Photon detectors operate on the principle of the liberation of electrons by

the absorption of a single quantum of radiation, and consequently have a
nonlinear spectral response. Examples of photon detectors include: photoemis-
sive types (vacuum phototube, gas-filled phototube, and photomultiplier tube);
junction photodetectors (e.g., Si, GaAsP, GaP photodiodes), which may be oper-
ated with a “zero bias” (sometimes called “photovoltaic mode”) or a “reverse
bias” (sometimes called “photoconductive mode”); and photoconductors (e.g.,
CdS, CdSe, PbS, InAs).
More detailed descriptions of physical optical radiation detectors can be
found elsewhere (3).
DOSIMETRY OF UV RADIATION
Dosimetry is the science of radiation measurement. There are two principal
reasons why UV radiation should be measured: to allow consistent radiation
exposure of irradiated subjects over many months and years within a local labora-
tory; and to allow the results of irradiations made in different laboratories to be
published and compared.
It is important to distinguish between these two objectives. The first
requires precision, or reproducibility. The radiometer is used as a monitor to
give a reference measurement and so it needs to be stable. Accuracy, that is,
absolute calibration against some accepted standard, is not essential. The
second objective requires both precision and accuracy. Here the radiometer
must not only be stable from one day to the next, but also the display (in, say,
milliwatts per square centimetre) must be traceable to absolute standards.
Whilst electro-optical technology has improved over the years, resulting in the
availability of versatile and precise UV radiometric equipment, these improve-
ments have not always been accompanied by improved accuracy due to
misunderstandings about calibration.
SPECTRORADIOMETRY
It is common practice to talk loosely of UV-A lamps or UV-B lamps. However,
such a label does not characterize UV lamps adequately, since nearly all UV
lamps will emit both UV-A and UV-B, and even UV-C, visible light, and infrared
radiation. The only correct way to specify the nature of the emitted radiation is by
reference to the spectral power distribution. This is a graph (or table) that indi-
cates the radiated power as a function of wavelength. The data are obtained by
a technique known as spectroradiometry. Figure 41.1 shows the UV spectral
emission from an optically filtered xenon arc lamp. This combination of lamp
and filter produces a spectrum of radiation, which is similar to that of terrestrial
sunlight (shown by the broken line in Fig. 41.1). For this reason it is often
referred to as a solar simulator, and used as a laboratory source for determining
832 Diffey
Figure 41.1 The spectral power distribution of clear sky, terrestrial UV radiation
measured at around noon in summer at a latitude of 388S (broken line) and a xenon arc
filtered with a WG320 (2 mm thick) and UG5 (1 mm thick) filter (solid line).
photoprotection achieved by sunscreens (see section titled “Simulated Sources of

Sunlight”).
Components of a Spectroradiometer
The three basic requirements of a spectrometer system are the input optics,
designed to conduct the radiation from the source into the monochromator,
which disperses the radiation onto a detector.
Input Optics
The spectral transmission characteristics of monochromators depend upon the
angular distribution and polarization of the incident radiation as well as the pos-
ition of the beam on the entrance slit. For measurement of spectral irradiance,
particularly from extended sources such as linear arrays of fluorescent lamps
or daylight, direct irradiation of the entrance slit should be avoided. There are
two types of input optics available to ensure that the radiation from different
source configurations is depolarized and follows the same optical path through
the system: the integrating sphere or diffusers made of either ground quartz
or polytetrafluoroethylene (PTFE). Both these types of input optics produce
a cosine-weighted response, since the radiance of the source as measured
through the entrance aperture varies as the cosine of the angle of incidence.
Monochromator
A blazed ruled diffraction grating is normally preferred to a prism as the dispersion
element in the monochromator used in a spectroradiometer, mainly because of
better stray radiation characteristics. High-performance spectroradiometers, used

for determining low UV spectral irradiances in the presence of high irradiances at
longer wavelengths, demand extremely low stray radiation levels. Such systems
may incorporate a double monochromator, that is, two single ruled grating mono-
chromators in tandem, or laser holographically produced concave diffraction
gratings can be used in a single monochromator.
Detector
Photomultiplier tubes, incorporating a photocathode with an appropriate spectral
response, are normally the detectors of choice in spectroradiometers. However, if
radiation intensity is not a problem, solid-state photodiodes may be used, since
they require simpler and cheaper electronic circuitry.
Calibration
It is important that spectroradiometers are calibrated over the wavelength range
of interest using standard lamps. A tungsten filament lamp operating at a colour
temperature of about 3000 K can be used as a standard lamp for the spectral
interval 250 –2500 nm, although workers concerned solely with the UV region
(200 – 400 nm) may prefer to use a deuterium lamp.
Sources of Error in Spectroradiometry

Accurate spectroradiometry, even where only relative spectral power distributions
are used, requires careful attention to detail. Factors that can affect accuracy
include wavelength calibration, bandwidth, stray radiation, polarization, angular
dependence, linearity, and calibration sources (4).
Commercial Spectroradiometers
Modern spectroradiometers (e.g., model OL754; Optonic Laboratories, Inc.,
Orlando, FL, USA) incorporate a number of features that include:
. automated computer control of data collection and display
. wavelength accuracy of typically +0.2 nm over the spectral range
200– 1600 nm
. low stray light rejection level of 1 1028 at 285 nm by using a double
holographic grating monochromator in combination with an order
blocking filter wheel
. high sensitivity and wide dynamic range
. user selectable bandwidths.
The above type of spectroradiometer operates by stepwise scanning through the
required wavelength range at scan speeds of 0.1 – 2 nm s21. By using a diode
array as the detector in conjunction with a single grating spectrograph, instan-
taneous spectral power distributions can be obtained in much more compact
834 Diffey
and portable systems (e.g., Solatell; 4D Controls Ltd, Redruth, Cornwall, UK).
What such a device gains in speed, cost and portability, it loses in performance
in terms of stray light rejection, which is typically at a level of no better than
1 1024 at 285 nm. This is particularly important in the spectroradiometry of
solar UV-B (wavelengths ,315 nm), but may not be problem in the spectral
characterisation of UV-A lamps in studies where the investigator believes the
small UV-B (and possibly UV-C) component is of no biological significance,
possibly because of optical filtering.
BROAD-BAND RADIOMETRY
Although spectroradiometry is the fundamental way to characterize the radiant
emission from a light source, radiation output is normally measured by tech-
niques of broad-band radiometry. Broad-band radiometers generally combine a
detector (such as a vacuum phototube or a solid-state photodiode) with a wave-
length-selective device (such as a colour glass filter or interference filter) and
suitable input optics (such as a quartz hemispherical diffuser or PTFE window).
Spectral Sensitivity
In order to meet the criterion for a UV-B radiometer, say, the sensor should have
a uniform spectral response from 280 to 315 nm (the UV-B waveband) with zero
response outside this interval. In other words, the electrical output from the
sensor should depend only on the total power within the UV-B waveband
received by the sensor and not on how the power is distributed with respect to
wavelength. In practice, no such sensor exists with this ideal spectral response
(neither does one exist that measures UV-A or UV-C correctly for that matter).
All radiometers that combine a photodetector with an optical filter have a
nonuniform spectral sensitivity within their normal spectral band. Consequently
it is important that broad-band radiometers are calibrated appropriately for every
type of UV source (where type refers to the spectral power distribution) that it is
proposed to measure (5).
Angular Response
Broad-band radiometers are often used to measure the irradiance from extended
sources of radiation such as linear fluorescent lamps or the sky. In these instances
it is important that the sensor “sees” radiation coming from all parts of the source,
and does not have a limited field of view; that is, the sensor is not collimated.
Furthermore, the sensor should have a cosine-weighted response; this means
that a sensor which is measuring irradiance on a plane must weight the incident
flux by the cosine of the angle between the incoming radiation and the normal to
the surface. In practice, it is very difficult to achieve a perfect cosine-weighted
response, but sensors incorporating a PTFE or quartz input optic can get very
close and only diverge significantly from a cosine-weighted response at angles
exceeding 708 from the normal.
Radiometers That Simulate Biological Action Spectra

In evaluating sunscreen sun protection factors (SPFs), the delayed erythemal
response of the skin is the relevant biological endpoint. It may be desirable there-
fore to use a radiometer with a spectral sensitivity to match the action spectrum
for cutaneous erythema. This can be achieved reasonably well by appropriate
choice of detector/filter combination, and the most widely used instrument
that has this property is the Robertson – Berger meter (6). The result is that the
radiometer can be calibrated to read the erythemally weighted irradiance directly.
The reading is then correct for any spectral power distribution with an accuracy
limited by the degree to which its spectral response differs from the erythema
action spectrum.
WAVELENGTH-INDEPENDENT RADIOMETRY
In this technique, a detector is used that responds equally to all wavelengths of
optical radiation, such as a thermopile, and so gives the unweighted irradiance
at the point of reference. Until a few years ago, commercial thermopiles
were hand-made, expensive, and fragile devices. A major advance came with
the production of multiple junction thermopiles based on thin-film technology.
These devices are rugged and much less expensive and typified by the Dexter
range of thermopiles (Dexter Research Center, Michigan), which have found a
role in dermatological photobiology.
Thermopiles measure absolute radiant power and calibration can only be
achieved satisfactorily by national standards laboratories, such as the National
Physical Laboratory in the UK and the National Bureau of Standards in the USA.
RADIOMETER STABILITY
It should be remembered that the sensitivity of all radiometers changes with time;
frequent exposure to high intensity sources of optical radiation will accelerate
this change. For this reason, it is always a sound policy to acquire two radio-
meters, preferably of the same type, one of which has a calibration traceable
to a national standards laboratory. This radiometer should be reserved solely
for intercomparisons with the other radiometer(s) used for routine purposes.
A measurement of the same source is made with each radiometer and a ratio
calculated. It is the stability of this ratio over a period of months and years,
which indicates long-term stability and good precision.
836 Diffey
MEASURING PERSONAL EXPOSURE TO UV RADIATION

In the laboratory, UV radiation is generally measured with bench-top radiometric
systems. But in studies where personal exposure to solar UV is required—for
example, in assessing the UV dose received by sunscreen compared with
nonsunscreen users—this type of instrumentation can be bulky and expensive.
Consequently, personal UV radiation dosimeters are available and these can be
based on physical, chemical or biological devices.
Physical Dosimeters
The availability of miniature electro-optical UV sensors means that it is possible
to construct small UV detectors that can be electrically coupled to a portable data
logger carried in a trouser pocket, worn on a belt or clipped to clothing. By this
means it is possible to record UV exposure on a second-by-second basis, which
permits a clearer understanding of human behavior in sunlight (7,8).
Chemical Dosimeters
The use of chemical methods, which measure the chemical change produced
by the radiation, is called actinometry. These techniques usually form the basis
of integrating personal UV dosimeters. The most commonly used material
for studies of personal UV dosimetry has been the thermoplastic, polysulfone.
The basis of the method is that when film is exposed to UV radiation at wave-
lengths principally in the UV-B waveband, its UV absorption increases. The
increase in absorbance measured at a wavelength of 330 nm increases with UV
dose (9). In practice, the film (40 – 50 mm thick) is mounted in cardboard or
plastic photographic holders. Applications of UV dosimetry with polysulfone
film have included:
. sun exposure of children
. sun exposure from different leisure pursuits
. sun exposure from different occupations
. anatomical distribution of sunlight in humans and animals
. clinical photosensitivity studies
. UV exposure of patients from therapeutic light sources
. UV exposure of workers in industry.
Biological Dosimeters
Biological techniques of measurement are generally limited to the use of viruses
and micro-organisms. The bacteriophage T7 has been described for use as a UV
biosensor (10). It has been used to monitor ambient UV radiation, and when
combined with an appropriate optical filter, a spectral response similar to the
action spectrum for erythema in human skin can be achieved (11).
SIMULATED SOURCES OF SUNLIGHT

Xenon Arc Lamps
For many experimental studies in sunscreen photobiology, it is simply not prac-
ticable to use natural sunlight and so artificial sources of UV radiation designed to
simulate the UV component of sunlight are employed. No such source will match
exactly the spectral power distribution of sunlight and as the shorter UV wave-
lengths (less than around 340 nm) are generally more photobiologically active
than longer UV wavelengths, the usual goal is to match as closely as possible
the UV-B and UV-AII regions.
The classical so-called solar simulator consists of an optically filtered xenon
arc lamp. This lamp has a smooth continuous spectrum in the UV region and
various models of solar simulator are available with input power in the range
75 W to 6 kW and above, from companies that include Oriel Corporation, Solar
Light Company, Spectral Energy Corporation and Schoeffel Optical (12).
Optical filters and dichroic mirrors are used to shape the spectrum. In most
cases, a 1-mm thick Schott type WG320 filter is used to control the short wave-
length end of the spectrum. By varying the thickness of the filter from 1 to 1.5
or 2 mm, spectra are obtained that approximate varying solar altitudes. The simu-
lator normally also incorporates an UV-transmitting, visible light absorbing filter
(e.g., Schott UG5 or UG11) or other filters or multiple dichroic mirrors to remove
visible and infrared wavelengths. The spectrum of a solar simulator is compared
with natural sunlight in Fig. 41.1. A comprehensive review of solar simulators,
with specific reference to sunscreen testing, is given by Wilkinson (12).
Fluorescent Lamps
A drawback of arc lamp solar simulators is that the irradiation field is generally
limited to less than around 15 15 cm, although it is possible to achieve uniform
flux over a larger area albeit with a reduction in irradiance. This may pose little
problem if the object is to irradiate small areas of skin but for studies where a
large area of skin or large numbers of experimental animals are to be irradiated,
the limited irradiation field is a real problem. Because of this attention has turned
to fluorescent lamps as sources of simulated UV (13). One way to evaluate can-
didate lamps and decide which is the most appropriate approximation to sunlight
is to calculate the % relative cumulative erythemal effectiveness (%RCEE) for a
number of wavebands and to compare these values with the %RCEE values of a
“standard sun” (see Table 41.1). The %RCEE for the spectral range 290 to lc is
the erythemally effective UV radiation within this waveband expressed as a per-
centage of the total erythemally effective radiation from 290 to 400 nm. This is
calculated mathematically as:
Pl c
E(l) 1(l) Dl
%RCEE ¼ 100 P290 400
290 E(l) 1(l) Dl
838
Table 41.1 Summer Solar Spectral Irradiance at Noon on Clear Days
388Na 388Sb 388Na 388Sb 388Nb 388Sb

l (nm) (W m22 nm21) (W m22 nm21) l (nm) (W m22 nm21) (W m22 nm21 l (nm) (W m22 nm21) (W m22 nm21)
290 0.0000 0.0000 327 0.473 0.618 364 0.648 0.808

291 0.0000 0.0000 328 0.501 0.566 365 0.683 0.766
292 0.0000 0.0001 329 0.517 0.629 366 0.718 0.967
293 0.0001 0.0002 330 0.532 0.708 367 0.740 0.911
294 0.0002 0.0004 331 0.533 0.612 368 0.762 0.861
295 0.0007 0.0009 332 0.533 0.632 369 0.764 0.872
296 0.0012 0.0019 333 0.528 0.630 370 0.766 0.975
297 0.0023 0.0030 334 0.523 0.601 371 0.758 0.856
298 0.0033 0.0048 335 0.514 0.667 372 0.750 0.814
299 0.0060 0.0089 336 0.504 0.575 373 0.706 0.787
300 0.0086 0.0111 337 0.502 0.536 374 0.661 0.705
301 0.0161 0.0196 338 0.499 0.617 375 0.664 0.685
302 0.0236 0.0235 339 0.519 0.660 376 0.666 0.845
303 0.0335 0.0513 340 0.539 0.765 377 0.706 0.876
304 0.0435 0.0574 341 0.549 0.650 378 0.746 1.10
305 0.0577 0.0807 342 0.559 0.680 379 0.750 0.917
306 0.0719 0.0812 343 0.547 0.719 380 0.754 0.839
307 0.0844 0.113 344 0.535 0.570 381 0.698 0.957
Diffey
308 0.0968 0.135 345 0.535 0.640 382 0.642 0.693

309 0.115 0.127 346 0.534 0.642 383 0.614 0.543
310 0.134 0.147 347 0.536 0.680 384 0.585 0.587
311 0.155 0.235 348 0.537 0.638 385 0.605 0.834
312 0.175 0.215 349 0.548 0.640 386 0.626 0.724
313 0.194 0.246 350 0.559 0.724 387 0.649 0.775
314 0.213 0.269 351 0.574 0.743 388 0.672 0.765
315 0.228 0.283 352 0.589 0.717 389 0.715 0.795
316 0.243 0.243 353 0.601 0.695 390 0.757 0.948
317 0.261 0.371 354 0.613 0.829 391 0.737 1.03
318 0.279 0.316 355 0.608 0.832 392 0.716 0.948
319 0.297 0.353 356 0.603 0.757 393 0.686 0.494
320 0.314 0.401 357 0.570 0.603 394 0.655 0.609
Dosimetry of Ultraviolet Radiation
321 0.323 0.400 358 0.538 0.582 395 0.668 0.988

322 0.332 0.405 359 0.551 0.594 396 0.681 0.862
323 0.346 0.359 360 0.564 0.854 397 0.741 0.510
324 0.361 0.444 361 0.582 0.669 398 0.801 1.02
325 0.403 0.448 362 0.600 0.671 399 0.906 1.25
326 0.445 0.600 363 0.624 0.795 400 1.01 1.27
a
Measured in Albuquerque (388N) at noon on 3 July. Measurements were made at 2-nm intervals and interpolated values have been added here to give points every
1 nm (15).
b
Measured in Melbourne (388S) at solar noon on 17 January 1990. Measurements were made at the Australian Radiation Laboratory with a Spex 1680B double
monochromator with a resolution of 1 nm (16).
839
840 Diffey
Table 41.2 The UV-B and UV-A Components and the Percentage Relative Cumulative
Erythemal Effectiveness (%RCEE) for the Summer Sun and a Number of Fluorescent
Lamps
Suna (%) A (%) B (%) C (%) D (%) E (%)
%UV-B (290– 315 nm) 3.35 55.64 2.58 4.54 4.30 3.43
% UV-A (315 – 400 nm) 96.65 44.36 97.42 95.46 95.70 96.57
Lower and upper limits of the %RCEE according to COLIPA (14)
,290 nm (,1.0%) 0.047 19.6 0.087 0.095 0.000 0.089
290 – 310 nm (46.0– 67.0%) 62.3 77.6 51.4 60.7 42.8 53.4
290 – 320 nm (80.0– 91.0%) 86.4 80.2 79.2 86.7 80.9 81.9
290 – 330 nm (86.5– 95.0%) 91.7 80.4 86.5 92.4 88.8 89.0
290 – 340 nm (90.5– 97.0%) 94.0 80.4 91.0 95.1 93.0 92.8
290 – 350 nm (93.5– 99.0%) 95.8 80.4 94.5 97.1 96.4 95.9
Note: Lamp A, TL-12 (“fluorescent sunlamp”); Philips Lighting, The Netherlands; Lamp B,
Bellarium S; Wolff System, Germany; Lamp C, Arimed B; Cosmedico, Germany; Lamp D, CLEO
Natural; Philips Lighting, The Netherlands; Lamp E, UV-A-340; Q-Panel Lab Products, Cleveland
OH, USA.
a
Melbourne summer sun (see Table 41.1).
E(l) is the relative spectral power distribution of the UV source and 1(l) is the
effectiveness of radiation of wavelength l nm in producing erythema in human
skin (2). Table 41.2 compares %RCEE values from a number of fluorescent
lamps with lower and upper acceptance limits for a “standard sun” given by
the European Cosmetic, Toiletry and Perfumery Association (COLIPA) (14). It
can be seen that the Arimed B lamp is perhaps the best choice as a source of simu-
lated solar UV radiation from those given, although there is little to chose
between this lamp and some of the others. The TL-12 (equivalent spectrum to
the Westinghouse sunlamp), a mainstay of photobiological research for many
years, is a poor surrogate for solar UV radiation.
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12. Wilkinson F. Solar simulators for sunscreen testing. In: Matthes R, Sliney D, eds.
Measurements of Optical Radiation Hazards. Vienna: International Commission on
Non-Ionizing Radiation Protection, 1998:653– 684.
13. Brown DB, Peritz AE, Mitchell DL, Chiarello S, Uitto J, Gasparro FP. Common flu-
orescent sunlamps are an inappropriate substitute for sunlight. Photochem Photobiol
2000; 72:340– 344.
14. COLIPA. Sun Protection Factor Method. Brussels: European Cosmetic Toiletry, and
Perfumery Association (COLIPA), 1994.
15. Sayre RM, Cole C, Billhimer W, Stanfield J, Ley RD. Spectral comparison of solar
simulators and sunlight. Photodermatol Photoimmunol Photomed 1990; 7:159– 165.
16. Gies HP, Roy CR, McLennan A, Diffey BL, Pailthorpe M, Driscoll C, Whillock M,
McKinlay AF, Grainger K, Clark I, Sayre RM. UV protection by clothing: an inter-
comparison of measurements and methods. Health Phys 1997; 73:456 – 464.
42
Spectral Standardization of Sources
Used for Sunscreen Testing:
5 Years of Compliance
Robert M. Sayre and John C. Dowdy

Rapid Precision Testing Laboratories, Cordova, Tennessee and
University of Tennessee Center for the Health Sciences,
Introduction 843
Methods 845
Instrumentation 845
Calibration Procedures 845
Measurement Procedures 845
Measurement Uncertainty 846
Results 846
Discussion 848
Conclusion 850
References 851
INTRODUCTION
In 1978, the US FDA published a report and monograph on sunscreen product
testing and labeling (1). This monograph established that a solar simulator
would be a source having a continuous emission spectrum from 290 to 400 nm
and be filtered for a solar zenith angle of 108 and have less than 1% of its
843
844 Sayre and Dowdy
energy contributed by wavelengths shorter than 290 nm. In addition, to avoid

purported thermal problems, they also required that the solar simulator could
not have more than 5% of its energy contributed by wavelengths longer than
400 nm. The beam uniformity is required to be within 10%. Specifically, latter
monographs have recommended that a solar simulator requires periodic
remeasurement with a calibrated spectroradiometer to insure the proper spectral
distribution (2 – 4).
Efforts to refine the specifications of the solar simulator used for SPF
testing have, over time, resulted in several additional proposed and adopted stan-
dards. In1990 Sayre et al. proposed a spectral standard for solar simulators
recommending an upper- and lower-wavelength range appropriate for SPF
testing (5). A similar, slightly less stringent, implementation of this approach
was subsequently adopted in the Australian/New Zealand Standard for evalu-
ation and classification of sunscreen products (6).
In 1994 COLIPA (The European Cosmetic, Toiletry, and Perfumery
Association) published a method to test sunscreen products together with
specifying a compliance standard for solar simulators (7). In 1999 the US
Food and Drug Administration (FDA) was petitioned urging the adoption of
the COLIPA Standard for Solar Simulators (8). The latest rendition of the
Final Monograph did not formally adopt this recommendation, but as of this
writing there is at least one petition to reopen the monograph pending (4).
The COLIPA standard requires that the spectrum of a solar simulator be
measured throughout the ultraviolet (UV) from 250 to 400 nm. The spectrum
measured is multiplied by the Commission Internationale de l’Éclairage (CIE)
(McKinlay –Diffey) erythemal action spectrum to calculate the effective irradi-
ance (9). The solar simulator is specified based on the percentage of erythemal
effective radiation within a series of overlapping spectral ranges (Table 42.1),
which is termed percent relative cumulative erythemal effectiveness (%RCEE).
An important point to consider about this standard is that unlike natural
sunlight, it requires only 1% of the erythemally effective risk to be at UV-A
wavelengths longer than 350 nm. The other point about this standard is that
Table 42.1 COLIPA (1994) Solar Simulator

Specifications
Percent erythemal effective Acceptance limits

irradiance (%RCEE) (nm) (%)
,290 ,1.0
290 – 310 46.0 –67.0
290 – 320 80.0 –91.0
290 – 330 86.5 –95.0
290 – 340 90.5 –97.0
290 – 350 93.5 –99.0
Spectral Standardization of Sources for Sunscreen Testing 845
there is no requirement that the source be absolutely continuous and a source with
prominent spectral lines is acceptable as long as it meets the overall requirements.
One finds that in addition to xenon arcs, mercury metal halide lamps and even flu-
orescent lamps can meet the standard. SPF testing labs in the USA and Canada,
however, almost exclusively use filtered xenon arc Solar Light (Solar Light Co.,
Inc., Philadelphia, PA) solar simulators of the single port or multiport design.
Unlike Europe, where sunscreens are typically categorized as cosmetics not
subject to regulatory mandate, the US FDA regulates sunscreen products as
over-the-counter drugs (1 – 3). Consequently, SPF testing laboratories servicing
the US market routinely monitor their solar simulators for compliance with all
applicable standards as part of their respective quality assurance programs.
This study, presented in part to the 2000 International Congress of Photobiology,
presents a retrospective compilation of solar simulator compliance data from six
participating North American SPF testing laboratories for the 5-year period from
1995 to 2000 (10).
METHODS
Measurement of a solar simulator requires three separate activities: calibration of
the spectroradiometer, measurement of the source, and finally a recheck of the
instrument response and recalibration of the system.
Instrumentation
The instrument used for these measurements is an OL-754 double grating spec-
troradiometer (Optronic Laboratories, Inc., Orlando, FL). For solar simulator
spectral measurement the spectroradiometer was configured with an integrating
sphere with a 6 mm entrance aperture to collect the radiation and 0.125/1.0/
0.125 mm slits. This spectroradiometer comes with a device to check the photo-
metric gain using a small tungsten – halogen source and check the wavelength
accuracy using a small fluorescent source. Before each calibration and measure-
ment the wavelength calibration and gain are checked or established.
Calibration Procedures
The OL 754 spectroradiometer was calibrated using a tungsten– halogen spectral
irradiance standard lamp annually certified traceable to NIST. The calibration
was transferred in 1 nm increments using procedures established by the manufac-
turer (Optronic Laboratories) of both the spectroradiometer and the NIST trace-
able tungsten standard source. The calibration spectrum used is the average of
three spectral measurements of the standard.
Measurement Procedures
Spectral irradiance measurements were made at 1 nm intervals from 250 to
800 nm. Data were saved to magnetic media and identified using a portion of
846 Sayre and Dowdy
the solar simulator site/serial number to establish the identity of the system
measured. The center of the beam at the site for irradiating human volunteers
was selected for spectroradiometric measurement and represents the highest
intensity to which a human volunteer might be exposed. A special plug-in aper-
ture was used to position the liquid waveguides of multiport solar simulators.
The final quality control check, conducted after solar simulator spectral
irradiance measurements, consisted of repeating all checks performed prior to
calibration. The result of this check and the subsequent recalibration of the
system with the tungsten standard source indicate that the spectral radiometer
functioned the same throughout this period of measurement.
Measurement Uncertainty
Our estimate is that the total possible uncertainty for measuring a solar simulator
is less than 12% (Table 42.2). The major sources of uncertainty, potentially up to
10%, is that which may be attributed to reproducible positioning of the spectro-
radiometer relative to the source and to changing laboratory environments. The
uncertainty from changing laboratory environments is due to different levels of
electronic noise, temperature, and humidity between laboratories and the same
laboratory from visit to visit.
RESULTS
A typical Solar Light single-port solar simulator, used for sunscreen SPF testing,
consists of a 150 W ozone-free xenon arc which is filtered with a WG-320 filter
Table 42.2 Measurement Uncertainty Factors
Uncertainty
Uncertainty factor Uncertainty (%) squared
1. Standard lamp uncertainty to NIST 2 0.0004000

