An in vitro systematic spectroscopic examination of thephotostabilities of a random set of commercial sunscreenlotions and their chemical UVB/UVA active agents

Nick Serpone,*a Angela Salinaro,a Alexei V. Emeline,a Satoshi Horikoshi,b Hisao Hidaka b

and Jincai Zhao c

a Department of Chemistry & Biochemistry, Concordia University,1455 de Maisonneuve Blvd. West, Montreal, Quebec, Canada H3G 1MB

b Frontier Research Center for the Global Environment Protection, Meisei University,2–1–1 Hodokubo, Hino, Tokyo 191–8506, Japan

c The Laboratory of Photochemistry, Center for Molecular Sciences, Institute of Chemistry,The Chinese Academy of Sciences, Beijing 100 080, China

Received 1st July 2002, Accepted 25th September 2002First published as an Advance Article on the web 15th November 2002

The photostabilities of a random set of commercially available sunscreen lotions and their active ingredients areexamined spectroscopically subsequent to simulated sunlight UV exposure. Loss of filtering efficacy can occurbecause of possible photochemical modifications of the sunscreen active agents. Changes in absorption of UVA/UVB sunlight by agents in sunscreen lotions also leads to a reduction of the expected photoprotection of humanskin and DNA against the harmful UV radiation. The active ingredients were investigated in aqueous media and inorganic solvents of various polarities (methanol, acetonitrile, and n-hexane) under aerobic and anaerobic conditions.The UV absorption features are affected by the nature of the solvents with properties closely related to oil-in-water(o/w) or water-in-oil (w/o) emulsions actually used in sunscreen formulations, and by the presence of molecularoxygen. The photostabilities of two combined chemical ingredients (oxybenzone and octyl methoxycinnamate)and the combination oxybenzone/titanium dioxide were also explored. In the latter case, oxybenzone undergoessignificant photodegradation in the presence of the physical filter TiO2.

IntroductionSunscreen lotions are meant to prevent skin damage (e.g., sun-burns, skin cancers) while permitting gradual tanning, bothof which are achieved when chemical sunscreens absorb UVB{290–320 nm} and UVA {320–400 nm} sunlight radiation.To preclude sunburns and protect people from serious skindamage, sunscreens must be photostable (ideally 100%) andmust dissipate the absorbed energy efficiently through photo-physical and photochemical pathways that rule out formationof singlet oxygen, other reactive oxygen species, and any otherharmful reactive intermediates. They should not penetrate theskin, and should not be transported into the human cells wherethey may damage DNA. Sunscreens should also minimize theextent of UVB and UVA radiation that might reach DNA incell nuclei. With few exceptions, sunscreens contain chemicalfilters (organic; absorb mostly UVB radiation) and physicalfilters. The latter have been said to block UVB/UVA sunlightthrough reflection and scattering 1 (however, see also ref. 2).A sunscreen active agent widely used for many years wasPABA (p-aminobenzoic acid), which filters out some but notall the UVB radiation. PABA was thought to be an effectiveagent, although harmful side effects were known.3–5 None-theless, PABA continues to appear on the list of approved andpermitted active agents in the United States (Table 1). Active

agents permitted in various other countries may be foundelsewhere.6

Chemical filters are classified into seven groups (Chart 1) andsubdivided into either UVA (benzophenones, anthranilates anddibenzoylmethanes) or UVB (PABA derivatives, salicylates,cinnamates and camphor derivatives) filters. Sunscreen lotionsare typically commercialized as cosmetic products 6 except inthe United States, where they are viewed as over-the-counter(OTC) drugs and thus controlled and regulated by the U.S.Food and Drug Administration (FDA: see Table 1). ChemicalUV filters are almost always used in combination because nosingle active agent, used at levels currently allowed by theFDA,1 provides high enough SPF (sun protection factor)protection or broad-spectrum absorption. Because of photo-instability and possible unfavorable synergistic interactionsbetween these agents, recent restrictions by FDA’s FederalRegister Administration Regulatory Affairs 1 limit the choice ofsuitable combinations of UVB/UVA chemical filters.

The PABA-related 2-ethylhexyl-4-dimethylaminobenzoateester (also known as Escalol 507 and Padimate-O; Table 2) ischemically and structurally similar to the industrial photo-initiator of polymerisation reactions, viz. the ethyl-4-dimethyl-aminobenzoate ester, known to generate carbon-centeredradicals upon illumination (see below).7 Accordingly, padimate-O is also expected to generate similar radicals, which in aerobic

Table 1 List and maximal quantity (wt.%) of some sunscreen active agents allowed in sunscreen products under the US Federal Register (May 21,2000); from ref. 1

PABA (15 %) Homosalate (15 %) Octyl salicylate (5 %) Sulisobenzone (10 %)Avobenzone (3 %) Menthyl anthranilate (5 %) Oxybenzone (6 %) Titanium dioxide (25 %)Cinoxate (3 %) Octocrylene (10 %) Padimate-O (8 %) Trolamine salicylate (12 %)Dioxybenzone (3 %) Octyl methoxycinnamate (OMC; 7.5 %) Phenylbenzimidazole sulfonic acid (4 %) Zinc oxide (25 %)

970 Photochem. Photobiol. Sci., 2002, 1, 970–981 DOI: 10.1039/b206338g

This journal is © The Royal Society of Chemistry and Owner Societies 2002

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Table 2 Chemical structures of some of the organic chemical sunscreen active agents and their commercial names (from ref. 8)

2-ethylhexyl-4-dimethylaminobenzoate

amyl-4-dimethyl-aminobenzoate

ethyl-4-dimethyl-aminobenzoate

4,4�-bis (dimethylamino)benzophenone benzophenone

dibenzoyl-methane

4-tert-butyl-4�-methoxy-dibenzoylmethane

Commercial names

Padimate-O Padimate-A Michler’s ketone Parsol 1789Octyl Dimethyl PABA Parsol AO-PABA Escalol 507 Escalol 506

aqueous media produce peroxy (�OOH) and hydroxyl (�OH)radicals. The latter is a very reactive species, which attacks awide variety of biomolecules, including DNA.8 Padimate-O isalso mutagenic to yeast cells, especially if they are incapableof repairing certain lesions, induces mutations, breaks singleDNA strands, and inflicts other damage most notably at GC(guanine–cytosine) base pairs.9 Unlike PABA, however,padimate-O does not appear to photosensitize formationof thymine dimers. Nonetheless, it is absorbed throughhuman skin and is 32–36% metabolized, the rest remainingunaffected.10 The related amyl ester PABA derivative(padimate-A or Escalol 506, Table 2) is known to causephoto-allergies and other skin problems. It was withdrawn fromthe European market in the late 1980s.11

Concerns with the effects of PABA fueled the search for inertUV protecting agents opaque to both UVA and UVB radiation,biologically and chemically inert, cosmetically acceptable,and compatible with other conventional components of

Chart 1 The seven major groups of chemical sunscreen filterscurrently used in the suncare industry.

sunscreen formulations. Formulators have increasingly turnedto inorganic metal oxides as possible UV sunblocks,12,13 e.g.micronized titanium dioxide (TiO2) particles 14 and ultrafineZnO.

Subsequent to absorption of UVB and UVA sunlightenergy sunscreen agents may undergo photofragmentationand/or photoisomerization as well as energy and/or electrontransfer.15,16 Photoisomerizations may yield species that arelikely less light absorbing than the parent species, and thus lessuseful as sunscreen agents, not to mention that any reactiveintermediate or photoproduct may be potentially toxic toDNA.17,18 Photofragmentation causes the absorbing moleculeto dissociate into reactive fragments (e.g., free radicals) orreactive intermediates. Formation of photoadducts betweenactive agents and thymine and thymidine bases does occur.19,20

Some active agents increase the rate of formation of potentiallycarcinogenic DNA photoproducts (e.g. the cyclobutane-typepyrimidine dimers 21) on irradiation, or else undergo photo-chemical changes that might result in a loss of UVB filteringability.

With PABA being most efficient, many sunscreens also act astriplet state sensitizers that convert 22 harmless triplet oxygen,3O2, into the genotoxic singlet oxygen, 1O2.

