From UV Protection to Protection

in the Whole Spectral Range 26

of the Solar Radiation: New
Aspects of Sunscreen
Development

Leonhard Zastrow, Martina C. Meinke,

Stephanie Albrecht, Alexa Patzelt,
and Juergen Lademann

Abstract
Sunscreens have been constantly improving in the past few years. Today,
they provide an efficient protection not only in the UVB but also in the
UVA spectral region of the solar radiation. Recently it could be demon-
strated that 50% of all free radicals induced in the skin due to solar radia-
tion are formed in the visible and infrared spectral region. The good
protective efficacy of sunscreens in the UV region prompts people to stay
much longer in the sun than if they had left their skin unprotected.
However, as no protection in the visible and infrared spectral region is
provided, high amounts of free radicals are induced here that could easily
exceed the critical radical concentration.
This chapter describes how the effect of sunscreens can be extended to
cover also the visible and infrared spectral region of the solar radiation by
adding pigments and antioxidants with high radical protection factors to
the sunscreen formulations.

Keywords
Sun protection • Skin cancer • Reactive oxygen species • Lipid peroxide
radicals • Critical radical concentration • Antioxidants

26.1 Introduction

Solar radiation has been an essential source for the

L. Zastrow (*) • M.C. Meinke • S. Albrecht development of life on earth. It is the basis for vita-
A. Patzelt • J. Lademann
Center of Experimental and Applied Cutaneous min D synthesis in the organism and indispensable
Physiology, Department of Dermatology, Venerology for human wellbeing [1]. However, next to genetic
and Allergology, Charité – Universitätsmedizin preconditions, solar radiation is also the main rea-
Berlin, 10117 Berlin, Germany son for premature skin ageing [2]. High doses of
e-mail: [email protected]
sun radiation incident on the human skin can t­ rigger
© Springer International Publishing AG 2017 311
S. Ahmad (ed.), Ultraviolet Light in Human Health, Diseases and Environment, Advances in
Experimental Medicine and Biology 996, https://doi.org/10.1007/978-3-319-56017-5_26
312 L. Zastrow et al.

processes leading to skin damage extending from 26.2  ree Radical Action
F
sunburn via immunosuppression to even skin can- Spectrum
cer [3, 4]. Among the reasons for the development
of these partially severe skin damages is the pro- In 2009, Zastrow et al. [5] (experimentally deter-
duction of free radicals that has been underesti- mined the action spectrum of free radical formation
mated, so far. These highly reactive molecules are proving for the first time that radical formation is
vital for signalling processes in our body. However, the general biophysical response to radiation in the
it is well established that at high concentrations of range between UVB (280 nm) and near infrared
excess free radicals, molecules that are essential for (NIR 1600 nm). Also the NIR’s radical forming
the function of the cells can be destroyed, e.g. capacity (700–1600 nm) was evidenced in separate
DNA, RNA, proteins and lipids [4]. EPR (electron paramagnetic resonance) spectrom-
Sunscreens contain filter substances with strong etry experiments, whereby it was found that the
protective efficacy against ultraviolet B (UVB radical generation (RG) depends not only on the
280–320 nm) and adequate protection against for- applied NIR irradiation dose but also on the
mation of free radicals in ultraviolet A (UVA 320– increase of the skin temperature related thereto.
400 nm). Recently, it could be demonstrated that The wavelength induced mixtures [6] of short-lived
50% of the free radicals are produced by solar reactive oxygen species (ROS) and long-lived lipid
radiation in the visible (VIS) and infrared (IR) peroxide radicals (LOS) together behave exactly
spectral region [5]. Therefore, ultimately for pre- like the UVA induced free radicals, which are clas-
venting skin cancerogenesis, new concepts need to sified as being carcinogenic. The action spectrum
focus on protecting the human skin in the com- is demonstrated in Fig. 26.1. Although the concen-
plete range of the earth’s solar spectrum, i.e. the tration of the free radicals in the VIS/IR spectral
UV, the VIS and IR spectral regions. The basics of region is lower than that in the UV region, its wave-
these developments are described hereinafter. length range is distinctly larger leading to the for-