2. Calibration transfer to spectroradiometer 3 0.0009000
3. Stray radiation 0.10 0.0000010
4. Nonlinearity of response throughout 1 0.0001000
measurement range
5. Wavelength uncertainty 0.20 0.0000040
6. Wavelength repeatability 1 0.0001000
7. Noise in measurements 0.10 0.0000010
8. Reproducibility of measurements 1 0.0001000
9. Source positioning uncertainty 5 0.0025000
10. Laboratory environment 10 0.0100000
Sum quadrature uncertainties 0.0141060
Uncertainty 11.88%
of appropriate thickness and generally a UG-11 to remove excess visible. A set

of representative spectral measurements collected on a typically configured
single-port solar simulator (Fig. 42.1) show from year to year that there has
not been much change in spectral distribution and only very slight variation in
power level. Only one solar simulator using the less common configuration of
a UG-5 filter in place of the usual UG-11 (Fig. 42.2) was monitored in this
study. Over the years there appear to be some minor changes in the UV-B
distribution; however, this variation is not progressing from year to year.
The other type of solar simulator commonly used for sunscreen SPF testing
in North America is the Solar Light multiport. It has six complete sets of optics,
configured with WG-320 and UG-11 filters, and six waveguides. The multiport’s
cooling fans force hot air over the waveguides, which consequently show thermal
aging over time and periodically must be replaced. Compared to the single-port
solar simulators, the multiport systems (Fig. 42.3) show a comparable magnitude
of spectral variability per waveguide from year to year.
To compare solar simulators within the framework of COLIPA, we
analyzed all data for each solar simulator, or multiport light guide, throughout
the period of measurement and calculated the mean COLIPA results along
with the standard deviation. This we have replotted (Fig. 42.4) within the
%RCEE limits for all COLIPA ranges plus an additional non-COLIPA category
for UV-A longer than 350 nm.
Figure 42.1 Spectral measurements collected on a typically configured Solar Light

single-port solar simulator. For over 5 years, with regular maintenance, there was little
detectable change in spectral cutoff or distribution over the 290 – 350 nm range and only
slight variation in power level. Typical configuration consists of a 150 W ozone-free
xenon arc combined with a WG-320 short-wavelength cutoff filter and a UG-11 UV
band pass filter to limit visible emission.
848 Sayre and Dowdy
Figure 42.2 Spectral measurement series of a UG-5 single-port solar simulator. Over
the measurement period reported, there is some variation in the 295 – 370 nm range,
which does not appear to be a function of measurement interval. This configuration
uses a UG-5 bandpass filter which does not limit visible emission to the same extent as
the UG-11.
For the single-port solar simulators (Fig. 42.4A), stray radiation of

,290 nm is in the lower half of the range allowed. In the 290– 310 nm range,
some diversity is observed. Over the next four ranges, the data for individual
single-port systems are consistently in the upper acceptable range tending to
push the limit. For the final non-COLIPA range of UV-A longer than 350 nm,
all single-port solar simulators are at the bottom of the range allowed, that is,
they have significantly less UV-A-1.
For the multiport solar simulator (Fig. 42.4B), stray radiation of ,290 nm
for all waveguides is also in the lower half of the range allowed. For the 290 –
310 nm range, there is some diversity, but unlike the single ports the waveguides
all lie at the bottom of the limit range. In the 290 – 320 nm range, the waveguides
lie just below midlimit range. Over the next three ranges, the data for individual
waveguides are uniformly in the middle of the acceptable range. For the final
non-COLIPA range of UV-A longer than 350 nm, all solar waveguides are at
the middle of the range allowed, still there is significantly less UV-A-1.
DISCUSSION
The solar simulators presented in this study are all commercial units. All units are
used daily and are well maintained. From the presentation of this set of represen-
tative solar simulators at six laboratories, it is clear that these devices not only are
consistently compliant but also have changed very little even with extensive
Figure 42.3 Characteristic multiport solar simulator spectral series. This model solar
simulator is arrayed with six identical sets of optics (1 – 6) incorporating liquid light
guides in addition to the usual WG-320 and UG-5 filter combination. Through several
cycles of annual remeasurement, the multiport solar simulators showed spectral distri-
bution and variability similar to comparably filtered single-port systems.
usage during the years reported. In spite of periodic lamp replacement, the long-
term changes to individual solar simulators or between different solar simulators
at various locations have all been minor. However, because many systems appear
to push limits, it is critical that exacting standards of measurement are followed.
It is equally important that the spectral radiometric equipment be rigorously
maintained and precise checks performed in association with each measure-
ment made.
It is unlikely that within this particular grouping of instruments, with the
possible exception of the UG-5 system, any test might be different because of
the particular solar simulator used. However, with only a single multiport solar
simulator being included in this review, potentially the multiport type may be
less stable from year to year because of the optical complexity of maintaining
waveguides and in essence having six independent optical systems potentially
aging at different rates.
850 Sayre and Dowdy
Figure 42.4 Comparison of single-port and multiport solar simulators. To compare solar
simulators over time within the framework of COLIPA, we have analyzed all data through-
out the period of measurement for each single-port solar simulator (A) or multiport
waveguide (B). The mean COLIPA %RCEE results along with the standard deviation
calculated are shown within the COLIPA limit range for all ranges. The single-port
solar simulators all invariably push the maximum limits of the acceptable COLIPA
ranges. An additional non-COLIPA .350 nm range shows that neither type of solar
simulator appears to have abundant levels of UV-A-1 radiation.
In this review we have shown that a particular set of solar simulators have
successfully been maintained to a rather tight and reproducible spectral profile
over a period of years. However, the emission limits of the COLIPA specification
have been suggested as being too broad (8). This was demonstrated by the failure
of identical products to produce comparable SPFs when tested with solar
simulators at opposite ends of the COLIPA acceptance limits (11). With
proper maintenance, solar simulators should be able to meet a tighter revised
standard in the future.
CONCLUSION
The spectral standardization of solar simulators used for sunscreen SPF testing is
important because the resulting SPF of a sunscreen product should be indepen-
dent of the solar simulator used for testing, the testing location, and the date
tested. Spectral standards for solar simulators used for SPF testing are specified
within the requirements of the 1978, and subsequent, US FDA sunscreen mono-
graphs and the 1994 COLIPA SPF test method. Most solar simulators employed
in sunscreen testing by reputable US and Canadian laboratories have been
routinely monitored for compliance with applicable standards for many years.
This retrospective presents a compilation of solar simulator compliance data
from six participating North American SPF testing laboratories over a 5-year
period from 1995 to 2000. During this period solar simulators, with proper
laboratory maintenance have met the standard(s) and have continued to do so
from year to year even when used daily.
REFERENCES
use. Fed Reg 1978; 45:38208 – 38269.
2. Food and Drug Administration. Tentative final monograph. Fed Reg 1993; 58:28194 –
28302.
3. Food and Drug Administration. Sunscreen Drug Products for Over-the-Counter
Human Use. Final Monograph. In: Federal Register, GPO, 1999:27666– 27693.
4. Part 352—Sunscreen Drug Products for Over-the-Counter Human Use. In: Code of
Federal Regulations, Title 21, US Government Printing Office, 2001:275 – 285.
5. Sayre RM, Cole C, Billhimer W, Stanfield J, Ley RD. Spectral comparison of solar
simulators and sunlight. Photodermatol Photoimmunol Photomed 1990; 7:159– 165.
6. Australian/New Zealand Standard. Sunscreen Products—Evaluation and classifi-
cation. Standards of Australia and Standards of New Zealand, 1998.
7. COLIPA. Colipa Sun Protection Factor Test Method. The European Cosmetic,
Toiletry and Perfumery Association—Colipa, 1994.
8. Sunscreen Drug Products for Over-the-Counter Human Use. Final Monograph.
Extension of Effective Date: Reopening of Adminstrative Record. In: Federal
Register, GPO, 1999:36319– 36324.
9. A reference action spectrum for ultraviolet induced erythema in human skin. In:
Human Exposure to Ultraviolet Radiation: Risks and Regulations. Proceedings of a
seminar held in Amsterdam, March 23– 25, 1987. Amsterdam: Excerpta Medica,
1987:83– 87.
10. Sayre RM, Dowdy JC, Damstra M, Harrison LB, Lockhart L, Schwartz S, Wood C,
Potrebka JL, Shanahan RW. 13th International Congress of Photobiology,
San Francisco, 2000:254.
11. Sayre RM, Stanfield J, Bush AJ, Lott DL. Sunscreen standards tested with differently
filtered solar simulators. Photodermatol Photoimmunol Photomed 2001; 17:278 – 283.
43
In Vitro Techniques in Sunscreen
Development
Joseph W. Stanfield
Suncare Research Laboratories, LLC, Winston Salem,
North Carolina, USA
Introduction 854
Basic Principles of In Vitro Measurements of Sunscreen Protection 854
Experience with In Vitro Measurements of Sunscreen Protection 856
Early In Vitro Measurements of Sunscreen SPF 856
The O’Neill Step Film Model 858
SPF Predictions Using the Step Film Model 860
Substrates for In Vitro Measurements of Sunscreen Protection 860
Critical Wavelength 861
Simultaneous In Vitro Measurement of SPF and Photostability 862
UV-A Index 865
Ring Test of In Vitro SPF, PPDPF, and UV-A Index Measurements 866
European Ring Test of In Vitro SPF Measurements 869
Discussion 873
Product SPF Values 873
Product Application and Substrate Considerations 873
UV Source 875
Beam Geometry 876
Photostability 876
Applications of Sunscreen Transmittance Spectra 877
Conclusions 877
References 877
853
854 Stanfield
INTRODUCTION
The ideal index of sunscreen protection would predict product performance in
understandable terms for all consumers over the full range of possible conditions
of use. Such an index would be measurable with reliability and precision for all
product forms and compositions, and its measurement would be rapid and inex-
pensive and would not require testing on humans or animals. Unfortunately, there
is no such index, at present, and the chronic effects of sunlight are not understood
sufficiently to permit rigorous definition of the need for sunscreen protection
beyond prevention of sunburn.
There is general agreement that the sun protection factor, SPF, is a valid
index of protection against acute sunburn, although the SPF measured on
human subjects has been reported to vary by as much as 20% among test subjects
and by as much as 40% among laboratories (1). Factors that make accurate SPF
measurements difficult include the inherent nonuniformity of product appli-
cation, variability of lamp spectra and the subjectivity of the minimal erythema
dose (2,3). At present, the SPF serves as an accepted measure of sunscreen
protection and the benchmark for in vitro methods of formula assessment.
A common misconception is that the goal of in vitro SPF measurement is to
quantitate protection against outdoor sunburn. The true goal of in vitro SPF
measurement is to predict the product SPF measured on humans in the laboratory
using an artificial light source. If the SPF measured in vitro is sufficiently accu-
rate, the sunscreen formulator has a powerful and economical resource for use in
screening new formulas for further testing. If the SPF predicted by in vitro
measurement matches the SPF measured in vivo, it is reasonable to assume
that the in vitro transmittance spectrum is correct. Then the formulator has a
valuable resource that can permit preliminary assessment of product protection
against any portion of the solar spectrum for any acute or chronic effect of sun-
light having a known action spectrum.
Over the past three decades, in vitro measurements of sunscreen SPF have
yielded varying degrees of success, particularly for the current generation of
sunscreens with high SPFs and finely tuned emulsions, and newer actives such
as avobenzone and others that are yet not approved for use in the USA.
This chapter will present basic principles, describe experience to date and dis-
cuss problem areas and solutions for in vitro measurements of sunscreen protection.
BASIC PRINCIPLES OF IN VITRO MEASUREMENTS OF

SUNSCREEN PROTECTION
The in vitro SPF test simulates the in vivo SPF test by measuring the sunburning
energy transmitted through a sunscreen on a suitable substrate. This is shown
schematically in Fig. 43.1.
The ultraviolet (UV) detector system may be a spectrophotometer, a spec-
troradiometer, or a photometer with a response corresponding to the erythema
action spectrum. For a spectrophotometer the UV source is a built-in xenon arc
In Vitro Techniques in Sunscreen Development 855
UV Source
I0 λ
I0 λ
Sunscreen
Substrate
Is λ I(s+ss) λ
UV Detector System
Figure 43.1 Schematic diagram of the in vitro SPF test.
or flash lamp or a tungsten lamp. For a spectroradiometer or photometer the

source is usually external and may be a xenon arc lamp solar simulator or
other type of lamp selected by the user.
The sunscreen spectral transmittance is given by:
I(sþss)l
Tl ¼ (1)
Isl
where I(sþss)l is the spectral irradiance transmitted by the sunscreen/substrate, Isl
is the spectral irradiance transmitted by the substrate alone, and I0l is assumed
constant.
The SPF of the sunscreen for a given UV source is then calculated using the
expression developed by Sayre et al. (4):
Ð 400
290 I0l sl dl
SPF ¼ Ð 400 (2)
290 I0l Tl sl dl
where I0l is the spectral irradiance of the UV source and sl is the erythemal effec-
tiveness factor for wavelength l as defined by MacKinlay and Diffey (5). The
erythemal effectiveness curve is shown in Fig. 43.2.
Figure 43.3 shows the standard solar spectrum, which represents a maximal
solar spectrum for a cloudless sky and high solar elevation angle at 35 – 408 north
latitude (6).
Figure 43.4 shows the spectrum of a typical 150 W xenon arc solar simu-
lator (Model 16S, Solar Light Company, Philadelphia) with a 1 mm WG320
UV-C-blocking filter (Schott), a heat-rejecting dichroic mirror, and a UG-11
visible/infrared-blocking filter (Schott).
856 Stanfield
1.000E+01 UVB UVA

Erythemal Effectiveness
1.000E+00
1.000E-01
1.000E-02 sλ
1.000E-03
1.000E-04
290 300 310 320 330 340 350 360 370 380 390 400
Wavelength (nm)
Figure 43.2 The erythemal effectiveness curve. [From McKinlay and Diffey (5).]
From Figs. 43.3 and 43.4, it is apparent that solar simulator spectra may
differ significantly from solar spectra, particularly at wavelengths shorter than
300 nm and longer than 370 nm.
EXPERIENCE WITH IN VITRO MEASUREMENTS OF

SUNSCREEN PROTECTION
Early In Vitro Measurements of Sunscreen SPF
In 1978, Sayre and coworkers (4), reported the results of SPF measurements of
seven commercially avaliable sunscreens on human volunteers, in isopropanol
solutions and from thin films on excised hairless mouse epidermis. The sunscreen
formulas had mean SPF values on human volunteers ranging from 4.6 to 17.4, for
panels of 10 or 11 volunteers, each. Measurements of sunscreen absorbance
1.000E+03
Spectral Irradiance (W/cm2/nm)
1.000E+02
1.000E+01
1.000E+00 Erythemally Effective
1.000E-01
1.000E-02
1.000E-03 UVB UVA
1.000E-04
1.000E-05
1.000E-06
290 300 310 320 330 340 350 360 370 380 390 400
Wavelength (nm)
Figure 43.3 The standard solar spectrum. [From COLIPA (6).]

1.000E-04
Spectral Irradiance (W/cm2/nm)
1.000E-05
1.000E-06
Erythemally Effective
1.000E-07
1.000E-08
1.000E-09
1.000E-10
1.000E-11
1.000E-12
290 300 310 320 330 340 350 360 370 380 390 400
Wavelength (nm)
Figure 43.4 A typical solar simulator spectrum.
spectra in isopropanol solutions and computation of SPF for these formulas

yielded values from 10 times to 1017 times the mean SPF values measured on
human volunteers. Measurements of sunscreen absorbance spectra on excised
hairless mouse epidermis yielded mean SPF values ranging from 57% to 131%
of mean SPF values measured on human volunteers for the same formulas.
These results are shown in Table 43.1.
In 1980, Sayre and coworkers (7) reported comparisons of water-resistant
SPF measured on hairless mouse epidermis and on human subjects for six sun-
screen formulas. The sunscreen formulas had mean SPF values on human subjects
ranging from 2.8 to 8.0 for panels of 10 –20 volunteers, each, after 40 min of
exposure to circulating water or outdoor swimming. Measurements of sunscreen
forward scattering spectra on excised hairless mouse epidermis after 40 min of
Table 43.1 SPF from the Human SPF Test, Isopropanol Solutions, and Hairless Mouse
Epidermis
SPF from human SPF from isopropanol SPF from hairless

Product volunteersa solutions mouse epidermis
A 17.4 + 3.2 3.9 1018 22.8 + 10.1

C 13.0 + 4.1 1.4 109 12.4 + 9.3
G 12.0 + 3.1 2.8 102 6.8 + 1.5
B 8.2 + 2.7 8.0 107 10.2 + 0.0
E 8.1 + 2.4 7.9 108 9.5 + 4.9
D 6.7 + 1.7 6.5 106 6.8 + 1.2
F 4.6 + 1.0 6.6 105 3.4 + 0.5
a
n ¼ 10 or 11.
Source: From Sayre et al. (4).
858 Stanfield
Table 43.2 Water Resistant SPF (40 min) Measured on Human Subjects and Hairless
Mouse Epidermis
Product
A B C D E
Human 2.8 3.7 5.1 5.8 8.0

Hairless mouse epidermis 2.5 5.3 4.8 7.8 13.0
Source: From Sayre et al. (7).
exposure to a water bath yielded mean SPF values ranging from 71% to 112% of
mean SPF values measured on human subjects for the same formulas. These
results are shown in Table 43.2.
Sayre and coworkers measured sunscreen absorbance spectra of sunscreen
films by obtaining forward scattering scans of hairless mouse epidermis, with and
without the sunscreens. Sunscreens were applied at 2 mL/cm2, which was the
same amount used for testing on human volunteers. Forward scattering spectra
were measured at 5-nm intervals from 250 to 400 nm, using a Beckman spectro-
photometer fitted with an integrating sphere. A 2-mm UG-5 filter was used in
both the sample beam and the reference beam to remove fluorescence emitted
in the visible region by the mouse epidermis and some of the sunscreen ingredi-
ents. The authors stated that without this correction the SPF values would have
been much less accurate for many of the sunscreens tested.
At that time, there was no satisfactory explanation for the discrepancy
between results for solutions of ingredients and SPF values measured on
human subjects. Similar discrepancies with SPF values measured on human sub-
jects were seen for measurements on quartz plates and thin film “sandwiches” of
products between quartz plates. The failure of these methods was attributed to
lack of interactions with the skin surface and even failure of the physical laws
governing spectroscopic measurements. The accuracy of results for thin films
on a biological substrate was a substantial improvement over solution methods.
The O’Neill Step Film Model

In 1984, O’Neill (8) used an elegant step film model to show that plausible
irregularities in sunscreen film thickness can account for large discrepancies in
predicted SPF. The step film model is shown schematically in Fig. 43.5 as a
uniform, homogeneous film of absorbing material of thickness d and unit length.
A portion of the film of length g and thickness fd is removed and added to the
remaining portion, as shown by the dashed line. This produces two film fractions
with thicknesses d 0 and (1 2 f )d and lengths g and 1 2 g.
Since the amount of absorbing material stays constant, the expression for d 0 is:

0 fg
d ¼d þ1 (3)
1g
g 1-g
fd d’
(1-f)d
Figure 43.5 O’Neill’s step film model.
O’Neill defined the opacity of a sunscreen at a given wavelength l as:
P(l) ¼ (I0 =I)l ¼ 10k(l)cd (4)
where I0 and I are the intensities of incident and transmitted light, respectively, k(l) is
the absorbtivity molar extinction coefficient, c is the molar concentration, and d is the
optical path length.
The average intensity of light transmitted by the step film is:
Is ¼ gI1 þ (1 g)I2 (5)

where I1 and I2 are the intensities of light transmitted by the depleted and
augmented areas, respectively.
Then the average opacity of the step film, Ps(l), can be written as a function
of d, f, and g as:
1
Ps (l) ¼ Pc (l) g 10k(l)cdf þ (1 g)10k(l)cd( fg=(1g)) (6)
where Pc(l) is the opacity of the original, undistorted film at wavelength l.

O’Neill calculated the opacities of step films derived from uniform films
with opacities of 10, 1000, and 1,000,000 for values of f and g ranging from
0.1 to 1.0. In all cases, the average opacity of the distorted film was significantly
less than that of the original, uniform film. He further noted that the greater the
opacity of the original film, the greater the relative decrease in opacity.
The step model is related to sunscreen applied to skin by the fact that a fluid
applied to the skin tends to accumulate in the sulci, which are furrows that unfold
with body movement, and recede from the plateaus, creating regions of relatively
thin coverage and relatively thick coverage. Nonhomogeneity of a sunscreen due
to an intact emulsion or poor distribution of absorbing ingredients would have
the same effect. The step model permits any number of elements of arbitrary
860 Stanfield
size and shape and is considered valid on the scale of irregularities of thickness or
concentration fine enough that the pattern of sunburned and protected skin would
be averaged by the eye when evaluating the degree of erythema. O’Neill con-
cluded that a highly absorbing sunscreen with non-uniform coverage would
exhibit an overall opacity many orders of magnitude lower than a uniform,
homogeneous film.
SPF Predictions Using the Step Film Model

Herzog (9) calibrated the step film parameters using three sunscreen standard for-
mulas [COLIPA Standards P1, P3, and P4 (10)] with known SPF values and
demonstrated SPF predictions for 36 different sunscreen formulations. The
calibration was accomplished using mean extinction coefficients derived for
the combination of active ingredients in the standard formulas to compute
values of f and g that approximated their in vivo SPF values. Since there was
no single set of f and g values that reproduced the in vivo SPF values for all
three standard sunscreen formulas, Herzog derived a function, Dfg , that described
the overall quadradic deviation of the calculated SPF values from the in vivo SPF
values. Then, using a 200 200 matrix of f and g values from 0 to 1, calculated
the minimum value of Dfg for the three standard sunscreen formulas by a compu-
terized numerical optimization process. The values of f and g were 0.935 and
0.269, respectively. The calculated SPF value for standard P1 was 5.0 (in vivo
SPF ¼ 4.2); the calculated SPF value for standard P3 was 10.9 (in vivo SPF ¼
15.5), and the calculated SPF value for standard P4 was 38.5 (in vivo SPF ¼
35.7). Finally, Herzog used the aforementioned values of f and g to calculate
the SPFs of 36 sunscreen formulas with known in vivo SPF values. From a
least squares linear regression curve fit of in vivo SPF vs. SPF from the step
film model, the slope was 0.83, the intercept on the ordinate was 0.55 and the
correlation coefficient, r 2, was 0.8.
Herzog observed that the accuracy of the estimation was in the same range
as that for in vitro SPF tests (11). Herzog’s approach was remarkable in that it
predicted synergisms of mixtures of active ingredients using mean extinction
coefficients derived for combinations of active ingredients in each formula.
Herzog also pointed out that the model does not consider the rheology of emul-
sions, which determine the homogeneity of sunscreen films, nor does the model
consider photostability. Based on the slope of 0.83 for the linear regression line,
the method tended to underestimate the in vivo SPF. Although the step film model
yields valuable insights, its shortcomings described above support the need for
accurate and reproducible in vitro SPF measurements.
Substrates for In Vitro Measurements of Sunscreen Protection

Diffy and Robson (12) introduced the use of a surgical tape known as Transporew
tape (3M Corporation) as a substrate for in vitro SPF measurements in 1989. The
advantages of Transporew tape included its transparency, the reservoir effect of
holes intended to allow the skin to “breathe” and its availability and economy,
compared to hairless mouse skin or human stratum corneum.
In 1993, Sottery (13) introduced Vitro-Skinw as a commercial sunscreen
testing substrate, containing protein and lipid components, that was designed
to have topography, pH, surface tension, and ionic strength similar to human
skin. The manufacturer recommended hydrating the substrate for at least 12 h
at approximately 90% relative humidity to ensure simulation of the moisture
content of human skin. Sottery compared in vitro SPF values obtained using
Vitro-Skinw to those obtained using Transporew tape and Naturalambw
condoms (Church & Dwight, Princeton, NJ). Results for a sunscreen product
with an in vivo SPF of 12 were SPF values of 4, 10.7, and 14.6, for Transporew
tape, the Naturalambw condom and Vitro-Skinw, respectively. For a sunscreen
product with an in vivo SPF of 21.8, results were SPF values of 57.8, 75, and
23.3, for Transporew tape, the Naturalambw condom, and Vitro-Skinw, respect-
ively. Another comparison, using a product with an in vivo SPF of 19.8, produced
values of 81.1 and 54.7, for Transporew tape and Vitro-Skinw, respectively.
Results appeared to favor Vitro-Skinw, and the investigators attributed results,
at least for the SPF 12 product, to emulsion breaking behavior on Vitro-Skinw
more similar to that on skin than for the other two substrates. There are few
literature reports on the use of the Naturalambw condom substrate, although
our laboratory has obtained results similar to those reported above.
Also in 1993, Pearse and Edwards (14) demonstrated the use of human
stratum corneum as a substrate for in vitro sunscreen testing, although results
were not sufficiently improved to justify wide usage.
Tunstall (10) analyzed Transporew tape and Vitro-Skinw using O’Neill’s
step model and demonstrated excellent agreement between measured and
calculated SPF values for 1%, 2.5%, and 10% solutions of octinoxate applied
at 2 mL/cm2. Tunstall found that Vitro-Skinw produced more uniform data
than Transporew tape by eliminating the small areas of uncovered substrate
present on the latter. Tunstall also pointed out that both Vitro-Skinw and Trans-
porew tape yield SPF values similar to that of the SPF test on human skin by pro-
viding a “sink” for a large portion of the formulation in deep crevices, similar to
those on the skin surface. Tunstall reported that Vitro-Skinw absorbed 81% of the
formulation and Transporew tape absorbed 56%, in this manner.
Results are described below for in vitro SPF measurements using rough-
ened plexiglass and polymethyl methacrylate (PMMA) substrates. For both
substrates, the sunscreen application amount was reduced to compensate for
their poor simulation of skin topography.
Critical Wavelength
In 1994, Diffey (15) proposed the use of critical wavelength as an index of
the relative UV-A protection provided by sunscreen products. The critical
wavelength was defined as the wavelength at which the integral of the absorbance
862 Stanfield
curve reaches 90% of the integral from 290 to 400 nm. The critical wavelength
test was designed to provide a rapid, inexpensive, and reliable measure of
broad spectrum protection that is essentially independent of SPF, but ensures
long-wavelength UV-A protection commensurate with SPF. In 2000, Diffey
and coworkers (16) reported results of a study of 59 commercially available
and several experimental sunscreen formulas. Sunscreens were applied at
1 mg/cm2 to hydrated Vitroskinw substrates, preirradiated with a full-spectrum
UV dose in J/cm2 numerically equal to 1/3 of the labeled SPF, to account for
any lack of photostability, and then subjected to spectrophotometry. The
authors defined a critical wavelength of 370 nm as a “significant” level of
broad-spectrum protection and found that ,10% of the commercial formulas
satisfied this criterion. They concluded that a recognized long-wave UV-A active
ingredient such as titanium dioxide, zinc oxide, or avobenzone is necessary for
a sunscreen formula to achieve a critical wavelength 370 nm. They also
found good correlation between the critical wavelength and UV-A protection
measured in vivo using the phototoxic protection factor. The use of a ratio inde-
pendent of absolute absorbance is considered attractive, because the amount of
sunscreen on the substrate may be adjusted to prevent “saturation” of a spectro-
radiometer, which occurs when the sunscreen absorbs too much of the sample
beam energy to permit measurements.
Simultaneous In Vitro Measurement of SPF and Photostability

In the SPF test conducted in vivo on human subjects (6,17), UV doses are admi-
nistered to sunscreen-protected and unprotected skin sites. For sites where the
erythemally effective UV dose crosses the threshold for minimally perceptible
erythema (MPE), the skin displays erythema responses that are apparent
16 –24 h later. The dose that produces MPE is the minimal erythema dose
(MED). The sunscreen SPF is the ratio of the MEDs for sunscreen-protected
and unprotected skin sites. Since there is no way to observe MPE during the
administration of UV doses, a series of progressively increasing doses is adminis-
tered to sunscreen-protected and unprotected skin sites and results for each UV
dose are evaluated the next day.
In 2001, Stanfield and coworkers (18,19) reported an in vitro method for
simulating the SPF test using a single UV dose administered to a sunscreen
applied to a substrate. The method employed a 150-W xenon arc lamp identical
to that used for in vivo SPF measurement to irradiate the sunscreen after
application to 5-cm diameter disks cut from Naturalambw condom material.
The substrate was placed over the aperture of an integrating sphere attached to
a spectroradiometer (Model OL 754, Optronic Laboratories, Orlando, FL) and
the spectral irradiance of the UV source and spectral transmittance of the sub-
strate were measured from 290 to 400 nm. Then the spectral transmittance
of the sunscreen/substrate combination was measured from 290 to 400 nm at
1- or 2-min intervals during irradiation, until the total erythemally effective
dose transmitted by the sunscreen exceeded 1 MED, where 1 MED was defined
as 0.020 erythemally effective J/cm2. Each 1- or 2-min interval represented a
2 –4 MED increase in the total dose applied by the UV source. This approach per-
mitted recording the time course of SPF during irradiation of the sunscreen. The
final cumulative SPF of the sunscreen corresponded to the SPF measured by the
in vivo SPF test, regardless of whether the SPF was constant during the UV
exposure. If the SPF was constant during the UV exposure, the sunscreen was
considered photostable and if the SPF decreased significantly during irradiation
the sunscreen was considered photolabile.
This approach to in vitro SPF measurement is shown schematically in
Fig. 43.6.
As shown in Figs. 43.1 and 43.6, the applied spectral irradiance is denoted
by I0l and the spectral irradiance transmitted by the substrate is denoted as Isl
and is measured before the sunscreen is applied. The spectral transmittance of
the substrate, tsl , is assumed to be constant and is calculated as:
tsl ¼ Isl =I0l (7)
The spectral irradiance transmitted by the sunscreen/substrate combination is

denoted by I(sþss)l and is given by:
I(sþss)l ¼ I0l tsl tssl (8)
Then
tssl ¼ I(sþss)l =I0l tsl (9)
I0 λ
I0 λ
Sunscreen
Substrate
I(s+ss) λ
Is λ
Figure 43.6 Schematic diagram of the in vitro SPF test.

