[LITERATURE REVIEW]

Sunscreening Agents
A Review
a
M.S. LATHA, MD; bJACINTHA MARTIS, MD; bSHOBHA V, MD; cRUTUJA SHAM SHINDE;
d
SUDHAKAR BANGERA, MD; eBINNY KRISHNANKUTTY, MD; aSHANTALA BELLARY, BDS;
a
SUNOJ VARUGHESE; aPRABHAKAR RAO; aB.R. NAVEEN KUMAR, MBBS
a
Global Medical Affairs, Dr. Reddy’s Laboratories Ltd., Hyderabad, India; bDepartment of Dermatology, Fr. Muller Medical College, Mangalore, India;
c
Department of Dermatology, Dr. Reddy’s Laboratories Ltd., Hyderabad, India; dClinical Research Consultant, Hyderabad, India;
e
Department of Pharmacology, Azeezia Medical College, Kollam, India

ABSTRACT
The increasing incidence of skin cancers and photodamaging effects caused by ultraviolet radiation has increased the
use of sunscreening agents, which have shown beneficial effects in reducing the symptoms and reoccurrence of these
problems. Many sunscreen compounds are in use, but their safety and efficacy are still in question. Efficacy is measured
through indices, such as sun protection factor, persistent pigment darkening protection factor, and COLIPA guidelines.
The United States Food and Drug Administration and European Union have incorporated changes in their guidelines to
help consumers select products based on their sun protection factor and protection against ultraviolet radiation, whereas
the Indian regulatory agency has not yet issued any special guidance on sunscreening agents, as they are classified under
cosmetics. In this article, the authors discuss the pharmacological actions of sunscreening agents as well as the available
formulations, their benefits, possible health hazards, safety, challenges, and proper application technique. New
technologies and scope for the development of sunscreening agents are also discussed as well as the role of the physician
in patient education about the use of these agents. (J Clin Aesthet Dermatol. 2013;6(1):16–26.)

P
hotoprotective agents protect the skin by preventing Effects of UVA manifest usually after a long duration of
and minimizing the damaging effects of ultraviolet (UV) exposure, even if doses are low. It has been postulated that
rays of natural light. They can be used as sunblock, UVA up regulates the formation of matrix metalloproteinase
which is opaque when applied over the skin and blocks a (MMPs), enzymes that degrade the matrix protein’s elastin
higher percentage of light as compared to sunscreens, which and collagen, which, if not prevented, can result in marked
are translucent and require frequent reapplication for reduction in skin elasticity and increased wrinkling. UVA
optimum efficacy. Photoaging—manifested as sagging, radiation damages skin by penetrating into the layers of skin
wrinkling, and photocarcinogenesis—is caused by damage to and producing reactive oxygen resulting in acute and chronic
cells and deoxyribonucleic acid (DNA). It has been observed changes.2 UVA radiation can induce polymorphous light
that sunscreens increase skin’s tolerability to UV rays.1 eruptions (PMLE) in sensitive skin,3 but in some it has also
UV radiation has broad spectrum, ranging from 40 to shown to reduce PMLE.4 UVA can also cause exacerbation of
400nm (30–3eV), which is divided into Vacuum UV cutaneous lupus erythematoses, whereas solar urticaria can
(40–190nm), Far UV (190–220nm), UVC (220–290nm), UVB be caused by both UVA and UVB radiation.5
(290–320), and UVA (320–400nm), of which the latter two are Studies have shown that UVA impairs the antigen
medically important. There are two distinct subtypes of UVA presenting cell (APC) activity of the epidermal cells and
radiation. Short-wave UVA (320–340nm) and long-wave UVA thereby causes immune suppression, thus contributing to the
(340–400nm), the latter constituting most of UVA radiation. growth of skin cancer. Sunscreening agents have shown to
The amount of exposure to UVA usually remains constant, provide significant protection against epidermal APC activity
whereas UVB exposure occurs more in the summer.2 induced by high UVA dose.6 Mutation occurring in human

DISCLOSURE: Dr. Latha, Ms. Sham Shinde, Dr. Bellary, and Mr. Rao are employed by Dr. Reddy’s Laboratories Ltd. and are stakeholders in Dr.
Reddy’s Laboratories Ltd. Dr. Krishnankutty, Dr. Kumar, and Mr. Varughese were former employees of Dr. Reddy’s Laboratories Ltd. and are
presently not stakeholders in Dr. Reddy’s Laboratories Ltd. Dr. Martis, Dr. Bangera, and Dr. Shobha report no relevant conflicts of interest.
ADDRESS CORRESPONDENCE TO: Dr. M.S. Latha; E-mail: [email protected]