0,008

0,007
RGact sp = X.1012 rad / mg per mJ / cm2

0,006

0,005

0,004

0,003

0,002

0,001

0
260 280 300 320 340 360 380 400 420 440 460 480 500 520 540 560 580 600 620 640 660 680 700
Wavelength (nm)

Fig. 26.1 Action spectrum – wavelength dependence for free radical formation in human skin [5]
26 From UV Protection to Protection in the Whole Spectral Range of the Solar Radiation: New Aspects… 313

mation of substantial amounts of free radicals. At the existence of the FRTV, separating the “benefi-
least 50% of the free radicals produced by the sun cially” from “deleteriously” acting free radicals,
originate from the VIS/IR spectral region. could be confirmed by quantitative EPR x-band
spectroscopy [6]. As described in [5–7], spin trap
PBN and spin labeled PCA were used to quantify
26.3 Critical Radical the free radicals. The spin traps DMPO and
Concentration (Free Radical DEPMPO allowed distinguishing ROS from car-
Threshold Value) bon-centred LOS.
Figure 26.2 summarizes the results. With
Using the free radical action spectrum, we calcu- increasing UV + VIS doses a rising number of
lated in 2009 (3) the amount of free radicals ROS/LOS is generated. Up to ~3.5 × 1012 rad/mg
induced by the dose of natural sunlight which is this increase is nearly linear. Once this concentra-
necessary to produce a recommended amount of tion is reached, the gradient of the curve
vitamin D. For estimated 1000 IU daily, a dose of changes – still being linear though clearly lower.
about a quarter of the minimum erythemal dose Further measurements with UV and VIS light
(MED) leads to a number of roughly 3.5 × 1012 alone (2) led to RG values between ~2.8 × 10
12
radicals per mg skin tissue. Based on this standard rad/mg to ~4.0 × 1012 rad/mg, all in the range of
vitamin dose, this amount of ~3.5 × 1012 rad/mg the calculated FRTV.
ROS/LOS represents the tolerated number of free Moreover it could be demonstrated that below
radicals in skin. At that concentration the ROS/ the critical radical concentration (FRTV) the mix-
LOS mixture does not show clinically detectable ture of ROS/LOS is dominated by short-lived
damage indicating that the excess free radicals are ROS. Above the FRTV RG ~ 3.5 × 1012 rad/mg the
still under the control of the antioxidative defense long-lived LOS are dominant. They are well-­known
system. We called this critical radical concentra- as measurable signs of cell destructive processes.
tion that exists on an essential biological endpoint The two circles in Fig. 26.2 show exemplarily this
Free Radical Threshold Value (FRTV). Recently dynamic switch in the free radical mixture.

5,5

5,0

4,5

4,0
RG 1012 rad / mg

3,5

3,0

2,5

2,0 45% 44%

55% 56%
1,5

1,0
0 2000 4000 6000 8000 10000 12000 14000 16000 18000

DOSE UV + VIS mJ / cm2

ROS radicals C-centered radicals

Fig. 26.2 Radical generation (RG) depending on the UV + VIS doses and the radical composition [6]
314 L. Zastrow et al.

