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Organic ultraviolet (UV) filters are used in cosmetic and personal care products (CPCPs) and over‐the‐counter (OTC) sunscreens, due to their ability to absorb solar radiation. When OTC and CPCP ingredients are washed down the drain, they can then enter freshwaters that receive wastewater treatment plant effluents. This paper presents a freshwater environmental safety assessment of a key UV filter, oxybenzone, used in OTC sunscreens and CPCPs in the United States. Exposure was characterized using iSTREEM®, a spatially resolved aquatic exposure model developed for chemicals disposed of down the drain. iSTREEM® provides a comprehensive exposure assessment of oxybenzone concentrations in United States receiving waters through predicted environmental concentration (PEC) distributions representative of conditions across the region. A review of available hazard data was used to derive a predicted no‐effect concentration (PNEC) using aquatic toxicity data and assessment factors. A safety assessment was conducted by comparing the PEC distribution with the PNEC. The results indicate that oxybenzone is of low concern and there is a significant margin of safety as the 90th percentile PEC is two orders of magnitude below the PNEC. These results are instrumental in demonstrating the environmental safety of key organic UV filters in the U.S. freshwater environment and will help prioritize future work. Integr Environ Assess Manag 2021;17:951–960. © 2021 Personal Care Products Council. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC), KEY POINTS A freshwater environmental risk assessment for oxybenzone was conducted that considered available aquatic toxicity data and down‐the‐drain emissions of sunscreen, cosmetic, and personal care products.A nationwide distribution of predicted environmental concentrations was modeled, using the spatially explicit iSTREEM® exposure model, and the median and 90th percentile oxybenzone concentrations were predicted to be 0.01 and 0.15 µg/L, respectively.The 90th percentile exposure prediction (reasonable worst case) is two orders of magnitude below the predicted no‐effect concentration value of 18 µg/L, indicating that risk is negligible.This paper provides a down‐the‐drain freshwater environmental risk assessment framework suitable for over‐the‐counter drugs, cosmetic, and personal care ingredients.

Rationale Exposure to UV light can induce adverse effects on human health, such as photo-aging, immunosuppression, and cancer. Sunscreens are used to prevent the absorption of UV rays, but certain UV-filtering compounds have been shown to disrupt endocrine systems or act as carcinogens. To assess the effects of the exposure to such compounds, it is important to study the pathways by which they are biotransformed in the body. Methods Liquid chromatography coupled to high-resolution tandem mass spectrometry (LC/HRMS/MS) was employed to evaluate the oxidative metabolism and, specifically, the formation of reactive metabolites of six active ingredients commonly used in sunscreen formulations: oxybenzone, avobenzone, homosalate, octisalate, octocrylene, and octinoxate. In vitro incubations were performed with human and rat liver microsomes in the presence of β-nicotinamide adenine dinucleotide phosphate and glutathione. An LC/HRMS/MS method was developed to identify metabolites employing a biphenyl reversed-phase column for separating parent molecules, metabolites, and glutathione (GSH) adducts. Results Each tested compound resulted in the formation of several metabolites, including at least one GSH adduct. Compounds containing ester groups were hydrolyzed, and some metabolites of the free acid forms were also detected. High-resolution MS/MS data was crucial for the structural elucidation of metabolites and GSH adducts. Fragmentation pathways were proposed for all parent compounds, as well as each described metabolite and adduct. Conclusions The results of this study will help better understand the metabolism and detoxification pathways of these xenobiotics.

Sunscreens are regulated as over-the-counter drugs in the United States. Some sunscreen ingredients are absorbed into the systemic circulation, which raises concerns about the safety of these drugs. There is limited information on the systemic exposure for most sunscreen ingredients. This report estimates the systemic absorption of two sunscreen active ingredients, oxybenzone and enzacamene, by developing a pharmacokinetic model from published sunscreen absorption data and compares the results with safety thresholds proposed by the US Food and Drug Administration and in the literature. Our analysis indicates that systemic absorption can be substantial, and evaluation of the systemic exposure of sunscreen ingredients is warranted to better assess any long-term risks of use.