17,23 Singlet oxygenand its subsequent reactions can damage skin constituents.Ultimately such reactions can also produce peroxide-typeintermediates that are similar to those formed by reactions withfree radicals.24 Sunscreens of the benzophenone structure yieldendoperoxides depending on the polarity of the solvent.Formation of 1O2 by sunscreen active agents or by constituentsof sunscreen products will have a non-insignificant effect onthe in vivo performance of these products. Consequently, not-withstanding the many studies of the photochemistry of somesunscreen agents (see e.g. refs 20,25), an in-depth and system-atic examination of the photostability and photochemistry ofcommercial sunscreen lotions and their active ingredients isdesirable,20 particularly under conditions that parallel thoseunder practical usage.Special attention must be paid to changesof sunscreen efficacy under sunlight UV exposure.

Most commercial formulations employ a combinationof physical (TiO2 and ZnO) and chemical filters to providebroadband protection over the UVA and UVB regions.12,13 Thecombination octyl methoxycinnamate (OMC)/butylmethoxy-dibenzoylmethane (Parsol 1789; also known as avobenzone)is not recommended 1 because of its photoinstability. Photo-adducts are formed between OMC and photogeneratedfragments of Parsol 1789.14

Table 3 summarizes the active ingredients in three well-known commercial sunscreen lotions. OMC is currently awidely used chemical sunscreen.26 The inert and nontoxic (in the

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Table 3 Typical active ingredients in three commercially popular sunscreen lotions (wt. %)

Sunscreen 1 Sunscreen 2 Sunscreen 3

4-Methylbenzylidine camphor; 6% 4-Methylbenzylidine camphor; 6% Octyl methoxycinnamate; 7.5% Oxybenzone; 5%Parsol 1789; 1% Parsol 1789; 2% Phenylbenzimidazole sulfonic acid triethanolamine salt; 2.3%Mexoryl SX; 1% Mexoryl SX; 2% Titanium dioxide; 3.2 Titanium dioxide; 5 Titanium dioxide; 4.5Pure melanin Vegetable extracts

Parsol 1789 = butylmethoxydibenzoylmethane; Mexoryl SX = terephthalydene dicamphor sulfonic acid.

Table 4 Summary of coded commercial suncreams, the active ingredients contained in sunscreen lotions, and their corresponding SPF numbers

Sunscreen lotion code SPF Active ingredients (as stated on product label) (wt.% loading)

NP1 15 Aloe; octyl methoxycinnamate; oxybenzone; titanium dioxideSN1 19 Ethyl hexyl para-methoxycinnamate, 7.5%; oxybenzone, 5%; 2-phenylbenzimidazole sulfonic acid

triethanolamine salt, 2.3%; titanium dioxide, 4.6%SN2 25 4-Methylbenzylidene camphor, 5%; butylmethoxydibenzoylmethane (Parsol 1789), 2%; terephthalydene

dicamphor sulfonic acid (Mexoryl SX), 1%; titanium dioxide, 2.5%SN3 25 4-Methylbenzylidene camphor, 6%; terephthalydene dicamphor sulfonic acid (Mexoryl SX), 2%;

butylmethoxydibenzoylmethane (Parsol 1789), 2%; titanium dioxide, 5%SN4 25 4-Methylbenzylidene camphor, 6%; terephthalydene dicamphor sulfonic acid (Mexoryl SX), 1%;

butylmethoxydibenzoylmethane (Parsol 1789), 2%; titanium dioxide, 3.2%SN5 15� Octyl methoxycinnamate, 4%; octyl salicylate, 4%; titanium dioxide, 0.65%SN6 20� Octyl methoxycinnamate; 4-methylbenzylidene camphor; titanium dioxide, 2.5%; Vitamin E, 0.3%;

Hydrolipidic complex, 10%SN7 30 Titanium dioxide; butylmethoxydibenzoylmethane (Parsol 1789); triethanolamine salicylate;

terephthalydene dicamphor sulfonic acid (Mexoryl SX)SN8 — Titanium dioxideSN9 15 Titanium dioxideSN10 25 Titanium dioxide, 7.75%; zinc oxide, 1.95%

Table 5 UVA and UVB spectral data of sunscreen active ingredients showing the wavelengths of maximal absorption in the UVB/UVA region andthe molar absorption coefficients (ε) in solvents of different polarity

p-Aminobenzoic acid Octyl methoxycinnamate Padimate-O Oxybenzone

Phenylbenzimidazolesulfonic acid

Solvent λmax/nm ε/M�1 cm�1 λmax/nm ε/M�1 cm�1 λmax/nm ε/M�1 cm�1 λmax/nm ε/M�1 cm�1 λmax/nm ε/M�1 cm�1

H2O 288 16,200 320 14,000 311 (21,500) 321 5,900 302 26,000 285 8,700 CH3OH 277 12,200 308 24,100 311 32,700 325 9,600 304 27,600 287 14,900 CH3CN 285 12,400 307 32,200 309 33,800 325 12,300 306 Saturated solution 287 18,900 C6H14 274 9,200 289 29,100 299 30,300 325 12,600 — Saturated solution 283 11,800 From waterto hexane

∆λ = �14 nm ∆λ = �31 nm ∆λ = �12 nm ∆λ1 = �4 nm∆λ2 = �2 nm

∆λ = �4 nm

dark) metal oxides TiO2 and ZnO attenuate light considerablyin the UVB/UVA regions.1 However, ultrafine sunscreen-gradeTiO2 irradiated with (simulated) sunlight is photocatalyticallyactive and is harmful to supercoiled plasmid DNA.2 Specific-ally, it causes single- and double-strand breaks in DNAplasmids. Photoexcited TiO2 specimens extracted from tencommercial sunscreens were shown earlier 2 to inflict similarDNA damage and similar strand breaks in nuclei of wholehuman skin cells. Titanium dioxide is known to be genotoxic tohuman skin.27 The nature of the oxygen radicals formedon illumination of physical and chemical sunscreens and theextent of damage to the skin and to DNA are thus a matter ofconcern.

Systematic photochemical studies are needed to assess whatchanges occur and what effects they have on DNA whensunscreens are exposed to sunlight UV radiation under con-ditions that parallel those encountered in typical usage ofsunscreen lotions. As a first step in achieving this goal, weexamined spectroscopically and herein report the photostability(or lack thereof ) of some typical commercially available

sunscreen lotions dispersed in neat solvents, as well as thephotostability of five sunscreen active agents in solvents ofvarying polarity from water (to mimic the water-in-oil (w/o)emulsion) to the least polar n-hexane (to mimic the oil-in-water(o/w) emulsion). Ideally, no ingredient used in a cosmetic (orOTC) product should unfavorably affect another. Accordingly,we also examined the photostability of the combinationof two chemical sunscreen agents (oxybenzone/OMC), andoxybenzone/titanium dioxide.

Experimental section

Materials

A random set of ten commercially available sunscreens (Table 4)was procured from commercial retail establishments in Europeand North America. They ranged from the very expensiveto the less expensive of well-known brands. The five chemicalsunscreen agents (Table 5) padimate-O, octyl methoxy-cinnamate (OMC), oxybenzone, and phenylbenzimidazole

972 Photochem. Photobiol. Sci., 2002, 1, 970–981

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sulfonic acid were of reagent grade quality and used as receivedfrom Acros Organics (Fisher), Aldrich, or Sigma. PABA wasalso of reagent grade quality.

SPF determination and photostability of sunscreen lotions

Where lacking, the sun protection factor (SPF) of a sunscreenlotion was estimated in vitro as described by Diffey andRobson 28 throughout the UVA/UVB region (290–400 nm)using a 4 × 4 cm piece of TransporeTM tape (3M Company,St. Paul, MN). The tape was placed over the quartz input opticsof a spectroradiometer (Bentham; wavelength resolution,1 nm). An appropriate volume of the sunscreen lotion toachieve a surface density of 2 µl cm�2 was applied to thetape surface by spotting the sunscreen (ca. 14 mg) over anapplication area of 7 cm2.