864 Stanfield
and the SPF is computed as:

Ð 400
290 I0l sldl
SPF ¼ Ð (10)
400 I(sþss)l sl dl
290 tsl
where sl is the erythemal effectiveness coefficient (5) for wavelength l and dl is

the wavelength increment.
The SPF computed using Eq. (10) represents the SPF at a given time during
irradiation of the sunscreen/substrate. The spectral irradiance of the UV source,
I0l , is assumed constant. Since the SPF of the sunscreen may vary with applied
UV dose, a more useful concept is the cumulative SPF, SPFc . To compute SPFc ,
it is necessary to replace the erythemally effective spectral irradiance values in
Figs. 43.1 and 43.6 with their integrals over time and wavelength, which yields
the applied erythemally effective UV energy dose, E0 , the erythemally effective
UV dose transmitted by the sunscreen/substrate, E(ssþs) , and, with the use of the
spectral transmittance of the substrate, the erythemally effective UV dose trans-
mitted by the sunscreen, Ess:
ð tMED ð 400
E0 ¼ I0l sl dl dt (11)
0 290
ð tMED ð 400
I(sþss)l sl dl
Ess ¼ (12)
0 290 ts l
The units of I0l and I(ssþs)l are power/unit area/length (W/cm2/nm), the units of
the erythemal effectiveness coefficient, sl , are erythemally effective energy per
unit area/energy per unit area [erythemally effective (J/cm2)/(J/cm2)], the
unit of dl is length (nm) and the unit of dt is time (s). Therefore, the units of
E0 and Ess are erythemally effective J/cm2. Since the erythemally effective
UV energy dose required to produce minimally perceptible erythema (1 MED)
ranges from 15 to 60 erythemally effective mJ/cm2 (20), E0 and Ess may be
divided by an arbitrary MED value of 20 erythemally effective mJ/cm2 and
expressed in multiples of the MED. Ideally, the MED value chosen would corre-
spond to the mean MED for the subjects of the in vivo SPF panel in which the
formula is tested.
From the definition of SPF (sunscreen-protected UV dose required to
produce minimally perceptible erythema/unprotected UV dose required to
produce minimally perceptible erythema), it follows that SPFc may be defined
as the value of the applied erythemally effective energy required to produce
1 MED of erythemally effective energy transmitted by the sunscreen. Thus,
SPFc is the value of E0 at time tMED , when Ess reaches 1 MED. This mimics
the sunscreen SPF test on humans, but requires only one UV dose instead of
the series of five or seven progressively increasing UV doses used in the
human SPF test. Typical transmission curves for photostable and photolabile
sunscreens are shown in Fig. 43.7.
UV-A Index
In 2001 Wendel and coworkers (21) proposed the UV-A index as a means of
labeling sunscreens according to their relative UV-A protection. The UV-A
index was defined as the ratio of the in vitro persistent pigment darkening
(PPD) factor to the labeled in vivo SPF. To determine the UV-A index the sun-
screen is applied to a substrate, its spectral transmission, Tl , is measured for
wavelengths from 290 to 400 nm, the in vitro SPF is determined using Eq. (1)
and the spectral absorbance, Al , is calculated for each wavelength as:
Al ¼ log(Tl ) (13)
Then the adjusted spectral transmittance, Tl , is calculated as:
Tl ¼ 10Alc (14)
where c is adjusted by trial and error until the in vitro SPF calculated by Eq. (1)
equals the in vivo SPF, that is,
Ð 400
290 Il sl dl
In vitro SPF ¼ Ð 400 ¼ In vivo SPF (15)

290 Il Tl sl dl
Then the adjusted spectral transmittance, Tl , is used to calculate the in vitro PPD
factor as:
Ð 400
320 El pl dl
PPDF ¼ Ð 400 (16)
E T p dl
320 l l l
SPF 30 Sunscreens
Photostable Photolabile
t MED
1.00
y = 0.033x
E ss ( M E D )
2
R =1
0.50
1.53
y = 0.0065x
2
R = 0.996
0.00
0 5 10 15 20 25 30
E0 (MED)
Figure 43.7 Typical transmission curves for photostable and photolabile sunscreens.
866 Stanfield
where El is the spectral irradiance of the UV-A source and pl is the PPD effec-
tiveness factor (22).
Finally, the UV-A index is defined as:
100 PPDF
UV-A index ¼ (17)
In vivo SPF
Ring Test of In Vitro SPF, PPDPF, and UV-A Index Measurements

In 2002, results were reported for a ring test of in vitro SPF, PPDPF, and UV-A
Index measurement in seven European test centers using five measuring devices
on five commercial sunscreens for which SPFs had been determined indepen-
dently on human subjects (23). The five measuring devices were spectropho-
tometers, as described in Table 43.3. The sunscreens included two formulas
with organic sunscreens and three formulas with a combination of organic and
inorganic sunscreens, and are listed in Table 43.4.
The substrates were roughened Plexiglasw (Type XT, colorless, 24770
UVD, Röhm GmbH, Darnstadt, Germany) plates for single use. A roughened
PMMA plate with a uniform layer of glycerin was used as a reference.
Although the method does not require a specific application amount,
0.75 mg/cm2 of each sunscreen was applied. The sunscreens were spotted
evenly across the plate surface and rubbed using a presaturated fingertip or
finger cot for 30 s with light pressure. After evaporation of the volatile com-
ponents, the spreading was continued for another 30 s with significantly higher
pressure. Plates were equilibriated in the dark for at least 15 min. The transmit-
tance was then measured from 290 to 400 nm in 1-nm steps. Measurements were
performed on at least three plates at four locations per plate.
Results for in vitro SPF measurements, PPD protection factor measure-
ments and UV-A index measurements are shown in Tables 43.5 –43.7,
respectively.
Correlations between in vitro and in vivo SPF values calculated by this
author are shown in Fig. 43.8. The correlation coefficient, R 2, for a linear
regression curve fit with a slope of 0.50 was 0.38, which showed poor reprodu-
cibility among laboratories. There was a pronounced increase in variability of
results with increasing SPF, which is consistent with the greater sensitivity of
high SPF values to small changes in transmittance.
Correlations between in vitro and in vivo PPD protection factors calculated
by this author are shown in Fig. 43.9. The correlation coefficient, R 2, for a linear
regression curve fit with a slope of 1.01 was 0.93, which shows excellent repro-
ducibility among laboratories. The improvement in reproducibility over the SPF
results shown in Fig. 43.8 is attributed to two factors. First, the transmittance
spectra of the sunscreens were adjusted to agree with the in vivo SPF, removing
the variability in the original in vitro SPF measurements. Second, the lower
numerical values of PPD protection factor are less sensitive to variability in trans-
mittance. The high reproducibility of PPD protection factors demonstrates that a
Table 43.3 UVA Index Ring Test Laboratories and Instruments
Lab Instrument/type Type of beam Light source Integrating device Detection system
1 Varian, Cary 3 Double beam, Deuterium D2/halogen H1 Integrating sphere Double monochromator
monochromatic before sample þ PMTa
2 Optometrics Single beam, Xenon arc 125 W Integrating sphere and Monochromator þ PMTa
SPF290 polychromatic quartz diffuser
3 Dr. Kockott Single beam, Xenon arc 150 W Integrating sphere or Grating, spectral detector
polychromatic dispersing disk or integral detector with
sensitivity adjusted to
erythema action
spectrum
In Vitro Techniques in Sunscreen Development

6 Varian, Cary 3 Double beam, Deuterium D2/halogen H1 Integrating sphere Double monochromator
monochromatic before sample þ PMTa
7 Perkin Elmer, Double beam, Deuterium D2/halogen H1 Integrating sphere Double monochromator
Lambda 16 monochromatic before sample þ PMTa
a
Photomultiplier tube.
Source: From Gers-Barlag et al. (23).
867
868 Stanfield
Table 43.4 UV-A Index Ring Test Sunscreen Products
Labeled
Product SPFa Type of emulsion Active ingredients
A 12 O/Wb Octinoxate
Avobenzone
B 15 W/Oc 4-Methylbenzylidene camphora
Octisalate
Avobenzone
Octocrylene
C 15 O/W Octinoxate
Zinc oxide
Octinoxate
D 24 Hydrodispersion 4-Methylbenzylidene camphora
(emulsifier-free) Ethylhexyl triazolea
Avobenzone
Titanium dioxide
E 30 O/W Octocrylene
Titanium dioxide
Avobenzone
Terephthalylidene dicamphorsulfonic
acida
a
Not approved in the USA.
b
Oil-in-water.
c
Water-in-oil.
simple correction factor applied uniformly across the transmittance spectrum

effectively corrects for variability of SPF measurements. The relatively high
reproducibility of UV index values reflects the high reproducibility of PPD pro-
tection factors.
For the five sunscreen products evaluated, the authors showed that the UV
index was a more sensitive measure of broad spectrum sunscreen performance
and permits more discrete labeling categories than critical wavelength.
Table 43.5 UV-A Index Ring Test Results for In Vitro SPF Measurements
Sample In vivo Lab 1 Lab 2 Lab 3 Lab 4 Lab 5 Lab 6 Lab 7
A 12 8.3 7.1 6.2 8.4 9.1 8.2 8.2

B 15 9.1 14.2 14.5 13.4 7.7 14.2 13.9
C 15 7.4 5.3 3.6 5.2 3.5 4.5 5.7
D 24 23.8 14.4 10.4 14.4 15.4 14.9 6.9
E 30 17.5 17.6 6.1 16.8 13.8 15.1 26.5

Table 43.6 UV-A Index Ring Test Results for PPD Protection Factor Measurements
Sample In vivo Lab 1 Lab 2 Lab 3 Lab 4 Lab 5 Lab 6 Lab 7
A 1.8 2.2 2.2 2 2 2.1 2.1 2.4

B 4.5 6 6.1 5.8 5.8 5.1 6.1 6.3
C ND 1.9 2.4 2.2 2.2 1.5 2.1 2.3
D 5 6.2 6.7 5.1 5.1 6.5 5.8 7.4
E 10.5 10.3 12.2 10.4 10.4 11.9 9.5 13.5
European Ring Test of In Vitro SPF Measurements

In 2003, results were reported for a ring test of in vitro SPF measurement in six
European test centers using two SPF calculation approaches and four measuring
devices on 10 commercial sunscreens whose SPF had been determined indepen-
dently on human subjects (24).
The four measuring devices included a spectroradiometer, two spectropho-
tometers and a photometer, and are described in Table 43.8. The sunscreens
included eight formulas with organic sunscreens and two formulas with a combi-
nation of organic and inorganic sunscreens, and are listed in Table 43.9.
The substrates were 50 mm 50 mm PMMA plates (Helioplates,
Helioscience, Creil, France) with a 5 mm medium roughness. The sunscreen
was spotted evenly on the plate and weighed before spreading or evaporation
occurred. Then using light pressure, the product was spread immediately until
a uniform distribution was achieved. Samples were allowed to settle at room
temperature for 15 min. A roughened PMMA plate with a uniform layer of gly-
cerin was used as a reference.
The transmittance was measured from 290 to 400 nm in 1-nm steps. Up to
nine UV transmittance spectra were measured from each substrate at different
locations, except for those instruments that measured the whole area of
the plate. Five different plates were used for each sunscreen (except Lab 6) for
Table 43.7 Ring Test Results for UV-A Index Measurements
Sample Lab 1 Lab 2 Lab 3 Lab 4 Lab 5 Lab 6 Lab 7
A 8.3 7.1 6.2 8.4 9.1 8.2 8.2

B 9.1 14.2 14.5 13.4 7.7 14.2 13.9
C 7.4 5.3 3.6 5.2 3.5 4.5 5.7
D 23.8 14.4 10.4 14.4 15.4 14.9 6.9
E 17.5 17.6 6.1 16.8 13.8 15.1 26.5

870 Stanfield
30
25
y = 0.50x + 1.59
20 R2 = 0.38
In Vitro SPF
15
10
0
0 5 10 15 20 25 30 35
In Vivo SPF
Figure 43.8 Correlations between in vitro and in vivo SPFs from the UV-A index ring
test. [From Gers-Barlag et al. (23).]
calculating average SPF data.The test was conducted in two rounds, the first
using an application amount of 1.4 mg/cm2. The results showed excessively
high values for the in vitro SPF, so the second round was conducted using a
lower application amount of 1.2 mg/cm2. Results of the first and second
rounds are shown in Tables 43.10 and 43.11, respectively.
author are shown for products with in vivo SPF values of 40 and lower in
Fig. 43.10. The correlation coefficient, R 2, for a linear regression curve fit with
a slope of 0.84 was 0.77, which showed good reproducibility among laboratories,
16
14
12 y = 1.01x + 0.83
In Vitro PPDPF
R2 = 0.93
10
8
6
4
2
0
0 2 4 6 8 10 12
In Vivo PPDPF
Figure 43.9 Correlations between in vitro and in vivo PPDs protection factor from the
UV-A index ring test. [From Gers-Barlag et al. (23).]
Table 43.8 European Ring Test Laboratories and Instruments
Integrating
Instrument Lab Type device Detection system
OL754a 1 Spectroradiometer Sphere Double monochromator

behind PMT
sample
UVIKON 3, 4 Spectrophotometer Sphere Single monochromator
933b behind PMT
sample
UV 1000Sc 2, 5 Spectrophotometer Sphere Diode array
before
sample
Sunscreen 6 Photometer Sphere Integrating detector
testerd behind with spectral sensitivity
sample approximating erythema
spectrum
a
Optronic 754, Optronic Laboratories, Inc. Orlando, FL, USA.
b
Kontron UVIKON, UVK-LAB Service, Trappes, France.
c
Labsphere UV 1000S, Labsphere, North Sutton, NH, USA.
d
Kockott UV Technik, UV technik, Hanau-Steinheim, Germany.
Source: From Pissavini et al. (24).
considering the wide variety of instruments and techniques used. Note that
product J, containing octinoxate, octisalate, and avobenzone, showed high varia-
bility among laboratories and poor distribution about the linear regression line.
This could be explained by a lack of photostability of product J. Other formulas
containing similar combinations of ingredients have been observed in our labora-
tory to have poor photostability. There was also high interlaboratory variability
for products with in vivo SPF values .17.
author are shown for products with in vivo SPF values 37 in Fig. 43.11. The
correlation coefficient, R 2, for a linear regression curve fit with a slope of 0.66
was 0.08, which showed very poor reproducibility between laboratories. The
authors pointed out that product E, containing microfine titanium dioxide, octi-
noxate, benzophenone-3, and octisalate was known to have “physical instability.”
Again, in our laboratory we have observed poor photostability for at least one
formula with a similar combination of active ingredients. The authors also
pointed out that product C showed good interlaboratory reproducibility, but
had in vitro SPF values well below the in vivo SPF. This was explained by the
presence of “anti-inflammatory” ingredients in the formula, which suppressed
erythema in the in vivo SPF test and raised the SPF by a mechanism other than
absorbing UV energy.
872 Stanfield
Table 43.9 European Ring Test Sunscreen Products
Product SPFa Active ingredients
A 6 + 1.2 Octinoxate
Avobenzone
4-Methylbenzylidene camphorb
B 7 + 1.4 Avobenzone
Methylene bis-benxotriazoleb
Tetramethylbutylphenolb
D 12 + 2.4 Avobenzone
Octinoxate
F 17 + 3.4 Octinoxate
Benzophenone-3
Octisalate
Avobenzone
J 18 + 3.6 Octinoxate
Octisalate
Avobenzone
I 37 + 7.4 Microfine titanium dioxide
Octinoxate
Benzophenone-3
H 38 + 7.6 Benzophenone-3
Avobenzone
4-Methylbenzylidene camphorb
Diethylhexyl butamido triazoneb
Ensulizole
K 40 + 8.0 Octinoxate
Isoamyl p-methoxycinnamateb
Octisalate
Benzophenone-3
Ensulizole
Avobenzone
Methylene bis-benzotriazoyleb
Tetramethylbutylphenolb
E 58 + 11.6 Microfine titanium dioxide
Octinoxate
Benzophenone-3
Octisalate
C 79 + 15.8 Avobenzone
Octyl triazoleb
Octocrylene
Octinoxate
a
20 Volunteers +20%.
b
Not approved in the USA.
Table 43.10 European Ring Test Results for In Vitro SPF Measurements with Products
Applied at 1.4 mg/cm2
Product
A B C D E F H I J K
In vivo 6 7 79 12 58 17 38 37 18 40
Lab 1 8 6 54 12 67 23 58 46 59 78
Lab 2 8 5 46 10 56 20 46 36 46 74
Lab 3 8 4 42 10 57 16 31 31 42 59
Lab 4 8 8 50 15 103 18 39 49 39 95
Lab 5 8 9 57 15
Mean 8 6 50 12 71 19 44 40 47 77
SD% 1 32 12 21 31 16 26 21 19 19
DISCUSSION
Product SPF Values
High SPF values are more sensitive to small changes in transmittance, as shown
in Table 43.12. This illustrates the necessity for precise control of the variables
discussed above to permit accurate and reproducible in vitro measurements for
high SPF products.
Product Application and Substrate Considerations

Application of a sunscreen product to the skin involves high shear forces. To
spread well over the uneven skin surface, sunscreens are formulated to have a
Table 43.11 European Ring Test Results for In Vitro SPF Measurements with Products
Applied at 1.2 mg/cm2
Product
A B C D E F H I J K
In vivo 6 7 79 12 58 17 38 37 18 40
Lab 2 6 4 28 7 37 16 20 21 19 37
Lab 3 4 3 32 5 31 12 23 22 21 34
Lab 4 6 4 33 5 69 17 24 28 21 37
Lab 5 6 6 40 10 59 17 36 40 31 41
Lab 6 6 5 43 8 50 13 30 44 25 28
Mean 6 4 35 7 49 15 27 31 24 36
SD% 17 29 17 34 32 16 23 34 20 14

874 Stanfield
1.2 mg/cm2
y = 0.84x
2
R = 0.77
50
In Vitro SPF
40 Product J
30
20
10
0
0 10 20 30 40 50
In Vivo SPF
Figure 43.10 Correlation between in vitro and in vivo SPF values for products with low
in vivo SPF values. [Modified from Pissavini et al. (24).]
1.2 mg/cm2
80 y = 0.66x Product E
In Vitro SPF
60 R2 = 0.08 Product C
40
20
0
0 20 40 60 80 100
In Vivo SPF
Figure 43.11 Correlation between in vitro and in vivo SPF values for products with high
in vivo SPF values. [Modified from Pissavini et al. (24).]
low viscosity at high shear. After the product has been spread over the skin, it
should recover its structure quickly to maintain an even film. If the viscosity
remains low, the product will flow into the sulci, or crevices, of the skin, resulting
in uneven coverage, with a thin layer on the plateaus and a large, ineffec-
tive reservoir in the sulci (25). This reduces SPF dramatically, as shown by
Table 43.12 Sensitivity of SPF to Small Changes in Transmittance
SPF
2 8 15 30 45 50 80
Transmittance of erythemally 50.0 12.5 6.7 3.3 2.2 2.0 1.3

effective energy (%)
% Decrease in SPF for a 1% 2 7 13 22 31 33 46
increase in transmittance
O’Neill (8). The topography of the skin has a strong influence on this process,
which is a major reason the substrate for in vitro measurements must resemble
skin to permit accurate SPF measurements.
Since many highly protective sunscreen products are oil-in-water emul-
sions with the UV absorbers in the oil phase, the emulsion must break to
achieve a continuous film of sunscreen on skin. Surface properties of skin such
as salt content influence the behavior of emulsions on skin. Since the water
content is significant, the degree of water absorption by skin also plays a large
role. The substrate should duplicate the properties of human skin to the
maximum extent possible, particularly topography, moisture content, surface
protein and lipid components, pH, critical surface tension, and ionic strength
(13). The substrate should also be as transparent to UV as possible.
In view of the foregoing considerations, Vitro-Skinw appears to be the best
choice of substrate available for in vitro SPF measurements.
In the in vivo SPF test, 2 mg/cm2 + 2.5% of each product is applied to the
skin by “spotting” droplets of product on the test site with a distribution of
approximately one droplet per 2 cm2, then rubbing lightly with a finger cot for
20 –50 s with circular, then linear motion. The amount of product applied must
be corrected for the amount lost on the finger cot. Products are allowed to dry
without any UV exposure for 15 –30 min. The recommended ambient tempera-
ture range is 18 –268C (26). Conditions of the in vitro SPF test should match
those of the in vivo SPF test, to the maximum extent possible.
UV Source
For the in vitro SPF test, the source of UV energy should be identical to that used
in the human SPF test in terms of spectrum, total power, beam uniformity and
collimation, and temporal stability. Ideally, the UV source will have a feedback
system for regulating output.
Newly published international spectral limits for lamps used for SPF
testing are shown in Table 43.13. The total irradiance is required to be below
Table 43.13 Solar Simulator Requirements
Measured % relative contribution

to erythemal effectiveness
Wavelength Standard solar
range (nm) Lower limit Upper limit spectrum %
,290 ,1 0.0
290 – 300 2.0 8.0 7.2
290 – 310 49.0 65.0 56.5
290 – 320 85.0 90.0 84.2
290 – 400 100.0 100.0 100.0
Source: Modified from Ref. (26).

876 Stanfield
the threshold for causing pain during UV doses on sunscreen-protected skin,

between 120 and 160 mW/cm2 (26). Most solar simulators used for in vivo
SPF testing operate at total power levels near 150 mW/cm2, or 2 erythemally
effective mW/cm2. Typical MEDs on the order of 20 erythemally effective
mJ/cm2 require exposure times on the order of 10– 30 s. Undoubtedly, there is
local heating of the sunscreen film by the lamp beam, which alters its distribution
on skin.
Obviously, the UV sources in many of the systems commonly used for
in vitro SPF measurements differ significantly from UV sources used for
in vivo SPF measurements, in spectral distribution of power and total irradiance.
This could partially account for discrepancies between in vitro and in vivo
measurements of SPF.
Beam Geometry
Solar simulators irradiate the skin with a collimated beam, which is absorbed,
transmitted, and scattered by the sunscreen. Transmitted and forward scattered
radiation produces the resulting erythema in the dermis. Forward scattering
may occur at more oblique angles when sunscreen is applied to the substrate,
as shown in Figs. 43.1 and 43.6. For accurate in vitro measurement of sunscreen
transmittance, the beam geometry must mimic that of the in vivo sunscreen test to
the maximum possible extent. It is also essential to collect as much of the forward
scattered radiation as possible. This requires the use of an integrating sphere, and
that the sunscreen/substrate must be as close to the sphere aperture as possible.
Photostability
Early in vitro predictions of the SPFs for sunscreen formulas containing avoben-
zone yielded erroneously high values. Subsequently it was shown that many
sunscreen formulas containing avobenzone were not photostable (27 – 31).
These formulas had high initial SPFs which declined rapidly during irradiation.
SPF ratings determined in the human in vivo test were valid, but were overesti-
mated by in vitro tests. Preirradiation with measured UV doses has permitted
more accurate in vitro estimates of SPF (29). However, these formulas may be
even more unstable in sunlight and significantly less protective for consumers
than the label indicates.
The method presented by Stanfield and coworkers described in the section
titled “Simultaneous In Vitro Measurement of SPF and Photostability” permits
assessment of sunscreen photostability using the UV doses encountered in the
in vivo SPF test. It may be possible to use the same approach with simulated
or actual sunlight to assess sunscreen protection of consumers under relevant
exposure conditions, particularly when there is concern about the photostability
of a particular formulation.
Applications of Sunscreen Transmittance Spectra

Once a valid transmittance spectrum is obtained for a sunscreen formula, it may
be possible to adjust the source spectrum to assess protection against sunburn
over the course of a day or year or effects of various ozone depletion scenarios.
In addition, exploratory assessments of protection against other effects of
sunlight that have known action spectra are possible. Preliminary action
spectra are available for nonmelanoma skin cancer (32), UV-B-induced
immune suppression (33), and photoelastosis (34).
CONCLUSIONS
Accurate and reliable in vitro measurement of sunscreen SPF is difficult due to
the large number of variables. These variables can be managed to produce accep-
table results. The in vitro SPF test should incorporate the best available substrate
for matching the properties of skin, and the application technique, UV source and
beam geometry should mimic those used in the in vivo test.
An accurate match of the in vivo SPF confirms the accuracy of the sun-
screen transmittance spectrum. An accurate sunscreen transmittance spectrum
permits evaluation of UV-A protection and useful assessments of sunscreen
protection against a wide variety of acute and chronic effects under relevant
conditions of UV radiation.
REFERENCES
1. Brown MW. The sun protection factor: test methods and legal aspects. SÖFW 2002;
128:10– 18.
2. Lott DL, Stanfield J, Sayre RM, Dowdy JC. Uniformity of sunscreen product appli-
cation: a problem in testing, a problem for consumers. Photodermatol Photoimmunol
Photomed 2003; 19:17– 20.
3. Sayre RM, Stanfield J, Lott D, Dowdy JC. Simplified method to substantiate SPF
labeling for sunscreen products. Photodermatol Photoimmunol Photomed 2003;
19:254– 260.
4. Sayre RM, Poh Agin PA, LeVee GJ, Marlowe E. A comparison of in vivo and in vitro
testing of sunscreening formulas. Photochem Photobiol 1979; 29:559– 566.
5. McKinlay A, Diffey B. A reference spectrum for ultraviolet induced erythema
in human skin. CIE J 1987; 6:17 – 22.
6. The European Cosmetic, Toiletry, and Perfumery Association. COLIPA Sun
Protection Factor Test Method. Brussels, 1994.
7. Sayre RM, Poh Agin P, Desrochers DL, Marlowe E. Sunscreen testing methods:
in vitro predictions of effectiveness. J Soc Cosmet Chem 1980; 31:133 – 143.
8. O’Neill JJ. Effect of skin irregularities on sunscreen efficacy. J Pharm Sci 1984;
7:888– 891.
calibrated step film model. J Cosmet Sci 2002; 53:11 – 26.
878 Stanfield
10. Tunstall DF. A mathematical approach for the analysis of in vitro sun protection factor
measurements. J Cosmet Sci 2000; 51:303– 315.
11. Sayre RM. Correlation of in vivo tests, in vitro SPF predictions—a survey of
published studies. Cosmet Toilet 1993; 108:111 –114.
13. FDC Reports: “The Rose Sheet”w Toiletries, Fragrances and Skin Care. FDC Reports,
Inc. Chevy Chase, MD. Vol. 14, No. 44, November 1, 1993, pp. 15.
14. Pearse A, Edwards C. Human stratum corneum as a substrate for in vitro sunscreen
testing. Int J Cosmet Sci 1993; 15:234 – 244.
15. Diffey BL. A method for broad spectrum classification of sunscreens. Int J Cosmet Sci
1994; 16:47 –52.
16. Diffey BL, Tanner PR, Matts PJ, Nash JF. In vitro assessment of the broad-
spectrum ultraviolet protection of sunscreen products. J Am Acad Dermatol 2000;
43:1024– 1035.
17. US Food and Drug Administration. Sunscreen drug products for over-the-counter
human use. Final Monograph; 21CRF Parts 310, 352, 700, and 740. Federal Register
64 (98) May 21, 1999, 27666– 27693.
18. Stanfield J, Stanfield W, Stanfield C. Sunscreen photostability assessment and SPF
estimation. Thirteenth International Congress on Photobiology, San Francisco,
July 3, 2000 (abstract).
19. Stanfield J. Sunscreen photostability and UVA protection. J Cosmet Sci 2001;
52:412– 413.
20. Diffey BL, Jansen CT, Urbach F, Wulf HC. The standard erythema dose: a new
photobiological concept. Photodermatol Photoimmunol Photomed 2003; 13:64 –66.
21. Wendel V, Klette E, Gers-Berlag H. A new in vitro test method to assess the UVA
protection performance of sun care products. SÖFW 2001; 127:12 – 30.
22. Moyal D, Chardon A, Kollias N. Determination of UVA protection factors using the
method. Photodermatol Photoimmunol Photomed 2000; 6:245– 249.
23. Gers-Barlag H, Wendel V, Klette E, Bimczok R, Springob C, Finkel P, Rudolph T,
Gonzenbach HU, Westenfelder H, Schneider P, Kockott D, Heinrich U, Tronnier H,
Johncock W, Langner R, Hansjürgen D, Pflücker F, Wünsch T. The reproducibility of
an in vitro determination of the UVA index describing the relative UVA protection of
sun care products. IFSCC Mag 2003; 5:161 – 166.
24. Pissavini M, Ferrero I, Alard V, Heinrich U, Tronnier H, Kockott D, Lutz D,
Tournier V, Zambonin M, Meloni M. Determination of the in vitro SPF. Cosmet
Toilet 2003; 118:63 –72.
25. Anderson MW, Hewitt JP, Spruce SR. Broad-spectrum physical sunscreens:
titanium dioxide and zinc oxide. In: Lowe NJ, Shaath NA, Pathak MA, eds.
26. Cosmetic, Toiletries and Fragrances Association of South Africa, The European
Cosmetic, Toiletry and Perfumery Association (COLIPA), Japan Cosmetics Industry
Association (JCIA), International Sun Protection Factor (SPF) Test Method, Final
Draft, October 17, 2002.
27. Kammeyer A, Westerhof W, Bolhuis P, Ris A, Hische E. The spectral stability of several
sunscreening agents on stratum corneum sheets. Int J Cosmet Sci 1987; 9:125–136.
28. Sayre R, Dowdy J. Photostability testing of avobenzone. Cosmet Toilet 1999;