16 [January 2013 • Volume 6 • Number 1] 16

Figure 1. Classification of sunscreening agents

melanocyte due to damage caused to DNA by UVA radiation is method of application, reapplication, and the importance of
one of the proposed reasons.7 In summary, UVA radiation can patient education in all populations in order to reduce the
cause nuclear and mitochondrial DNA damage, gene damaging solar effects on skin.
mutations and skin cancer, dysregulation of enzymatic chain
reactions, immune suppression, lipid peroxidation (membrane COMPOSITION AND MECHANISM OF ACTION
damage), and photoallergic and phototoxic effects. Sunscreening agents contain titanium dioxide (TiO2),
UVB radiation can also cause acute changes, such as kaolin, talc, zinc oxide (ZnO), calcium carbonate, and
pigmentation and sunburn, and chronic changes, such as magnesium oxide. Newer chemical compounds, such as
immune-suppression and photocarcinogenesis. Both UVA bemotrizinol, avobenzone, bisoctizole, benzophenone-3 (BZ-
and UVB radiation can cause sunburn, photoaging reactions, 3, oxybenzone), and octocrylene, are broad-spectrum agents
erythema, and inflammation.2 and are effective against a broad range of solar spectrum both
Sunburn is the most commonly encountered skin damage in experimental models and outdoor settings. Ecamsule
caused by natural light. Improper sunscreen usage and (terephthalylidene dicamphor sulphonic acid), dometrizole
inadequate application also contribute to the increased trisiloxane, bemotrizinol, and bisoctrizole are considered
prevalence of sunburn, despite the frequent use of organic UVA sunscreening agents. Classification12 of
sunscreening agents. Available evidence indicates that sunscreening agents is shown in Figure 1. Commercial
sunburn is more commonly seen in white-skinned people and preparations available in the market include a combination of
young people with sensitive skin. Sunburn is common in the these agents to cover a wide range of UV rays.
United States with 34.4 percent of adults affected.8 In Composition and mechanism of action of sunscreening
Sweden, children are frequently affected, and use of agents vary from exerting their action through blocking,
sunscreen among children has been found to be protective.9 reflecting, and scattering sunlight. Chemical sunscreens
With the increased incidence in skin cancer cases, such as absorb high-energy UV rays, and physical blockers reflect or
squamous and basal cell carcinomas, reported worldwide, scatter light. Multiple organic compounds are usually
use of photoprotective agents has increased over the incorporated into chemical sunscreening agents to achieve
years.10,11 There has been symptomatic improvement and protection against a range of the UV spectrum. Inorganic
inhibition of reoccurrence of these conditions when particulates may scatter the microparticles in the upper
photoprotective agents are used either therapeutically or layers of skin, thereby increasing the optical pathway of
prophylactically, indicating the need to promote and photons, leading to absorption of more photons and
regularize their application. enhancing the sun protection factor (SPF), resulting in high
The authors intend to spread awareness among physicians efficiency of the compound.13,14
regarding the amount of sunscreening agents needed, Researchers are postulating that the generation of