Oxybenzone (Benzophenone-3) is an emerging human and environmental contaminant used in sunscreens and personal care products to help minimize the damaging effects of ultraviolet radiation. The Center for Disease Control fourth national report on human exposure to environmental chemicals demonstrated that approximately 97% of the people tested have oxybenzone present in their urine, and independent scientists have reported various concentrations in waterways and fish worldwide. Oxybenzone can also react with chlorine, producing hazardous by-products that can concentrate in swimming pools and wastewater treatment plants. Moreover, adverse reactions could very well be increased by the closed loop of ingesting fish contaminated with oxybenzone and/or washing the ingredient off our bodies and having it return in drinking water as treatment plants do not effectively remove the chemical as part of their processing protocols. In humans, oxybenzone has been reported to produce contact and photocontact allergy reactions, implemented as a possible endocrine disruptor and has been linked to Hirschsprung's disease. Environmentally, oxybenzone has been shown to produce a variety of toxic reactions in coral and fish ranging from reef bleaching to mortality. Lastly, with the rise in skin cancer rates and the availability of more effective sunscreen actives such as micronized zinc oxide and titanium dioxide, serious doubts about the relative prevention benefit of personal care products containing oxybenzone must be raised and compared with the potential negative health and environmental effects caused by the accumulation of this and other chemicals in the ecosystem.

A fast gas chromatography/mass spectrometry method was developed and validated for the analysis of the potential endocrine disrupters octinoxate and oxybenzone in swimming pool water samples based on the solvent-free solid-phase microextraction technique. The low-pressure gas chromatography/mass spectrometry method used for the fast identification of UV filter substances was compared to a conventional method in terms of sensitivity and speed. The fast method proposed resulted in 2 min runs, leading to an eightfold decrease in the total analysis time and a sevenfold improvement in detection limits. The main parameters affecting the solid-phase microextraction process were also studied in detail and the optimized conditions were as follows: fiber coating, polyacrylate; extraction mode, direct immersion; extraction temperature, 25°C; sample volume, 5 mL; extraction time 45 min; pH 6.5. Under the optimized conditions, a linear response was obtained in the concentration range of 0.5-25 μg/L with correlation coefficients in the range 0.990-0.999. The limits of detection were 0.17-0.29 μg/L, and the recoveries were 80-83%. Combined method uncertainty was assessed and found to be less than 7% for both analytes for concentrations equal to or higher than 5 μg/L. Pool water samples were analyzed to demonstrate the applicability of the proposed method. Neither octinoxate nor oxybenzone were detected in the swimming pool water samples at concentrations above the respective limits of detection.

Diverse and functionalized 2-hydroxybenzophenone derivatives were synthesized efficiently in good to excellent yield via the highly regioselective indium(III)-catalyzed [2+2+2] benzannulation of 3-formylchromones with β-enamino esters or β-enamino ketones. This benzannulation reaction proceeds via a domino Michael/retro-Michael/6π-electrocyclization/deformylation reaction. In addition, 2-hydroxybenzophenones were also prepared by the indium(III)-catalyzed [4+2] benzannulation reaction between 3-substituted chromen-4-ones and β-enamino esters or β-enamino ketones. Furthermore, the effects of substituents and π conjugation on the characteristics of the UV-Vis spectrum of synthesized 2-hydroxybenzophenones were examined. Compound 10s exhibited higher sun protection activity than oxybenzone which is used in most popular sunscreens.

Synopsis In this study, high-temperature liquid chromatographic (HTLC) and subcritical water chromatographic (SBWC) separations of sunscreens contained in skincare creams were achieved at temperatures ranging from 90 to 250°C. The columns employed in this work include a ZirChrom-DiamondBond-C18, a XTerra MS C18 and a XBridge C18 column. The quantity of methanol consumed by the greener HTLC sunscreen methods developed in this project is significantly reduced although the HTLC separation at this stage is not as efficient as that achieved by traditional HPLC. SBWC separation of sunscreens was also achieved on the XTerra MS C18 and the XBridge C18 columns using pure water at 230–250°C. Methanol was eliminated in the SBWC methods developed in this study.