26.4 I nfluence of Sunscreen of an adaption of the optical skin parameters to

Application on the Free intense light exposure. This means that after
Radical Formation in Human exposure of the skin to solar radiation the stratum
Skin corneum becomes thicker thus increasing the
absorption and scattering of the sunlight. The
Standard commercial sunscreens contain only second protective mechanism is the reactive
UVB and UVA filters aimed to suppress the increase of melanin production. It is well known
development of sunburn and at the end of a long that people exposing their skin to intense solar
chain of biomolecular processes, skin cancer. radiation get tanned and are therefore better pro-
Today, sunscreens with very high sun protection tected due to increased melanin quantities. The
factors (SPF) are available. People exposing third protective mechanism is supportable by the
themselves to intense direct sunlight after having uptake of antioxidants with a diet rich in fruits
applied sunscreens with an SPF of 30 or 50, and vegetables [8]. These antioxidants strengthen
imagine that they can stay much longer in the sun the skin’s own anti-oxidative defence system,
without being affected by solar-induced damage which neutralizes free radicals before they start
as their skin shows no signs of warning over an damaging the skin.
extended period of time. In addition, the high In principle, these protective mechanisms
protective efficiency of these sunscreens in the are – often nearly unintentionally – integrated
UV spectral region leads to a strongly reduced in modern sunscreens. To our knowledge a
free radical ROS/LOS mixture. In the absence of commercial product stimulating light callosity
sunburn as an unmistakeable warning, applicants does not yet exist. However, sunscreens often
use to over-exposing themselves to solar radia- contain pigments, so called physical filters, e.g.
tion, sometimes up to 10 times longer. As the titanium dioxide or zinc oxide, to increase the
standard commercial sunscreens, however, pro- SPF values. These pigments act as micro mir-
vide no protection in the VIS/IR spectral region, rors in the human skin, reflecting the sunlight
the free radicals being formed in this spectral not only in the UV but also in the VIS/IR spec-
region can easily overcome the critical radical tral regions [9, 10]. In addition, modern sun-
concentration (FRTV). Thus, it is not surprising screens contain antioxidants to protect the UV
that skin cancer incidence is still rising although filters from damage caused by solar radiation
the use of sunscreens exhibiting high SPF values supporting simultaneously the skin’s antioxida-
has become increasingly popular. tive defense system. To elucidate the exact light
protective efficacy of commercial sunscreens,
the Department of Dermatology of the Charité –
26.5  ow We Can Protect Our
H Universitätsmedizin Berlin conducted a study
Skin in the VIS/IR Spectral investigating four sunscreen products, two of
Region of the Solar which were bought in drugstores and the other
Radiation two in supermarkets, for their radical protection
efficiency in the IR spectral region [11]. The
In the UV spectral region, highly efficient UVB experiments were carried out with a water-fil-
and UVA filters are used to protect the human tered infrared lamp at physiological doses. In
skin from being damaged. This strategy is these experiments, the radical formation after
impracticable in the VIS/IR spectral region as IR irradiation was investigated for untreated
suitable filter substances are lacking. Developing and for skin treated with standard COLIPA sun-
a new concept – sunscreen products should reflect screens containing neither pigments nor anti-
the skin natural light defense systems. Three nat- oxidants. Under the same conditions the four
ural protective mechanisms of the skin have to be commercial products were investigated for their
taken into consideration. The first mechanism is radical formation during exposure to IR radia-
the formation of light callosity as an expression tion. The results are presented in Fig. 26.3.
26 From UV Protection to Protection in the Whole Spectral Range of the Solar Radiation: New Aspects… 315

Fig. 26.3 Amount of

free radicals produced 0.4
*
by IR irradiation in
untreated skin, treated
with standard COLIPA
sunscreen and four
commercial sunscreens
*
0.3

Radical formation [a.u.]

[11]

0.2

0.1

0.0
No pre- COLIPA Cream 1 Cream 2 Cream 3 Cream 4
treatment standard

Table 26.1 Radical protection factor of the sunscreens

[11] could penetrate the skin. The situation for
cream 3, which ranged second best, is differ-
RPF
ent. This cream yielded high RPF values but
Standard 22
strongly inferior optical properties compared
Cream 1 47
to cream 4.
Cream 2 61
These results reveal that protection in the
Cream 3 119
VIS/IR spectral region of the solar radiation
Cream 4 40
can be obtained by application of pigments and
antioxidants. While the application of pig-
To explain the obtained results, the radical ments is limited to a concentration of less than
protection factors (RPF) of the five sunscreens 8% of the formulation, antioxidants are appli-
were investigated. The radical protection factor cable even at high concentrations with high
(RPF) describes the number of the by test sub- RPF values.
stance reduced test radicals with RPF = N × 1014
DPPH radicals/mg test substance. For practical
reasons it is useful to present only the real num- 26.6 I ntegrating VIS/IR Protection
ber N. The results are presented in Table 26.1. into Sunscreens
Furthermore, the optical properties, i.e. scat-
tering, reflectance and absorbance of the Taking into consideration the above basics and
­sunscreens were investigated. These results are results, there is no doubt that future sunscreens
summarized in Fig. 26.4. must provide protection not only in the UV but
As can be seen from Fig. 26.3, the best also in the VIS/IR spectral regions. Interestingly,
results were obtained for sunscreen 4. Although while we are discussing the epidemic increase of
this sunscreen exhibited not the best RPF, its skin cancer, in some cultures, sun protection has
optical properties proved highly efficient. As been performed in an optimized way since
the pigments are highly reflecting and scatter- ancient times. Asians, e.g. often use sun umbrel-
ing, only a few photons of the solar radiation las to protect themselves against solar radiation.
316 L. Zastrow et al.