[ January 2013 • Volume 6 • Number 1] 17

sunlight-induced free radicals causes changes in skin; use of of sunscreening agent to obtain the claimed benefit (i.e.,
sunscreens reduces these free radicals on the skin, 2mg/cm2, which is shown to be effective on Asian skin as
suggesting the antioxidant property.15 Broad-spectrum well). Studies have shown that people apply about a quarter
agents have been found to prevent UVA radiation-induced of the recommended dose of sunscreen, which is an
gene expression in vitro in reconstructed skin and in human inadequate amount.23,24
skin in vivo.16 Protection offered by a sunscreening agent against UVA
Insect repellents, such as picaridin and N, N-diethyl-3- radiation is measured by the Persistent Pigment Darkening
methylbenzamide (DEET), have been incorporated into (PPD) Protection Factor. This technique was developed in
sunscreening agents to minimize the risk of developing Japan and has been routinely used by manufacturers.
insect-borne infections. Picardin was found to be a more Stanfield25 has discussed its disadvantages. PPD is not done
suitable component than DEET when used along with BZ-3, in skin type 1, which is the skin type more prone to solar
as it minimizes the penetration of chemicals.17 damage. For wavelengths less than 320nm, action sprectrum
Ideal sunscreening agents should be safe, chemically inert, is not defined; moreover, clinical significance of PPD is not
nonirritating, nontoxic, photostable, and able to provide very clear.
complete protection to the skin against damage from solar Immediate pigment darkening response is calculated as
radiation. They should be formulated in a cosmetically the dose of UVA required to produce the effect with the
acceptable form and ingredients should remain on the upper sunsceening agent to that produced without an agent.26
layers of the skin even after sweating and swimming. Although this test gives rapid results for low doses of UVA,
Sunscreening agents should provide efficient scavenging responses have been found to be highly variable and an
activities against singlet oxygen and other reactive oxygen accurate reproduction of results is difficult. This is usually
species.18 They should also effectively block both UVB and performed in skin types III and IV and its clinical significance
UVA rays, which is possible with an agent that has an SPF of is unknown.27
30 or greater. Sunscreens with an SPF of 30 or greater that COLIPA guideline is a new standardized, reproducible,
incorporate photostable or photostabilized UVA filters and in-vitro method to measure UVA protection offered by
(labeled as “broad spectrum” in the US) are usually ideal.19 sunscreening products and was developed by “In-Vitro Sun
Sunscreens should not only protect the skin from the sun, but Protection Methods” group. This has been in use by
also minimize the cumulative health hazards from sun damage European Union (EU) countries for testing and labeling
caused over time. sunscreen products as it is in line with regulatory
recommendation.28
FACTORS DETERMINING EFFICACY Immunoprotection factor is a measure of a sunscreening
SPF and substantivity (the property of continuing agent to prevent UV-induced immunosuppression.12
therapeutic action despite removal of the vehicle ) are the
factors that contribute to the effectiveness of sunscreening REGULATORY GUIDELINES
agents.20 UVB protection is measured by a product’s SPF, Misguiding information on sunscreen labels has compelled
which theoretically indicates that products with high SPFs regulatory agencies to make changes in the international
provide more protection against hazardous effects of sunlight regulatory guideline on sunscreens to avoid confusion among
than those with low SPFs.21 SPF is measured as the ratio of the general public, to assist them in selecting a suitable agent,
the amount of UV radiation required to burn the protected to provide adequate sun protection, and to minimize health
skin (with sunscreen) to that required to burn the same hazards of solar damage including the occurrence of skin
unprotected skin (without sunscreen), all other factors being cancers.
constant. SPF is measured using the following formula: United States Food and Drug Administration (FDA)
SPF = MED of protected skin/MED of unprotected skin guidelines. Previously, FDA guidelines29,30 aimed at
(MED = minimal erythemal dose). protection against UVB radiation and sunburns, not toward
This means when a product with SPF 50 is applied, it will protection against UVA radiation and prevention of skin
protect the skin until it is exposed to 50 times more UVB cancers. Inappropriate and misguiding labeling with false
radiation than that is required to burn the unprotected skin. claims has made the FDA revise its guidelines on
SPF level, efficacy against a wavelength of UV radiation, sunscreening agents. New, improvised guidelines address
and UVA/UVB ratio can be calculated using a computer such issues as “broad-spectrum designation, use claims,
program or software, such as sunscreen simulators, and can waterproof, sweat proof, sun proof, and water resistance
determine if the product meets the regulatory standards. claims and drug facts”. According to the new guidelines,
Bodekaer et al22 studied the reduction in SPF of organic claims about UVA and UVB protection should be made only
and inorganic sunscreening agents in participants who, over after the specific tests have proved the same. It is mandatory
the course of eight hours, performed physical activities, were to test both UVA and UVB radiation. A product can be
then exposed to a hot environment, and finally bathed. There classified as a broad-spectrum sunscreening agent if it passes
was a reduction in SPF of 38 and 41 percent after four hours the required test, but the reduction in the risk of skin cancer
and of 55 and 58 percent after eight hours of application of and early skin aging when used as per direction can be stated
organic and inorganic sunscreen, respectively.22 Hence, it is by only those with SPF 15 or higher. Those with SPF 2 to 14
necessary to apply the adequate and recommended amount cannot state the latter.

18 [January 2013 • Volume 6 • Number 1] 18

 TABLE 1. Photoprotection grades according to Japanese cosmetic industry association guidelines