Background/purpose: Sunscreens are believed to be a valuable tool in providing photoprotection against the detrimental effects of UV radiation, a known carcinogen. However, a number of controversies have developed regarding their safety and efficacy. This review summarizes the relevant studies surrounding these controversies. Methods: Evidence of the prevention of skin cancer, an oft-cited reason for sunscreen use, was examined as it pertains to squamous cell carcinoma, basal cell carcinoma and melanoma. We also reviewed studies examining the effects of sunscreen on the synthesis of vitamin D, an essential nutrient whose role in health and disease continues to grow. Lastly, we analyzed studies surrounding the safety and toxicity of oxybenzone, retinyl palmitate and nanoparticles of zinc oxide (ZnO) and titanium dioxide (TiO2). Results: The overwhelming majority of available data is drawn from studies conducted using antiquated sunscreen formulations. Nonetheless, our research revealed that topical use of sunscreen protects against squamous cell carcinoma, does not cause vitamin D deficiency/insufficiency in practice and has not been demonstrated to adversely affect the health of humans. Conclusion: Given the established benefits of UV protection, the use of sunscreens remains an important part of an overall photoprotective strategy. Future sunscreens with improved formulation should ideally offer superior protection. With increased usage of sunscreen by the public, continuous and vigilant monitoring of the overall safety of future products is also needed.

Nanostructured lipid carriers (NLCs) are potential active delivery systems based on mixtures of solid lipids and liquid oil. In this paper, aqueous dispersions of NLCs were prepared by a hot high-pressure homogenization technique using carnauba wax as the solid lipid and isodecyl oleate as the liquid oil. The preparation and stability parameters of benzophenone-3-loaded NLCs have been investigated concerning particle size, zeta potential and loading capacity to encapsulate benzophenone-3, a molecular sunscreen. The current investigation illustrates the effect of the composition of the lipid mixture on the entrapment efficiency, in vitro release and stability of benzophenone-3-loaded in these NLCs. A loading capacity of approximately 5% of benzophenone-3 (m(BZ-3) /m(lipids) ) was characteristic of these systems.

Oxybenzone (OXB) is one of the most widely employed sunscreen ingredients, yet its allowed load is limited to a maximum of 6% reflecting the frequency with which adverse effects are reported. From a spectroscopic point of view, OXB has excellent absorption properties in both the UVB and UVA regions. We propose that zeolite encapsulation can lead to a sunscreen composite ingredient, that we describe as a supramolecular sunscreen, that will retain the excellent spectroscopic properties of OXB, while preventing contact between the skin and the active ingredient. OXB is very photostable, with the only photodegradative pathway observed being the monophotonic photoejection of electrons that leads to trace yields of phenoxyl radicals; this trace reaction is so minor that it cannot be detected from the recovery of unreacted OXB following UV exposure. Solution, as well as powder and in vitro studies of the supramolecular sunscreen, demonstrate that the protective properties of OXB are totally preserved when encapsulated in zeolite NaY.