The photostability of commercial sunscreen lotions wasascertained by simulating the exposure of real sunscreen lotionsto simulated sunlight (wavelengths longer than 290 nm) usinga solar simulator {CO.FO.MEGRA; 1500 W xenon lamp;irradiance was 48 W m�2; note that for natural sunlight theirradiance is about 60 W m�2 on a sunny day and ca.10 W m�2

on a cloudy day 29}; the temperature inside the simulator wasca. 30 �C. The lotions were dispersed in water, except for NP1,SN9, and SN10, which were first dispersed in a small quantityof acetonitrile followed by addition of water to achieve thedesired loading. The dispersions were continually stirred duringillumination. Changes in light attenuance 30 were recorded on adouble-beam Shimadzu Model UV-2401PC spectrophotometerat various time intervals using a 1 cm quartz cuvette.

The NP1 sunscreen contained the natural product Aloe leafgel. The Aloe leaf gel extract (NP2; 200 mg in powder form)was added to distilled water (200 ml), filtered to removethe green organic precipitate, and then illuminated in thesolar simulator. Attenuance/absorbance changes were recordedspectroscopically as above.

Spectroscopy and photostability of active agents

The photostability of five active agents was examined spectro-scopically: they were (i) p-aminobenzoic acid (PABA); (ii) 2-ethylhexyl-p-methoxycinnamate (octyl methoxycinnamate, orOMC), (iii) the 2-ethylhexyl-ester of N,N-dimethyl-4-amino-benzoic acid (padimate-O), (iv) 2-hydroxy-4-methoxybenzo-phenone (oxybenzone), and (v) 2-phenylbenzimidazole-5-sulfonic acid (PBSA). The light source was an Oriel 1000 W Hg/Xe lamp, and the emitted radiation was filtered through a waterfilter to remove infrared radiation. Appropriate solutions ofthese substrates were made-up in doubly distilled water andin three different spectrograde organic solvents (methanol,acetonitrile, and n-hexane). An air-equilibrated 3 ml solutioncontained in a 1 cm cuvette quartz reactor was stirred andirradiated at wavelengths longer than 290 nm followed byspectroscopic analysis. Unless noted otherwise, the concen-tration of these active ingredients was 8 mg L�1. PBSA was onlyslightly soluble in acetonitrile and n-hexane; the solutions weresaturated in these solvents

The photodegradation of the five UV chemical filters wasalso examined under anaerobic conditions (argon purging for30 min prior to UV illumination) to probe the influence ofmolecular oxygen on the spectra.

The effect of one sunscreen agent on the photostability ofanother when both are exposed to sunlight UV radiation wasinvestigated using a solution (or dispersion) consisting of atypical combination of oxybenzone and OMC, or oxybenzoneand TiO2 (surface-treated Degussa P25; loading, 300 mg L�1).The concentrations of oxybenzone and OMC were also 8 mgL�1. The illumination setup was the same as the one describedabove for the photodegradation of the active agents. Changes inabsorbance (or attenuance) were monitored spectroscopically.

Initial quantum yields of photodegradation (Φi) of the activeagents were estimated spectroscopically in aqueous media or inn-hexane solutions under air-equilibrated conditions for muchless than 10% degradation to avoid interfering absorptionby intermediates and/or products. In our estimates of Φi weassumed that the molar extinction coefficient ε of the primaryproduct(s) is similar to or less than the ε of the sunscreen activeagents at the analyzing wavelength of maximal absorption ineach case. This is not unreasonable as ε of the active agents arefairly high (see Table 5 below). Regardless, Φi’s should be con-sidered as lower limits of the actual quantum yields. Theincident photon flow (1.9 × 10�6 Einstein s�1; that is, ca.1.1 × 1016 photons s�1) of the irradiation source was establishedby Aberchrome-540 actinometry 31 at the appropriate excitationwavelengths (see text below).

Results and discussion

Photostability of commercial sunscreen lotions

Results reported herein pertain to the photostability of sun-creams coded NP1, SN4, SN5, and SN10. Table 4 gives a briefdescription of the sunscreen lotions and lists their SPF factorsand the active ingredients contained in the lotions.

Fig. 1A illustrates the spectral changes of SN5 followingexposure to simulated sunlight. After 2 h there was a 40 % dropin the attenuance around 300 nm. Some scattering was seen atlonger wavelengths caused by finely suspended TiO2 colloidalparticles (loading 0.65% w/w, on product label). The SN5specimen also contained OMC and octylsalicylate. This com-bination displayed maximal UV absorption at 310 nm.

In lotion SN10, the spectral features are due mostly to thetwo physical UV filters TiO2 (loading 7.5% w/w) and ZnO

Fig. 1 (A) Temporal changes in attenuance that occur during thesimulated sunlight UV exposure of the SN5 sunscreen lotion; loading,0.32 g L�1 in air-equilibrated aqueous suspensions. (B) Temporalattenuance changes in the spectrum of the SN10 sunscreen specimen(0.57 g L�1 in air-equilibrated acetonitrile media) during simulatedsunlight UV illumination.

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(1.95% w/w) that cause extensive scattering in the visible regionabove 400 nm (Fig. 1B). The spectra also display a band at 315nm indicating the presence of an organic chemical filter. Aftercorrecting for the extent of scattering, the data showed that thisUVB filter degraded fairly rapidly; ∼95% of the attenuance at315 nm disappeared within 2 h of simulated sunlight exposure.

The sunscreen lotion SN4 contains the UVA absorbersParsol 1789 (2% w/w) and terephthalydenedicamphor sulfonicacid (Mexoryl SX) along with a UVB filter {a camphor deriv-ative}, together with titanium dioxide: see Table 4. Photo-degradation of this lotion led to a 10% decrease in theattenuance at 300 and 360 nm after 2 h displaying an isosbesticpoint around 265 nm. Some new photoproduct(s) were likely tohave been formed that absorbed in the UVC region (λ < 290nm). The spectral features of titanium dioxide in lotion SN4were rather insignificant.

Fig. 2A displays the time-dependent spectral changes in thesunscreen NP1 dissolved in aqueous methanolic media. This

lotion contained TiO2, OMC and oxybenzone as the activeagents. The attenuance of NP1 was reduced by ∼65% after 2 hof simulated sunlight exposure. The SPF factor was reducedaccordingly. Since one of the main active agents was OMC,which also degraded under sunlight exposure (see below), theNP1 lotion was photochemically unstable under practicalconditions. It contains chemical active agents embedded inthe aloe gel (Table 4), an original Brazilian plant juice used incosmetics to heal skin damaged from sunburns. The aloe leafgel extract NP2 contains a natural UV sunscreen whichphotodegraded only slightly (ca. 5% or less after 2 h) onexposure to simulated sunlight (Fig. 2B).

The above results demonstrate that the sunscreen lotions arenot photochemically stable and confirm recent findings ofMaier and coworkers 32 and those of others.33,34 They photo-degrade to produce some unknown photoproduct(s) whoseeffect on human skin remains to be determined. Also, the con-

Fig. 2 (A) Temporal attenuance changes observed during thesimulated sunlight UV illumination of the NP1 sunscreen specimen (1 gL�1) in air-equilibrated aqueous methanolic media (80% water, 20%methanol). (B) Absorbance spectral changes during the simulatedsunlight illumination of the aloe plant gel (NP2 lotion; 1 g L�1) in anair-equilibrated aqueous solution.

centrations of the active UV chemical filters decreased whenexposed to simulated sunlight. This impacts on the relativemerits of the SPF factor, which is strictly defined for UVBradiation.1 The photodegradation witnessed spectroscopicallyfor these emulsions indicates that the absorbed sunlight energyis dissipated through photochemical processes, the nature ofwhich will be the object of in-depth systematic investigations,35

notwithstanding the many but non-exhaustive studies.25 Sufficeto note that reactive intermediates, such as radical species,and various photoproducts formed in illuminated sunscreenlotions 36,37 may cause damage to DNA.