PHOTOPROTECTION FACTOR OF UVA VALUE PROTECTION GRADE OF UVA (PA) PROTECTION LEVEL

2 or more, but less than 4 PA+ Low

4 or more, but less than 8 PA++ Moderate

8 or more PA+++ High

Source: JCIA/persistent pigment darkening protocol

Labels claiming sunscreens are “waterproof,” “sweat compound when the transmission of sunlight between a
proof,” or “sun blocks” are not legally permitted as these wavelength of 320 and 360nm (at a path length of 8µm) is
claims overemphasize the product’s efficacy. If a product less than 10% (of the incoming light that is passing
claims to be water resistant, the label should clearly indicate through).
the duration of effectiveness (e.g., 40 minutes or 80 minutes) New Australian guidelines have set SPF 50+ as a
during activities such as swimming. If the product does not benchmark for sunscreening agents. It has also endorsed
claim to be water resistant, consumers should be instructed to the revisions by international standards on terminology,
use a water-resistant sunscreen during swimming and those such as “water resistant,” “waterproof,” “sun block,” and
activities that produce sweat. Reapplication for better efficacy “sweat resistant,” as these terms are misleading to
has to be mentioned on the label, and manufacturers are not consumers. High requirements have been set by the
allowed to claim sun protection lasting more than two hours guideline regarding water resistance as per their lifestyle
without reapplication. Claims, such as instant protection, are requirement.33
also not permitted. If any such claims are made, supporting Japanese regulatory guidelines34 describe the method of
data should be submitted to obtain FDA approval. testing the photoprotection factor of UVA (PFA) as the amount
Labels should also include standard drug facts. Products of product to be applied, dose of radiation, and radiation field.
containing an SPF of more than 50 should mention in the These guidelines define minimal persistent pigment darkening
label that there is a lack of evidence to support that (MPPD) dose as the minimum dose of UV rays required to
sunscreens with an SPF of more than 50 have better efficacy produce slight darkening over the whole radiation area within
than those containing SPF 50 or below. Manufacturers have 2 to 4 hours after exposure. The guidelines also define the time
to submit supporting data if the formulation is a spray or to measure MPPD and who should measure it. PFA is
another dosage form of which comparison with the regular calculated using the following formula:
dosage form, such as cream or lotion, is not possible. These PFA = MPPD of protected skin/MPPD of unprotected skin.
new rules became effective June 18, 2012. Products are graded based on the PFA value (Table 1).
EU guidelines. Revised EU guidelines31,32 mandate a Korea follows Korean measurement standards for UV
minimum level of UVA protection in terms of SPF. The UVA protection effects (KFDA) and has standards for UVB
protection factor measured by PPD (in vivo) or COLIPA (in protection (SPF measurement) and protection grade of
vitro) must be at least one-third of the SPF in-vivo value. UVA (PA). On labels, SPF should be listed for UVB and PA
Products with SPF 6, 10, 15, 20, 25, 30, 50, 50+ are permitted for UVA.35
for consumer use and are categorized as low (SPF 6, 10), India guidelines. In India, there are no industry guidelines
medium (SPF 15, 20, 25), high (SPF 30, 50), and very high for standardizing sunscreen agents and there is no detailed list
(SPF 50+). Compounds should provide protection against a of approved products. The Indian regulatory agency’s official
minimum critical wavelength of 37nm, which is also under website lists only two combination products as approved drugs
consideration. Products that meet the regulatory standard (Table 2). Many products are classified as cosmetics and are
will have the UVA seal. not listed in this section. Apart from routinely used agents,
Actual protection against UVA is represented by a star such as BZ-3, ZNO, and TiO2, other agents, such as camphor
system for easy understanding by consumers. This measure benzalkonium methosulfate (6%), octyl salicylate (5%),
was developed by Boots Company in Nottingham, United camphor derivatives, and broad-spectrum UV filters (i.e., bis-
Kingdom, and was based on Diffey’s UVA/UVB ratio. The star ethylhexyloxyphenol mcthoxyphcnyl triazine [10%] and
system ranges from one to five stars where 1=minimum sun methylene bis-benzotriazolyl tetramethylbutylphenol [10%])
protection, 2=moderate, 3=good, 4=superior, and 5=ultra. are widely used. Table 2 lists some of these agents, which are
Guidelines from other countries. Japan, Australia, manufactured by pharmaceutical companies and are available
and New Zealand have their own indices on UV protection in India. Most of the products available are combination
factor.12 Australian standards define UVA protection in a products.

[ January 2013 • Volume 6 • Number 1] 19

 TABLE 2. Approved sunscreeening agents (combination products) and available preparations in India

PROTECTION GRADE OF UVA (PA)

COMBINATION APPROVED BY INDIAN REGULATORY AUTHORITY*
APPROVED CONCENTRATION (%)

Octinoxate + Avobenzone + Oxybenzone + Octocrylene + Zinc Oxide lotion (approved on March 19, 2009) 7.5+2+3+3+2

Octinoxate + Avobenzone + Oxybenzone + Titanium dioxide lotion (approved on March 23, 2009) 7.5+3+3+2

COMPOUNDS AVAILABLE IN INDIA† CONCENTRATION (%) SPF

Bis-Ethylhexyloxyphenol Methoxyphenyl Triazine ((Tinosorb S, Bemotrizinol )+ Butyl

Methoxydibenzoylmethane ((Tinosorb M- active, Avobenzone)+ Methylene Bis-Benzotriazolyl 2+2+5+2+7 30
Tetramethylbutylphenol ( Bisoctrizole )+ Benzophenone-3 (Uvinul M40)+ Octocrylene (Uvinul N539T)