114:84– 90.
29. Diffey B, Stokes R, Forestier S, Mazilier C, Richard A, Rougier A. Suncare product
photostability: a key parameter for a more realistic in vitro efficacy evaluation. Part I.
In vitro efficacy assessment. In: Rougier A, Schaefer H, eds. Protection of the Skin
Against Ultraviolet Radiations. Paris: John Libbey Eurotext, 1998:137 – 142.
30. Forestier S, Mazilier C, Richard A, Rougier A. Suncare product photostability: a key
parameter for a more realistic in vitro efficacy evaluation. Part II. Chromatographic
analysis In: Rougier A, Schaefer H, eds. Protection of the Skin Against Ultraviolet
Radiations. Paris: John Libbey Eurotext, 1998:143 – 147.
31. Gonzenbach H, Pittet G. Photostability, a must? Proceedings of Broad Spectrum Sun
Protection: The Issues & Status. The Commonwealth Institute, London 1997.
32. de Gruij F, Forbes P. UV-induced skin cancer in a hairless mouse model. BioEssays
1995; 17:651– 660.
33. DeFabo EC, Dang V, Noonan FP. UV-induced immunosuppression: wavelength
dependency and its implications. In: Matthes R, Sliney D, eds. Measurements of
Optical Radiation Hazards. International Commission on Non-Ionizing Radiation
Protection and International Commission on Illumination, 1998:115– 123.
34. Kligman L, Sayre R. An action spectrum for ultraviolet induced elastosis in hairless
mice: quantification of elastosis by image analysis. Photochem Photobiol 1991;
53:237– 242.
44
Prediction of Sun Protection Factors
and UV-A Parameters by Calculation
of UV Transmissions Through
Sunscreen Films of Inhomogenous
Surface Structure
Bernd Herzog
Ciba Specialty Chemicals Inc., Grenzach-Wyhlen, Germany
Introduction 882
Materials and Methods 883
UV Filters and Formulations 883
Measurement of UV Spectra 884
Measurement of UV-A Parameters 885
Introduction of Step Film Inhomogeneity by Mathematical Models 885
Calculation of Average UV Spectra from the Spectra of Individual
UV Filters 885
The Step Film Model by O’Neill 886
Using a Distribution Function for Introduction of Film Inhomogeneity 889
Correlation of Experimental and Calculated Data 891
Calculated SPF and SPF In Vivo 891
Correlation of Calculated UV-A Parameters and UV-A Parameters
Measured In Vitro 895
Summary 899
References 899
881
882 Herzog
INTRODUCTION
The measure of the protection against sunburn achieved by application of
sunscreens is the sun protection factor (SPF). The SPF is defined as the ratio
of the minimal erythemal doses of solar radiation directed to human skin in the
presence and in the absence of a sunscreen (1).
The protection by sunscreen formulations is mainly due to their extinction
efficiency. This is linked to the spectral properties and the concentration of the
filters inside. In addition, the homogeneity of the sunscreen film distributed on
the skin plays an important role. For instance, a film showing blank spots,
which may have been left out during distribution of the sunscreen on the skin,
will show weak overall extinction even when the concentration and efficiency
of the UV absorbers inside would have suggested a stronger effect.
The physical quantity which describes the protection of a layer of absorb-
ing material is the transmission T. The inverse of the transmission defines the
factor by which the incoming radiation is attenuated:
1 I0
¼ (44:1)
T I
where I0 is the intensity of light before it penetrates the layer and I the intensity of
light after it has passed through the layer (Fig. 44.1). This is reflected in the
concept of the so-called monochromatic protection factor (MPF):
1
MPF ¼ (44:2)
T(l)
which is the protection factor at a certain wavelength. In order to proceed toward
an expression for calculating the SPF from transmission data, one has to consider
the whole UV spectral range between 290 and 400 nm. Thus, 1/T(l) must be
I0 I
Figure 44.1 Transmission through an absorbing layer.

Prediction of Sun Protection Factors and UV-A Parameters 883
averaged over this spectral range. Since the intensity of the solar light at the
surface of the earth S(l) varies with wavelength as well as the erythemal effect
of UV light called the erythemal action spectrum EA(l), the average of 1/T(l)
has to be weighted by those functions leading to the equation for the SPF first
given by Sayre et al. (2):
P400
S(l) EA(l)
SPF ¼ P400 l¼290 (44:3)
l¼290 S(l) EA(l) T(l)
Data for S(l) and EA(l) are available in the literature (3,4). With in vivo
measurements of the SPF, an amount of 2 mg/cm2 is applied on the skin corre-
sponding to a volume of approximately 2 mL/cm2. The theoretical optical thick-
ness of the resulting film is 20 mm. This thickness may be used to calculate the
transmission of a sunscreen formulation, knowing also the concentrations and
extinction coefficients of the filters inside and using Lambert –Beer’s law:
T ¼ 10E (44:4)
with the extinction E, and
E ¼ 1cd (44:5)
where 1 is the molar decadic extinction coefficient and c the molar concen-
tration. When transmissions are calculated according to Eqs. (44.4) and (44.5)
and used for the SPF calculation with Eq. (44.3), the resulting SPF values are
a factor of 4 – 5 higher than would be expected from in vivo data. This discre-
pancy can be overcome when using instead of a film with homogenous thickness
a film with a certain inhomogeneity, which may be introduced mathematically.
Inhomogenous films are already physically realized with in vitro methods for
SPF determination, where porous substrates like TransporeTM tape or PMMA
plates are used in analogy to the human skin, which has itself an inhomogenous
surface structure. In contrast to such in vitro methods, reproducibility of results
is not a problem when the transmissions are calculated from the UV spectra of
the UV absorbers, applying a mathematically defined inhomogenous film
structure. It has been shown, that the film structure may be calibrated using
sunscreen standards (5), resulting in satisfactory correlations of calculated and
in vivo SPF data.
MATERIALS AND METHODS

UV Filters and Formulations
The UV filters used are listed in the following table. The International Nomencla-
ture of Cosmetic Ingredients (INCI) names are followed by their abbreviations,
which are used throughout this work.
884 Herzog
INCI name and abbreviation Trade name and supplier

UV-B filters
Ethylhexyl methoxycinnamate (EHMC) Parsolw MCX (DSM)
2-Phenylbenz-imidazole-5-sulfonic Acid Eusolexw 232 (Merck)
(PBSA)
4-Methylbenzylidene Camphor (MBC) Eusolexw 6300 (Merck)
Ethylhexyl triazone (EHT) Uvinulw T150 (BASF)
Padimate O Eusolexw 6007 (Merck)
Ethylhexyl salicylate (EHS) Escalolw 587 (ISP)
Titanium dioxide (TiO2) Eusolexw T2000 (Merck)
Octocrylene (OCR) Uvinulw N539 (BASF)
Diethylhexyl butamido triazone (DBT) Uvsorb HEB (3V Sigma)
Benzylidene malonate polysiloxane (BMP) Parsolw SLX (DSM)
Broadband and UV-A filters
Benzophenone-3 (B3) Uvinulw M40 (BASF)
Butyl methoxydibenzoyl methane Parsolw 1789 (DSM)
(BMDBM)
Bis-ethylhexylphenol methoxyphenyl Tinosorbw S (Ciba Specialty Chemicals)
triazine (BEMT, Bemotrizinol)
Methylene bis-benzotriazolyl Tinosorbw M, aqueous dispersion of
Tetramethylbutylphenol (MBBT, 50% particulate MBBT of particle size
Bisoctrizole) ,200 nm (Ciba Specialty Chemicals)
Zinc oxide (ZnO) Nanoxw, ZnO with small particle size of
about 60 nm (Elementis Specialties)
Sunscreen formulations were of the O/W type and manufactured according to the
procedures described in Refs. (5,6).
Measurement of UV Spectra
In order to be able to calculate transmissions through films of inhomogenous
structure, UV spectra of the UV absorbers listed in the table have been recorded.
The UV spectroscopic measurements were carried out using a Perkin Elmer
Lambda 16 spectrometer. For the oil-soluble filters ethanol was used as
solvent. UV spectra of particulate UV absorbers in aqueous suspensions were
recorded with the same instrument using an integration sphere attachment
(Labsphere B009-4012).
While with all soluble UV absorbers an optical pathlength of 1 cm has been
employed, the spectra of the particulate filters MBBT, ZnO, and TiO2 , for reasons
of dispersion stability, were measured at an optical pathlength of 0.0008 cm
(optical cells manufactured by Hellma, Germany) using concentrations of the
UV absorber between 0% and 3%. In those cases at each concentration 10
measurements were carried out and the results were averaged (5).
Measurement of UV-A Parameters

The UV-A/UV-B ratio and the critical wavelength were evaluated from trans-
mission measurements with a Labsphere 1000S UV transmittance analyzer
(Labsphere, North Sutton, NH). Samples were prepared by distributing the formu-
lations on quartz plates with a rough surface (UQG Ltd., UK) and an area of 40 cm2
(8 cm 5 cm). The plates were cleansed by rinsing first with a solution of a com-
mercial dish washing agent, and then immersing them into concentrated sulfuric
acid for 12 h followed by rinsing with deionized water. Formulations were
applied as an amount per area of 1 mL/cm2. Before taking measurements, the
samples were allowed to equilibrate for 15 min. A reference plate was equally pre-
pared by distributing 1 mL/cm2 of deionized water in order to reduce the scattering
of the incident beam of the transmittance analyzer due to the rough surface of the
plate (instead of water, glycerol may also be used, which is recommended when
working with scanning analyzers where measurements take longer). First, the
transmission of the reference plate was measured, and after that the transmissions
of the sample plates. With each sample plate, transmission data were recorded at 11
different locations on the plate. The spectra were depicted as extinction vs. wave-
length and the curves with the highest extinction and the lowest extinction were
discarded, ending with a set of nine spectra. The experimental error of the extinc-
tion in terms of confidence limits based on a significance level of 95% was between
4% and 15%. Extinctions were always below the upper limit (E ﬃ 2) of the linear
dynamic range of the Labsphere 1000S UV transmittance analyzer.
INTRODUCTION OF STEP FILM INHOMOGENEITY BY

MATHEMATICAL MODELS
Calculation of Average UV Spectra from the Spectra of Individual UV Filters
Before introducing film inhomogeneities one has to know the spectroscopic prop-
erties of the respective formulation. With cosmetic sunscreens in most cases
several UV absorbers are combined. Considering a mixture of n different UV
absorbers, the concentrations of the individual absorbers are most conveniently
given as percentages bi (weight per volume). The corresponding molar
extinction coefficients are 1(l)i , and the molecular weights Mi . The average
molar absorption coefficient 1(l) of the mixture can then be calculated
according to
Pn
1(l) b =M
1(l) ¼ Pn i i i
i¼1
(44:6)
i¼1 bi =Mi
The formation of 1(l) from the spectra of the individual filters is visualized for
the COLIPA P3 standard in Fig. 44.2.
886 Herzog
Figure 44.2 Formation of the overall spectrum of the COLIPA P3 standard from the
spectra of the individual filters.
The Step Film Model by O’Neill

The derivation of the step film model by O’Neill (7) is visualized in Fig. 44.3 as a
two-dimensional sketch. The starting point is a homogenous film of absorbing
material of a certain thickness d and a horizontal extension of 1. A portion of
the homogenous film given by the horizontal extension g and the thickness fd
is removed from its original position and added to the remaining thicker part
of the film. This results in two film fractions of different thicknesses d0 and
(1 2 f )d with horizontal extensions (1 2 g) and g, respectively. Thus, the step
film parameters f and g define the difference in thickness and the relative
amounts of the two parts of the film. Both can adopt any value between 0 and 1.
In this way transformations of the film geometry can be carried out keeping
constant the amount of absorbing material.
f·d d'
d
(1-f)·d
g (1-g)
Figure 44.3 Step film model as introduced by O’Neill.

Figure 44.4 shows two extreme cases of possible structures of the step film.
Since f defines the depth of the film pores and g the fraction of pores relative to
the overall film area, the case of f ! 1 and g ! 1 describes a film with a large
fraction of pores where only little of the absorbing material is located resulting in
a transmission close to 100%. The bulk of the absorbing material is concentrated
on small spots where the transmission is almost blocked completely. Since most
of the film transmits nearly 100% of the UV light, the calculated SPF will be
much smaller than the in vivo SPF. On the other hand, for f ! 0 and g ! 0
the limit of a nearly homogenous film is approached, for which the calculated
SPF is much higher than the in vivo SPF. However, in between those two
extremes there should be values of f and g reproducing the correct in vivo SPF.
The transmission as a function of wavelength of a step film T(l) can be
written as the sum of the transmissions through the two fractions of the film:
T(l)g, f ¼ g101(l)cd{1f } þ (1 g)101(l)cd{g f =(1g)þ1} (44:7)
where d is the average thickness of the step film. As pointed out before, in accord-
ance with the conditions of in vivo determinations of the SPF, this is set to 20 mm.
1(l) is the average molar extinction coefficient calculated according to Eq. (44.6)
and c is the sum of molar concentrations of the UV absorbers based on the
average molecular weight of the UV absorber mixture (5).
Step film transmissions in the spectral range between 290 and 400 nm can
be calculated by the use of Eq. (44.7) as a function of g and f. The resulting trans-
missions are transferred afterward into Eq. (44.3) for calculation of the SPF as
function of g and f. This is shown in Fig. 44.5 for the example of the COLIPA
P3 standard. There is a strong dependence of the calculated SPF on the step
film parameters. As discussed before, for g ! 1 and f ! 1 the SPF is
approaching unity. For g ! 0 and f ! 0 the SPF is about 70, reflecting the
case of a homogenous film. But as is also obvious from Fig. 44.5, there are
pairs of step film parameters, which would result in the value of 15.5 representing
the in vivo SPF of the COLIPA P3 standard.
f 1 f 0
g 1 g 0
(1-f)·d
(1-f)·d
g g
SPFcalc << SPFin vivo SPFcalc >> SPFin vivo
Figure 44.4 Two extreme cases of a step film.

888 Herzog
80
60
40
SPF
20
0 0.0
0.2
0.0 0.4
0.2
0.4 0.6 g
0.6 0.8
f 0.8
1.0 1.0
Figure 44.5 SPF of the COLIPA P3 standard from step film calculation as a function of
the parameters g and f; the in vivo SPF of the P3 standard is 15.5.
It is desirable to identify one set of step film parameters with which sun-
screen formulations with a wide range of in vivo SPF values would be described
satisfactorily. In order to identify those parameters we looked at three sunscreen
standards covering a wide range of SPF values. Those were the COLIPA stan-
dards P1 and P3 and a third standard P4 manufactured in our laboratory the in
vivo SPF of which had been measured with 25 volunteers. The in vivo SPF of
P1 and P3 had been determined in a multicenter study. Thus, the statistical sig-
nificance of the corresponding in vivo data of those standards is higher than with
the normal COLIPA procedure requesting only 10 volunteers. For that reason the
standards have been used for the calibration of the film parameters. Their filter
contents and in vivo SPF values are as follows:
P1: 2.7% EHMC, in vivo SPF ¼ 4.2 (+0.2).

P3: 3.0% EHMC, 0.5% BMDBM, 2.78% PBSA, in vivo SPF ¼ 15.5 (+1.5).
P4: 5.0% EHMC, 10% MBBT (active ingredient), in vivo SPF ¼ 35.7 (+3.2).
The calibration of the model parameters was performed in the following

way: First, the SPF values of each sunscreen standard were calculated as a
function of both parameters g and f as described before (see also Fig. 44.5).
Then, for each calculated SPF value the square of the difference to the corre-
sponding in vivo SPF was determined and summed up for the three stan-
dards. Eventually, the pair g and f was identified, which led to the minimal
overall quadratic deviation to the in vivo data. Thus, the task was to search the
f
d
Figure 44.6 Visualization of the calibrated step film model with optimized parameters
g ¼ 0.269 and f ¼ 0.935.
minimum of the following function Dg, f .

SPF(P1)g, f 4:2 2 SPF(P3)g, f 15:5 2 SPF(P4)g, f 35:7 2
Dg, f ¼ þ þ
4:2 15:5 35:7

½SPF(P1)g, f 4:2 ½SPF(P3)g, f 15:5 ½SPF(P4)g, f 35:7 2
þ þ þ
4:2 15:5 35:7
ð44:8Þ
The procedure, which is described in more detail elsewhere (5), led to the result
of g ¼ 0.269 and f ¼ 0.935. The result is visualized in Fig. 44.6. For the sun-
screen standards described previously. Table 44.1 shows the results of calculated
SPF values with these parameters and the corresponding in vivo data.
Table 44.1 SPF Values from In Vivo Measurements and Calculations with a Calibrated
Step Film Model of Sunscreen Standards P1, P3, and P4
SPF SPF from

UV absorber content in vivo step film
P1: 2.7% EHMC 4.2 + 0.2 5.0

P3: 2.78% PBSA þ 3% EHMC þ 0.5% BMDBM 15.5 + 1.5 10.9
P4: 10% MBBT þ 5% EHMC 35.7 + 3.2 38.5
Using a Distribution Function for Introduction of Film Inhomogeneity

An alternative approach to O’Neill’s two-step film model would be to introduce a
distribution function in order to describe the film inhomogeneity. This was rea-
lized using the Gaussian type distribution function h(i):
" #
i 2
h(i) ¼ A exp B (44:9)
n
890 Herzog
with i ¼ 1, 2, . . . , n, where n is the number of steps which the distribution func-

tion is cut into for numerical treatment. A is introduced for normalization (8) and
B is the fitting parameter defining the film inhomogeneity. The normalization
condition for A is
" #
AX n
i 2
exp B ¼1 (44:10)
n i¼1 n
With this normalization the total amount of absorbing material is kept constant,
irrespective of the structure of the film (which varies with parameter B).
In Fig. 44.7, h(i) is shown as a function of i. The area under this curve is
normalized to 1 as expressed by Eq. (44.9), thus being equal to the area under
the corresponding homogenous film also drawn (as a dashed line) in the same figure.
The transmission through an inhomogenous layer of a Gaussian distri-
bution of layer thickness can be calculated as the sum of the transmissions
through the different steps in which the function is divided. The number of
those steps is n. The overall transmission then becomes
1X n
T(l)B ¼ 101(l)cdh(i) (44:11)
n i¼1
where 1(l) and c have the same meaning as in the step film model of O’Neill.
Again, the transmission of the inhomogenous film is put into Eq. (44.3) to
2
h(i)
0
0 0.2 0.4 0.6 0.8 1
i/n
Figure 44.7 Gaussian model of film inhomogeneity with the distribution film thickness
h(i) as a solid line; the corresponding homogenous film of the same amount of material is
shown as a dashed line.
Table 44.2 SPF Values from In Vivo Measurements and Calculations with a Calibrated
Gaussian Distribution Model of Sunscreen Standards P1, P3, and P4
SPF SPF from Gaussian

UV absorber content in vivo distribution
P1: 2.7% EHMC 4.2 + 0.2 5.2

P3: 2.78% PBSA þ 3% EHMC þ 0.5% BMDBM 15.5 + 1.5 11.2
P4: 10% MBBT þ 5% EHMC 35.7 + 3.2 35.8
calculate the respective SPF value. The parameter B has to be optimized, so that
the minimal quadratic deviation between calculated and in vivo SPF data of the
sunscreen standards P1, P3, and P4 is obtained. Thus, the minimum of the func-
tion DB was obtained:

SPF(P1)B 4:2 2 SPF(P3)B 15:5 2 SPF(P4)B 35:7 2
DB ¼ þ þ
4:2 15:5 35:7

½SPF(P1)B 4:2 ½SPF(P3)B 15:5 ½SPF(P4)B 35:7 2
þ þ þ
4:2 15:5 35:7
(44:12)
In the fitting procedure n had been set to 10 (see also Fig. 44.7). Larger values of n
did not lead to significant changes in the results. The result of the fitting was
B ¼ 2.0409 and the normalization led to A ¼ 2.6096.
For the sunscreen standards P1, P3, and P4 the results of the calculated SPF
values using these parameters are compared to the in vivo data in Table 44.2. The
similarity between the results using a Gaussian distribution and those obtained
from O’Neill’s step film model (Table 44.1) is striking. In contrast to the step
film model of O’Neill where two parameters had to be optimized, the Gaussian
distribution needs only one adjustable parameter.
CORRELATION OF EXPERIMENTAL AND CALCULATED DATA

Calculated SPF and SPF In Vivo
In Tables 44.3 –44.5 the in vivo SPF results of 56 sunscreen formulations with
SPF values ranging between 3 and 36 are compared to the corresponding
results of the SPF obtained from calculations with the calibrated step film
model as well as with the calibrated Gaussian distribution model. The UV absor-
bers and their concentrations are specified for each formulation. Tables 44.4 and
44.5 contain data from other authors (9,10) which have been added in order
to increase the data pool. Figure 44.8 shows the SPF calculated with the
step film model as a function of the SPF in vivo for all results listed in
Tables 44.1– 44.5 (n ¼ 59). There is a satisfactory correlation characterized by
892 Herzog
Table 44.3 SPF Values from In Vivo Measurements of Sunscreen O/W Formulations
and the Corresponding Calculations with the Calibrated Step Film Model (11) and the
Calibrated Gaussian Distribution Model
SPF SPF from SPF from Gaussian

UV absorber content in vivo step film distribution
5% EHMC þ 1% MBBT 12 + 4.9a 10.8 11.4

5% EHMC þ 2% MBBT 12 + 4.5a 12.7 13.7
5% EHMC þ 4% MBBT 19 + 2.8b 16.9 18.2
5% EHMC þ 8% MBBT 30 + 7.1a 29.3 29.1
2% MBBT 3 + 0.7a 4.9 4.3
4% MBBT 5 + 2.2a 6.5 7.0
8% MBBT 11 + 2.3a 11.3 13.1
5% EHMCþ 2% MBBT þ 2% BEMT 29 + 5.0 24.3 24.8
3% BEMT 7.7 + 0.8 6.3 6.8
3% BEMT þ 4% B3 15.2 + 2.0 9.9 11.2
3% BEMT þ 4% EHT 29.6 + 2.7 20.4 20.2
3% BEMT þ 4% Padimate O 13.3 + 1.4 14.5 15.5
3% BEMT þ 4% MBC 15.5 + 1.9 13.8 14.8
3% BEMT þ 4% EHMC 17.6 + 1.5 13.2 14.4
3% BEMT þ 4% DBT 19.7 + 1.8 21.7 21.2
3% BEMT þ 1% BMDBM 9.4 + 0.7 7.1 7.8
3% BEMT þ 2% BMDBM 9.4 + 1.0 7.9 8.8
3% BEMT þ5% MBBT þ 1% BMDBM 15.5 + 1.9 14.5 16.4
3% BEMT þ5% MBBT þ 2% BMDBM 13.5 + 1.1 16.0 17.9
2% BEMT 7.9 + 1.0 5.2 5.1
2% BEMT þ 2.5% MBBT 10.2 + 0.8 7.7 8.6
2% BEMT þ 5% MBBT 13.6 + 2.0 10.9 12.5
2% BEMT þ 7.5% MBBT 16.1 + 1.9 15.4 17.3
5% BEMT 8.8 + 0.7 9.2 10.4
5% BEMT þ 2.5% MBBT 15.2 + 1.6 13.4 15.1
5% BEMT þ 5% MBBT 30.1 + 2.8 19.0 20.6
5% BEMT þ 7.5% MBBT 30.6 + 4.3 26.8 27.2
5% EHMC 7.6 + 1.4 7.1 7.6
a
In vivo results with five volunteers.
b
In vivo results with 20 volunteers.
a correlation coefficient of r ¼ 0.8941. The slope of the linear regression is

0.846, indicating the tendency of the model to slightly underestimate the
in vivo results. Figure 44.9 shows the SPF calculated with the Gaussian distri-
bution model as a function of the SPF in vivo again for all the results listed in
Tables 44.1 – 44.5. The correlation coefficient in this case is 0.8917 and the
slope of the linear regression is 0.851. Thus, the results of correlations of
in vivo data and calculated data are very similar with both models. This is also
confirmed in Fig. 44.10, where the correlation of the results of both models is
shown, which is excellent.
Table 44.4 SPF Values from In Vivo Measurements of Sunscreen O/W Formu-
lations (9) and the Corresponding Calculations with the Calibrated Step Film Model
and the Calibrated Gaussian Distribution Model
SPF SPF from

SPF from Gaussian
5% TiO2 7 9.1 9.9

5% EHMC 9 7.1 7.6
7% OCR 8 6.1 5.2
2% EHT 8 5.0 5.3
3% EHT 9 6.2 6.5
4% MBC 10 6.1 6.4
2% BMDBM 6 4.1 3.4
5% EHMC þ 5% TiO2 20 20.5 19.7
4% MBC þ 5% TiO2 23 18.1 17.8
7% OCR þ 5% TiO2 24 15.9 16.5
2% BMDBM þ 5% TiO2 25 11.5 13.1
2% EHT þ 5% TiO2 21 16.4 16.4
5% EHMC þ 7% OCR 10 12.6 12.7
3% EHT þ 4% MBC 11 10.1 9.8
3% EHT þ 5% EHMC 12 11.7 11.3
5% EHMC þ 7% OCR þ 2% BMDBM 23 20.7 21.2
3% EHT þ 4% MBC þ 2% BMDBM 26 23.7 23.2
3% EHT þ 5% EHMC þ 2% BMDBM 20 26.6 25.5
Table 44.5 SPF Values from In Vivo Measurements of Sunscreen O/W

Formulations (10) and the Corresponding Calculations with the Calibrated
Step Film Model and the Calibrated Gaussian Distribution Model
SPF SPF from

SPF from Gaussian
7.5% Padimate O þ 2% B3 18 14.1 13.4

7.5% Padimate O þ 3% B3 19 15.8 15.0
7.5% Padimate O þ 4% B3 23 17.5 16.5
7.5% Padimate O þ 5% B3 23 19.4 17.9
7.5% Padimate O þ 6% B3 28 20.8 19.3
7.5% EHMC þ 2% B3 21 13.3 13.1
7.5% EHMC þ 3% B3 20 14.8 14.5
7.5% EHMC þ 4% B3 22 16.4 15.8
7.5% EHMC þ 5% B3 19 17.9 17.2
7.5% EHMC þ 6% B3 23 19.6 18.5
894 Herzog
40
Calibration Standards
T. Meadows (1990)
T. Wünsch(2000)
30 B. Herzog et al. (2003)
Regression
Calculated SPF
20
10
0
0 10 20 30 40
SPF in vivo
Figure 44.8 Correlation of SPF from step film calculations and in vivo data; correlation
coefficient ¼ 0.8941, slope ¼ 0.846, n ¼ 59.
40
Calibration Standards
T. Meadows (1990)
T. Wünsch (2000)
B. Herzog et al. (2003)
30
Regression
Calculated SPF
20
10
0
0 10 20 30 40
SPF in vivo
Figure 44.9 Correlation of SPF from Gauss function calculations and in vivo data;
correlation coefficient ¼ 0.8917, slope ¼ 0.851, n ¼ 59.
40
Gaussian distribution model
30
20
10
0
0 10 20 30 40
Step film model
Figure 44.10 Correlation of SPF values calculated according to the Gaussian distri-
bution model and the step film model; correlation coefficient ¼ 0.9905, slope ¼ 1.002,
n ¼ 59.
Correlation of Calculated UV-A Parameters and UV-A Parameters