We have already alluded to the notion that the presence ofmolecular oxygen (O2) inevitably yields reactive oxygen (ROS)radical species when sunscreens are exposed to UV radiation.These species react with a variety of organic molecules either byH atom abstraction or by addition across unsaturated bonds.Peroxidation reactions with cellular lipids produce hydro-peroxide products.38 Generated electrons on illuminated TiO2

reduce O2 to superoxide radical anions O2��, which are sub-

sequently in acid-base equilibria with HOO� radicals dependingon the prevailing pH. The O2

�� radical anion is a selectiveoxidant and is relatively unreactive toward most biomolecules.It dismutates in acid media (eqn. (1)) to yield the relatively weakoxidant H2O2,

39 which in turn yields a �OH radical throughthe Fenton-type reaction (2) or through the Haber–Weissreaction (3):

Hydroxyl radicals produced 40 in illuminated sunscreenlotions containing padimate-O, oxybenzone and OMC causeconsiderable damage to DNA inducing strand breaks,2 andlead to cell mutations and cell death. Indirect evidence alsoindicates formation of �OH radicals in illuminated solutions ofpadimate-O.8

Loss of absorption in sunscreen lotions can also be causedby photoisomerization of the active agent, as evidenced bycinnamate 37 and dibenzoylmethane derivatives 15 when UVirradiated (Φ = 0.5–1.0 for OMC 37). The trans form of OMCphotoisomerizes across the ethylenic double bond to yield thecis form, a less efficient UV filter. Non-absorbing degrad-ation products also cause additional decrease in absorbance.Dibenzoylmethane derivatives display loss of absorbanceduring keto/enol tautomerization.

Spectroscopy and photostability of (organic) chemical UVA/UVB filters

A complete understanding of a photoreaction (e.g., photo-degradation) that involves sunscreen lotions requires know-ledge of the events occurring at the molecular level, togetherwith the isolation and identification of intermediate products.A goal of the present study was to obtain useful spectroscopicdata on five sunscreen active agents identified from current (andpast) commercial lotions: (i) PABA, (ii) Padimate-O, (iii) OMC,(iv) Oxybenzone), and (v) 2-phenylbenzimidazole-5-sulfonicacid. Solutions of these active agents in various solvents weresubjected to equivalent UV exposures under air-equilibratedconditions. Temporal absorbance changes were recorded atvarious time intervals in four solvents of different polarity:water, methanol, acetonitrile, and n-hexane since sunscreenlotions consist of water-in-oil (w/o) or oil-in-water (o/w)emulsions. It was imperative to assess the photostability ofthese active ingredients and how photostability changes withsolvent polarity. Additionally, it was relevant to determine therole of oxygen on the photodegradation.

O2�� � O2

�� � 2H� H2O2 � O2 (1)

H2O2 � Fe2� FeOH2� � �OH (2)

O2�� � H2O2 O2 � OH� � �OH (3)

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Table 5 summarizes the UVA and UVB spectral data of thefive active ingredients, listing the wavelengths of maximalabsorption in the UVB/UVA spectral region, and the molarabsorption coefficients(ε) in the respective solvents.OMC is oil-soluble and only slightly miscible with water so that the low εvalue in water represents an estimate. Nonetheless, the molarabsorption coefficient is relatively high (see Table 5). TakingOMC as an example, the absorption maximum in methanoloccurs at 308 nm, blue-shifted to 289 nm in hexane andred-shifted to 320 nm in water. Clearly, sunscreen formulationsof this active agent in highly non-polar media should beavoided since such formulations would display absorptionfeatures that would filter less of the UVB radiation. PABAillustrates a most dramatic example of this feature. We havere-examined this sunscreen agent to provide a benchmark, sinceit has been the one most extensively examined photochemicallyin aqueous media (see e.g. refs. 19 and 41).

p-aminobenzoic acid (PABA)

Fig. 3 illustrates the time-dependent spectra of PABA in water{Fig. 3A; isosbestic points at 231, 256 and 318 nm; onset of UVabsorption at 325 nm}, methanol {Fig. 3B; isosbestic pointsat 252 and 311 nm; onset at 325 nm}, acetonitrile {Fig. 3C;isosbestic points at 205, 214, 227, 257 and 309 nm; onset at 320nm}, and n-hexane {Fig. 3D; isosbestic points at 227, 248 and298 nm; onset at 305 nm} under aerobic conditions. In theleast polar solvent, the onset of absorption of the low energyband is blue-shifted from ca. 325 nm in water to 305 nm; i.e.,to such an extent that PABA no longer absorbs significantUVB radiation. The usefulness of this chemical UV filter insunscreens is critically dependent on the solvent, and thus onthe composition of the vehicle. Other spectroscopic features aresummarized in Table 5. The long wavelength band in n-hexane(274 nm) is red-shifted by ∼14 nm in water (288 nm) witha concomitant increase in intensity. These observations areconsistent with a band originating from π π* electronictransitions.42

It is also evident in both aqueous and non-aqueous mediathat the extent of PABA photodegradation is rather extensive.After 60 min of UV illumination, the order of loss of UV filter-ing ability was hexane (87%) > water (65%) > methanol (60%) >acetonitrile (45%). Moreover there was a significant blue shiftof the UVB band position in methanol (∼15 nm) and inn-hexane (∼20 nm) as degradation progressed {Φ303 ≥ 5 × 10� 3;water; analyzing wavelength, 288 nm}.

Ethylhexyl-N,N-dimethylamino-p-benzoate (padimate-O)

Not unexpectedly, this agent manifests a behavior that parallelsthat of PABA. The absorption band envelope is red-shifted 12nm on increasing solvent polarity (n-hexane to water; Fig. 4 andTable 5). The molar absorption coefficient is relatively high,which impacts significantly on the efficacy of the sunscreenlotion. In keeping with PABA, the longest wavelength absorp-tion is also due to a π π* transition related to the C6H5–C��Ogroup;42 see structure in Table 2, which summarizes similaritiesbetween suncreen structures and well-known carcinogenicsubstances.

Fig. 4 also shows that padimate-O photodegrades in two ofthe solvents used {water (Fig. 4A) and n-hexane (Fig. 4B)} inaccord with earlier findings 43 but contrary to those of Shaathand coworkers who found no degradation of this active agentin polar solvents.44 In n-hexane and acetonitrile solutionsphotodegradation was nearly complete after only 20 min of UVexposure: hexane (97%) ∼ acetonitrile (94%) > water (75%) >>>methanol (15%). Quantum yield in aerobic aqueous media Φ313

≥ 3.6 × 10�2 (analyzing λ, 310 nm). Padimate-O differs fromPABA by the considerably greater blue shift of the UVB 300-nm band with increase in exposure times: from 311 nm to 277nm in water (30 min); 311 nm to 292 nm in methanol (80 min);

309 nm to 266 nm in acetonitrile (30 min); and from 299 nm to259 nm in n-hexane (20 min). These data confirm the significantloss of UVB filtering ability by padimate-O sunscreen on

Fig. 3 Time-dependent absorption spectra of PABA in various air-equilibrated solutions (8 mg L�1; 5.8 × 10�5 M) using solvents from verypolar to non-polar: (A) aqueous media; (B) methanolic media, (C)acetonitrile solution, (D) hexane solution.

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exposure to UV radiation, and this in very short times in certainmedia. Not surprisingly, padimate-O offers little protectionagainst damage to DNA.9

Octyl methoxycinnamate (OMC)

The loss of photostability of OMC in water (A) and n-hexane(B) is displayed in Fig. 5. In all solvents examined, photo-degradation of OMC was rather significant in the most polarsolvent after 30 min of UV exposure: 90% in water; 40% inmethanol; 45% in acetonitrile; and 40% in n-hexane. Nearlycomplete degradation (ca. 95%) occurred in this least polarsolvent (Fig. 5B) after 2 h of illumination. Quantumyields of degradation Φ313 ≥ 4 × 10�2 (water) and Φ313 ≥ 2 × 10�2

(n-hexane); analyzing wavelengths were 320 nm and 290 nm,respectively. Loss of absorption was no doubt caused by sometrans–cis isomerization occurring at the double bond,37 with thecis isomer absorbing less UV radiation, and by formation ofseveral photodegradation products.45

The spectral band positions of OMC are also affected by thenature of the solvent. The 289-nm band in n-hexane isred-shifted by nearly 31 nm to 320 nm in water (Table 5). Thisred shift is in keeping with π π* parentage.42 As well, the shiftin absorption in aerobic aqueous media from 320 nm to ∼280nm after 30 min of UV exposure is notable in terms of loss ofUV filtering ability.