A fast gas chromatography/mass spectrometry method was developed and validated for the analysis of the potential endocrine disrupters octinoxate and oxybenzone in swimming pool water samples based on the solvent-free solid-phase microextraction technique. The low-pressure gas chromatography/mass spectrometry method used for the fast identification of UV filter substances was compared to a conventional method in terms of sensitivity and speed. The fast method proposed resulted in 2 min runs, leading to an eightfold decrease in the total analysis time and a sevenfold improvement in detection limits. The main parameters affecting the solid-phase microextraction process were also studied in detail and the optimized conditions were as follows: fiber coating, polyacrylate; extraction mode, direct immersion; extraction temperature, 25 degrees C; sample volume, 5 mL; extraction time 45 min; pH 6.5. Under the optimized conditions, a linear response was obtained in the concentration range of 0.5-25 mu g/L with correlation coefficients in the range 0.990-0.999. The limits of detection were 0.17-0.29 mu g/L, and the recoveries were 80-83%. Combined method uncertainty was assessed and found to be less than 7% for both analytes for concentrations equal to or higher than 5 mu g/L. Pool water samples were analyzed to demonstrate the applicability of the proposed method. Neither octinoxate nor oxybenzone were detected in the swimming pool water samples at concentrations above the respective limits of detection.

Background: Evaluation of sunscreen efficacy is most relevant when measured on the surface it is meant to protect, namely on human skin in vivo. Application of any material to the surface of the skin alters its optical properties. Diffuse reflectance spectroscopy (DRS) is a non-invasive technique to measure changes in the optical properties of the skin decoupled from its biological responses following sunscreen application. Methods: This study compared measurements of UVA efficacy of oxybenzone and avobenzone at different concentrations (0–5%) using DRS, human phototest and an in vitro technique. Twenty subjects were enrolled for each product measured by DRS and 10 different subjects were enrolled for each product measured by human phototest. Six areas 5 cm × 10 cm were outlined on each subject's back. DRS measurements were performed on four subsites within each area before and 20 min after sunscreen application. UVA efficacy for each concentration of product was calculated from the measured transmission spectrum of a given product convoluted with the spectrum of a Xenon light source adequately filtered to obtain the UVA spectrum from 320 to 400 nm and the erythema action spectrum. Phototesting was performed using the same light source and persistent pigment darkening as the biological endpoint. Measurements were made with sunscreen coverage of 2 mg/cm2. In vitro measurements were performed using an Optometrics instrument. Results: All three techniques showed a linear response between calculated UVA efficacy and product concentration. Conclusions: This study showed that DRS is a rapid and reproducible method to calculate UVA efficacy of sunscreen materials and that its results correlate closely with those obtained by human phototesting.

The aim of this research was the development and validation of a high performance liquid chromatography (HPLC) method for the simultaneous and quantitative determination of benzophenone-3, octyl methoxycinnamate and octyl salicylate contained in sunscreen emulsions. The separation and quantitative determination was achieved using a LiChrospher((R)) 100 RP-18 (5 microm) Merck column, a mobile phase constituted of methanol/water (85/15, v/v), a flow-rate of 1.0 mL min(-1) and UV detection at 310 nm. The correlation coefficients and percentage of recovery for benzophenone-3, octyl methoxycinnamate and octyl salicylate were 0.9999 and 99.46%; 0.9995 and 98.85%; 0.9998 and 98.84%, respectively. The relative standard deviations (RSD) for commercial samples were between 0.50 and 0.70%.

The aim of this study was to determine the effects of the vehicles on the release and permeation of the UV filters. Therefore, the release and permeation of lipophilic oxybenzone and hydrophilic sulisobenzone were investigated from four different vehicles; petrolatum, o/w and w/o emulsions and hydroxyethyl cellulose (HEC) gel. Both release and permeation studies were performed by using glass diffusion cells. The vehicle in which oxybenzone has the highest released amount was petrolatum, whereas the highest released amount for sulisobenzone was obtained in HEC gel. The difference between the released amounts of oxybenzone in the other three vehicles was not significant but the released amount of sulisobenzone was least in petrolatum, whereas no significant difference was seen between o/w and w/o emulsions. The results of skin permeation experiments were similar those from release experiments. The order of permeated amounts from highest to lowest was petrolatum, o/w emulsion and HEC gel for oxybenzone, and HEC gel, o/w emulsion and petrolatum for sulisobenzone. These results demonstrate that permeation of the UV filters can be optimized by a suitable vehicle. As the percutaneous absorption of sunscreens should be avoided, the vehicle suggested for oxybenzone and sulisobenzone is o/w emulsion because of its permeation properties and cosmetic acceptance.