Bis-Ethylhexyloxyphenol Methoxyphenyl Triazine

+ Butyl Methoxydibenzoylmethane
5+2+7+3+10 50
Methylene Bis-Benzotriazolyl Tetramethylbutylphenol ((Tinosorb M, active) + Benzophenone-3 (Uvinul
M40)+ Octocrylene (Uvinul N539T)

Tinosorb M; Octinoxate; Octyl triazone [EHT/Uvinul T150] – S3 Complex 60

Octinoxate +Avobenzone + Oxybenzone + Octocrylene + Zinc Oxide 7.5 +2+3+3+2 50+

Oxybenzone + OMC + Tinosorb M 3+5+8 30

Tinosorb M +Octinoxate 30

Octinoxate +Avobenzone +Oxybenzone + Zinc Oxide 7.5 +2+3+2 26

Octinoxate +Avobenzone +Oxybenzone + Zinc Oxide (micronized) 7.5 +2+3+6 NA

OMC + Oxybenzone + Titanium Dioxide 7.5 +3+3 20.47

OMC + Oxybenzone + Titanium Dioxide 8+3+6 50+

Zinc Oxide + Octinoxate 15.5+7.5 30

Octylmethoxycinnamate+oxybenzene+Titanium dioxide 8.5+3+6.5% 50+

OMC+Avobenzone+Phenyl benzimidazole suphomived 7.5+2+2 30+

*
Source: Central Drugs Standard Control Organization, New Delhi, India
†
Although many sunscreening products are available in India, composition details are not available, as they are marketed as cosmetics. The
authors have mentioned only a few agents for which composition details are available. Most of the products are combination products and a
branded product containing one active ingredient other than ZnO is rare in the Indian market.

PHARMACOKINETICS and excreted, even after five days after the last application.37
It was observed that lipid microparticles loaded with In another study, pharmacokinetics of BZ-3 was studied in 11
ethylhexyl methoxycinnamate (EHMC), which filters UVB, healthy volunteers after topical application. After 48 hours,
and butyl methoxydibenzoylmethane (BMDBM), which the average amount of BZ-3 excreted in urine was 11mg
filters UVA, had reduced skin penetration, thus preserving (median=9.8mg). In some volunteers, BZ-3 was excreted
the UV filter efficacy and limiting potential toxicological even after 48 hours. This study showed that BZ-3 undergoes
risks.36 Gonzalez et al37 studied the percutaneous absorption conjugation and converts to a water-soluble compound. The
of BZ-3 after repeated whole-body applications, with and age at which liver attains maturity and is able to metabolize
without UV irradiation in 25 volunteers. They observed that these chemicals and conjugate is unknown. Therefore, it is
large amounts of BZ-3 is absorbed, accumulated in the body, recommended that physical filters (i.e., zinc oxide, titanium