Oxybenzone

The spectral behavior of UV-exposed oxybenzone solutions inwater (A) and in n-hexane (B) is summarized in Fig. 6. Com-pared to the three previous active agents, oxybenzone is some-what photochemically stable in acetonitrile degrading only byca. 5–10% after 2 h of exposure, followed by ∼15% in n-hexane

Fig. 4 Temporal spectral changes occurring during the UVB/UVAirradiation of padimate-O (loading, 8 mg L�1) under aerobic conditionsin (A) water, (B) hexane.

and ca. 20% in water. However, it is particularly unstable inmethanol, photodegrading almost completely (ca. 90%) after2 h. Acetonitrile or n-hexane solutions of this agent producedno new absorbing photoproducts.46 Quantum yields ofphotodegradation are Φ334 ≥ 3.1 × 10�5 in n-hexane and Φ334 ≥1.3 × 10�4 in water under otherwise identical conditions(analyzing wavelength, 320 nm). The spectral features ofoxybenzone are not greatly affected by the nature of the solvent(Table 5).

By comparison, the related benzophenone system displaystwo major bands (in ethanol); an intense π π* band at280 nm and a less intense n π* band at 325 nm.42 The formerband is expected to red-shift significantly from non-polar topolar solvents, whereas the 325-nm band blue-shifts withincrease in solvent polarity.42 Consistent with this, the π π*band of OMC is significantly red-shifted from 289 nm inn-hexane to 320 nm in water (Table 5), whereas for oxybenzonethe two bands in the UVB/UVA region remain somewhatinvariant with changes in solvents. We attribute the oxybenzonefeature at 283–287 nm also to π π* transitions, and thefeature at 321–325 nm to n π* electronic transitions (Fig. 6and Table 5).

Phenylbenzimidazole sulfonic acid (PBSA)

The temporal course of the photodegradation of this agent inaqueous (A) and acetonitrile (B) media is illustrated in Fig. 7. Itis nearly insoluble in non-polar solvents (n-hexane), and thusof limited usefulness in water-based (w/o) emulsions. Thephotodegradation of PBSA is particularly fast and extensivein water (∼90% after only 10 min of UV illumination). Inacetonitrile it is ca. 50% after only 20 min of UV exposure andca. 70% complete after 2 h. The degradation is also significantin methanol.

Fig. 5 Temporal spectral changes occurring during the UVB/UVAirradiation of octyl methoxycinnamate (OMC loading, 8 mg L�1) underaerobic conditions in (A) water, (B) hexane.

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Table 5 shows no wavelength shift for the UVB absorptionspectral feature of this sulfonic acid, regardless of the nature ofthe solvent. The relevant band around 302–304 nm is likely ofπ π* parentage.

Influence of molecular oxygen on the photostability of chemicalUVB/UVA filters

Exposure of PABA to UVB radiation in aerobic aqueous mediacaused ∼60% of PABA to degrade after 1 h (Fig. 3A), comparedto 55% in anaerobic media (Fig. 8A). In the latter case, the278 nm band blue shifted to 263 nm with irradiation time,unlike the temporal behavior seen in Fig. 3A. This callsattention to a reaction between PABA and molecular oxygento yield 1O2 (see below).18 A different photochemistry takesplace under air-equilibrated conditions. Moreover, PABA’s lowenergy band blue-shifted 10 nm from aerobic to anaerobicmedia.

UV-illuminated PABA is a good photosensitizer yielding1O2,

18 and is also an efficient sink for this species which causesPABA to self-destruct; k = 8.6 × 108 M�1s�1.47 UV photolysis ofPABA also generates aqueous electrons, e�

aq (eqn. (4)) 36 and H

atoms. Scavenging of the electron by O2 yields the O2�� radical

anion (eqn. (5)), which dismutates (eqn. (1)) and ultimatelyproduces the reactive hydroxyl radical �OH (reaction 3). Freeradicals probably play an important role in the phototoxic and

Fig. 6 Temporal spectral changes occurring during the UVB/UVAirradiation of oxybenzone (loading, 8 mg L�1) under aerobic conditionsin (A) water, (B) hexane.

(4)

O2 � e�aq O2

�� (5)

photo-allergenic responses elicited by this OTC drug in someindividuals.

The effect of oxygen when an aqueous solution of padimate-O (8 mg L�1) is exposed to UV radiation is seen on comparingthe spectra of Fig. 4A with those of Fig. 8B. This active agentdegrades faster under aerobic conditions (Fig. 4A; 55% in10 min and 80% after 30 min) than in the absence of molecularoxygen (Fig. 8B; 20% in 10 min). Padimate-O also appears tophotosensitize formation of singlet oxygen,1O2.

18

The photodegradation of OMC (8 mg L�1) on illuminationwith UVB/UVA radiation and its dependence on oxygen inaqueous media is illustrated in Fig. 5A (aerobic) and Fig. 8C(anaerobic; Ar purging for ca. 30 min). In anaerobic media, themain absorption band red-shifted by nearly 8 nm and was lessintense. OMC photodegraded faster in the presence of oxygen(85% after 20 min of UV exposure) in comparison to 65% inanaerobic media (20 min); compare Figs. 5A and 8C. Moreover,the intermediate product(s) (note the 230 nm band) also photo-degraded. The two sets of spectra of Figs. 5A and 8C showconsiderable variations in spectral behavior inferring a differentphotochemistry takes place.

Figs. 6A and 8D compare the oxygen dependence of thephotodegradation of oxybenzone under aerobic and anaerobicconditions, respectively. Photodegradation is about three timesslower in the absence of oxygen (15% after 260 min of UVexposure) compared to 50% in aerobic media (260 min).

The photodegradative behavior of phenylbenzimidazolesulfonic acid in aqueous media with (Fig. 7A) and withoutoxygen (Fig. 8E) also showed substantial differences. In aeratedaqueous media, ca. 85% degraded after only 10 min of UVexposure; considerably less of this agent degraded (ca. 10%)after this time under anaerobic conditions. Evidently, oxygen isconverted into some reactive oxygen species such as singletmolecular oxygen 1O2, and superoxide radical anions O2

� �

Fig. 7 Temporal spectral changes occurring during the UVB/UVAirradiation of phenylbenzimidazole sulfonic acid (loading, 8 mg L�1)under aerobic conditions in (A) water, (B) acetonitrile.

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Fig. 8 Temporal spectral changes occurring during the UVB/UVA irradiation of sunscreen active agents (loading, 8 mg L�1) in aqueous mediaunder anaerobic conditions: (A) PABA, (B) padimate-O, (C) OMC, (D) oxybenzone, and (E) PBSA.

and �OH radical species as evidenced by spin-trap ESRtechniques.48 This sunscreen is also an effective photosensitizerfor DNA damage when exposed to natural sunlight UVBradiation.48,49 It induces formation of piperidine-labile cleavagesites that chart rather exclusively positions of guanine residues.The pattern of attack on single-stranded DNA is similarto photooxidation by singlet oxygen. Accordingly, the photo-sensitizing features of this sunscreen active agent can detractfrom its usefulness as a UV filter.49

Clearly, oxygen-dependent photodegradations of sunscreenactive agents likely involve the cytotoxic 1O2 species, an effectiveoxidant of most (bio)molecules relative to ground-state molec-ular oxygen as reactions of 1O2 with singlet state (bio)moleculesare spin allowed. The energy required to promote 3O2 to singletoxygen 1O2 is 22.7 kcal mol�1 (94.9 kJ mol�1).50 The triplet stateenergies of PABA is 75 kcal mol�1 (313.5 kJ mol�1) and that ofOMC is 57 kcal mol�1 (238.3 kJ mol�1).51 Evidence of singletoxygen formation was also reported for padimate-O.18a To ourknowledge, the energy of the triplet excited state of oxybenzonehas not been reported, but Allen and coworkers 18a found nosignificant formation of singlet oxygen with this sunscreen.