Measured In Vitro
The UV-A/UV-B ratio and the critical wavelength are derived from the extinc-
tion spectra of sunscreen formulations (12). Both are reductions of the complete
spectral information to one number, characterizing in some way the shape of the
spectrum in terms of the amount of UV-A coverage in relation to the amount of
UV-B coverage. The UV-A/UV-B ratio is calculated according to Eq. (44.13)
Ð 400 Ð 400
320 log (1=T(l)) dl dl
UV-A=UV-B ratio ¼ Ð 320 Ð320
320
(44:13)
290 log (1=T(l)) dl 290 dl
where T(l) is the transmission at wavelength l. The integration limits correspond

to the respective wavelength ranges (in nm) of the spectra. The UV-A/UV-B
ratio typically varies between 0.1 and 1.5. Based on the level of the UV-A/
UV-B ratio a classification into five categories had been proposed (12), where
the highest rating in terms of relative UV-A protection is obtained with a
UV-A/UV-B ratio .0.9.
The critical wavelength lc is defined according to Eq. (44.14)
ð lc ð 400
log (1=T(l)) dl ¼ 0:9 log (1=T(l)) dl (44:14)
290 290
896 Herzog
1.5
Experimental
Calculated UVA/UVB-ratio
points
1.2
Correlation line
0.9
0.6
0.3
0.0
0 0.3 0.6 0.9 1.2 1.5
UVA/UVB-ratio in vitro
Figure 44.11 Correlation of UV-A/UV-B ratios from step film calculations and
corresponding data from in vitro measurements; correlation coefficient ¼ 0.9776,
slope ¼ 1.015, n ¼ 47.
Also, with respect to the critical wavelength a grouping into five categories was
suggested (12), where the highest category in terms of a broad-spectrum claim is
achieved with lc 370 nm.
As Figs. 44.11 and 44.12 show, there is an excellent correlation between
UV-A/UV-B ratios measured in vitro and by both types of calculations, accord-
ing to the step film model and the Gaussian distribution model. The same is true
for the critical wavelength results as shown in Figs. 44.13 and 44.14.
1.5
Experimental
points
Calculated UVA/UVB-ratio
1.2
Correlation line
0.9
0.6
0.3
0.0
0 0.3 0.6 0.9 1.2 1.5
UVA/UVB-ratio in vitro
Figure 44.12 Correlation of UV-A/UV-B ratios from Gauss function calculations and
slope ¼ 1.001, n ¼ 47.
390
Experimental
380 points
Correlation line
Calculated λc / nm
370
360
350
340
330
320
320 330 340 350 360 370 380 390
λ c / nm (in vitro)
Figure 44.13 Correlation of critical wavelengths lc from step film calculations and
slope ¼ 1.003, n ¼ 47.
Although for both UV-A/UV-B ratio and critical wavelength the same set
of 47 formulations were used, the distribution of the correlated data points in the
plots is quite different. For the UV-A/UV-B ratio the points are evenly scattered
over the whole data range, whereas for the critical wavelength most of the points
390
Experimental
380 points
Correlation line
Calculated λc / nm
370
360
350
340
330
320
320 330 340 350 360 370 380 390
λ c / nm (in v itro)
Figure 44.14 Correlation of critical wavelengths lc from Gauss function calculations

and corresponding data from in vitro measurements; correlation coefficient ¼ 0.9889,
slope ¼ 0.999, n ¼ 47.
898 Herzog
are concentrated in the region of higher values. This indicates a limited dynamic
range of the critical wavelength compared to the UV-A/UV-B ratio.
In order to tune the UV-A/UV-B ratio or the critical wavelength of a for-
mulation to a certain value, the ratio of the UV-A and UV-B filter concentrations
has to be adjusted. This can be calculated rather conveniently using one of the
models. In Fig. 44.15 an example is shown with combinations of EHMC and
BEMT. The UV-A/UV-B ratio and critical wavelength are plotted as function
of the ratio of the concentration of the UV broad-spectrum filter BEMT and
the overall UV filter concentration (in %). Since both models lead to nearly
the same results, only the step film model calculations are discussed. The calcu-
lations are in good accordance with the experimental data. Using such model
calculations is a convenient way to study the effect of arbitrary filter combi-
nations on the UV-A parameters of the respective sunscreen formulations.
It is obvious from Fig. 44.15 that in contrast to the UV-A/UV-B ratio the
critical wavelength approaches saturation already at low levels of UV-A
protection. Again, this indicates a limited dynamic range of the critical wave-
length, demonstrating that this parameter is not really suited for the characteriz-
ation of UV-A protection.
It is also possible to calculate whether the Australian standard will be
achieved or not. According to this standard a layer of a broad-spectrum sunscreen
product with a thickness of 8 mm shall not transmit more than 10% of radiation at
any wavelength from 320 to 360 nm inclusive (13). This criterion can be checked
by calculation of transmissions using the averaged molar extinction coefficients
from Eq. (44.6) for a homogenous film with a thickness of 8 mm. It has been
demonstrated that such calculations are in good accordance with the experimen-
tal work (6).
Figure 44.16 shows the concentrations of several UV-A absorbing filters
necessary to meet the requirement in the presence and absence of the UV-B
absorber EHMC. The presence of EHMC does not have a strong influence on
the results for the broad-spectrum filters ZnO, MBBT, and BEMT. However,
Figure 44.15 Prediction of UV-A parameters for different concentration ratios of a UV

broad-spectrum (BEMT) and a UV-B absorber (EHMC).
Figure 44.16 Minimum concentrations for achieving the requirements of the Australian
Standard calculated from (mixed) spectra using a homogenous film with an optical
pathlength of d ¼ 8 mm.
there is quite an impact on BMDBM, which is a pure UV-A absorber. Since this
compound has weak absorption in the range between 320 and 340 nm, addition
of EHMC helps to fill this gap. However, due to a chemical interaction under
UV irradiation the combination of BMDBM and EHMC shows increased photo-
instability and are not recommended to be used (14,15).
SUMMARY
Mathematical simulation of sun protection factors and UV-A parameters can be
performed based on calculation of mixed spectra of the respective sunscreen for-
mulation and on the introduction of a certain inhomogeneity of the sunscreen
film. Two mathematical models were employed in order to simulate such inho-
mogeneities. The first model is the step film model introduced by O’Neill
using two parameters, the second one is a Gaussian distribution for the variation
of the film thickness with only one parameter. In both models the amount of the
film forming material is fixed, while the structure of the film is changed. The
model parameters were calibrated using standard sunscreen formulations with
well-known in vivo SPF values. Both calibrated models are able to estimate rea-
listic SPF values of sunscreen formulations with arbitrary filter combinations and
the results of the two models were very close. The simulation of UV-A
parameters such as the UV-A/UV-B ratio and critical wavelength works even
better. In addition, it is possible to check the Australian Standard criterion by cal-
culating the transmission of the filter mixture of a homogenous film of 8 mm
thickness in the spectral range between 320 and 360 nm.
REFERENCES
1. Schulze R. Einige Versuch und Bemerkungen zum Problem der handelsüblichen
Lichtschutzmittel. Parfüm Kosmet 1956; 37(6,7):310 –315, 365 –372.
900 Herzog
2. Sayre RM, Agin PP, LeVee GJ, Marlowe E. A comparison of in vivo and in vitro
testing of sunscreening formulas. Photochem Photobiol 1979; 29:559– 566.
4. McKinlay AF, Diffey BL. A reference action spectrum for ultraviolet-induced
erythema in human skin. CIE Journal 1987; 6:17– 22.
calibrated step film model. J Cosmet Sci 2002; 53:11– 26.
6. Herzog B, Mongiat S, Deshayes C, Neuhaus M, Sommer K, Mantler A. In vivo and
in vitro assessment of UVA protection by sunscreen formulations containing either
butyl methoxy dibenzoyl methane, methylene bis-benzotriazolyl tetramethylbutyl-
phenol, or microfine ZnO. Int J Cosmet Sci 2002; 24:170– 185
7. O’Neill JJ. Effect of film irregularities on sunscreen efficacy. J Pharm Sci 1984;
73:888– 891.
8. Ferrero L, Pissavini M, Marguerie S, Zastrow L. Efficiency of a continuous height
distribution model of sunscreen film geometry to predict a realistic sun protection
factor. J Cosmet Sci 2003; 54:463– 481.
9. Wünsch T. Synergistic effects with high performance UV-filters. Proceedings of the
XXIst IFSCC International Congress, 2000:530 –535.
10. Meadows T. The effect of various sunscreen combinations on a product’s SPF value.
J Soc Cosmet Chem 1990; 41:141 – 146.
11. Herzog B, Mendrok C, Mongiat S, Müller S, Osterwalder U. The sunscreen simulator:
a formulator’s tool to predict SPF and UVA parameters. SÖFW J 2003; 7:25 – 36.
12. Diffey BL. A method for broad spectrum classification of sunscreens. Int J Cosmet Sci
1994; 16:47 –52.
13. AS/NZS. Australian/New Zealand Standard. AS/NZS, 1998:2604.
14. Rudolph T. Photochemische Aspekte von Lichtschutzstoffen. Behr’s Seminar
Kosmetische Lichtschutzmittel, 1999.
15. Herzog B, Sommer K. Investigations on photostability of UV-absorbers for cosmetic
sunscreens. Proceedings of the 21st IFSCC, Berlin, 2000. Poster P60 (CD ROM).
Marketing and Information
45
Single Sunscreen Application Can
Provide Day-Long Protection
Robert M. Sayre
Rapid Precision Testing Laboratories, Cordova, Tennessee and
University of Tennessee Center for the Health Sciences,
John C. Dowdy
Rapid Precision Testing Laboratories, Cordova, Tennessee, USA
William Shields
CCI, Rockledge, Florida, USA
Introduction 903
Methods 904
Protocol 904
Sunlight Exposure Dosimetery 904
Statistical Methods 907
Results 909
Discussion 910
Acknowledgment 911
References 911
INTRODUCTION
Today it is generally professed that sunscreen users do not apply sufficient sunsc-
reen to achieve all-day protection and that the sun protection actually achieved
903
904 Sayre, Dowdy, and Shields
outdoors is significantly over rated by current sun protection factor (SPF) testing
procedures (1 – 6). Such hypothesis suggests that users of sunscreens are fre-
quently sunburned and consequently sunscreen users are admonished to
frequently reapply the sunscreen. In the summer of 2000, we had the opportunity
to observe sunscreen usage during a weeklong soccer camp for young adolescent
ladies 9 –16 years old. Each young lady was required to wear a sunscreen of at
least SPF 30 self-applied each morning. They could either use their own sunsc-
reen or were provided a selection of sunscreens. Each camper applied what she
believed to be a sufficient amount of sunscreen. The campers were in sunlight
from 9 a.m. to noon and then from 1 p.m. to 4 p.m. During these sun-exposed
periods, the campers underwent strenuous exercise and activity. This paper
reports the results of that experience.
METHODS
Protocol
Volunteers gave informed consent to participate in a study of the protective
capabilities of a sunscreen product through outdoor use conditions.
Initial skin grading using a five-point scale (0—no erythema, ?—ambiguous,
1—minimally perceptible, 2—well developed, T—tanned) and photographs
showing the volunteer’s face, arms, and legs documented that there was no
sunburn at the beginning of the study. Before the initial exposure, volunteers
applied the sunscreen product to their faces, arms, legs, and other exposed
skin areas.
Each participating volunteer received a sunlight dosimeter badge to wear
during sunlight exposure. The badge’s serial number was recorded. The badge
was worn throughout the day on the volunteer’s wrist or shirt and returned at
the end of the day and logged in. Each day three control dosimeters were also
exposed to incident solar radiation for a.m., p.m., and all-day hours.
When the badge was returned, the volunteer’s face, arms, and legs were
graded for possible erythema using a five-point scale (0, ?, 1, 2, T). Burns on
volunteers are not counted unless apparent at the next mornings examination.
Burns were only counted once on initial development and persistent erythema,
while noted, was not included for statistical analysis. Each day the volunteers
were regraded (Table 45.1) and photographed at the beginning of the day and
provided with a new badge whose serial number was recorded for the volunteer’s
use that day. The volunteer then applied the sunscreen. At the day’s end, the
volunteer was graded and photographed.
Sunlight Exposure Dosimetery

Wearable Ultraviolet Dosimeters for Spectrally Varying Environments, Rapid
Precision Testing Laboratories, Patent Pending (Fig. 45.1) were used to
measure exposure to ultraviolet (UV) radiation.
Table 45.1 Visual Grading of Major Body Sites
Day 2 Day 3 Day 4 Day 5

Soccer Scored Other Scored Other Scored Other Scored Other
camper sites sites sites sites sites sites sites sites
12 0 1—below eyes 2 1—below eyes 0 0

10 0 0 1—below eyes 2 0
1 0 0 0 0
3 0 0 0 0 1—below eyes
1—tip nose
4 0 1—below eyes 0 1—back neck 0 2—below eyes 0 1—tip nose
1—below eyes 2—top ears
2—tip nose
9 0 0 0 2—below eyes 0
11 0 0 1—below eyes 0 1—forehead 0
18 0 1 2—back neck 0 0 1—below eyes
21 0 0 0 1—back neck 0 1—tip nose
2 0 0 1—back neck NP 0 1—below eyes
Single Sunscreen Application for Day-Long Protection
1—back neck
20 0 1—below eyes 0 1—below eyes NP 0 1—tip nose
6 0 0 NP NP
13 NP 0 NP NP
5 0 NP NP NP
8 0 1—below eyes NP NP NP
15 0 NP NP NP
19 0 1—below eyes NP NP NP
(continued )
905
906

Day 2 Day 3 Day 4 Day 5
Soccer Scored Other Scored Other Scored Other Scored Other

camper sites sites sites sites sites sites sites sites
17 NP NP 0 2—below eyes 0 1—below eyes

2—throat
7 NP NP NP NP
14 NP NP NP NP
16 NP NP NP NP
Product failure 5/224 8/195 8/164 7/179
p value 1.37 1026 0.0019 0.0137 0.0021
Note: Scored sites: 14 body and face sites were evaluated: frontal view—left/right (L/R) face, L/R upper and lower arms, L/R legs. Back view—L/R upper and
lower arms, L/R legs. Other sites scored only when evident and included as one additional statistical site. NP indicates nonparticipants, p values based on population
proportion of 0.1 (90% unburned).
Sayre, Dowdy, and Shields
Single Sunscreen Application for Day-Long Protection 907
These dosimeters are based on the UV response of GAFChromic radio-

graphic media (ISP Technologies Inc., product HD-810) which has a spectral
response spectrum (7) similar to human UV risk spectra (Fig. 45.2). The
dosimeters (Fig. 45.1) consist of two pieces of radiographic film, one of which
is covered with a layer of UV-B cut-off filter material, sealed inside an airtight
polymer sheath, which transmits sufficiently in the UV-B to allow differential
determination of exposure to erythemic radiation in the UV-A and UV-B bands.
Following exposure, the color change of the film pieces were separately
evaluated by densitometric scanning (8,9) with the difference between the
detected values of total UV exposure and the detected UV-A exposure defining
the erythemically significant UV-B exposure. Film response was correlated to
solar exposure using calibration curves derived from simultaneous dosimeter
exposures and spectroradiometric measurement of sunlight (Fig. 45.3).
Statistical Methods
Response grading involved a series of sites on each volunteer participating each
day. The sites, when viewed from the front, were: right and left side of face, right
and left upper arm, right and left lower arm, right and left leg. When viewed
from the rear the sites were: back right and left upper arm, right and left lower
arm, right and left leg. This totaled 14 primary opportunities for each product
to fail because of product application, product rub off during the day, or simple
product ineffectiveness. It was decided to treat each volunteer test day as a
unique individual test and the 14 sites as test replicates adopting a simple
burn, no burn binary statistic. Burns that occurred outside these 14 primary
sites were combined as one “other” site.
The procedure used is similar to that recently proposed for substantiation
that the labeled SPF of a sunscreen is correct (10). Results were evaluated
Figure 45.1 Ultraviolet dosimeters. Wearable ultraviolet dosimeters for spectrally

varying environments (Rapid Precision Testing Laboratories, Patent Pending) were used
to monitor daily exposures. These personal UV dosimeters provide differential monitoring
of full-spectrum UV, UV-A, and UV-B (by difference).
Figure 45.2 Comparison to other action spectra. The GAF film UV action spectrum
shows remarkable correlation to several photobiologically important UV action specrta.
The response drops almost two orders of magnitude through the UV-B and then drops
slightly more than two more orders of magnitude through the UV-A as do most of these
reference action spectra.
Figure 45.3 Dosimeter calibration curves. Densitometric scans of exposed dosimeters

correlated with simultaneous measurement of sunlight with a calibrated spectroradi-
ometer, Optronic Laboratories Model OL-754, traceable to NIST.
using simple binomial statistics, based on the premise that users of high SPF
products, self-applied only once at realistic application rates, should expect a
reliable chance (90 – 95%) of all-day protection during an active day of
outdoor sunlight exposure. For a given set of exposure site evaluations, if the
number of visible responses was lower than a predicted limit, based on the
binomial distribution, then the expectation of all day protection was supported.
The acceptance level for the number of sites without responses was set for a
95% or greater probability that the actual protection applied was at least as
high as the dose accumulated during the exposure day. Look-up tables of cumu-
lative exact binomial probabilities for each day’s evaluations were generated
for the total number of exposure sites. If the number of sunburned sites was
less than or equal to the number that could be reasonably expected (p , 0.05),
the product is considered adequately protective for all-day use. If there were
too many sunburned sites ( p . 0.05), the product was ruled to be inadequate
to provide day-long protection.
RESULTS
On June 19 –23, 2000, a soccer camp for young ladies was held in Clearwater,
Florida. The ages ranged from approximately 9 to 16 years. Campers were
required to apply a sunscreen each day and could either bring their own or use
a product supplied by the camp. Those discussed in this report applied Baby
Blanket SPF 50þ, Sawyer Products System-2 SPF 45, or REI System-2 SPF
45 or Rocky Mountain SPF 50 (supplied by the camp) only once a day, in the
morning.
The young ladies participating in the study were in direct sunlight for more
than 6 h each day and even when covered by an awning at noon may have
received additional scattered exposure. The exposure monitoring indicated that
while the campers were engaged in sun exposed activities at least 13 (MED:
minimum erythemal dose) MED were available each day with as many as
20 MED on one test day (Fig. 45.4).
While the participating campers ranged from skin types 1 –5, none experi-
enced any sunburn where the sunscreen had been applied to their arms and legs.
While no swimming occurred, the fact that the subjects were engaged in strenu-
ous soccer activities, sweating and sometimes colliding with each other or the
ground, no failure due to these activities was observed. The only product-
protected sites where slight sunburn occurred were on the faces of two of the
subjects (Table 45.1). This observation may be attributed in part to avoidance
of the eyes during application and/or wiping and toweling of sweat from
the face. Many individuals seem to miss small areas particularly below their
eyes, above their ears, and the tips of their noses (Table 45.2).
The most severe sunburn observed was seen when a young lady applied the
sunscreen with her hair down, and sometime during the day’s activities tied
Figure 45.4 Full-spectrum and UV-A dosimetry. Average dosimeter values for each
study day are plotted against that day’s control dosimeter. Personal dosimeters registered
2 – 5 MED accumulated dose of the 13– 20 MED possible daily exposure. Control
dosimeters were exposed face up on a flat surface while personal dosimeters worn on
the wrist or pinned onto the shirt were oriented at variable angles to the sun. The relative
proportion of UV-A exposure was also significantly less than the control exposures.
her hair up in a ponytail. The sunburn, visible the next morning, was confined to
where she failed to apply sunscreen to the back of her neck.
DISCUSSION
Each camper applied the amount of sunscreen she felt necessary without
instruction and none of the six 6-oz. sunscreen bottles were emptied during
the week’s use. This suggests that while reapplication is probably desirable, a
single application of a high SPF product used at a realistic application density
can provide day-long protection.
Moreover, concerns about a user’s ability to uniformly apply sufficient sun-
screen to provide all-day protection would appear unfounded. These adolescent
Table 45.2 Cumulative Product Failures at “Other” Localized Sites
Day 2 Day 3 Day 4 Day 5 Total
Below eyes 5 3 2 3 13
Tip of nose 1 3 4
Throat 1 1
Back of neck 2 1 3
Top of ears 1 1
Forehead 1 1
Number of subjects 16 13 10 11 50
to teenage children were able to apply the product sufficiently to provide ade-
quate protection for extended periods of vigorous athletic exertion in sunlight.
Clearly, a single application the high-SPF sunscreen products used was
protective all day. In fact, this single daily application repeatedly provided
protection under a variety of different sunlight/cloud conditions. Even young
sunscreen users seem to universally apply the sunscreen at adequate levels to
completely protect large body areas. However, they miss, sometimes persistently,
small particularly sensitive body areas such as below their eyes, above their ears,
and the tips of their noses. Missing tops of ears and backs of necks at the hairline
could be explained by avoidance of their hair followed by rearranging hair, for
example as a ponytail, for outdoor activities.
It is important to realize that while a single sunscreen company sponsored
this study, most adolescent soccer campers did not directly participate in
the study by using the product supplied. However, they were all required to
use the sunscreen of their choice in no case was sunburn observed during the
camp on any volunteer. Clearly, many different SPF 30 products were applied
adequately and did provide the protection expected. In no instance was
inadequate product application observed for large body areas. More importantly,
in west-central Florida, in mid-June, there was ample sunlight to cause serious
sunburns on anyone who chose to spend the day unprotected or had not
applied adequate levels or misapplied sunscreen.
ACKNOWLEDGMENT
This study was supported in part by a grant from Baby Blanket by the Children’s
Healthcare Research Group.
REFERENCES
1. Wulf HC, Stender IM, Lock-Andersen J. Sunscreens used at the beach do not protect
against erythema: a new definition of SPF is proposed. Photodermatol Photoimmunol
Photomed 1997; 13:129– 132.
2. Bech-Thomsen N, Wulf HC. Sunbathers’ application of sunscreen is probably
inadequate to obtain the sun protection factor assigned to the preparation.
3. Azurdia RM, Pagliaro JA, Diffey BL, Rhodes LE. Sunscreen application by photosen-
sitive patients is inadequate for protection. Br J Dermatol 1999; 140:255 –258.
4. Diffey BL. Sunscreens, suntans and skin cancer. People do not apply enough
sunscreen for protection. Br Med J 1996; 313:942.
5. Stokes R, Diffey B. How well are sunscreen users protected? Photodermatol Photoim-
munol Photomed 1997; 13:186 – 188.
6. Taylor S, Diffey B. Simple dosage guide for suncreans will help users. Br Med J 2002;
324:1526.
7. Dowdy JC, Sayre RM. UV response spectrum of GAF chromic film. Photochem
Photobiol 1997; 65:82S.
8. Sayre RM, Sayre DL, Dowdy JC. Determination of the UV transmittance properties of
fabrics using UV sensitive film and densitometric techniques (abstract V-3o/04). 6th
Congress of the European Society for Photobiology. Churchill College, University of
Cambridge, UK, 1995:46.
9. Sayre RM, Dowdy JC. Defining beam uniformity of UV sources using UV sensitive
film and densitometric techniques. Photodematol Photoimmunol Photomed 1996;
12:40.
10. Sayre RM, Stanfield J, Lott DL, Dowdy JC. Simplified method to substantiate SPF
labeling for sunscreen products. Photodermatol Photoimmunol Photomed 2003;
19:254– 260.
46
The Role of Publications
in the Industry
Nancy Allured
Allured Publishing Corporation, Carol Stream, Illinois, USA
Trade Publications 914

Scientific Journals 915
Technical Books 915
Electronic Information 915
More Resources 916
Appendix—Industry Publications 916
Trade Publications 916
Scientific Publications 917
Electronic Information 917
Consumer Press 917
Regulatory Resources 918
Getting started on a new research project would be nearly impossible without

industry publications. The first step in your search should be to peruse industry
publications to get as much current information as possible. Publications are a
very important resource. This is true for the general public and also for industry.
In the sun products field, there are great resources at our disposal and I will cover
them and how best to use these resources.
913
914 Allured
Publications bring the reader the most current information. When you need
the newest and the most up-to-date news, look to trade publications. When you
need to research history on a subject, look to technical books and scientific
journals to help you look back. There are many levels of publications that we
use to keep abreast of the sun products industry and the trends.
There are an extraordinary number of published resources for the sun
products researcher. Most chemists start a new project using publications as a
first step to develop a new sun product. This field has frequent new technologies
being introduced and new research adding knowledge to our category. And, the
chemists use these resources heavily to develop the best product for the time.
TRADE PUBLICATIONS
Trade publications are very industry focused but most importantly they are the
most current on news and information. Industry publications know the manu-
facturers, the suppliers, regulatory issues, and the market statistics. The most
important service trade magazines provide is keeping the newest information
circulating in the industry. Trade publications cover the news—regulatory
issues and changes, new ingredients, and new products on the market. And this
being an international industry, the magazines cover new developments from
around the world.
Trade publications are a part of the industry. This is a distinct difference
from other publications. Trade publications are connected to the many resources
the industry provides and they are directly a resource to people in the industry.
Look to these publications to provide ingredient information, prototype formu-
lations, regulatory restrictions and updates, directories of resources, supplier
information, packaging and contract manufacturing services. They can be your
practical resource to getting started and keeping connected.
In the sun product category there are many changes happening quickly. It is
a very dynamic category. As a result, the trade publications help the industry stay
up-to-date on new technologies being developed, and new regulations affecting
the category. Due to strong regulatory restrictions on sun products, there is
more development taking place in delivery systems and the base product technol-
ogies. There is also more development in testing methodologies. The trade
publications keep the industry informed on these changes as new discoveries
are introduced.
Trade publications provide many of the newest formulas available to try.
These prototype formulas are a great starting place to learn new combinations
of ingredients and develop new forms of product. As a high-growth category,
sun products continue to be the subject of many conferences and seminars.
Trade magazines track events and keep calendars current of relevant programs
for sun products. These magazines provide a quick overview of everything
happening in the industry. They are at the center of information for the industry.
It is also very internally focused—industry talks with industry. Readers scan
The Role of Publications in the Industry 915
them monthly to keep on top of industry changes. Many researchers file articles
by key words to keep information organized for future projects.
SCIENTIFIC JOURNALS
Scientific journals are used in an entirely different way in the sun products
category. The journals contain the history and in-depth research. They hold the
history of the science behind chemical sunscreens as they are developed,
researched, and improved.
Because journals are peer reviewed, the science is scrutinized and
evaluated for its integrity before allowing publication. Journals are a forum for
pure research. They provide the scientific community a place to present new
research and discoveries in sun research. These publications are extremely
important for new findings on skin and skin’s reaction to photoaging, normal
aging, and physiology of skin. These scientific publications carry a lot of research
on sun, effects of sun on skin and hair, and the new chemistries in sunscreen
development. They also provide insights into many testing methodologies.
These papers are also filed by keyword for future projects.
Many researchers watch the scientific journals to see a progression of
incremental findings on sun research. This points the way to future sun product
discoveries.
TECHNICAL BOOKS
One of the first places a researcher will start in new project is with technical
books. Books such as this one on sunscreens offer a tremendous amount of
information to get started. It is specifically focused on the project at hand and
offers a wide variety of approaches.
Technical books on chemistry, photochemistry, formulations, and ingredi-
ents are invaluable. All research chemists working on product development or
new research must have technical books at their fingertips.
ELECTRONIC INFORMATION
The Internet is a library at your fingertips. There is a lot of good information
available via the Internet. We should never underestimate the value of getting
information online. That being said, the Internet is the most difficult to use
efficiently and the least organized of all the information resources available
to our industry. It is not easy finding the information you want without some
experimenting with the use of key words and searching through many websites.
But once you become more familiar with the good information out there, it will
be a tremendous resource to your work.
Searches using Google can be rewarding in finding some of the latest news
or publications available. Some suppliers of sunscreen ingredients have a vast
916 Allured
amount of information available online. Web-based compendiums of literature

such as STN have a cost but make the use of the Internet more efficient.
The Internet can also be a great resource for regulatory and patent informa-
tion on sun products. Some key websites are the US Patent and Trademark
Office (uspto.gov), US Food and Drug Administration (fda.gov), The European
Union (europa.eu.int/index-en.htm#), and US Federal Register (archives.gov/
federal_register/index.html) to name a few.
Sun product formulations are available online from many of the suppliers
of sunscreens. There are also several trade publications that provide hundreds of
formulations online with free access.
MORE RESOURCES
There is a wealth of information available in the sun products industry. Suppliers
of ingredients conduct regular research for new discoveries. The suppliers
publish data, share the data, and many times, provide full booklets on their tech-
nical information in print or online. They supply formularies to help chemists
develop products and share the scientific data, clinical data, and test results.
And, last but not least is the consumer press. Many women’s and men’s
beauty or lifestyle magazines help us as an industry to keep on top of what the
consumer is focused on to help us target our product development more
closely to the customer.
This industry has a lot of information available. Through trade publica-
tions, scientific journals, the Internet, books, and many other industry resources,
quality information is readily available and accessible to those working in the sun
product field.
APPENDIX—INDUSTRY PUBLICATIONS
Trade Publications
Chemical & Engineering News—(ACS Publications, USA)
Cosmetic Technology—Technical magazine for the cosmetic industry in
Italy (CEC, Italy)
Cosmetics & Toiletries magazine—Technical magazine, peer reviewed, for
the international industry (Allured Publishing, USA)
Cosmetics & Toiletries, Portuguese Edition—Technical magazine for the
cosmetic industry in Brazil (Tecnopress, Brazil)
Fragrance Journal—Technical magazine for the cosmetic industry in
Japan (Fragrance Journal, Japan)
Global Cosmetic Industry magazine—Business magazine for the inter-
national cosmetic industry (Allured Publishing, USA)
Happi magazine—Cosmetic and household industry magazine for inter-
national industry (Rodman Publishing, USA)
The Role of Publications in the Industry 917
PCA magazine—Cosmetic industry magazine in France (Cosmedia,