Background: In parallel with the popular usage of topical ketoprofen, the number of reported cases of ketoprofen-induced photoallergic contact dermatitis has been increasing. It is clinically important to know the cross-reactivity of ketoprofen in order to avoid cross-sensitization caused by several structurally similar non-steroidal anti-inflammatory drugs (NSAID) on the market. Methods: To evaluate the spectrum of cross sensitization, photopatch testing was performed on five patients with ketoprofen-induced photoallergic contact dermatitis using ketoprofen and other structurally similar chemicals, such as oxybenzone, tiaprofenic acid and suprofen. Results: All five patients reacted positively to ketoprofen or ketoprofen plaster on photopatch testing. All four patients photopatch tested with related chemicals showed cross-photosensitization with tiaprofenic acid and suprofen. However, none of the patients reacted positively to oxybenzone. Conclusion: Either the diphenylketone moiety or a structurally similar tiophene-phenylketone moiety is important as the antigenic determinants of ketoprofen photoallergy. The arylpropionic acid side chain would not be involved.

Topical application of alpha-tocopherol (alphaTH), the most prominent naturally occurring form of vitamin E, inhibits ultraviolet (UV) B-induced photocarcinogenesis and DNA photodamage in C3H mice in vivo. In this study, we compared alphaTH with other vitamin E compounds and with three commercial sunscreen compounds for their ability to inhibit DNA photodamage in C3H mouse skin in vivo. When applied in a 5% dispersion in a neutral cream vehicle, alpha-tocopherol (alphaTH), gamma-tocopherol (gammaTH), and delta-tocopherol (deltaTH) each produced a statistically significant inhibition of thymine dimer formation, whereas alpha-tocopherol acetate (alphaTAc) and alpha-tocopherol methyl ether (alphaTOMe) did not. Application of 5% dispersions of the commercial sunscreen agent octylmethoxycinnamate also inhibited dimer formation, whereas ethylhexyl salicylate and oxybenzone did not, despite their considerably greater UVB absorbances than alphaTH. To test the hypothesis that cellular uptake and distribution are necessary for optimal photoprotection by tocopherols, photoprotection was studied in mouse 308 keratinocyte cells in vitro. Preincubation of 308 cells with 1 microM alphaTH for at least 2 h before exposure to 2.5 J/m2/s UVB for 10 min significantly (P < 0.05) attenuated thymine dimer formation. Pre-incubation with 1 microM gammaTH, deltaTH, alphaTAc, or alphaTOMe for 2 h did not inhibit thymine dimer formation significantly. Uptake of alphaTH was measured after incubation with 1 microM [2H3]alphaTH (d3-alphaTH) and resulted in a time-dependent increase in alphaTH levels. Use of d3-alphaTH allowed separate, simultaneous measurement of added d3-alphaTH and unlabeled endogenous alphaTH by gas chromatography-mass spectrometry. Accumulation of 167 +/- 62 pmol d3-alphaTH/mg protein was measured within 1 h in whole-cell fractions. d3-AlphaTH in the nuclear fraction reached levels of 15 +/- 4 pmol d3-alphaTH/mg protein at 2 h. Accumulation of alphaTH in the whole cell and nuclei corresponded temporally with significant protection against DNA photodamage. The kinetics of accumulation of the three tocopherols in whole cells and in nuclei were similar. Although only alphaTH conferred significant protection compared with irradiated controls at 2 h, the differences between individual tocopherols were not statistically significant. This work suggests that incorporation of tocopherol compounds into sunscreen products confers protection against procarcinogenic DNA photodamage and that cellular uptake and distribution of tocopherol compounds is necessary for their optimal photoprotection.