Synergy between two sunscreen active agents

Oxybenzone offers UVB/UVA broadband protection. However,its molar absorption coefficient (γ) is rather small relative tothat of other active agents (see Table 5), so that higher con-centrations are needed to offer the appropriate broadbandprotection especially against UVA radiation. An increase inconcentration causes it to crystallize and causes photo-allergenic responses in some individuals.52

Since sunscreen lotions contain more than one active agent,the photochemical synergy between UVB/UVA radiation filtersneeds to be assessed when two (or more) chemical and physicalsunscreens are combined into a single solvent vehicle.53 Thespectral behavior of the combination oxybenzone/OMC (8 mgL�1 each) in air-equilibrated aqueous media is summarized inFig. 9A. UV absorption by the combined agents is greater thanthat of the single components for the same concentrations (seeFigs. 5A and 6A). Since ε for oxybenzone (5,900 M�1 cm�1 inwater and 12,600 M�1 cm�1 in n-hexane; Table 5) is smaller than

for OMC (14,000 M�1 cm�1 and 29,100 M�1 cm�1, respectively),the principal sunscreen agent in this mixture was OMC. Signifi-cant photodegradation of OMC occurred in less than 15 min of

Fig. 9 (A) Temporal spectral changes occurring during the UVB/UVAirradiation of the combination octyl methoxycinnamate/oxybenzone(loading of each component, 8 mg L�1) in air-equilibrated aqueousmedia. (B) Temporal spectral changes occurring during the UVB/UVAirradiation of the combination of oxybenzone (loading, 8 mg L�1) andtitanium dioxide (surface-treated Degussa P25; loading, 300 mg L�1) inan air-equilibrated aqueous dispersion.

978 Photochem. Photobiol. Sci., 2002, 1, 970–981

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UV exposure in aerobic aqueous media {compare Fig. 5A(OMC alone) with Fig. 9A (OMC/oxybenzone)} leavingoxybenzone as the sole UV filter remaining in solution. Thelatter is more photostable than OMC, degrading by ∼50% after260 min of irradiation (4.3 h; see Fig. 6A). In the presence ofOMC ∼60% of oxybenzone degraded after 260 min (compareFig. 6A to Fig. 9A).

The combination oxybenzone/titanium dioxide was exam-ined in aerobic aqueous media (Fig. 9B) and is compared withthat of oxybenzone alone (Fig. 6A) under otherwise identicalconditions. About 70% of oxybenzone degraded after 20 minof UV exposure (Fig. 9B), whereas it necessitated 260 min toachieve 50% degradation (Fig. 6A). This is not surprising sinceUV illumination of TiO2 yields conduction band electrons andvalence band holes (eqn. (6)), which interact with surface-adsorbed molecular oxygen to yield superoxide radical anions,O2

�� (eqn. (7)), and with water to produce the highly reactive�OH radicals (eqn. (8)), respectively. The latter radical speciesare well known to oxidize a large number of organic substrates(eqn. (9)),54 including DNA.2

Concluding remarksThe photostability of the chemical UV filters padimate-O,oxybenzone, octyl methoxycinnamate, and phenylbenzimid-azole sulfonic acid was examined in very polar to non-polarsolvents (e.g., water, mehanol, acetonitrile, and n-hexane).Photostability is a prime requirement for a commercialsunscreen to provide protection against the harmful effects ofUVA and UVB sunlight radiation. Although many sunscreenproducts have been widely claimed to be photostable up untilrecently (3–4 years ago), the many recent patents and reports(see e.g. ref. 55), which describe ways to improve the photo-stability of the active agents and the lotions suggest otherwise.The results obtained in this study lead to two importantconclusions.

(1) Commercial sunscreen lotions are not photochemicallystable (see also ref. 56). This impacts negatively on the SPFfactor and on the efficacy of commercial sunscreens to providethe claimed total protection of human skin against UVB/UVAharmful radiation. The available evidence shows that com-mercial sunscreen formulations lose a large part of their activityafter only ∼60 min of exposure to sunlight UV radiation.24,33

(2) The active agents in sunscreens are not photochemicallystable (see also refs. 32,34 and 57) in aerobic neat solvent mediaof various polarities. The temporal spectral behavior of theseagents suggests significant photochemistry when exposed toUV, a photochemistry that is likely to be solvent dependent 58

and controversial as the present data contrast with earlierreports.59,60 In this regard, some workers have reported thatoxybenzone, padimate-O and Parsol 1789 (among others) 59 andPABA 60 display very good photostability when exposed to UVradiation. The present results show otherwise.

Despite the numerous reports,20,25 additional in-depth,systematic and detailed studies are necessary to ascertain themodes by which the absorbed sunlight energy is dissipated inactual sunscreens. The photochemical changes that take placewhen a chemical filter is exposed to UVB/UVA sunlight need tobe determined under conditions that parallel those encounteredin typical usage of sunscreen lotions. The present report is but afirst step toward achieving this goal. There is also a need to

TiO2 � hν e�cb � h�

vb (6)

e�cb � O2(ads) O2

�� (7)

h�vb � Ti–OH2 �OHads � H� (8)

�OHads � substrate photooxidized products (9)

develop additional chemical filters 61 that, while providing theneeded broadband UV protection, will also be photochemicallystable and non-toxic to human skin and DNA. Photoinduceddecomposition will always be a significant path for loss ofsunscreen efficacy. TiO2 specimens currently used in com-mercial sunscreen lotions are too photocatalytically active.They have been shown to cause considerable damage to DNA.2

Accordingly, their photocatalytic activity needs to be severelycurtailed if they are to be used safely in suncare products.Surface coating of TiO2 and ZnO with other metal oxides(alumina and silica) has been reported, but there is no indi-cation that the specimens were tested against DNA.62 A studydescribing sunscreen-grade titanium dioxide specimens that areharmless to DNA and yeast cells will be reported elsewhere.

Acknowledgements

We are grateful to the Natural Sciences and EngineeringResearch Council of Canada for support of this work (A5443;to NS). Studies carried out in Tokyo are sponsored by theFrontier Research Center as well as Grants-in-Aid (No.10640569; to HH) from the Japanese Ministry of Education,whereas the research carried out in Beijing is supported by theNational Natural Science Foundation of China (No.29677019and No.29725715; to JZ) and the Foundation of the ChineseAcademy of Sciences.

References1 Sunscreen Drug Products for Over-the-Counter Human Use; Final

Monograph, Federal Register 64 27666, U.S. Food and DrugAdministration, Rockville, MD, 2000, http://www.cfsan.fda.gov/∼lrd/fr990521.html.

2 R. Dunford, A. Salinaro, L. Cai, N. Serpone, S. Horikoshi,H. Hidaka and J. Knowland, Chemical oxidation and DNA damagecatalyzed by inorganic sunscreen ingredients, FEBS Lett., 1997, 418,87–90.

3 N. D. M. Hodges, S. H. Moss and D. J. G. Davies, The sensitizingeffect of a sunscreening agent, p-aminobenzoic acid, on nearUV induced damage in a repair deficient strain of Escherrichia coli,Photochem. Photobiol., 1977, 26, 493–498.

4 B. M. Sutherland, p-Aminobenzoic acid-sunlamp sensitizationof pyrimidine dimer formation and transformation in human cells,Photochem. Photobiol., 1982, 36, 95–97.

5 J. C. Sutherland and K. P. Griffin, p-Aminobenzoic acid cansensitize the formation of pyrimidine dimers in DNA: directchemical evidence, Photochem. Photobiol., 1984, 40, 391–394.

6 (a) K. Klein, Encyclopedia of UV absorbers for sunscreen products,Cosmet. Toiletries, 1992, 107, 45–55; (b) N.J. Lowe and N.A. Shaath,Sunscreens: Development, evaluation and regulatory aspects,Cosmet. Sci. Technol. Ser., 1990, 10, 370.

7 M. Forster and R. E. Hester, Photoionization of dimethyl-aniline and of the donor-aromatic-acceptor moleculesp-(CH3)2NC6H5R, R��CN, COOEt, CHO, NO2, in glasses of ethanoland ethanol/water at 77–125 K, J. Chem. Soc., Faraday Trans. 2,1981, 77, 1521–1534.

8 J. Knowland, E. A. McKenzie, P. J. McHugh and N. A. Cridland,Sunlight-induced mutagenicity of a common sunscreen ingredient,FEBS Lett., 1993, 324, 309–313.

9 P. J. McHugh and J. Knowland, Characterization of DNA damageinflicted by free radicals from a mutagenic sunscreen ingredient andits location using an in vitro reversism assay, Photochem. Photobiol.,1997, 66, 276–281.

10 G. E. Kenney, A. Sakr, J. L. Lichtin, H. Chou and R. L. Bronangh,In vitro skin absorption and metabolism of Padimate-O and anitrosamine formed in Padimate-O-containing cosmetic products,J. Soc. Cosmet. Chem., 1995, 46, 117–127.