30

25
µs ' cream 4

20 µs ' cream 1
µa, µs' [1/mm]

µs ' cream 2
15

10
µs ' cream 3

5 µs ' standard

µa cream 1-4 + standard

0
600 800 1000 1200 1400 1600 1800
Wavelength [nm]

Fig. 26.4 Optical properties of the five investigated sunscreens [11]

These sun umbrellas shield their users against which are derived from the biological response of
solar radiation in the complete spectral range. In the skin in form of erythema (minimal erythemal
Arab countries people are wearing garments dose MED), were standardised. Later on, it could
which cover their skin almost completely. These be demonstrated that the skin has to be protected
people have been practising light protection also against UVA radiation as this type of radia-
instead of UV protection. tion create excess ROS/LOS which can induce
Taking into account the results of the above skin cancer [2]. Even with persistent pigment
Charité study [11] it may be highlighted that for- darkening (PPD) as measurable parameter for the
mulators of sunscreens have broad room for biological response in this specific region, the
designed products with advanced protection in determination of the efficiency of UVA protec-
VIS/NIR area. An important role for further tion is a topic of ongoing research. Therefore, the
progress in this field plays the EPR spectroscopy, European Commission recommended in 2006
the only method able to detect directly free radi- that sunscreens must provide a 3:1 absorption in
cals [12]. This technique allows optimisation and the UVB and UVA fraction of the solar spectrum
standardisation of sunscreens not only in the UV to be labelled as sunscreen products [13]. This
but also the VIS/IR spectral regions. It is encour- was a foresighted decision, indeed, as the gener-
aging that there is a variety of commercial sun- ally known and well accepted SPF should con-
screens meanwhile being available which claim tinue to be used in the future. But how can the
to provide also protection in the VIS/IR spectral protection against VIS/IR radiation be included
region. in this concept? Specific legislation will have to
be adopted, whereby the protective function in
the VIS/IR spectral region will be determined by
26.7  tandardisation of SPF
S EPR spectrometry.
Values in the VIS/IR Spectral As described earlier in this chapter, people
Region applying sunscreens with a high SPF use to
stay longer in the sun so that in the VIS/IR
Since the first sunscreens were developed in spectral region free radicals can be produced
1933, the efficiency of sunscreen products has at concentrations exceeding the critical radical
always been improving. In 1956, the SPF values, concentration (FRTV). For a sunscreen prod-
26 From UV Protection to Protection in the Whole Spectral Range of the Solar Radiation: New Aspects… 317

uct with a declared SPF of 10, it is to be sup- tection is necessary. Therefore there is an urgency
posed that applicants stay up to 10 times for new innovative concepts, including intelligent
longer in the sun. Now it has to be checked if behaviour in the sun, mimicking natural protec-
the free radicals (ROS/LOS) produced in the tion mechanisms, e.g. by specific modification of
VIS/IR spectral region for an irradiation dose skin reflectance and scattering. The focus of the
of 10 MED are below or above the FRTV. If innovation needs to be put on systems for con-
the concentration proves to be below the trolling the prevention of free radical formation
FRTV, the SPF value could remain unchanged. above the FRTV.
If the radical concentration is found to exceed The protection efficacy, especially in the VIS/
the critical concentration value, the FRTV IR should, as proposed above, find entrance in an
value of 3.5 × 1012 rad/mg of tissue has to be “Integral SPF” giving a realistic exposure recom-
divided by the actual free r­adical concentra- mendation to the applicants.
tion. Subsequently the SPF will be divided by
the obtained quotient.
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