The arylpropionic acid derivatives (APADs) ketoprofen and tiaprofenic acid can provoke photoallergic dermatitis. Possible cross-reactivity between APADs is of importance in patients using nonsteroidal anti-inflammatory drugs. Because of the similarities in chemical structures, we investigated patients with photoallergy to ketoprofen or tiaprofenic acid, in order to study cross-reactivity between APADs and a possible pattern of cross-reactivity between benzophenone-containing molecules, so as to determine the molecular basis of photoallergy to ketoprofen or tiaprofenic acid. 10 patients with photoallergy to topical ketoprofen, 2 with photoallergy to oral tiaprofenic acid, and 15 control subjects with no history of contact dermatitis from APADs, nor from benzophenone-containing molecules, were photopatch tested in triplicate with ketoprofen, tiaprofenic acid, other APADs (alminoprofen, fenoprofen, flurbiprofen, ibuprofen and naproxen), benzophenone-containing molecules (fenofibrate, oxybenzone, sulisobenzone), and unsubstituted benzophenone. 1 set was irradiated with UVA light, 1 with solar-simulated irradiation and 1 dark control. Tests were read at 2, 3 and 4 days. Patients reacted to both ketoprofen and tiaprofenic acid (12/12), fenofibrate (8/12), oxybenzone (3/12) and unsubstituted benzophenone (11/12), but not to other APADs, nor to sulisobenzone. Tests remained negative in control patients. Photoallergy is due to the benzophenone moiety of ketoprofen, or to the very similar thiophene-phenylketone of tiaprofenic acid, but not to their arylpropionic function. This induces cross-reactivity to fenofibrate and oxybenzone but not to APADs without a benzophenone moiety, which may therefore probably be used in such patients. Unsubstituted benzophenone should be added to standard phototesting series.

We report a case of photoallergic contact dermatitis to two sunscreen agents, methoxycinnamate and oxybenzone, occurring in a 6-year-old Asian boy.

Hair damage, caused by sunlight, and the possibility to protect hair against sunlight by means of cosmetic formulations was studied. For this, five UV-filters were tested: benzophenone-3 (UV-A/UV-B); benzophenone-4 (UV-A/UV-B); phenylbenzimidazole sulfonic acid (UV-B); butylmethoxydibenzoylmethane (UV-A); octyl dimethyl PABA (UV-B). The stability of the UV-filters was tested as pure substances as well as in two cosmetic formulations: a setting lotion and a shine spray. The degree of decolouration and stress strain behaviour were determined. The benzophenones had the best protection ability both on colour and on morphology. Stability data and UV-spectra are discussed Les effets nocifs de la lumiere solaire sur les cheveux, ainsi que les possibilites de proteger ces derniers des rayons solaires avec des formules cosmetiques ont ete etudies. A cet effet, cinq filtres d'UV ont ete testes: benzophenone-3 (UV-A/UV-B); benzophenone-4 (UV-A/UV-B); phenylbenzimidazole sulfonique acide (UV-B); butylmethoxydibenzoylmethane (UV-A); octyl dimethyl PABA (UV-B). La stabilite des filtres d'UV a ete testee, d'une part en tant que substances a l'etat pur et d'autre part integres dans deux formules cosmetiques: une lotion de mise en plis et un spray brillance. On a determine le degre de decoloration et la resistance a la tension. Resultat: les benzophenones ont la meilleure capacite de protection de la couleur et de la structure du cheveu. La stabilite des resultats et le spectre des UVs sont egalement discutes

Summary Metarhizium flavouiride conidia formulated in oil or water were exposed to simulated solar radiation. Radiation below 320 nm killed conidia and caused delays in the germination of survivors; germination was greater after 48 h of incubation than after 24 h. UV exposure of conidia formulated in oil for 2 h reduced germination from 99% to 37.5% after incubation for 48 h. Exposure of conidia in water to UV for 1 h resulted in 4.7% germination after 24 h incubation compared with 36.5% for conidia formulated in oil. The addition of 1% oxybenzone resulted in 81.9% conidial germination after 3 h exposure and 48 h incubation compared with 28.1% in oil without the sunscreen.