20 [January 2013 • Volume 6 • Number 1] 20

Figure 2. SPF profile of a product with SPF 30
(Source: Data on file, BASF sunscreen simulator predictions of
clinical and outdoor SPF based on UV filter composition. Shadows
Figure 3. UV protection profile of a product with SPF 30. Profiles
30, Dr. Reddy’s Laboratories Ltd., India.)
before (initial) and after (final) irradiation dose of SPF x MED (1
Minimal Erythema Dose passes through sunscreen onto skin).
(Source: Data on file, BASF sunscreen simulator predictions of
dioxide, ferrous oxide) be used in children.38 BZ-3 is FDA
clinical and outdoor SPF based on UV filter composition. Dr. Reddy’s
approved for use in children above six months of age.
Laboratories Ltd., India.)
Pharmacokinetics of the following three chemical UV
absorbers—benzophenone-3 (BZ-3), octyl-methoxy-
cinnamate (OMC), and 3-(4-methylbenzylidene) camphor formulation.41
(4-MBC)—were studied in 32 healthy volunteers, 15 of Filipe et al42 studied the localization of TiO2 and ZnO
whom were young male volunteers and 17 of whom were nanoparticles and their skin penetration levels and concluded
postmenopausal women. The volunteers were exposed to that drug concentration was either undetectable or
daily whole-body topical application of 2mg/cm2 of sunscreen insufficient under the stratum corneum, indicating minimal
formulation at 10% (weight/weight) for four days. Blood and systemic absorption with no or minimal penetration into
urine concentrations were measured at regular intervals as keratinocytes and good skin retention.42–44 Lacatusu et al45
specified in the protocol. Before the first application of these showed that coupling UV absorbers and lipid nanoparticles
agents, their concentration was undetectable in plasma and makes the combination photostable and provides better
urine, but was detectable 1 to 2 hours after the first photoprotection.45
application. In female volunteers, the maximum median
plasma concentrations of 187ng/mL BP-3, 16ng/mL 4-MBC, EFFICACY
and 7ng/mL OMC were seen. In male volunteers, maximum Efficacy of a sunscreen is tested in vitro and in vivo for
median plasma concentrations were 238ng/mL (BZ-3), SPF, UVA indices, and UV protection profile. Figures 2 and 3
18ng/mL (4-MBC), and 16ng/mL OMC. show the SPF and UV indices for a product with SPF 30 and
The urinary concentration level of BZ-3 was higher in men Figures 4 and 5 show that for a compound with SPF 50. The
(81ng/mL) than women (44ng/mL). However, no significant ability of a sunscreen to absorb UV radiation is measured in
changes were seen with other agents (female volunteers = terms of extinction coefficient value. Figure 6 shows the
4ng/mL of 4-MBC and 6ng/mL OMC; male volunteers = optimal UV protection across the full UV spectrum of various
4ng/mL of 4-MBC and OMC). Men showed a higher UV filters.
concentration of 4-MBC and OMC, whereas women showed a
similar pattern in BZ-3 and 4-MBC when 96-hour median STUDIES
concentrations were compared to 24-hour concentrations.39 Studies are suggesting the use of broad-spectrum
Janjua et al40 studied the absorption of sunscreens BZ-3, sunscreening agents for greater protection.46 Daily
octyl-methoxycinnamate (OMC), and 3-(4-methyl- application of these agents helps in minimizing solar UV-
benzylidene) camphor (4-MBC) from topical application and induced skin changes.47 Results of a study by Diffey11
their effects on the endogenous reproductive hormones in 32 indicated that regular use of topical photoprotective agents
healthy volunteers. After two-week, whole-body application, significantly reduces lifetime UV exposure to the face
there was no change in follicle-stimulating hormone (FSH) compared to nonuse. The study also emphasized that it is
levels or luteinizing hormone (LH) levels, but there was a very important to begin regular daily use of topical
minor difference in testosterone levels. In men, a minor sunscreens early in life. Sunscreens are used more during
difference in serum estradiol and inhibin B levels were the summer season than throughout the year in some
observed.40 regions. Consumers consider SPF, action of sunscreens
Formulation also plays a role in the penetration of the against UV range, and the usage pattern as less important.11
compound to the skin. Skin penetration of BZ-3 is faster and Green et al48 observed reduction in the incidence of
greater if formulated as emulsion. However, the rate of squamous cell carcinoma (40%) and basal cell carcinoma
penetration is dependent on the concentration of BZ-3 in the with regular use of sunscreens, supporting their role in the

[ January 2013 • Volume 6 • Number 1] 21

Figure 4. SPF profile of a product with SPF 50 Figure 5. UV protection profile of a product with SPF 50
(Source: Data on file, BASF sunscreen simulator predictions of (Source: Data on file, BASF sunscreen simulator predictions of
clinical and outdoor SPF based on UV filter composition. Shadows clinical and outdoor SPF based on UV filter composition. Shadows
50, Dr. Reddy’s Laboratories Ltd., India.) 50, Dr. Reddy’s Laboratories Ltd., India.)