11 Off. J. Eur. Commun. L, March 8, 1989, L64, pp. 10–12.12 B. Catlow, Formulating of sunscreen with ultrafine titanium dioxide,

Seifen Oele Fette Wachse, 1993, 119, 497–500.13 Formulators Fine-Tune TiO2-Based Screens, Manuf. Chem., 1993,

64, 2633.14 W. Johncock, Cosmet. Toiletries, 1999, 114, 75–80.15 (a) A. Deflandre and G. Lang, Photoisomerization of benzylidine

camphor and derivatives, Cosmet. Toiletries, 1988, 103, 69–75; (b)A. Deflandre and G. Lang, Photostability assessment of sunscreens.

Photochem. Photobiol. Sci., 2002, 1, 970–981 979

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ishe

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15

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, Mon

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Benzylidine camphor and dibenzoylmethane derivatives, Int. J.Cosmet. Sci., 1988, 10, 53–62.

16 (a) I. Andrae, A. Bringhen, F. Boehm, H. Gonzenbach, T. Hill,L. Mulroy and T. G. Truscott, A UVA filter (4-tert-butyl-4�-methoxydibenzoylmethane): photoprotection reflects photo-physical properties, J. Photochem. Photobiol. B, 1997, 37, 147–150;(b) M. Dubois, P. Gilard, P. Tiercet, A. Deflandre and M. A.Lefebbre, Photoisomerization of the sunscreen filter PARSOL1789, J. Chim. Phys. Phys-Chim. Biol., 1998, 95, 388–394; (c) I. Beck,A. Deflandre, G. Lang, R. Arnaud and J. Lemaire, Study of thephotochemical behavior of sunscreens – benzylidine camphor andderivatives, Int. J. Cosmet. Sci., 1981, 3, 139–152; (d ) I. Beck,A. Deflandre, G. Lang, R. Arnaud and J. Lemaire, Study of thephotochemical behavior of sunscreens-benzylidine camphorand derivatives. II. Photosensitized isomerization by aromaticketones and deactivation of the 8-methoxypsoralen triplet state,J. Photochem., 1985, 30, 215–227.

17 B. Epe, Genotoxicity of singlet oxygen, Chem. Biol. Interact., 1991,80, 239–260.

18 (a) J. M. Allen, C. J. Gossett and S. K. Allen, Photochemicalformation of singlet molecular oxygen in illuminated aqueoussolutions of several commercially available sunscreen active agents,Chem. Res. Toxicol., 1996, 9, 605–609; (b) J. M. Allen, C. J. Gossettand S. K. Allen, Photochemical formation of singlet molecularoxygen (1O2) in illuminated aqueous solutions of p-aminobenzoicacid (PABA), J. Photochem. Photobiol. B, 1996, 32, 33–37.

19 (a) A. A. Shaw, L. A. Wainschel and M. D. Shetlar, Thephotochemistry of p-aminobenzoic acid, Photochem. Photobiol.,1992, 55, 647–656; (b) A. A. Shaw, L. A. Wainschel andM. D. Shetlar, Photoaddition of p-aminobenzoic acid to thymineand thymidine, Photochem. Photobiol., 1992, 55, 657–663.

20 B. S. Martincigh, J. M. Allen and S. K. Allen, Sunscreens: Themolecules and their photochemistry, in Sunscreen Photobiology,ed. F. P. Gasparro, Springer-Verlag, New York, 1997, pp. 11–45.

21 Photochemistry and Photobiology of Nucleic Acids, ed. S. Y. Wang,Academic Press, New York, 1976, vol. I.

22 (a) W. C. Dunlap, M. Inoue, M. Kashiba-Iwatsuki, M. Yamaguchiand K. Tomita, Uric acid photooxidation assay: in vitro comparisonof sunscreening agents, Int. J. Cosmet. Sci., 1998, 20, 1–18; (b)A. Cantrell, D. J. McGarvey, L. Mulroy and T. G. Truscott, Laserflash photolysis studies of the UVA sunscreen Mexoryl SX,Photochem. Photobiol., 1999, 70, 292–297.

23 A. Stari and A. Sarasin, Ultraviolet A- and singlet oxygen-inducedmutation spectra, Methods Enzymol., 2000, 319, 153–165.

24 M. M. Rieger, Photostability of cosmetic ingredients on the skin,Cosmet. Toiletries, 1997, 112, 65–72.

25 (a) A. Cantrell, D. J. McGarvey and T. G. Truscott, Photochemicaland photophysical properties of sunscreens, Neth. Compr. Ser.Photosci., 2001, 3, 495–519; (b) C. Bonda and P. Marinelli,The photochemistry of sunscreen photostability, Agro Food Ind.Hi-Tech, 2000, 11, 29–31; (c) N. A. Shaath, The chemistry ofsunscreens, Cosmet. Toiletries, 1986, 101, 55–70.

26 N. A. Shaath, Photochemistry and Photostability of SunscreenComponents, Mixtures, and Products, Discussion of thePhotochemistry and Photobiology of Sunscreens: Public Meetingand Reopening of the Administrative Record, U.S. Food and DrugAdministration, Rockville, MD, 1996.

27 Y. Nagakawa, S. Wakuri, K. Sakamoto and N. Tanaka, Thephotogenotoxicity of titanium dioxide particles, Mutat. Res., 1997,394, 125–132.

28 B. L. Diffey and J. Robson, A new substrate to measure sunscreenprotection factors throughout theultraviolet spectrum, J. Soc.Cosmet. Chem., 1989, 40, 127–133.

29 H. Hidaka, H. Kubota, M. Graetzel, E. Pelizzetti and N. Serpone,Photodegradation of surfactants II. Degradation of sodiumdodecylbenzenesulfonate catralyzed by titanium dioxide particles,J. Photochem., 1986, 35, 219–230.

30 (a) J. W. Verhoeven, Glossary of terms used in photochemistry, PureAppl. Chem., 1996, 68, 2223–2286; (b) N. Serpone and A. V. Emeline,Suggested terms and definitions in photocatalysis and radiocatalysis,Int. J. Photoenergy, 2002, 4, 91–131.

31 The procedure and protocol used were suggested by AberchromicsLtd., University of Wales Cardiff, Wales.

32 H. Maier, G. Schauberger, K. Brunnhofer and H. Honigsmann,Change of ultraviolet absorbance ofsunscreens by exposure tosolar-simulated radiation, J. Invest. Dermatol., 2001, 117,256–262.

33 K. Bredholt, T. Christensen, M. Hannevik, B. Johnsen, J. Seimand J.B. Reitan, Effects of sunscreening agents and reactionswith ultraviolet radiation, Tidsskr. Nor. Laegeforen., 1998, 118,2640–2645.

34 J. M. Allen, S. K. Allen and B. Lingg, Photostabilities of several

chemical compounds used as active ingredients in sunscreens, Spec.Publ. R. Soc. Chem., 1998, 225, 171–181.

35 N. Serpone and A. Albini, work in progress.36 C. F. Chignell, B. Kalyanaraman and R. P. Mason, Spectroscopic

studies of cutaneous photosensitizing agents. I. Spin trapping ofphotolysis products from sulfanilamide, 4- aminobenzoic acid, andrelated compounds, Photochem. Photobiol., 1980, 32, 563–571.

37 (a) P. Morliere, O. Avice, T. S. Melo, L. Dubertret, M. Giraud andR. Santus, A study of the photochemical properties of somecinnamate sunscreens by steady-state and laser flash photolysis,Photochem. Photobiol., 1982, 36, 395–399; (b) J. K. Broadbent,B. S. Martincigh, M. W. Raynor, L. F. Salter, R. Moulder, P. Sjobergand K. E. Markides, Capillary supercritical fluid chromatographycombined with atmospheric pressure chemical ionization massspectrometry for the investigation of photoproduct formationin the sunscreen absorber 2-ethylhexyl-p-methoxycinnamate,J. Chromatogr., 1996, 732, 101–110.

38 B. Halliwell and J. M. C. Gutteridge, Free Radicals in Biology andMedicine, Clarendon Press, Oxford, 2nd edn., 1995, pp. 1–20.

39 D. T. Sawyer, Oxygen Chemistry, Oxford University Press, NewYork, 1991, pp. 120–160.

40 M. Gulston and J. Knowland, Illumination of human keratinocytesin the presence of the sunscreen ingredient Padimate-O and throughan SPF-15 sunscreen reduces direct photodanage to DNA butincreases strand breaks, Mutat. Res., 1999, 444, 49–60.