We report on our experience with sunscreen allergy between 1992 and 1999 and also review the international literature on sunscreen allergy. There were a total of 21 allergic reactions to sunscreen chemicals observed in 19 patients over the 8 years. There were nine positive photopatch reactions to oxybenzone, eight to butyl methoxy dibenzoylmethane, three to methoxycinnamate and one to benzophenone. No positive reactions were observed to para aminobenzoic acid. Six patients also had positive patch tests to components of the sunscreen base. In our experience, sunscreen chemicals are the most common cause of photoallergic contact dermatitis.

A new diketopiperazine alkaloid, golmaenone (1). and related alkaloids, neoechinulin A (2). and L-alanyl-L-tryptophan anhydride (3). have been isolated from the culture broth of the marine-derived fungus Aspergillus sp. The structure and absolute stereochemistry of the new compound (1). was assigned by spectroscopic methods and the advanced Marfey's method. Compounds 1 and 2 exhibited a significant radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) with IC(50) values of 20 and 24 microM, respectively, which are similar to the positive control, ascorbic acid (IC(50), 20 microM). Compounds 1 and 2 also showed an ultraviolet-A (UV-A) (320--390 nm) protecting activity with ED(50) values of 90 and 170 microM, respectively, which are more active than oxybenzone (ED(50), 350 microM) currently being used as sunscreen.

Photopatch testing, although widely used in the diagnosis of photosensitivity disorders, is not standardized. We performed this study to determine the threshold ultraviolet light A (UV-A) dose required to elicit photopatch test responses. 4 patients with previously positive tests were reexposed to the offending allergen, using an incremental dosage regime. Isopropyl dibenzoylmethane (Eusolex 8020), mexenone (benzophenone-10) and oxybenzone (benzophenone-3) produced positive responses at 1.0, 1.0 and 0.7 J/cm2, respectively. Responses to phenothiazines were deemed phototoxic. These results demonstrate that high doses of UV-A (e.g., 10-15 J/cm2) are unnecessary, and that 5 J/cm2 should become the current standard.

A retrospective study was done of allergic contact dermatits to cosmetics, seen at the department of dermatology of Curry Cabral Hospital, over a six year period (1998 to 2003). Of 2848 patients patch tested during this period, 314 had cosmetic contact allergy and represented about 15.7% of all patients with at least one positive patch test. The patients aged between 13 and 82 years old, and were mostly female (78%). Skin reactions occurred most often on the face, followed by hands, neck and the eyelids. All the patients were tested with the standard series, with supplementary series when appropriate, and whenever possible, with the personal cosmetic products. 92% had positive reactions to standard series allergens; 226 patiens to allergens of the standard series, which may be used in cosmetics. The majority of reactions were due to fragrance mix, followed by balsam of Peru, p-phenylenediamine, kathon CG and colophony. Fragrance series was tested in 118 patients, with the following most frequent positive reactions: oak moss absolute, isoeugenol, hydroxycitronellal. Cosmetic series was tested in 147 patients with the following most frequent positive reactions: toluenesulphonamide-formaldehyde resin and propolis. 30 patients tested with photoallergen series, 4 reacted to oxybenzone. Skin care products and fragrances were the most commonly involved product categories. Twelve patients reacted only with their own products. The fragrances were the most frequent ingredient recorded as the cause of cosmetic contact allergy. Our standard series detected 70% of cases of allergic contact dermatitis to cosmetics.

A major concern raised about photostability studies of sunscreen products is that the photodegradation of sunscreens does not readily translate into changes in product performance. This study examines the correlation between photochemical degradation of sunscreen agents and changes in protection provided by sunscreen films. Films of a commercial sunscreen product containing avobenzone, oxybenzone and octinoxate were irradiated using a fluorescent UV-A phototherapy lamp with additional UV-B blocking filter. Periodically, during irradiation the transmittances of the films were measured and samples collected for chemical analysis of the sunscreen agents using high-performance liquid chromatography techniques. The results show that UV-induced changes in UV transmittance of sunscreen films correlate with changes in concentration of sunscreen agents. In a parallel experiment, we also irradiated a thin film of the same product in the cavity of an electron spin resonance (ESR) spectrometer. We report the concomitant photolysis of avobenzone and octinoxate that predominates over expected E/Z photoisomerization and that irradiation of a film of this product produced free radicals detected by ESR spectroscopy that persisted even after exposure had ended.