France)
Rose Sheet newsletter—Weekly news on products, regulations, companies,
and events (Elsevier Science, USA)
SOFW journal—Technical magazine for cosmetic and household industry
(Verlag H. Ziolkowsky GmbH, Germany)
SPC magazine—Business magazine for the cosmetic industry (Wilmington
Press, UK)
Scientific Publications
International Journal of Cosmetic Science—Original papers and review
papers in skin and cosmetic research. (Society of Cosmetic Scientists/
Societe Francaise de Cosmetologie, UK and France)
Journal of Applied Cosmetology—Original papers and research reviews on
skin and cosmetics. (International Society of Cosmetic Dermatology,
Italy)
Journal of Cosmetic Science—Papers on the science underlying cosmetics
(Society of Cosmetic Chemists, USA)
Journal of Investigative Dermatology—Original papers and reviews
pertinent to the normal and abnormal function of the skin. (Society for
Investigative Dermatology, Blackwell, UK)
Journal of Organic Chemistry—(ACS Publications, USA)
Journal of Toxicology—Cutaneous and Ocular Toxicology—Original
research papers, short communications and case studies reporting all
types of harm to cutaneous and ocular systems from medical products,
consumer and household products, as well as environmental and
occupational exposures. (Marcel Dekker, USA)
Skin Research and Technology—Clinically oriented journal on biophysical
methods and imaging techniques for noninvasive quantification of skin
structure and functions. (International Society for Bioengineering and
the Skin, Blackwell, UK)
Electronic Information
Dialog.com—a Thomson business
www.nerac.com—Nerac, Inc. (USA)
Consumer Press
Jane—Fairchild Publications (USA)
Cosmopolitan—Hearst magazines (USA)
Vogue—Conde Nast Publications (USA)
Elle—Hachette Filipacchi Media (USA)
918 Allured
Allure—CondéNast (USA)
Lucky—CondéNast (USA)
Regulatory Resources
U.S. Food and Drug Administration (FDA)
5600 Fishers Lane, Rockville, MD 20857-0001 (USA)
Cosmetic, Toiletry, and Fragrance Association (CTFA)
1101 17th Street, NW, Suite 300, Washington, DC 20036-4702 (USA)
Research Institute for Fragrance Materials (RIFM)
Two University Plaza, Suite 406, Hackensack, NJ 07601 (USA)
47
Technical Information in the Expanding
Sunscreen Field
Regina Lim
Product Quest, Inc., Daytona Beach, Florida, USA
Christopher D. Vaughan
SPF Consulting Labs, Inc., Pompano Beach, Florida, USA
Edwin D. Leonard, Jr.
Patriot Distributors, Inc., DeLand, Florida, USA
Introduction 920
Technical Conferences 921
The Florida Sunscreen Symposium 921
The European UV Sunfilters Conference and Exhibition 921
The Sun Protection Conference 922
Educational Courses 922
Scientific Societies 923
The American Society for Photobiology (ASP) 923
The Society of Cosmetic Chemists (SCC) 923
The American Academy of Dermatology (AAD) 923
Scientific Journals 923
Scientific Books 925
Internet Websites 925
Conclusions 927
References 927
919
920 Lim, Vaughan, and Leonard
INTRODUCTION
Currently, the spread of new discoveries and scientific studies relating to human
protection from ultraviolet (UV) damage is fragmented. Dissemination of pub-
lications, and presentations of new techniques, and results in this field has
been severely hampered by widespread location of the scientific work.
Because of the wide range of disciplines required to address the requirements
of UV Protection, information in this field presents a twofold challenge. First,
its requirements for expertise are so broad that no scientific journal exists
which adopts such broad interests, and second, its technology is covered by
much proprietary secrecy, as is typical of any emerging science. Figure 47.1
shows the number of new US patents issued for sunscreens and skin coloring.
This pattern usually defines an emerging technology, and it is too early to
predict when the technological influx will peak, but it appears that this will
not occur for many years.
The technical requirements of the UV protection field include: biologists
and physiologists—to study the effects of UV radiation on living creatures; che-
mists and pharmacists to formulate products to deliver UV protection; physicists
to study the effects and response of the UV radiation as it interacts with both
formula and skin; lawyers and regulators who assure the safety and effectiveness
of UV protection products in the market; and of course, marketers who apply
their research to evaluate product acceptability among the population. Sales
and marketing professionals are rarely given recognition for their contribution
to the delivery of public health. Of course, we know that even the greatest
health care advancement is valueless without consumer acceptance. These
broad requirements force publication of advancements in sun protection into a
wide array of channels.
Figure 47.1 Sunscreen patents issued in the USA 1974– 2004.

Technical Information in the Sunscreen Field 921
TECHNICAL CONFERENCES
The Florida Sunscreen Symposium
The Florida Sunscreen Symposium ranks first in the field as a source for new
information on sunscreen technology. It was the first major sun protection con-
ference, and has been presented continuously over almost 20 years. The
Florida Sunscreen Symposium has seen excellent success dealing with the
broad range of interests required by UV protection technology. Unfortunately,
it is only presented in odd numbered years. Its continual location in Florida
places it in a region suited for sun protection study, and recreation. Instigated
in 1987 by Ed Leonard Jr. and Chris Vaughan through the Florida Chapter of
the Society of Cosmetic Chemists, this conference has become the largest scien-
tific meeting of its kind, and was the first to address the broad range of scientific
disciplines required by the field. One of the most successful aspects of this
conference arising under the scientific program direction of Regina Lim has
been its readiness to air both controversial and problematical aspects arising in
sun protection. As a result, much advancement in photostability, optimization
of pigmentary reflection, and absorber synergism has been developed.
This three-day conference includes two scientific sessions, usually moder-
ated by Nadim Shaath, and Chris Vaughan, a poster session, an educational
seminar course, and a social banquet. This conference regularly attracts approxi-
mately 50 suppliers who are limited to presenting materials directed toward sun
protection at their booths in the product showcase which is open throughout the
conference. Many new ingredients have made a debut in this milieu.
The 8th Symposium was held in 2002 due to the 9/11 tragedy and a
simultaneous hurricane in Orlando (in 2001). This conference was rescheduled
at Walt Disney World’s Coronado Springs Resort in Orlando, Florida. Some of
the topics of the scientific sessions covered USP Requirements for Sunscreens,
A New way to Characterize Sunscreen Stability, and Thin Film Spectro-
photometric Determination of UV-A Protection. The next conference, in
September 2003, at Disney’s Grand Floridian Hotel & Resort highlighted
topics on UV-A Protection, Indoor Tanning Exposure to UV-A, New US Sun-
screen Regulations, and the steps ongoing toward Harmonization of International
Sunscreen Requirements.
Many new materials and discoveries have debuted at the Florida Sym-
posium, which is sponsored by the Florida Chapter of the SCC each September
in odd numbered years. Information may be found on their website: http//
www.scconline.org/members/chapters.
The European UV Sunfilters Conference and Exhibition

The European Sunfilters Conference is a privately organized, two-day English
language conference held at the Palais de Congress in Paris, France Sponsored
by Step Exhibitions, Ltd, Stephouse, North Farm Rd., Tunbridge Wells, Kent,
TN2 3DR, UK. This is a new conference similar to the Florida Symposium. This
conference will likely be repeated.
The Sun Protection Conference

This is a new conference organized by the Royal Society in England. It is pre-
sented in November, Annually by Summit Events, Ltd., 29– 35 Lordship La.,
London, SE22 8EW, UK who also can be reached on the web at: info@summit-
events.com.
EDUCATIONAL COURSES
The Society of Cosmetic Chemists (SCC) sponsors a course (1) twice each year.
This course is currently taught by the two of the most respected experts in the
field: Ken Klein of Cosmetech, Inc. and David Steinberg of Steinberg Assoc.,
Their expertise centers on formulation, new technical developments, and regulat-
ory requirements. Both instructors are currently byline contributors and Advisors
to Cosmetics & Toiletries Magazine. They also manage consulting firms specia-
lizing in sunscreens. Information on the time and location of these courses are
available from the Society of Cosmetic Chemists, 120 Wall Street, New York,
NY 10005, or from their website www.scconline.org.
IMS Testing Group, 282 Quarry Rd., Milford, CT 06460 offers occasional
courses on Testing and evaluation of sunscreens, in conjunction with IFSCC, or
SCC—John Sottery, PhD is the usual instructor. They can be reached through
their website: www.ims-usa.com.
The University of Cincinatti, 3223 Eden Avenue, Cincinatti, OH 45267, is
the first of only a few American universities which offer a Masters Degree in
Cosmetic Chemistry. Their website http://www.uc.edu provides an Altavista
powered search engine, which only turned up two sites when queried for “sun-
screen.” Neither site directed you to their program on cosmetic science. Never-
theless, this university’s School of Pharmacy offers a very active and respected
cosmetic science program, which covers all aspects of cosmetic formulation
including sunscreen technology. Unfortunately, their website is poorly con-
structed, and requires perseverance and magnification to glean scraps of
information.
Fairleigh Dickinson University, 100 River Road, Teaneck, NJ 07666 also
offers an MS in Cosmetic Science. Directed by Dr James Dougherty at their
school of Natural Sciences. This university curriculum provides an excellent cov-
erage of sunscreens. Information is available on the web at http://www.fdu.edu,
where a fast, and very user friendly search for cosmetic science will provide
details.
The Institute for Applied Colloid Technology—directed by Gerd Dahms,
PhD also provides instruction in UV protection technology especially with
respect to formulation variables and product stability.
SCIENTIFIC SOCIETIES
The American Society for Photobiology (ASP)
This scientific society promotes original research, provides a forum for the
integration of various disciplines in the study of photobiology, and provides
information on the photobiological aspects of national and international
problems. Founded in 1972, they produce a journal, online newsletter, and an
annual meeting in July. The basic areas of this society’s interest are: photochem-
istry, photosensory biology, environmental biology, and photosynthesis. They
operate from the University of Kansas, and can be contacted at ASP Business
office, PO Box 1897, Lawrence, KS 66044. Phone (785) 843-1235x216/Fax
(785) 843-1287 or at [email protected]. Their European counterpart, The
European Society for Photobiology (ESP) is associated with the University of
Dundee.
The Society of Cosmetic Chemists (SCC)

This scientific society has 18 regional chapters across the USA. Their concen-
tration is in the formulation, function, and testing of UV protecting materials.
Their national meetings usually devote one of four scientific sessions to the
sunscreen field. These meetings are held early in December in New York City,
and mid-year at varying locations. They can be contacted at: SCC, 120 Wall
Street, New York, NY 10005. Phone: (212) 668-4088, fax: (212) 668-1504.
The American Academy of Dermatology (AAD)

The AAD is a specialized medical society founded in 1938 with the mission to
improve the level of dermatological care. They sponsor a journal, the Journal
of the American Academy of Dermatology, which publishes cutting edge research
in the medical aspects of skin cancer. They also sponsor research on skin cancer
treatment and prevention at the Sulzberger Institute. The AAD annual meeting is
a fertile forum for the reporting of new skin cancer research results, and treatment
discoveries. They can be reached in Shaumberg, IL through their website at:
http//www.skincarephysicians.com.
SCIENTIFIC JOURNALS
There is at this time no scientific journal which deals solely with the broad appli-
cation of science and technology as applied to UV protection. The peer-reviewed
journals which most often publish on this topic are:
1. Photochemistry and Photobiology: The Journal of the American
Society for Photobiology provides the best coverage of new research
in the photobiological aspects of sun protection and UV damage.
But this journal limits its range to biological interactions with UV.
Abstracts and tables of contents are available free online at www.

aspjournal.com.
2. The Journal of Photochemistry and Photobiology covers topics on
bioluminescense, chronobiology, DNA repair, photocarcinogenesis,
photomovement, photoreception, photosynthesis, spectroscopy of
biological systems, and UV or visible radiation effects and vision.
This independent journal is published by Elseivier Press: 6277 Sea
Harbor Drive, Orlando FL 32887-4200, or at PO Box 211, 1000AE
Amsterdam, The Netherlands.
3. Cosmetics & Toiletries Magazine: This peer-reviewed journal pub-
lishes documentary issues specializing in new sunscreen technology,
usually twice each year. Its range of topics in the widest of any
journal, although it leans toward chemistry of UV interacting
systems. It is available from Allured Pulishing, Carol Stream, IL.
4. IFSCC Magazine is published quarterly in Germany by Verlag fur
Chemische Industrie, PO Box 10 25 65, D-86015 Augsburg, Germany.
This journal offers five original scientific papers in each issue. Usually,
one or two papers address some aspect of sunscreen technology. It is
sponsored by the International Federation of Societies of Cosmetic
Chemistry, and can be contacted by email at [email protected].
5. Photodermatology, Photoimmunology and Photomedicine is the offi-
cial publication of the Photomedicine Society. It concentrates on direct
and distant effects of electromagnetic radiation mediated through
the skin. It is published by Blackwell Ltd. in London, and current
abstracts are available online at http://www.blackwellmunksgaard.
dk/Journal.
6. The Journal of Cosmetic Science (formerly the Journal of the Society
of Cosmetic Chemists) is a peer-reviewed journal which generally has
one or more UV-related papers in each issue. It is published by the
Society of Cosmetic Chemists, New York, NY 10005.
With the exception of the very few focused scientific conferences, and
journals mentioned in the aforesaid list, articles on research and new develop-
ments in sun protection may occasionally be found scattered amongst the
following (re)sources: Journal of the American Academy of Dermatology,
British Journal of Dermatology, Soap and Cosmetics, published by Chemical
Week Associates, 110 William St., New York, NY. HAPPI (Household &
Personal Products Industry) Published by Rodman Publishing, 17 S.Franklin
Tpke., Ramsey, NJ and The Newsletter of the Florida Chapter of the Society of
Cosmetic Chemists. This newsletter promotes sunscreen technology, and
covers recent leading developments in the field. It is circulated to members of
the Florida Chapter of the SCC and prior attendees of the Florida Sunscreen
Symposium.
SCIENTIFIC BOOKS
This book, Sunscreens, has for over 15 years been the only book of its kind
addressing the broad field of UV protection issues. It has numerous reference
citations (ISI) and 52 US patent citations since its first publication. Other
useful books addressing biology and physics of UV light are:
Understanding Physics, Light, Magnetism and Electricity, Issac Asimov,
New American Library, (1985) is very readable, and basic.
Waves and Grains, Mark P. Silverman, Princeton University Press, (1998)
offers a more advanced explanation of light refraction, reflection, and
polarization.
Light in Biology and Medicine, Ron H. Davis, ed., Plenum Press (1991).
This book contains 56 peer-reviewed and edited chapters covering the
latest topics in photobiology. It is an expensive, but thorough reference.
INTERNET WEBSITES
The Internet has recently become a prime information source (2) for technology
transfer. It began its rapid growth in 1990, and surpassed 1 million participating
host computers in only 2 years (3). By now, over 20 million computers and
3 billion webpages may be accessed through the Internet.
The ASP website http://www.pol-us.net is named Photobiology Online.
They offer news on pertinent publications, and an online textbook.
The US Department of Commerce sponsors the US Patent and Trademark
website: http://patft.uspto.gov. This website offers complete text of all US
patents since 1974, and currently publishes an average of 10 new patents each
week, which can be retrieved by entering “sunscreen” into their internal search
engine.
The US Food and Drug Administration currently is enacting a regulatory
program which adopts sunscreens into the category of OTC drug products.
This herculean effort has been legendary in its tortuosity. Proposed rules have
been repeatedly confounded by new scientific discoveries, yet the agency has per-
severed to respond to the challenge. Most recently, they have expanded their
regulatory concern to cover UV-A as well as UV-B radiation. Their website,
http://www.fda.gov is a remarkably voluminous and accessible resource. The
FDA home page contains a powerful Google-driven search engine which pro-
vides current information regarding regulations being developed to control the
manufacture, testing, and distribution of sunscreens in the USA.
The United States Pharmacopeia (USP) hosts a slow but searchable
website, http://www.usp.org containing official regulatory requirements for
the naming (USAN) and testing of Active Pharmaceutical Ingredients (APIs)
including the UV absorbers permitted in sunscreens. They are the ones respon-
sible for new shorter drug names, such as Octinoxate, and Ensulizole being
recently applied to sunscreen APIs.
COLIPA is the official European Association of Cosmetic Manufacturers

available at their web location http://www.colipa.com. This searchable
website uses an Atomz search engine, and provides much more unrestricted
information than the domestic CTFA site. Through this site COLIPA provides
regulatory guidance over the control and harmonization of requirements for
sunscreen products throughout Europe. The information available from this
agency is absolutely necessary for anyone producing sun protection products
designed for sale in Europe. As a reflection of their openness, and in
promulgating information, COLIPA has emerged as the world leader in
guiding the harmonization and uniformity of sunscreen regulations around the
world.
The Cosmetic Toiletries and Fragrance Association (CTFA) is located in
Washington, DC. Their website http://www.ctfa.org contains some limited
public information on current regulatory issues, but the details of their
(sizable) efforts impacting the regulation of sunscreens are only available to
members through a password system. The CTFA serves as an industrial lobby
protecting the interests of the cosmetic industry in the USA. As such, they
have been instrumental in providing FDA both guidance and industrial consensus
on many issues surrounding the enactment of regulations.
The Research Institute for Fragrance Materials (RIFM) has a website
under construction; http://www.urifm.org, at the time of this writing.
Information about RIFM is available through an associated website http://
ultrainternational.com/rifm.htm. This organization generates and maintains
information on safety and compatibility of fragrance materials as applied to
sunscreen products.
Medline—The US National Library of Medicine is the world’s largest
medical library. It collects material in all major areas of health science. It is a
wonderful resource, searchable from the web at http://www.nlm.nih.gov.
Med Scape at www.medscape.com is another huge medical database which
requires a password and a one time free registration.
Zebrafish Information Network (http://zfin.org) is a well-organized new
biological database (4) from the University of Oregon. The zfin database is
divided into nine searchable categories.
Commercial sites of most of the UV absorber manufacturers provide valu-
able data on their application in sun protection products. Some major industrial
suppliers are ISP ([email protected]), Presperse ([email protected]),
Cardre, BASF, Haarman & Reimer, Kobo Products, Degussa (surfactants@de.
goldschmidt.com), Roche, Ciba ([email protected]), and others.
Major marketers of sun protection products such as L’Oreal, Playtex, Schering
Plough, and Hawiian Tropic also sponsor websites which promote their products
but also provide excellent information on sunscreen function. Finally, the American
Cancer Society and the Skin Cancer Foundation and the National Institutes of
Health (especially the National Cancer Institute) support websites and report
on research in the field.
CONCLUSIONS
The resources identified in this chapter form the current technological core of the
rapidly developing science of sun protection. These are the very same resources
we utilize when developing the program for the biennial Florida Sunscreen
Symposium Series. To attract the attention, and attendance, of the majority of
the sun care scientific community it is necessary to find and recruit the most
cutting-edge researchers. The resources enumerated in this chapter allow us to
do this. They will also help you access the latest developments in the field.
Although our resources have changed over the years, many of the core sources
have not only maintained their contact with new developments, but some have
gained more power as the technology accelerates. The world wide web of Internet
computer servers, has by far produced the biggest change in the way we search
for innovation (5). However, it is possible that this resource may become less
dynamic, and responsive as the Internet website load increases over time. At
the time of this publication website searches for several general sun protection
topics, using the Internet search engine; Google (6) provided voluminous
responses: “Sun Protection” provided 4,180,000 results; “Skin Cancer” produced
3,158,00 results; “Sunscreen” yielded 743,000 results; “SPF 45” elicited 107,000
results; “UV Absorber” gave up 33,400 responses, and “Sunscreen Book” was
cited 17,200 times.
Huge internet responses make searching the web progressively more
difficult. For example, no one could hope to read all 17,000 sunscreen book refer-
ences provided by Google, so in the future Internet, searches must be made more
specific. And, simultaneously scientific journal hardcopy is rapidly declining in
availability, being replaced by online journal editions. Therefore, it seems appar-
ent that courses and seminars may continue to be the main channel for spreading
new sun protection technology. Currently, and in the forseeable future, mining
information from many varied sources is the only way to fully maintain
cutting-edge technology in the sunscreen field.
REFERENCES
1. Society of Cosmetic Chemists, 120 Wall St, New York, NY 10005
(http//www.scc-online.org/).
2. Plonsker L. Technology transfer. Cosmet Toilet 2001; 116(4):30.
3. Internet Information Superhighway. J NIH Res 1995; 7:72.
4. Surfing for the Best Biotech. Genet Eng News 2001; 21(18):82.
5. Hodel AE. Sharing the chemical industry’s little secrets. Chemical Processing, (April,
2001), www.chemical processing.com.
6. Souped up Search Engines. News feature; Nature 2000; 405:112.
48
Recent Sunscreen Market Trends
Nadim A. Shaath and Mona Shaath

Introduction 929
Classification of the Sunscreen Market 931
Daily Wear and Long-Term Protective Products 931
Premium and Specialty Brands 932
Mass Market Brands 933
Direct Sales Brands 933
Tanning Products 934
Recreational Products 935
Future Trends 937
New Regulations 937
Advances in Technology 938
Conclusions 940
References 940
INTRODUCTION
The sunscreen market is expanding dramatically in response to the alarming
increase in the incidence of skin cancer worldwide (this volume, chapter by
Nelson). Fears of excessive tanning have done away with the old days of greasing
up with coconut fragranced oil for hours motionless under the sun. This, however,
has neither quelled the desire for a healthy glow nor has it stopped consumers
929
930 Shaath and Shaath
from pursuing an active lifestyle. A general survey of the sunscreen products

currently available reveals a market that mirrors the changing behaviors of
today’s consumer. Consumers have become more diligent than they once were
about sun protection and the industry has responded with creativity in ingredi-
ents, packaging, and applications.
Sunscreen products have crossed over the traditional boundaries that once
restricted ultraviolet (UV) filters to summertime sunbathing applications and
have infiltrated the daily wear skin care market. Although a “sunscreen lotion”
may seem to have applications similar to “skin lotion,” innovators in the skin
care industry and scientists in the sun protection business have only recently
joined forces. UV filters, functional botanicals, antioxidants, and other natural
ingredients have entered skincare formulations full force, never to be omitted
again. Products have evolved into an impressive array of lotions, creams, sprays,
gels, and oils that can handle the demands of consumers who wish to simplify
their daily beauty routine while maintaining a sunburn protection regimen.
The recent trend in the daily wear sunscreen market is multifunctionality.
Now just one jar can contain vitamins, botanicals, and essential oils in an
enriched, skin-smoothing body lotion that is hypoallergenic while also providing
protection from the harmful UV rays. Consumers want products that both protect
and beautify their skin and they do not want to buy too many bottles to get that
done. Sunscreens are now an indispensable component of most skin care, lip care,
makeup, and even hair care products. In the future, sunscreen products will con-
tinue this trend incorporating new and innovative ingredients into their
formulations.
One major obstacle to a healthy avoidance of the sun is pale skin. A tanned
glow is still considered aesthetically pleasing in our culture and the chances of
this preference fading quickly are slim. Again, we find the industry reflecting
the needs of the consumer. The sunscreen industry has responded to the consumer
demand for color in a number of innovative ways. Most notable of these is the
expansion of the industry into self-tanners and bronzers for those who wish to
avoid the damaging rays of the sun but who still enjoy a tan.
Even the sunscreen market’s traditional core, the familiar recreational use
products, has adapted to the new consumer attitudes towards fun in the sun.
Fragrances in a typical sunscreen lotion are less overpowering and the product
is generally more functional for active lifestyles. Claims of water and sweat
resistance and oil-free protection allow the consumer to participate in outdoor
activities unencumbered by their method of sun protection. Consumers can
pursue sports, including swimming, without excessive reapplications. Again,
we find the sunscreen market responding creatively to the needs of the consumer.
Our changing relationships with exposure to the sun have been supported
by the sunscreen industry. It is now possible to maintain continual coverage
more easily and more pleasingly than it was in the past. This is a responsive
industry, continually growing to responsibly meet the needs of consumer. With
new consumer demands, advances in technology and new regulatory changes,
Recent Sunscreen Market Trends 931
future sunscreen products will also have to adhere to new guidelines that might
necessitate reformulation.
CLASSIFICATION OF THE SUNSCREEN MARKET

The sunscreen market1 may be classified into three categories:
1. Daily wear skin care with UV filters
2. Tanning products
3. Beach, recreational and sports wear products.
A review of each of these categories in the US market will serve to illustrate the
recent trends in the worldwide sunscreen markets. The listing is not intended to
be an exhaustive one, listing of all products in the US market and the reader is
referred to the many chapters that have tackled marketing issues in their technical
presentations.2
Daily Wear and Long-Term Protective Products

This multibillion dollar industry has realized the benefits of incorporating UV
filters in year-round daily wear and other long-term protective products.
Today, UV filters are present in daily-use moisturizers, aftershave and soothing
products, antiwrinkle, antiaging and other medical products, in makeup and
foundation creams, in lipsticks and lip balms, in a number of hair products
including shampoos, conditioners, gels, as well as hair growth and stimulating
preparations. Clothing with UV filters has become an industry of its own that
is closely governed and regulated (this volume, chapter by Hatch).
In these products, the levels of the UV filters are generally much lower than
those present in recreational products, relying heavily on inorganic particulates.
The types of cosmetic vehicles are generally simpler and limited to light oil in
water emulsions. Harsh emulsifier systems are avoided and the formulation
is loaded with moisturizers, antioxidants, vitamins, essential oils, botanical
1
The sun care market includes fabrics with UV filters (Chapter 28) as well as a multitude of after-sun,
medicated sunburn treatment products that are outside the scope of this monograph.
2
SaNogueira cites ACNielsen Scan Track Data reporting sales of almost half a billion dollars for the
recreational sunscreen products (Chapter 25). Lott and coauthors list the sales of the mass sunscreen
market in the USA to exceed 600 million dollars and classify these products into 12 categories
(Chapter 27). Gonzalez and Kalafsky cite IRI Infoscan Review and list the sales of the tanning pro-
ducts on the US market to exceed 100 million dollars annually (Chapter 29). Chaudhuri (Chapter 30)
as well as Epstein (Chapter 32) report on consumer products on the market that contain antioxidants,
free radical scavengers and other botanical and biologically active ingredients. Buccellato lists the
fragrances in a wide variety of sunscreen products (Chapter 23). Shaath and Walele reviewed the cos-
metic products in the US market that contain inorganic particulate ultraviolet filters (Chapter 15).
extracts, enzymes, skin lighteners, and other biologically functional ingredients

(“cosmeceuticals”) including coenzyme Q10, theophyllene, AHA, BHA, reti-
noids, creatine, isoflavones, matrikines, etc. (1). The products are either fragrance
free or are lightly perfumed. The claims are generally more aggressive than those
found in recreational products addressing claims of antiaging, antiwrinkle,
barrier and tissue repair, hydration, and moisturizing (this volume, chapter by
Lentini).
This industry may be classified into premium and specialty brands, mass
market brands, and direct sales brands. The products generally contain UV
filters along with natural extracts, antioxidants, essential oils, and other important
biologically active ingredients to repair the damage of the sun and other environ-
mental agents as well as ingredients to combat the effect of reactive oxygen species
(ROS) and free radical damage to the skin (this volume, chapter by Lintner).
Premium and Specialty Brands