prevention of these skin cancers. sunburn. The formation of freckles in the Asian population is
Kuhn et al49 assessed the exclusive use of a broad- encountered much less frequently. However, overexposure to
spectrum sunscreen in preventing the skin lesions in patients sunlight can cause photodamaging effects, including skin
with different subtypes of cutaneous lupus erythematosus cancers. Hence, it is advisable for Asians to use sunscreening
(CLE) induced by UV irradiation under standardized agents regularly as a preventive measure just as it is in other
conditions in 25 patients. They concluded that use of broad- parts of the world. However, since Asian skin is more prone
spectrum sunscreening agents prevents skin lesions in these to hypersensitivity reactions, cosmetic products should be
patients. Efficacy of sunscreens depends upon skin type, used with care.
amount and frequency of application, exposure to sunlight
and time of day, environmental factors, and the amount of SUNSCREEN USE IN SPECIAL POPULATIONS
product absorbed by the skin. Studies have shown that dialysis and organ transplant
patients, including renal transplantation patients, should follow
SAFETY photoprotective measures, as they are more prone to develop
The safety of sunscreening agents is determined by skin cancers. Use of sunscreening agents have prevented the
toxicity studies, ability to cause irritation, sensitization, development of premalignant skin changes in these
phototoxicity, and its impact on environment. Hayden et al50 patients.53,54 Hence, physicians should educate these patients
studied the safety of five commonly used sunscreen agents regarding the regular use of preventive measures against sun
(avobenzone, octinoxate, octocrylene, BZ-3 [oxybenzone] damage, including the regular use of appropriate sunscreens.
and padimate O) by determining the penetration of topical
agents and found that BZ-3 penetrated the epidermis the FORMULATIONS
most after 24 hours of exposure; however, the concentration Generally, sunscreens are available in the form of creams,
in the stratum corneum was too low to cause toxicity. lotion, gels, ointments, pastes, oils, butters, sticks, and
Toxicities have been reported with BZ-3, which has been sprays, which are considered over-the-counter (OTC)
associated with anaphylaxis.51 The inhalation of spray products. Less frequently used products include wipes,
sunscreens can pose a danger as well. McKinney et al towelettes, powders, body washes, and shampoos, which are
observed pulmonary and cardiovascular changes in rats on considered non-OTC products by the FDA. Of late, these
inhalation of a product containing TiO2 nanoparticles. types of products have been marketed as multifunctional
cosmetic formulations incorporated into other cosmetics,
USE OF SUNSCREENING AGENTS IN ASIAN SKIN such as moisturizers, facial foundations, and foam
Asian skin is classified as type IV,26 which is darker in color, foundations (mousse). Spray or gel-based sunscreens are
rarely burns, and is more prone to rapid tanning. Asian skin preferred in oily skin and acne. New sunscreens with
is comparatively smoother, with a slight yellowish tinge and is microfine particles are found to be safe and effective in
more prone to pigmentation. Presence of protein melanin in patients with acne and rosacea. Sunscreen filters are also
the skin of Asians differentiates it from the skin of added to hair care products, such as shampoo, to minimize
Caucasians. It has been observed that melanin equally filters sun damage to hair.
all wavelengths of light, thereby receiving five times less UV Sunscreen-containing moisturizers usually have SPFs
radiation. This protein provides photoprotection to a certain between 15 and 30. Coverage foundations are transparent
extent, minimizing phototoxicity and making the skin less formulations containing titanium dioxide with an SPF of 2
vulnerable to the acute and chronic phototoxic effects.52 while moderate coverage foundations are usually translucent
Nevertheless, this population shows the effects of with an SPF of 4 to 5.
photodamage in terms of pigmentation, wrinkling, and Gogna et al55 observed that the use of polymethyl-

22 [January 2013 • Volume 6 • Number 1] 22

methacrylate (PMMA) microspheres of ethylhexyl
methoxycinnamate (EHM) increases the efficacy of the latter
by four times and also improves photostability of the
preparation. Sprays containing sunscreening agents with high
concentrations have been found to retain the medicaments on
the top layers of skin, minimizing deeper penetration.56
Studies have shown that microspheres increase the
efficacy of sunscreening agents.55 Incorporation of
nanoparticles has shown to increase the efficacy of sunscreen
agents in terms of superior UV protection and reduced
whitening on the skin in comparison with the older
generations of sunscreens.57 Currently, formulations Figure 6. Optimal UV protection across the full UV spectrum of
containing nanoparticles of TiO2 and ZnO are available. various UV filters
However, studies have shown that nanoparticles of these two (Source: Sun Care, Optimal Sun Protection, BASF.)
compounds cause cytotoxicity, genotoxicity,58,59 and potential
photocarcinogenecity.60 In addition, nanoparticles of ZnO,
even at a much lower concentration, may induce potential for the general public.68
inflammation by releasing inflammatory mediators, such as Exacerbation of acne and rosacea can also occur with the
cytokines interleukin (IL)-6 and tumor necrosis factor use of sunscreen agents that contain physical blockers, such
(TNF)-α.61 Sunspheres and microencapsulations are newer as ZnO and TiO2, that are greasy and have large particle sizes,
technologies in the preparation of sunscreen formulation.12 thereby blocking skin pores.