41 F. P. Gasparro, UV-induced photoproducts of para-aminobenzoicacid, Photodermatology, 1985, 2, 151–157.

42 N. J. Turro, Modern Molecular Photochemistry, Benjamin/Cummings, Menlo Park, CA, 1978.

43 C. D. M. Ten Berge and C. H. P. Bruins, Synopis-photochemistry ofsunscreens. II. Photochemistry of methyl p-dimethylaminobenzoate,J. Soc. Cosmet. Chem., 1974, 25, 263–269.

44 N. A. Shaath, H. M. Fares and K. Klein, Photodegradation ofsunscreen chemicals: Solvent considerations, Cosmet. Toiletries,1990, 105, 41–44.

45 (a) A. Schrader, J. Jakupovic and W. Baltes, Photochemical studieson trans-3-methyl-4-methoxycinnamate, J. Soc. Cosmet. Chem.,1994, 45, 43–52; (b) N. Tarras-Wahlberg, G. Stenhagen, O. Larko,A. Rosen, A.-M. Wennberg and O. Wennerstrom, Changes inultraviolet absorption of sunscreens after ultraviolet irradiation,J. Invest. Dermatol., 1999, 113, 547–553.

46 N. M. Roscher, M. K. O. Lindemann, S. B. Kong, C. G. Cho andP. Jiang, Photodecomposition of several compounds commonlyused as sunscreen agents, J. Photochem. Photobiol. A, 1994, 80,417–421.

47 J. M. Allen, S. Engenolf and S.K. Allen, Rapid reaction of singlermolecular oxygen (1O2) with p-aminobenzoic acid (PABA)in aqueous solution, Biochem. Biophys. Res. Commun., 1995, 212,1145–1151.

48 J. J. Inbaraj, P. Bilski and C. F. Chignell, Photophysical andphotochemical studies of 2-phenylbenzimidazole and UVBsunscreen 2-phenylbenzimidazole-5-sulfonic acid, Photochem.Photobiol., 2002, 75, 107–116.

49 C. Stevenson and R. J. H. Davies, Photosensitization of guanine-specific DNA damage by 2- phenylbenzimidazole and the sunscreenagent 2-phenylbenzimidazole-5-sulfonic acid, Chem. Res. Toxicol.,1999, 12, 38–45.

50 W. H. Koppenol and J. Butler, Energetics of interconversionreactions of oxyradicals, Adv. Free Radical Biol. Med., 1985, 1,91–131.

51 H. Gonzenbach, T. J. Hill and T. G. Truscott, The triplet energylevels of UVA and UVB sunscreens, J. Photochem. Photobiol. B,1992, 16, 377–379.

52 E. Knobler, L. Almeida, A. M. Ruzkowski, J. Held, L. Harber andV. DeLeo, Photoallergy to benzophenone, Arch. Dermatol., 1989,125, 801–804.

53 W. Johncock, Formulation of sunscreens. Favorable and unfavorableinteractions, Cosmet. Technol. (Milano), 2000, 3, 25–31.

54 (a) S. Horikoshi, N. Watanabe, M. Mukae, H. Hidaka andN. Serpone, Mechanistic examination of titania-photocatalyzedoxidation of ethanolamines, New J. Chem., 2001, 25, 999–1005;(b) A. Emeline, A. Salinaro, V. K. Ryabchuk and N. Serpone,Photo-induced processes in heterogeneous nanosystems. Fromphotoexcitation to interfacial chemical transformations, Int. J.Photoenergy, 2001, 3, 1–16; (c) N. Serpone and E. Pelizzetti, Solarphotochemical remediation of air and water, in Photoconversion ofSolar Energy – Photochemical and Photoelectrochemical Approaches,ed. M. D. Archer and A. J. Nozik, Imperial College Press, London,vol. 3, ch. 17, 2002, in press.

55 See for example, (a) M. S. Reisch Spotlight on Sunscreens, Chem.Eng. News, December 3, 2001, pp. 25–29; (b) E. Chatelain andB. Gabard, Photostabilization of butyl methoxydibenzoylmethane

980 Photochem. Photobiol. Sci., 2002, 1, 970–981

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(Avobenzone) and ethylhexyl methoxycinnamate by bis-ethylhexyloxyphenol methoxyphenyl triazine (Tinosorb S), a newUV broadband filter, Photochem. Photobiol., 2001, 74, 401–406; (c)S. Scalia, S. Villani and A. Casolari, Inclusion complexation of thesunscreen agent 2- ethyl hexyl-p-dimethylaminobenzoate withhydroxypropyl β-cyclodextrin: effect of photostability, J. Pharm.Pharmacol., 1999, 51, 1367–1374; (d ) G. Birrenbach (Spirig PharmaA.-G., Switzerland), Photostabilization of dibenzoyl- methanederivatives using 2,4-bis[[4-(2-ethylhexyloxy)-2-hydroxy]phenyl]-6-(4-methoxy- phenyl)-1,3,5-triazine, Patentschrift (Switz.), CH2000–933, 2000; (e) (Bio Sources Industries S.r.l., France), Methodfor photostabilizing butylmethoxydibenzoyl- methane, and its usein sunscreen compositions, Fr. Pat. Appl., FR 99–14450 19991117;( f ) D. Candau and A.-M. Pisson (L’Oreal, France), Process for thephotostabilization of sunscreens derived from dibenzoylmethane byan insoluble organic sunscreen, Eur. Pat. Appl., No. EP 1093797 A1,2001; (g) N. Lapidot, S. Magdassi, D. Avnir, C. Rottman, O. Gans,and A. Seri-Levy (Sol-Gel Technologies Ltd., Israel), A method forobtaining photostable sunscreen compositions, US Pat. Appl., US1999–136030, 1999; (h) C. Bonda and D. C. Steinberg, A newphotostabilizer for full spectrum sunscreen, Cosmet. Toiletries, 2000,115, 37–45; (i) J. N. Thorel, Method for photostabilization of 4-tert-butyl-4�-methoxydibenzoylmethane and sunscreen compositions, Fr.Pat. Appl., FR 99–8343, 2000; ( j ) S. Chodorowski, F. X. Quinn andC. Sanchez (L’Oreal, Fr.), Method for improving UV radiationstability of photosensitive sunscreen filters, PCT Int. Appl., WO 2000-2000FR2688 20000928, 2001.

56 A. Kammeyer, W. Westerhof, P.A. Bolhuis, A.J. Ris andE.A. Hische, The spectral stability of several sunscreening agentson stratum corneum sheets, Int. J. Cosmet. Chem., 1987, 9,125–136.

57 D. N. Biloti, M. M. dos Reis, M. M. C. Ferriera and F. B. T. Pessine,Photochemical behavior under UVA radiation of β-cyclodextrinincluded Parsol 1789 with a chemometric approach, J. Mol. Struct.,1999, 480–481, 557–561.

58 L. E. Agrapidis-Paloympis, R. A. Nash and N. A. Shaath, The effectof solvents on the ultraviolet absorbance of sunscreens, J. Soc.Cosmet. Chem., 1987, 38, 209.

59 V. Vanquerp, C. Rodriguez, C. Coiffard, L. J. M. Coiffard andY. De Roeck-Holtzhauer, High-performance liquid chromato-graphic method for the comparison of the photostability of fivesunscreen agents, J. Chromatogr., A, 1999, 832, 273–277.

60 C. Stenberg, T. Mellstrand and O. Larko, Stability of PABA afterUV irradiation in vivo and in vitro, Photodermatology, 1987, 4,201–204.

61 A. Malpede and S. Fumagalli, Diethyl-hexylbutamide triazole.New UVB filter for skin protection, Cosmet. Technol. (Milano),2000, 3, 33–38.

62 (a) R. M. Sayre and J. C. Dowdy, Titanium dioxide and zinc oxideinduce photooxidation of unsaturated lipids, Cosmet. Toiletries,2000, 115, 75–82; (b) H. M. Swartz, K. J. Liu, T. Walczak, T. Panz,M. Kobayashi and W. Zavadowski, Effects of coatings on thereactivity of inorganic sunscreen agents to light, J. Cosmet. Sci.,1998, 49, 125–135.

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