These products are generally sold at high-end retail stores, beauty salons, and
spas and their prices vary from $30 to over $150 per unit. They include such inter-
national brands as Aveda, Bath & Body Works, Biotherm, Clarins, Clinique,
Elizabeth Arden, Estee Lauder, Lancome, La Prairie, Origins, Prescriptives,
and Shiseido to name only a few.
Aveda has Daily Light Guard SPF15, Tourmaline Charged Protecting
Lotion and Sunsource Sunless Tanning, all with specialty extracts and
essential oils.
Bath & Body Works has a suntan lotion with an SPF8 and extracts including
green tea.
Biotherm has De-Age SPF15 containing olive extracts, grapeseed, and retinol.
Clarins has Suncare Cream with aloe, silver birch, camellia, and palm and
also Hydrating after Sun with walnut, linden, and vitamins.
Clinique has a number of products including Anti-gravity with green tea,
wheatgerm and Sea whip and Total Turnaround with salicylic acid.
Estee Lauder has the Advanced Night Repair, Resilience SPF15, Light
Source, and Day Wear with SPF15.
Lancome has Primordiale Intense, Renergie, and Absolue with specialty
ingredients.
La Prairie has Cellular antiwrinkle SPF30, Sun block SPF50, body
emulsion SPF30 and Cellular Retinol Complex PM with retinol and
coenzyme Q10.
Origins carries Have A Nice Day with gingko, birch extracts, and licorice,
Origins Sunshine State SPF20 and Beach Blanket SPF15.
Prescriptives has the Super Line Preventer with vitamins C and E, green tea
extract, and hyaluronic acid.
Shiseido has Benefiance with a biohyaluronic complex and Avessa SPF50
PAþþþ Neo Sunscreen.
Mass Market Brands

These products are generally sold in drugstores and super markets and
their prices range from $10 to $25 per unit. They include such brands
as Almay, Beiersdorf, Johnson & Johnson, L’Oreal, Proctor & Gamble, and
Schering-Plough.
Almay has the Kinetin skin care line and Milk Plus with tocopheryl acetate,
green tea, and other plant extracts.
Beiersdorf carries the Nivea line (Visage) and the Eucerin brands with
products such as Antiwrinkle and Firming cream with vitamin E, and
Q10 Plus with coenzyme Q10, and Daily Defense with an SPF15,
tocopheryl acetate, glucosylrutin and isoquercetin.
Johnson & Johnson carries the Aveeno brand with Skin Brightening Daily
treatment and Radiant Skin daily moisturizer with vitamins and soya
extract. Their Neutrogena brand has Anti-Wrinkle, Healthy Skin, and
Visibly Firm with vitamins.
L’Oreal has the Dermo-expertise line, and the Ombrelle line with vitamins
and Ambre Solair with cactus nutriflavones.
Proctor & Gamble has the Olay brand Regenerist with vitamins and green
tea extracts and Complete UV Defense moisturizers.
Schering-Plough carries the Endless Summer line with antioxidants and
vitamins.
Finally, the lip care market is a significant one that delivers protective
balms with ultraviolet filters. This market is dominated by two brands, Blistex
and Chapstick.
Blistex has a number of brands with SPF protection, namely, Ultra, Clear
Advance, Complete Moisture, Medicated Lip Balm, Liptone, and Silk
& Shine.
Chapstick carries Fruit Smoothies, Lipbalm, Lipbalm Ultra, and Lipbalm
Moisturizer.
There are many other lip care brands including Coppertone, Hawaiian
Tropic, Neutrogena, and Banana Boat.
Direct Sales Brands

These products are sold generally online or at-home parties with prices ranging
from $10 to $50 and generally contain antioxidants and botanical extracts.
They include such brands as Avon, Mary Kay, Nu Skin, and Shaklee.
Avon has Hydrofirming cream with SPF15, Beautifying Morning Revitalis-
ing with SPF10, Sun-so-soft SPF30 and 40 for kids.
Mary Kay has Time-Wise with botanicals and vitamin E, Problem Solvers
with vitamins C and E and Skin Revival.
Nu Skin has UV Block Hydrator with plankton extracts and Skin Mist
with willow herb, algae, mushroom, and cucumber extracts, also Night
Supply.
For commercial sunscreen products incorporating inorganic particulates
read the chapter by Shaath and Walele (this volume).
Tanning Products
This sector represents sales of about a hundred million dollars in the US sunsc-
reen market and is subdivided into three categories:
A. Sunless tanning products
B. Tanning accelerators
C. Tanning bed products.
The sunless tanners are products that impart a tanned appearance to the skin
by the use of colorants or ingredients, mostly dihydroxy acetone (DHA), that
interact with the free amino acids on the skins surface. These products are also
called bronzers and this category accounts for more than two-thirds of all
tanning products sold in the USA. The Maillard (nonenzymatic browning)
reaction between DHA and free amino acids on the skin produces colored
melanoidins, which are responsible for the bronze appearance of the skin after
application. The use of antioxidants, colors, or natural extracts and other ingredi-
ents is responsible for imparting the most suitable skin coloration simulating a
tanned appearance to the individual. Products are sold for a light, medium, or
dark tan.
Tanning accelerators are products that enhance the body’s natural tanning
processes but have been restricted by FDA’s enforcement of any drug claims that
these products purport to possess. There are two key enzymes for melanogenesis,
namely tyrosinase, which catalyzes the conversion of tyrosine to DOPA
(dihydroxy phenyl alanine) and Dopachrome tautomerase which catalyses the
DOPA into melanin.
Tanning bed products have increased dramatically with the proliferation of
artificial tanning parlors across the country in the last decade. Many tanning
salons are also outlets for sunless tanning products where proper application
and administration of these products by a professional is crucial for its success.
The reader is referred to the chapter on tanning products (this volume, chapter
by Gonzalez and Kalafsky).
A review of the three categories, other than the skin lightening products
popular in Asia, is given in the following list:
A. Sunless tanning: This category represents about 80% of the dollar
sales of all tanning products, and is dominated by Coppertone
(Endless Summer), Neutrogena (Instant Bronze Sunless Tanner),
Bain De Soleil (Radiance Eternelle Sunless Tan), and Banana Boat

(Sunless Tan).
B. Tanning bed products: This category is dominated by a few
companies, including Hawaiian Tropic (Tan 2 Max Tanning Bed),
Banana Boat (Tanning Bed), LA Express (Expresso Tanning Bed),
and Euro (Optimizer Cobalt Tanning Bed).
C. Tanning accelerators: Few manufacturers in the US market produce
formulations in this category. The top brands are Hawaiian Tropic
(Tan Accelerator and Ultra Sun), Banana Boat (Tan Accelerator)
and other brands such as Ocean Potion Australian Brand, Australian
Gold Tan, and Panama Jack Accelerator.
Recreational Products
This ever-expanding, several billion dollar worldwide industry produces a
multitude of products primarily designed to protect individuals from the
harmful rays of the sun while sunbathing, playing, working, or participating in
any sun-exposed activity.
The classification of these products depends upon the degree of sun pro-
tection (low, medium to high SPF products), the mode of application (cream,
lotion, milk, gel, spray, oil, towelettes, etc.), functionality (water-resistant,
sweat-resistant, tanning accelerators, presun and postsun applications, healing
products, hair products, etc.) and other specialized products for golfers, tennis
and soccer players, skiers, snowboarders, climbers, as well as a number of
“combination” products. Combination products for sunscreen include insect
repellents, lip care, and antiaging products, where more than one regulatory
monograph may need to be satisfied. Natural sunscreen products with little or
no synthetic ingredient additives, including “organically” grown ingredients,
are part of a rapidly growing sector in this field of sun protection.
Recreational products are generally formulated with multiple UV filters
(occasionally exceeding 25% of the total emulsion formulation) and containing
water proofing film formers. The emulsifier system is generally a soap system
or a nonionic with a high HLB, and contains humectants, shine enhancing
emollients and a fragrance (coconut, tropical fruits, orange flower, and rarely,
subtle floral types). The claims address protection and prevention as specified
by the Final Monograph (2).
The US industry in 2003 dollar figures has exceeded a half billion dollars
(this volume, chapter by SaNogueira) and is dominated by four major manu-
factures, namely, Schering-Plough (Coppertone), Playtex (Banana Boat),
Neutrogena and Tanning Research (Hawaiian Tropic).
A. Schering-Plough (Coppertone): This is the leading sunscreen
manufacturer in the USA for recreational and tanning products.
Their Coppertone brand has become a household name in the US
market. They are constantly introducing new products, brands and line
extensions. These include the Shade line, Water Babies and Kids line,
Endless Summer, Coppertone brand, and their new brand, Spectra 3,
with their marketing campaign that their products reflect, scatter and
absorb the harmful UV rays. Some of their specific products
include: Coppertone oil free SPF30, Endless Summer SPF30, Ultra
Sweat proof SPF30, Sunblock lotion SPF15, Day Oil SPF4, Copper-
tone Spectra 3 SPF30, Water Babies SPF45, Kids Coppertone
SPF30 and 50, and Sports Gel Coppertone.
B. Playtex (Banana Boat): This company had entered the market rela-
tively recently with their Banana Boat line of sunscreen products but
managed to earn the distinction of running a close second to Schering-
Plough and gaining with each new product introduction. Some of their
specific products include: Sports Block SPF50, Kids SPF30, Baby
Magic SPF48, Suntannicals, Faces Plus SPF23, Ultra Sun Block
SPF30, and Protective Tanning Oils.
C. Neutrogena: Neutrogena has developed from a West Coast specialty
cosmetics house to a major sunscreen company after being acquired
relatively recently by Johnson & Johnson. They formulate products
for all of the above three categories in the sunscreen industry. In
fact in the sunless tanning market reviewed earlier, six of their pro-
ducts rank in the top ten sellers (Plough’s Endless summer holds the
first place position). Some of their specific products include:
Healthy Defense with SPF30, Neutrogena brand with SPF, Ultra
sheer Day Dry Touch SPF30, and Visibly Younger Sunblock lotion
SPF30.
D. Tanning Research (Hawaiian Tropic): This Florida-based company
originally famous for their beach tanning oils has made substantial
contributions to the sunscreen industry by introducing a number of
innovative products including products for the children and baby cat-
egory as well as the tanning accelerator market (holding the top two
tanning accelerator products). Some of their specific brands include:
Baby Faces SPF50, Sport SPF30, Protection Plus SPF15-45, Ozone
SPF70, GoldenTan SPF6, Barbie SPF30, Kids Splash SPF30, and
Dark Tan Gel.
There are countless other brands and manufacturers including Ban De

Soleil, Blue Lizard, Bullfrog, California Baby, Clearasil, Credentials, DDF,
Dermalogica, Dr. Hauschka, Fallene, Fruit of the Earth, Glyderm, Jack Black,
Lancaster, M.D.Forte, Dr.Murad, Mustela, Neostrata, No Ad, Nu Derm, Obagi,
Peter Thomas Roth, Philosophy, Phytomer, Sea & Ski, Skinceuticals, Ti-silc,
Vanicream, Zirh, and many drug store brands.
FUTURE TRENDS
A number of factors will dictate the future development of sunscreen products in
the USA. These factors include:
1. New regulations
2. Advances in technology.
New Regulations
With the anticipated publication of the Final Rule by December 2005, a number
of changes in future products are imminent (this volume, chapter by Holmann
and Shetty). Specifically, two issues will have broad implications on current
and future products, namely:
A. Limits on the SPF label: Despite the fact that the Tentative Final
Monograph and the recently published Final Rule (2) clearly specifies
a maximum limit of SPF30þ (plus) for all sunscreen products, the fate
of all the current products with SPF .30þ is in question. Marketers
and dermatologists all favor values .30þ and today we have seen
a significant increase in products labeled 45, 50, 70, and even 100.
Those concerned are hoping that the FDA will allow claims of SPF
.30þ. Despite the lobbying efforts of individual companies, the
CTFA and Dermatologists, there are no concrete indications that the
FDA will allow claims over 30 in their Final Rule. In any scenario
imagined, marketers of sunscreen products will scramble in 2005
or thereabouts to accommodate either the status quo (of SPF 30þ)
or the hoped for higher SPF values. This could obviously create a
major hardship for those companies who may have to withdraw,
repackage, relabel, and reformulate their existing products. Change
and upheaval in any industry, however, also represents opportunities
and challenges for marketers and entrepreneurs, who will be inclined
to introduce a number of new products complying with the new
regulations.
B. UV-A and broad-spectrum protection labeling: Any protocol that
the FDA adopts for requiring sunscreen products to be labeled for
“UV-A” protection and/or “broad spectrum” protection will favor
one way or another those manufacturers who use specific UV-A
ingredients and cosmetic formulations. The type of in vitro or in
vivo protocols adopted may have a significant effect on efficacy label-
ing and cost of compliance with the proposed requirements. Again,
this challenge represents both an opportunity and a barrier to a few
for the marketing of sunscreen products.
C. Other regulations: Other regulations that may have an effect on the

marketing of sunscreen products if changed in the Final Rule when it
is published in 2005 include:
a. Photostability of ingredients
b. Photoreactivity of inorganic particulates
c. Use of natural UV absorbers
d. Use of biologically active ingredients
e. Tanning accelerators and sunless tanning
f. Medical and drug claims
g. Worldwide UV testing protocols
h. “Organic” and “biodynamic” farming certifications
i. Clothing with sun protection regulations.
Advances in Technology
Despite the fact that the cosmetic industry has made significant strides in the for-
mulation of a multitude of sunscreen products, significant opportunities still exist
for technologically advanced new ingredients. Today, we can formulate products
with SPFs as high as 100 that are water resistant and aesthetically appealing.
Nevertheless, there is a serious shortage of ingredients in the USA for enhanced
protection in the future. Specifically:
A. New UV Filters: European regulations (COLIPA) have allowed for
the adoption of a variety of new filters that have not found their
way into the US market. It is totally impractical for a growing industry
as the sunscreen industry to introduce new UV filters only through the
NDA process. This process is time consuming (3 –5 years), expensive
(several million dollars) and limited to basically one formulation, with
financial rewards that are extremely limited (under 50 million dollars
per annum when the ingredient is highly successful). This is unlike the
pharmaceutical industry where a patented ingredient with an NDA
permit may yield financial returns in the hundreds of millions of
dollars per year. It is heartening to see the new TEA process that
may allow UV actives with 5-year history of use in foreign countries
to be included in the Category I listing of actives (this volume, chapter
by Holmann and Shetty). Three ingredients are currently under serious
review and their adoption will witness a growth of new cosmetic
sunscreen formulations that may incorporate these UV filters.
B. New cosmetic ingredients: With reports that emollients and emulsi-
fiers may have an effect on the efficacy of sunscreen products, many
new types will be created and marketed in the future (3). These
include ingredients that solubilize UV actives, disperse inorganic
particulates, increase SPF, assist in waterproofing, improve the film
formation of the product on the skin (more uniform, thick and
nontransparent film), and ingredients that will reduce the

photostability and photoreactivity of UV filters. New sunless
tanning ingredients other than DHA will ultimately be developed in
combination with new additives and ingredients that will impart a
more stable, natural-looking tan.
C. New packaging: Our concern for ecologically and environmentally
safe packaging should be foremost on the minds of developers.
Material that can be recycled and reprocessed is paramount.
However, innovations in delivery, durability, practicality, safety,
and convenient packaging are key in the promotion of sunscreen
products to the consumer. Multicomponent packaging such as those
delivering sunless tanning products and other hair and skin multicom-
ponent products will greatly enhance their use and adoption by the
consumer.
D. New biologically active ingredients: It is inevitable that new
biologically active ingredients will be developed that address not
only the discomfort of sunburn but the medical problems associated
with photodamage. These include both the direct effects of sun
damage to the skin such as DNA dimerization and photo adduct
formation as well as the indirect effects of producing free radicals
and reactive singlet oxygen species (ROS) (this volume, see chapters
by Lentini and Epstein). Today we have witnessed a plethora of
ingredients from antioxidants such as green tea to vitamins, as well
as a variety of antiaging and antiwrinkle ingredients. Many more
ingredients will be introduced in the future attempting to rectify a
number of biological functions that may be implicated in sun
damage and skin cancers. For a discussion on the topic, read the
several chapters in this book by Nelson, Diffey, Giacomono,
Lintner, Epstein, and Chaudhuri.
E. New natural ingredients: The essential oil and botanical extract
industry has researched a variety of natural ingredients that provide
UV protection, boost SPF and film formation on the skin, and add a
variety of functional properties that address a number of consumer
concerns. The essential oil and botanical extract industry has experi-
enced major growth in the development of a multibillion dollar indus-
try for aromatherapy, massage and spa products. The use of these
ingredients will create new outlets and unconventional avenues for
the promotion of new sunscreen products.
We hope that with the unearthing of these natural treasures for incorpor-
ation into sunscreen products that extreme care is given to all the concerns of
safe mining, sustainability of natural ingredients and the use of renewable
resources. We must also support and sustain indigenous people’s dependence
on these resources, diversify and strengthen the local economies and develop
new agricultural techniques for maximizing farming practices such as “organic”

and “biodynamic” farming.
An additional word of caution is appropriate with the use of natural
ingredients and botanicals in sunscreen products. Their inclusion should be
based upon sound medical research and the amounts included should be sufficient
to impart the desired biological action. The purity and consistency of those
extracts should also be well documented and supported (this volume, see chapters
by Epstein, and Shaath and Flores).
CONCLUSIONS
Advances in technology, the impact of imminent regulations, and the publication
of new statistics and research on the developing dangers of the UV rays of the
sun will clearly fuel research and development projects worldwide. As a result,
the sunscreen industry may experience major growth in the future in the follow-
ing categories:
i. Daily wear and long-term protection.
ii. Specialized products such as children products, antiaging products,
sports products, etc.
iii. Reformulations for SPF, water resistance, UV-A and broad-
spectrum protection claims, and line extensions.
iv. Sunless tanning and tanning accelerator products.
v. Multifunctional products (e.g., sunscreen and insect repellent,
aromatherapy, etc.).
vi. Suncare products with functional biological ingredients.
vii. Suncare products with natural ingredients.
The sunscreen industry is gradually maturing and will reach its zenith in
this coming decade with improved, functional products that will address both
the concerns of the medical community and those desiring natural ingredients.
Pricing, packaging, cosmetically innovative and esthetically appealing products
will naturally add to the growth and success of this vital industry.
REFERENCES
1. Kligman A. Cosmeceuticals: Do we need a new category. In: Elsner P, Maibach H, eds.
Cosmeceuticals. New York: Marcel Decker, 2000, Chap. I.1.
2. Federal Register, 27666, May 21, 1999.
Index
Absorption, optical behavior, ARTG (Australian Register of

UV filters, inorganic, 247 Therapeutic Goods), 130
Acne, mallorca, 446 Australia sunscreen
Actinic dermatitis, chronic, 27 cosmetic/therapeutic interface,
Active ingredients, monographs, 139, 140
sunscreen 207– 210 definition of, 128, 129
Actives facilities licensing, 136
new, overview of, 291– 320 ingredients
photostability, organic sunscreen, new, 132 – 134
321 – 346 permitted, 135
UV filters, new, 303– 312 under review, 136
Acute solar damage new product listing, 132
histology, 22, 23 regulations, 127 – 140
mechanism of, 22 labeling regulations, 137
Additives, emulsifiers, SPF and, 269 testing methods, 131
Adventitious exposure, 49 Therapeutic Goods Administration
Aerosols, formula types, (TGA), 128
sunscreen, 362 Australian Register of Therapeutic
Agglomeration, dispersion Goods (ARTG), 130
index, 265, 266 Autoxidation emulsifiers, 446 – 448
Alcohol, fatty, HLB and, 366 Avobenzone, 329, 331 – 334, 341 – 344
Aminobenzoic acid, as organic butyl methoxydibenzoylmethane
sunscreen, 370 (BMDM) and, 323
Anthranilates, UV filters and, 229 as organic sunscreen, 370
Antiaging/antiwrinkling/healing photostabilization, 341 – 334
products, 10 solubility of, 451
Antioxidant therapies, promotion, 31, 32 titanium dioxide and, 255
Antioxidants zinc oxide and, 255
formula goals, in sunscreen, 376
labeling caveats, 109 Bain de Soleil, 495
as sunscreen, 11 Carcinoma (BCC), basel cell, 46
941
942 Index
BBET (bis-benzoxazoylphenyl progression of, 33

ethylhexylimino triazine), promotion of, 31, 32
308, 309 three phases of, 34
BCC (basel cell carcinoma), 46 CFR 352.10, 208
BDHB (bis-diethylamino Carcinoma, squamous cell (SCC), 46
hydroxybenzoyl benzoate), Caveats, in product labeling. See
307, 308 Labeling, caveats
BEMT (bis-ethylhexyloxyphenol Chemical absorbers, organic, 10
methoxyphenyltriazine), 295, Chemical properties
300, 301, 311, 312 titanium dioxide, 242 – 248
molecular design, 300, 301 zinc oxide, 242 – 248
spectrum/structure, 312 Chemical-free ingredients, labeling
Benzophenone-3, solubility of, 452 caveats, 110
Benzophenones, UV filters, 228 Choline, phosphatidyl, 469
Benzylidene malonate polysiloxane Chronic actinis dermatitis,
(BMP), 305, 306 photosensitivity skin disorder, 27
spectrum/structure, 306 Chronic solar damage
Bis-benzoxazoylphenyl ethylhexylimino histology of, 24
triazine (BBET), 308, 309 human skin and, 23
spectrum/structure, 310 mechanism of, 23, 24
Bis-diethylamino hydroxybenzoyl Cinnamates, UV filters, 227
benzoate (BDHB), 307, 308 Cinoxate, organic sunscreen, 370
spectrum/structure, 309 Compounds, miscellanous,
Bis-benzotriazolye UV filters, 231
tetramethylbutyephenol Cosmetic emollients
spectrum/structure, 311 sunscreen emulsions, 450 – 455
Bis-ethylhexyloxyphenol pigment-dispersing
methoxyphenyltriazine. properties, 451 – 453
See BEMT solvent properties, 450, 451
BMDM (butyl Cosmetic formulations, sunscreen,
methoxydibenzoylmethane), 9 – 12
avobenzone and, 323 Cosmetic foundations, SPF, 270
BMP (benzylidene malonate Cosmetic, FDA, definition of, 86, 87
polysiloxane), 305, 306 Cosmetic solvents, 305
Bronzers, in sunscreen, 10 Cosmetic/therapeutic interface, in
Burning rays, UV-B as, 220 Australia, 139, 140
Butyl methoxydibenzoylmethane Cosmetics, UV filters, effects on, 232
(BMDM), avobenzone, 323 Crystal gel networks, 409
Crystalline phase, Lalphn, 470
Camphor, 4-methylbenzylidene,
solubility of, 452 DBT (dioctyl butamido trizone), 303
Camphor derivatives, UV filters, 230, 231 DEET (diethyl-m-toluamide), 505
Carbonyl model, 326 Dermal/systemic safety testing, 66
Carcinogenesis Dermatitis, actinic, 27
initiation of, 31 DHA (dihydroxy acetone), 10
mechanism of, 30, 31 DHHB (diethylamino hydroxybenzolyl
pathway of, 31– 33 hexyl benzoate), 307
photoexposure and, 30– 33 spectrum/structure, 308
Index 943
Diethylhexyl bufamido trizine, 306 sunscreen allowable ingredients,

Dibenzoylmethanes, 119 – 122
UV filters and, 230 sunscreen, definition of, 117, 124
Diethylamino hydroxybenzoyl hexyl sunscreen regulations, 117 – 125
benzoate (DHHB), 307 EHT (ethylhexyl triazone), 303
Diethyl-m-toluamide (DEET), 505 spectra/structure, 305
Dihydroxy acetone (DHA), 10 Elective exposure, 49
Dioctyl butamido triazone (DBT), Electron pair, vectoral model, 325
303, 305 Emollient(s)
Dioxybenzone, as organic cosmetic, sunscreen, 450 – 455
sunscreen, 370 emulsifiers, 367, 368
Disodium phenyl dibenzimidazole sunscreen formulation, 449 – 460
tetrasulfonate (DPDT), 295, 307 oil-soluble, organic, as UV filters, 393
spectrum/structure, 308 SPF evaluation, 454
Dispersion index, agglomeration, UV absorption, effect on, 453
265, 266 UV filters, effect on, 233, 234
Dispersion process, objectives, Emulsification principles, formulating
264, 265 basics, 362 – 365
Dispersion(s) Emulsifier(s)
advantages, 266 additives and SPF, 269
aesthetic modifications, 478 autoxidation, 446 – 448
formulating with, 475– 480 emollients, 367, 368
incorporating into formulations, 266 ethoxlates, 366
lamellar phase, 469– 474 film formers, 368, 369
manufacturers of, 266, 267 hydrophilic-lipophilic balance system
MBBT, structure/spectra, 298 (HLB), 365 – 367
particulate, organic, ingredients, in sunscreen, 365, 366
UV absorbers, 297 O/W, 456, 457
quantifying aesthetic scale, role of, sunscreen formulations,
475 – 479 414, 415
sunscreen, homogenous/ specialized, SPF modulations, water
heterogeneous, 476 resistance, 408
surfactant-free, final formulation, 479, stabilizers/protectants, 369
480 sunscreen formulation, 449 – 460
titanium dioxide, 261– 263 W/O, 457
UV filters, inorganic, 264– 267 Emulsion content, skin penetration, 468
zinc oxide, 261– 263 Emulsion effect, oil-soluble, organic
DPDT (disodium phenyl dibenzimidazole UV filters, 392
tetrasulfonate), 295 Emulsion type effect, water soluble,
Drometrizole trisiloxane (DTS), organic UV filters, 394
309, 310 Emulsion(s)
spectrum/structure, 310 breakdown of, 391
Drug, FDA, definition of, 86, 87 film formation, 415 – 422
DTS (drometrizole trisiloxane), 309, 310 formula type, sunscreen, 356 – 358
issues with, in sunscreen products,
EEC (European Economic Community) 465 – 468
sun protection measurements, O/W sunscreen, quick-breaking,
124, 125 433 – 437
944 Index
Emulsion(s) (Contd.) sunscreen application process, 87 – 89

phase inversion temperature, sunscreen sunscreen regulation, 85 – 94
applications, 457– 459 test methodology, 111
rheology, 389–391 Film formation, emulsion, 415 – 422
sprayable, O/W, 437–440 Film formers
sunscreen, as emollients, cosmetic, emulsifiers, 368, 369
450 –455 polymers, SPF modulations, water
W/O, 440– 446 resistance, 409
SPF modulations, water sunscreen, 11
resistance, 408 Fluid lamellar, liquid crystalline
Energy diagram, 234 phase, L alpha, 470
excited state, 234 Formula goals, sunscreen, 373 – 382
grounded state, 234 antioxidants, 376
End recovery, 332 high SPF, 373, 374
Ensulizole, organic sunscreen, 371 mild formulations, 374, 375
Erythema, sunburn, 46 organoleptic considerations, 375
Erythemal rays, UV-B, 220 patent issues, 375
Erythemogenic radiation, UV-B, 75, 76 stability evaluation, 375
ESIPT (excited-state intramolecular water resistance, 374
proton transfer), 345 Formula types, sunscreens, 356 – 362,
Ethoxlates, nonionics, 366 376 – 382
Ethylene model, 326 aerosols, 362
Ethylhexyl triazone (EHT), 303 emulsions, 356 – 358
spectra/structure, 305 gels, 359 – 361
European Economic Community (EEC), mousses, 361
sunscreen regulations, 117– 125 oils, 358
Excited-state intramolecular proton sticks, 361
transfer (ESIPT), 345 Formulating, basics of sunscreens,
Extinction coefficient, UV filters, 235 362, 363
emulsification principles, 362 – 365
FDA methods, Japan, SPF test methods, ingredients, 365 – 373
158 –161 Formulating, inorganic sunscreens,
FDA 304 – 404
active ingredients/combinations, basic principles, 394, 395, 400, 401
101 –103 Formulating, organic sunscreens, 391, 392
combination sunscreen-skin Formulating, titanium dioxide, 283, 284
protectants, 103, 104 oil-dispersed, 403, 404
definition of cosmetic, drug, 86– 87 water-dispersed, 401 – 403
effective date, extension of, 111–114 Formulating, zinc oxide, 283, 284, 404
history, 96– 101 Formulations, combined, UV filters,
ingredients, active, sunscreen, 200 404 – 406
key provisions, 101 –103 inorganic sunscreens, 406
labeling requirements, 104– 111 organic sunscreens, 405, 406
regulatory mechanisms, sunscreen Formulations
products, 87 mild, sunscreen, 374, 375
ruling, sunscreen vs. drug products, organic/inorganic particulates,
96 –115, 200 286 – 289
scope, 96– 101 SPF, 267 – 275
Index 945
Fragrance INCI designation, UV filters, 180, 181

alternatives, 505 Index, agglomeration, dispersion,
future developments, 504, 505 265, 266
odor stability, 504 Ingredients, sunscreen,
safety, sunscreens, active, final FDA ruling, 200
photosensitization, 502 biologically active, 14
stability, 502 emulsifiers, 365, 366
sunscreen, 373 formulating basics, 9 – 12, 365 – 373
Fragrancing of future use, 14, 15
history, 494 natural, future use of, 13
sunscreen products, 493, 501, 502 permitted, UV absorbers, Japan,
Freckles, labeling caveats, 110, 111 150, 151
Initiation, carcinogenesis, interrupting
Gel networks, 426 the pathway of, 31
Gels, formula type, sunscreen, 359– 361 Inorganic absorption, optical behavior,
Germicidal region, UV-C, 219 UV filters, 247
Inorganic chemical particulates, sunscreen,
Heterogenous vs. homogenous sunscreen active ingredients, 9, 10
dispersions, 476 Inorganic particulate
HLB (hydrophilic-lipophilic balance background, 282, 283
system), 365– 367 SPF, US consumer products, 286
fatty alcohol and, 366 suppliers, 284, 285
phase/volume relations, 366, 367 titanium dioxide, 283, 284
Homogenous/heterogenous, sunscreen UV filters, commerce, 281 – 290
dispersions, 476 zinc oxide, 283, 284
Homosalate, organic sunscreen, 371 Inorganic absorption, optical behavior,
HPT (hydroxyphenyltriazine), 300 UV filters, 247
structural/spectral performance, 301 Inorganic organic, sunscreens,
HRIPT (human repeat insult patch combining, 406
test), 67 Inorganic scattering, optical behavior,
Human repeat insult patch test UV filters, 247
(HRIPT), 67 Inorganic SPF, suitable level, actives,
Human skin, acute solar damage, 21– 23 269, 270
Hydroa vacciniforme, as photosensitivity Inorganic sunscreens, 37, 38
skin disorder, 29 combined formulations,
Hydrophilic surface treatments, 255 UV filters, 406
Hydrophilic-lipophilic balance system. formulations, 394 – 404
See HLB basic principles, 394, 395, 400, 401
Hydroxyphenyltriazine (HPT), 300 powder form, 395
structure/spectral performance, 301 predispersions, 396 – 399
Inorganic surface treatments, UV filters,
IEP (isolectric point), 244 244 – 246
titanium dioxide and, 244 Inorganic UV filters, 239 – 276
zinc oxide and, 244 dispersion, 264 – 267
Immediate pigment darkening (IPD), 21 evolution, 240, 241
Immunopathology, of skin cancer, 33 manufacturers, 248 – 252
In vivo dermal/systemic safety optical behaviors, 246 – 248
testing, 66 zinc oxide, 241
946 Index
Inorganic/particulate sunscreens, antiaging/antiphotoaging, 109