HEALTH HAZARDS OF SUNSCREENING AGENTS EFFECTIVE PRACTICE

Although considered safe, sunscreening agents are not According to the Environmental Working Group’s 2010
free from adverse effects. Sensitivity, though rare, can occur Annual Sunscreen Guide, zinc and titanium-based
in the form of photoallergic reactions, including contact sunscreens are considered more safe and effective than other
dermatitis. Photopatch testing helps to identify sensitivities.62 products available in the United States.69 Powder and spray
There have been reports of increased incidence of sunscreens should be avoided, as they may lead to inhalation
melanoma as a result of sunscreen use. Gorham et al63 of particles, which is hazardous. The FDA recommends
reviewed the risk of developing melanoma as a result of applying 2mg/cm2 of sunscreen to achieve maximum benefits.
sunscreen use and opined that those who live in latitudes Sunscreen should be reapplied every two hours as well as
greater than 40 degress may have an increased risk of after sweating, toweling off, bathing, and swimming. It is
melanoma. The reason for this may be because sunscreens recommended that sunscreen labels highlight the importance
absorb UVB almost completely, but transmit large quantities of reapplication.70
of UVA.63 Sunscreen use may prolong the duration of Avoiding exposure to sunlight during the time of day when
intentional exposure giving people a false sense of security, UV radiation is at its highest—between 10 am and 3 pm—is
especially when using products that have high SPF ratings, recommended. When sun exposure during this time is
thereby increasing the risk of skin cancer.64 A similar trend unavoidable, it is advisable to use sun protection (i.e.,
was observed in European countries as well.65 umbrella and sun protection clothing).
A product assessment in the United States in January
2011 revealed that retinyl palmitate, a form of vitamin A, CAUSES OF SUNSCREEN FAILURE
which is a widely used compound in cosmetics and Underapplication and failure to reapply sunscreen every
sunscreens (as an antioxidant against the aging effects of UV two hours are the main reasons sunscreens fail. Additionally,
radiation), is thought to increase the rate of the development these agents are unaffordable by many in developing and
of skin tumors and lesions. However, Wang et al66 opined that underdeveloped countries. Sunscreen use year round is
its role in human carcinogenesis is doubtful as there is a lack expensive,71 which is why some people do not use sunscreen
of evidence. Fourschou et al67 noted an exponential increase regularly. Another contributing factor to sunscreen failure is
in vitamin D levels with the application of thinner layers of the mismatch between the labeled SPF and that delivered on
sunscreen after UVB exposure, indicating that application of application to skin and exposure to sunlight.
thicker layers can cause a decrease in vitamin D levels
resulting in its deficiency. PROMOTING THE USE OF SUNSCREEN AGENTS
It is postulated that BZ-3 can disrupt the hormones in As the rate of sunscreen use is low, education and
the body. The Centers for Disease Control and Prevention awareness about the hazards of sun exposure and the
has detected BZ-3 in the 97 percent of Americans tested benefits of regularly applying sunscreening agents to reduce
during biomonitoring surveys. Although there have been these effects must be spread.23,72,73 Outdoor activities should
reports of adverse events with this agent, studies have be performed before 10 am or after 3 pm.74 Education should
shown that products formulated with 1 to 6% of BZ-3 do target preadolescents so they develop the habit of using
not possess a significant sensitization or irritation sunscreening agents at a young age, particularly as

[ January 2013 • Volume 6 • Number 1] 23

adolescents are more prone to seek sun exposure for to spread awareness regarding sunburn, skin cancer, and the
intentional tanning purposes.75 Organ transplant patients benefits of regularly using sunscreening agents, treatment
need to be educated regarding the regular use of adherence is low.78 Providing cosmetically acceptable
sunscreening agents as well. preparations and educating people about following the
Lack of awareness among the public regarding the use of application instructions, is a challenge often faced by treating
sunscreening agents is more evident in the United States, physicians. Pricing sunscreens reasonably and making them
where only about 3 in 10 adults routinely practice sun- water resistant and non-sticky are a few of the challenges
protection behaviors. Women and older adults have been faced by manufacturers. Manufacturers must also consider
found to practice sun protection more than others.8 sensitization reactions, especially in those having eczema or
photodermatoses.79 Narrow-spectrum sunscreening agents,
ROLE OF PHYSICIAN/DERMATOLOGIST especially those that absorb only UVB rays, may contribute to
Physicians should be aware of the composition of the development of melanoma at latitudes over 40 degrees
sunscreen agents and the UVA protection factors of due to transmission of UVA rays in large amounts.63
formulations. They should also instruct their patients about
the proper application technique and insist on reapplication. CONCLUSION
Additionally, they should counsel preteens and adolescents Use of sunscreening agents is beneficial in minimizing the
regarding the regular and proper use of broad-spectrum occurrence of skin cancers in people with fair skin. However,
sunscreens. the same effect on Asian skin is debatable, as this skin type is
considered to be resistant to skin cancers. Sunscreen use is
RECENT DEVELOPMENTS advisable in young adults to prevent and minimize other
Newer broad-spectrum chemical agents, such as bis- photodamaging effects. Affordability and proper application
ethylhexyloxyphenol methoxyphenyl triazine (BEMT), techniques are the challenges that must be addressed in
methylene bis-benzotriazolyl tetramethylbutylphenol order to achieve regular sunscreen usage. The authors
(MBBT), and butyl methoxy-dibenzoyl methane (BMDBM), recommend further comparative studies on sunscreens as
have been found to be effective against UVA and UVB rays well as studies on the Indian population, as there is
ranging from 280 to 400nm. These new agents have been insufficient data in this population.
formulated to be more fat soluble (oil soluble in cosmetic
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