372, 373 chemical-free ingredients, 110
titanium dioxide, 373 extended protection claims, 110
UV filters, formulations, containing, freckles, uneven skin tone, 110, 111
286 –289 natural ingredients, 110
zinc oxide, 373 PABA-free ingredients, 110
Interim Revision Announcements tanning accelerators, melanin,
(IRAs), 207 antioxidants, 109
International method, Japan, SPF test warnings for tanning products without
methods, 158–161 sunscreens, 109, 110
IPD (immediate pigment darkening), 21 Lamellar phase, dispersions, 469 – 474
IRAs (Interim Revision Light reaction, persistent, 29
Announcements), 207 Light eruption, polymorphous, 29
Isolectric point (IEP), 244 Light/particle interaction equation, 246
titanium oxide, 244 Lip balm products, manufacturer, 500
zinc oxide, 244 Liquid crystal gel networks, SPF
Isomerization resonance schemes, UV modulations, water
filters, 330, 331 resistance, 409
Liquid crystalline phase, fluid
Jablonski diagram, 299 lamellar, L alpha 470
Japan, sunscreens in Lupus erythematosus, photosensitivity
development, 148, 149, 154 skin disorders, 27
labeling, UV protection, 164– 167
measurement standards, UV-A MAAs (mycosporine-like amino
protection, 157, 162– 164 acids), 504
SPF test method, JCIA standards, Malignant melanoma (MM), 46
154 –157, 165, 166 Mallorca acne, 446
UV absorbers Manufacturers
application, required data, 152 of dispersions, 266, 267
permitted ingredients, 150, 151 of titanium dioxide, 250
Japanese skin characteristics, sensitivity of UV filters, inorganic, 248 – 252
to sun, 143–147 of zinc oxide, 250 – 252
JCIA standards, SPF test method, Manufacturing requirements, sunscreen,
Japan, 165, 166 in USA, 196, 197
MBBT (methylene bix-benzotriazolyl
La , fluid lamellar, liquid crystalline tetramethylbutylphenol),
phase, 470 297, 311
Labeling photostability, 297 – 300
in Australia, 137, 196 structure spectra dispersion, 298
drug facts panel, 106, 107 Melanin, labeling caveats, 109
in European Union, 196 Melanoma, 5
FDA final rule, 104– 111 malignant, 46
in Japan, 196 Meradimate, 229
principal display panel, 105, 106 organic sunscreen, 372
in the USA, 193– 196 Methylene bix-benzotriazolyl
UV protection tetramethylbutylphenol (MBBT),
Japan, 164– 167 297, 311
Labeling caveats, 108, 109 structure/spectra/dispersion, 298
Index 947
Micronized pigments, surface Oil-soluble, organic UV filters, 392

treatments, 255 emollients in, 393
Mie scattering, OMC (octyl methoxycinnamate),
equation of, 248 octinaxate, 334, 335
pattern, 248 Optical behavior
Miscellaneous compounds, absorption, UV filters,
UV filters, 231 inorganic, 247
MM (malignant melanoma), 46 inorganic, UV filters, 246 – 248
Modifiers, rheological, 481, 482 scattering, UV filters,
Molecular design, inorganic, 247
broad-spectrum, 301 Optisol, 504
Monograph development, USP, 204 Organic chemical absorbers, sunscreen,
contributors, 204, 205 active ingredients, 10
overview, 204 Organic particulates
pharmacopoeial forum, 207 active ingredients, 10
revision process, 205–207 UV filters, formulations, containing,
Mousses, types, of sunscreen, 361 286 – 289
Mycosporine-like amino acids Organic sunscreen, 37, 370 – 372
(MAAs), 504 aminobenzoic acid, 370
avobenzone, 370
National Formulary, 201 cinoxate, 370
Natural ingredients, labeling combined formulations, UV filters,
caveats, 110 405, 406
NDA (new drug application), 87 dioxybenzone, 370
OTC drug monograph, ensulizole, 371
comparison, 88 formulating, 391, 392
New drug application (NDA), 87 homosalate, 371
New sunscreen actives, 291– 320 meradimate, 372
Nonionic, ethoxlates, 366 octinoxate, 371
octisalate, 371
O/W emulsifiers, 456, 457 octocrylene, 370
O/W emulsion, 419 oxybenzone, 370
formulations, 422– 433 padimate-O, 371
phase behavior, 458 sulisobenzone, 371, 372
quick-breaking, 433– 437 trolamine salicylate, 371
sprayable, 437– 440 Organic sunscreen actives,
Octinoxate photostability, 321 – 346
octyl methoxycinnamate (OMC), Organic surface treatments,
210 – 213, 334, 335 UV filters, 254
as organic sunscreen, 371 Organic UV filters
Octocrylene, as organic oil-soluble, 392
sunscreen, 370 emulsion effect, 392
Octyl methoxycinnamate (OMC), water soluble, 394
octinaxate, 334, 335 emulsion type effect, 394
Odor stability, fragrance, 504 Organic, UV absorbers, 474, 475
Oil-dispersed, titanium dioxide, dispersions, particulate, 297
formulating, 403, 404 Organoleptic considerations, formula
Oils, formula types, sunscreen, 358 goals, sunscreen, 375
948 Index
OTC drug monograph Photosensitive reaction, 24

system, 89– 94 Photosensitivity agents, 25, 26
amendment of, 93 Photosensitivity
NDA, comparison, 88 photoallergy, 27
sunscreen monograph, 87 phototoxicity, 26, 27
Oxybenzone, as organic sunscreen, 370 Photosensitivity skin disorder, 27 – 29
chronic actinic dermatitis, 27
PABA (p-aminobenzoates), hydroa vacciniforme, 29
UV filters, 224– 226 lupus erythematosus, 27
PABA-free ingredients, labeling miscellaneous dermatoses, 29
caveats, 110 persistent light reaction, 29
Padimate-O, as organic sunscreen, 371 polymorphous light eruption, 29
p-Aminobenzoates (PABA), 224– 226 porphyries, 29
Particle/light interaction equation, 246 solar urticaria, 29
Particle size, UV attenuation, 256, 257 xeroderma pigmentosum, 27
Particulates Photosensitization, fragrance safety,
inorganic, UV filters, formulations, sunscreens, 502
containing, 286– 289 Photostability
organic, UV absorbers, actives, organic sunscreen,
dispersions, 297 321 – 346
Patent issues, sunscreen formula, 375 avobenzone, 341 –344
PBS (schedule of pharmaceutical MBBT, 297 – 300
benefits), 130 molecular strategies, 344, 345
PCD (product category SPF active ingredients, 328 – 330
designations), 104 sunscreen formulations, commercial,
Persistent light reaction, in 339 – 341
photosensitivity skin disorder, 29 UV filters, other solutions,
Persistent pigment darkening (PPD), 21 335 – 338
PFA, titanium oxide, particle size, 259 Phototoxicity, photosensitivity, 26, 27
pH effects on, UV filters, 233 Physical properties
Pharmacopeial forum, monograph titanium dioxide, 242 – 248
development, USP, 207 zinc oxides, 242 – 248
Phase inversion temperature (PIT), 438 Pigment, surface treatment/
Phosphatidyl, Choline, 469 prewetting, 265
Photoaging, UV, effect on skin, 46 Pigment-dispersing properties, sunscreen
Photoallergy, photosensitivity, 27 emulsions/cosmetic emollients,
Photocatalytic activity 451 – 453
titanium dioxide, 244– 246 Pigments, micronized, 255
zinc oxide, 244– 246 PIT (phase inversion temperature), 438
Photodermatititis, plants and lichens Polymorphous light eruption,
causing, 28 photosensitivity skin disorder, 29
Photoexposure Porphyries, as photosensitivity skin
carcinogenesis related to, 30– 33 disorder, 29
effects, 24 PPD (persistent pigment darkening), 21
photosensitive reaction, 24 Prewetting, of pigment, 265
Photon absorption, 299 Product category designations
diagram, 324 (PCD), 104
Photoprotection, 19– 39 Production, of zinc oxide, 250 – 252
Index 949
Progression, carcinogenesis, interrupting Skin treatment products, manufacturer,

the pathway of, 33 498, 499
Promotion Solar damage, acute, 21 –23
of antioxidant therapies, 31, 32 Solar radiation
of carcinogenetic pathway, 31, 32 beneficial exposure, 74, 75
early evidence of harmful
Radiation, erythemogenic, effects, 74, 75
UV-B, 75, 76 effects on skin, early history, 72 – 75
Rays, erythemal, UV-B, 220 Solar spectrum, UV rays, 20, 21
Rayleigh, scattering pattern, 247 Solar urticaria, photosensitivity skin
Regulations, sunscreen, disorder, 29
titanium dioxide, claims, toxicity, Solvent properties, sunscreen emulsions,
testing, 275 cosmetic emollients, 450, 451
worldwide overview, 174 Spectrum, solar, UV rings, 20, 21
worldwide, 173– 197 SPF active ingredients, photostability,
zinc oxide, claims, toxicity, testing, 275 328 – 330
Regulatory framework, Australia, 129 SPF efficacy
Resonance isomerization schemes, UV benefits of daily use, 50, 51
filters, 330, 331 sunscreen composition and, 485
Rheological modifiers, 481, 482 surfactant-free vs. traditional, 484
Rheology SPF evaluation
emulsion, 389–391 emollients, 454
SPF modulation, 388–391 in vitro vs. sunscreen composition, 486
Risk assessment, safety testing, test formulation, 454
sunscreens, 67, 68 SPF level vs. base composition, 487
SPF modulation
Safety efficacy, 385 – 410
testing, risk assessment, sunscreens, rheology, 388 – 391
67, 68 water resistance, 406 – 409
UV absorbers, new, 315– 317 emulsifiers, specialized, 408
Salicylates, UV filters, 226, 227 film-forming polymers, 409
Scattering, as optical behavior, liquid crystal gel networks, 409
UV filters, 247 requirements, 407
SCC (squamous cell carcinoma), 46 silicones, 408
Schedule of pharmaceutical benefits strategies, 408, 409
(PBS), 130 W/O emulsions, 408
SED (standard erythema dose), 48 SPF test method
SFP actives, new, overview, 302– 312 JCIA standards, Japan, 165, 166
Silicones, SPF modulations, water vs. FDA methods, 158 – 161
resistance, 408 SPF values, test methods, international
Skin, UV radiation effect on, 220 status, 169
Skin cancer SPF (sun protection factor)
immunopathology of, 33 cosmetic foundations with, 270
melanoma, 5 definition, 47
UV, effect on skin, 46 effective levels, 48
Skin penetration, emulsion content, 468 effectiveness over lifetime, 49
Skin tone, uneven, labeling caveats, efficacy requirements, 387, 388
110, 111 emulsifiers, additives, effects on, 269
950 Index
SPF (sun protection factor) (Contd.) Sunscreen product listing, by

formulation levels, 267– 275 manufacturer, 496 – 500
high, formula goals, 373, 374 Sunscreen product(s)
ineffectiveness of, 48, 49 basic types, 6
inorganic particulates and, 286, current issues with, 462 – 465
269, 270 emulsions, 465 – 468
limitations of, 78, 79 FDA regulatory mechanisms, 87
recommended usage strategy, 51, 52 in Japan, 141 – 169
titanium dioxide, effect on, 258, 259 regulatory and safety issues, 6– 12
UV absorbers and, 295–297 Sunscreen regulation
water resistance tests, 192, 193 Australia, 127 – 140
zinc oxide, effect on, 260, 261, European Economic Community
272 –275 (EEC), 117 – 125
Spray O/W emulsions, 437– 400 FDA, 85– 94
Squamous cell carcinoma (SCC), 46 Japan, 148 – 149, 154
Stability evaluation, formula goals, 375 worldwide, 173 – 197
Stabilizers/protectants, emulsifiers, 369 Sunscreen(s)
Standard erythema dose (SED), 48 active ingredients, 101, 102
Stardards development, USP, 206 allowable ingredients, EEC, 119 – 122
Sticks, formula type of sunscreen, 361 antiaging/antiwrinkle/healing
Sulisobenzone, as organic sunscreen, products, 10
371, 372 antioxidants, 11
Sun care products biologically active ingredients, 14
fragrancing of, 493 combining, inorganic, organic, 406
surfactant-free, 461– 488 commercial, photostability,
Sun protection factor. See SPF. 339 – 341
Sun sensitivity, Japanese skin, 143–147 cosmetic formulation, 9 – 12
Sunburn, erythema, 46 development, in Japan, 148, 149, 154
Sunburn, UV, effect on skin, 46 dispersions, homogenous/
Sunless tanners, 10 heterogenous, 476
Sunscreen actives, new, 291– 320 EEC, definition of, 117, 124
Sunscreen applications, phase inversion emollients, emulsifiers, 449 – 460
temperature emulsions, emulsifiers, role of, 414, 415
457 –459 ethical issues, 354 – 356
Sunscreen characteristics, desired by FDA-OTC category I, 222
Japanese, 147, 148 film formers, 11
Sunscreen composition vs SPF, formula goals, 373 – 382
485, 486 antioxidants, 376
Sunscreen emulsions high SPF, 373, 374
cosmetic emollients mild formulations, 374, 375
pigment-dispersing properties, organoleptic considerations, 376
451 –453 patent issues, 375
solvent properties, 450, 451 stability evaluation, 375
emulsifiers role, 455, 456 formula types, 9, 356 – 362
O/W, quick-breaking, 433– 437 aerosols, 362
Sunscreen evolution, 3 –16 emulsions, 356 – 358
Sunscreen formulation, active gels, 359 – 361
ingredients, 9– 12 mousses, 361
Index 951
oils, 358 safety testing, 68

sticks, 361 in vitro models, 59 – 61
formulating basics, 362– 373 in vivo models, 61 – 65
emulsification principles, 362– 365 stability, 8
ingredients, 365– 373 surfactant(s) in, 413 – 448
formulations, 353– 382 surfactant-free, advantages of, 480,
fragrances in, 373, 502 483 – 485
fragrancing of, 501, 502 types, 37, 38
hair, 10, 11 UV filters in, 12
historical background, 4, 5 combined formulations, 404
in vitro models, 60 isomerization schemes, 330
in vivo dermal safety models, water resistance, 7, 374
animals, 62 Sunscreen suspensions, 475
ingredients active ingredients
emulsifiers, 365, 366 FDA ruling, 200
emulsions, 11, 12 inorganic chemical particulates,
ingredients for future use, 14, 15 9, 10
inorganic, 37, 38 organic chemical absorbers, 10
particulate, 372, 373 organic particulates, 10
powder form, 395 USP monographs, 207 – 210
predispersions, 396– 399 Sunscreen-skin protectants, FDA final
labeling requirements, 193– 196 rule, permitted combinations,
Australia, 196 103, 104
European Union, 196 Suntan products, manufacturer, 496 –498
Japan, 196 Suppliers, inorganic particulate, 284, 285
USA, 193– 196 Surface properties, titanium dioxide, zinc
limitations of, 78, 79 oxide, 253, 254
manufacturing and quality control, 8, 9 Surface treatment
USA, 196, 197 choices, 255, 256
marketing issues, 12 hydrophilic, 255
marketplace trends, 292– 293 micronized pigments, 255
models, 60, 62 titanium dioxide, 253
natural ingredients, 11, 37, 370– 372 zinc oxide, 253
future use of, 13 Surfactant-free, 461 – 488
O/W sunscreens, 422– 433 advantages of, 480, 483 – 485
photostability and photoreactivity, 7, 8 dispersions, use of, 468 – 475, 479, 480
proper use of, 38 future of, 485, 487, 488
protection factor, 7 vs. traditional, SPF efficacy, 484
protection in UV spectrum, 7 Surfactants, in sunscreen formulations,
reasons for use, 47 413 – 448
requirements, 293 Suspensions
efficacy, 293 titanium dioxide, 477
global registration, 294 zinc oxide, 477
patent freedom, 294, 295 Systemic safety models, 65, 66
safety, 293– 294
risk assessment, 67, 68 Tanning, effect on skin, 46
safety dossier, 294 Tanning accelerators, labeling
safety parameters and programs, 56–58 caveats, 109
952 Index
Tanning products, without sunscreens, Toxicity of

labeling caveats, 109 titanium dioxide, 275
TDSA (terephthalylidene dicamphor zinc oxide, 275
sulfonic acid), 306, 307 Traditional sunscreens, vs.
Terephthalylidene dicamphor sulfonic surfactant-free, 484
acid (TDSA), 306, 307 Transipidermal water loss (TEWL), 426
Spectrum/structure, 307 Trolamine salicylate, organic
Testing/testing methods sunscreen, 371
HRIPT, 67
inorganic UV filters, 244– 246 Ultraviolet radiation. See UV
SPF values, international status, 169 United States Pharmacopeia. See (USP)
zinc oxide, 244– 246 United States Pharmacopeia and
titanium dioxide, toxicity, 275 National Formulary
zinc oxide, toxicity, 275 (USP-NF), 201
TEWL (transipidermal water loss), 426 USP
TGA (Therapeutic Goods history of, 200, 201
Administration), Australia, 128 legal recognition, 201
Therapeutic/cosmetic interface of mission, 201
sunscreens, 139, 140 monograph development, revision
Therapeutic Goods Administration process, 204
(TGA), 128 active ingredients, 208
Titanium dioxide contributors, 204, 205
avobenzone and, 255 overview, 204
chemical properties, 242– 248 pharmacopeial forum, 207
formulations, 283, 284 revision process, 204 –207
IEP, 244 national formulary, 201 – 203
inorganic particulates and, zinc oxide, Octinoxate monograph, 210, 211
283, 284, 373 reference standards, 203
manufacturers of, 250 standards-setting body, 203
oil-dispersed, formulating, sunscreen monographs, active
403, 404 ingredients, 207 – 210
particle size, 257, 258, 264 USP-NF (United States Pharmacopeia
physical properties, 242–248 and National Formulary), 201
production of, 249, 250 UV absorbers
protection, broad-spectrum, assessment of human safety, 315
271 –275 dispersions, particulate,
suppliers, 268 organic, 297
surface treatments, most common, 253 emollients, influence for, 453
suspensions, 477 L alpha, 474, 475
toxicity, testing, 275 organic, 474, 475
typical specifications, 251 permitted, in Japan, 150 – 152
UV filters, inorganic, 241 photostability, 303
water-dispersed, formulating, safety, of new, 315 –317
401 –403 solubility, 302
and zinc oxide SPF, new, 295 – 297
dispersions, 261– 263 properties of, 302, 303
sample formulations, SPF, 272– 275 UV absorption data, 234, 453, 454
surface properties, 253, 254 UV attenuation, particle size, 256 – 264
Index 953
UV broad-spectrum absorbers, UV-A, PABA (p-aminobenzoates), 224 – 226

312 – 315 permitted
UV filters, 217– 238 Australia, 179, 182, 183
active ingredients European Union, 178, 182
approval process, in USA,176, 177 Japan, 177, 181
179, 181 pH effects on, 233
new, 303– 312 photochemistry review, 323 – 327
worldwide review, 175, 176 photostability, other solutions,
anthranilates, 229 335 – 338
benzophenones, 228 regulations, worldwide, 174
broad spectrum, 309– 312 Resonance schemes, 330
camphor derivatives, 230, 231 salicylates, 226, 227
cinnamates, 227 SPF, testing methods, 183, 184 –187
classification of, 221 spreading properties, 454 – 455
combinations of, 338, 339 standards
combined formulations, organic Australia, 190
sunscreens, 405, 406 European Union, 188, 189
cosmetics, effect on, 232 Japan, 189
dibenzoylmethanes, 230 USA, 183, 188
electromagnetic spectrum, 218– 220 UV light, 34
emollients, effect on, 233– 235 protective clothing, 34
extinction coefficient, 235 sunscreens, 36
formulations, organic, inorganic, UV protection, labeling requirements in
particulates, containing, 286– 289 Japan, 164, 167
future of, 235– 237 UV radiation, 5
INCI designation, 180, 181 photoaging, 47
inorganic, 239– 276 protection from, 5, 6
dispersion, 264– 267 skin, effect on 45 – 47, 220
evolution, 240, 241 skin cancer, 46
manufacturers, 248– 252 sunburn, 46
optical behavior, 246– 248 tanning, 46
test methods, 244– 246 types of, 5
titanium dioxide, 241 vitamin D production, 46
zinc oxide, 241 UV rays, solar spectrum, 20, 21
inorganic particulate, commerce, UV spectroscopic performance, 302
281 – 290 UV-A
inorganic sunscreens, combined absorbers, 312 – 315
formulations, 406 damage, 75, 76
inorganic surface treatments, 254 filters
isomerization resonance schemes, avobenzone, 323
330, 331 new, 306 – 309
mechanisms of, 231– 235 protection, 312 – 315
miscellaneous compounds, 231 reasons for, 76, 77
molecular designs, new, 300– 302 sunscreens, 76 – 78
organic tests
oil-soluble, emollients, added, 393 Australia, 192
surface treatments, 254 European Union, 190, 191
water soluble, 394 USA, 190
954 Index
UV-B Water soluble, organic UV filters, 394

burning rays, 220 emulsion type effect, 394
erythemal rays, 220 Water-dispersed, titanium dioxide,
erythemogenic formulating, 401 – 403
radiation, 75, 76
filters, new, 303, 305, 306 Xeroderma pigmentosum,
sunscreens, 77, 78 photosensitivity skin
UV-C disorders, 27
germicidal region, 219
UVR (ultraviolet radiation). Zinc oxide
See UV avobenzone as, 255
broad-spectrum protection, 271 – 275
chemical properties, 242 – 248
Volume/phase relations, HLB and, formulations, 270, 283, 284, 404
366, 367 IEP, 244
Vitamin D, UV and, inorganic
effect on skin, 46 UV filters, 241
particulate, 373
manufacturers, 250 –252
W/O baby sunscreen particle size, 259, 260, 264
cream, 458 SPF, 260, 261
W/O emulsifiers, 457 photocatalytic activity, 244 – 246
W/O emulsions, 419, 440– 446 physical properties, 242 – 248
Water loss, transpidermal, 426 production, 250 – 252
Water resistance regulations, claims, toxicity,
formula goals, sunscreen, 374 testing, 275
SPF modulation, 406– 409 suppliers, 268
dual-strategy, requirements for, surface treatments, common, 253
407, 409 suspensions, 477
emulsifiers, specialized, 408 test methods, 244 – 246
film-forming polymers, 409 titanium dioxide and
liquid crystal gel dispersions, 261 – 263
networks, 409 inorganic particulates, 283, 284
silicones, 408 SPF, sample formulations, 272 – 275
strategies, 408, 409 surface properties, 253, 254
W/O emulsions, 408 typical specifications, 253

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DK3046_half-series-title 2/1/05 9:45 AM Page A

COSMETIC SCIENCE AND TECHNOLOGY

1. Cosmetic and Drug Preservation: Principles and Practice,

16. Preservative-Free and Self-Preserving Cosmetics

Boca Raton London New York Singapore

Library of Congress Cataloging-in-Publication Data is available.

Visit the Taylor & Francis Web site at

The sunscreen industry is achieving remarkable worldwide prominence by

I. Introductory chapters on the evolution of sunscreens, photo

sunscreen regulations, a summary chapter on regulations of sun-

Nadim A. Shaath, Ph.D.

Dr. Nadim A. Shaath is President of Alpha Research & Development, Ltd.,

Patricia P. Agin Schering-Plough HealthCare Products Inc., Memphis,

Lawrence Evans III United States Pharmacopeia, Rockville, Maryland, USA.

Dennis L. Lott Tanning Research Laboratories, Inc., Ormond Beach,

Ko-ichi Shiozawa Aveda Corporation, Minneapolis, Minnesota, USA.

3. A Perspective on the Need for Topical Sunscreens . . . . . . . . . . . . 45

4. Safety Considerations for Sunscreens in the USA . . . . . . . . . . . . . 55

5. Sunprotection: Historical Perspective . . . . . . . . . . . . . . . . . . . . . . 71

6. The Role of FDA in Sunscreen Regulation . . . . . . . . . . . . . . . . . . 85

7. The Final Monograph . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95

8. Regulatory Aspects of Suncreens in Europe . . . . . . . . . . . . . . . . . 117

9. Regulation of Sunscreens in Australia . . . . . . . . . . . . . . . . . . . . . 127

10. Legal and Regulatory Status of Sunscreen

11. Regulations of Sunscreens Worldwide . . . . . . . . . . . . . . . . . . . . . 173

12. Sunscreen Products: The Role of the US

13. The Chemistry of Ultraviolet Filters . . . . . . . . . . . . . . . . . . . . . . . 217

14. Inorganic Ultraviolet Filters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239

15. Inorganic Particulate Ultraviolet Filters

16. New Sunscreen Actives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291

17. The Photostability of Organic Sunscreen

18. Formulating Sunscreen Products . . . . . . . . . . . . . . . . . . . . . . . . . 353

19. SPF Modulation: Optimizing the Efficacy

20. The Role of Surfactants in Sunscreen Formulations . . . . . . . . . . . 413

21. Role of Emollients and Emulsifiers in

22. Surfactant-Free Sun Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 461

23. Fragrancing of Sun Care Products . . . . . . . . . . . . . . . . . . . . . . . . 493

24. Formulating Natural Sun Care Products . . . . . . . . . . . . . . . . . . . . 507

Consumer Products with Ultraviolet Filters

25. Recreational Sunscreens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 525

26. Daily Use Sunscreens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 535

27. Valuable Properties for Baby and Kids Segments . . . . . . . . . . . . . 541

28. Fabrics as UV Radiation Filters . . . . . . . . . . . . . . . . . . . . . . . . . . 557

29. Sunless Tanning and Tanning Accelerators . . . . . . . . . . . . . . . . . . 573

Other Actives in the Sun Care Industry

30. Role of Antioxidants in Sun Care Products . . . . . . . . . . . . . . . . . . 603

31. Photoprotection by Green Tea Polyphenols . . . . . . . . . . . . . . . . . 639

32. Botanicals in Sun Care Products . . . . . . . . . . . . . . . . . . . . . . . . . 657

33. Antiaging Actives in Sunscreens . . . . . . . . . . . . . . . . . . . . . . . . . 673

Production and Quality Control

34. The Manufacture of Suncare Products . . . . . . . . . . . . . . . . . . . . . 699

35. Quality Control of Finished Sunscreen Products . . . . . . . . . . . . . . 719

36. Quality Control of Ultraviolet Filters . . . . . . . . . . . . . . . . . . . . . . 735

37. Modern Analytical Techniques in the

Analytical Testing Procedures

38. US FDA Protocol for Determining Sun

39. SPF Testing in Europe . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 779

40. Balancing UV-A and UV-B Protection in Sunscreen

41. Dosimetry of Ultraviolet Radiation: An Update . . . . . . . . . . . . . . 827