The main objectives of this thesis were to study: (i) the effect of an enzyme-containing dentifrice (Zendium Dentine®), with addition of xylitol on mutans streptococci (MS) in saliva and dental plaque (Paper I) (ii) the effect of a combination of triclosan and xylitol in a dentifrice (Colgate Total®) on MS in saliva and dental plaque (Paper II), and (iii) the effect of oxybenzone on prostaglandin E2 (PGE2)-production in cell culture and the effect of an oxybenzone-containing dentifrice on plaque, gingivitis and MS (Paper III). In Paper I, the subjects were divided into two test groups: one using a 10% xylitol and the other using a 5% xylitol dentifrice for 3 months. The addition of 10% xylitol to Zendium Dentine® had an inhibitory effect on MS in both saliva and dental plaque, and the effect of xylitol seemed to be dose dependent. In Paper II, three groups were using one of the following dentifrices: (i) Colgate Total® with addition of 10% xylitol; (ii) Colgate Total®; and (iii) Colgate Total® without triclosan and without xylitol. The results showed that the addition of 10% xylitol to Colgate Total® reduced the number of MS in saliva and plaque. This effect was more pronounced at 6 months than at 2 months. In Paper III, the effect of oxybenzone was studied in vitro and in vivo. Human Embryo Palatal Mesenchyme (HEPM) cells were used to test the inhibition of IL-1β-stimulated PGE2 production by different concentrations of oxybenzone. The results revealed that there was no decrease of cell viability up to 50 µm. A dose-dependent inhibition of stimulated PGE2 production was found: 50% inhibition (IC50) was found at 0.6 µm. Paper III also included a double-blind clinical trial testing two fluoride dentifrices: one with the addition of 0.5% oxybenzone and one without. Plaque index was reduced in both groups. There was no difference between the groups. A 25% reduction in gingival index was observed in the oxybenzone group after 6 weeks, compared to 2% in the placebo group, indicating an anti-inflammatory effect of oxybenzone.

A variety of in vitro and in vivo methods have been proposed to evaluate the UVA efficacy of sunscreens. Diffuse reflectance spectroscopy (DRS) is a recent approach that allows measuring sunscreen protectiveness in the UVA portion of the spectrum. FDA representatives have shown a marked interest for the development of this alternative method. The absorption spectrum of the product is obtained by measuring the change in skin reflection due to the product. From this absorption spectrum the UVA efficacy of a sunscreen product can then be calculated for an appropriate UV source and a given skin response action spectrum. One major advantage of this test method is that the UVA protection is determined directly on human skin, thus accounting for sunscreen/skin surface and emulsion interactions encountered in vivo, but not in vitro. Both DRS and in vivo persistent pigment darkening (PPD) method were used to compare the UVA efficacy of various UVA sunscreens (such as oxybenzone, avobenzone, ecamsule and zinc oxide at different concentrations) and of marketed products. A significant correlation was found between DRS and PPD results only for photostable products. To get a correlation with PPD results with photo-unstable products, a pre-exposure of the products applied on skin was found necessary before performing the DRS measurements. The DRS method allows evaluating both the UVA absorption spectrum of the products and their broadness of absorption and can thus be considered as a powerful tool for the in-vivo evaluation of sunscreen UVA protective efficacy.

Sunscreens penetrate human epidermis and modify the biology of proliferating cells. This study addressed the question whether the UV response of cultured human cells is affected by direct treatment with nontoxic levels of sunscreens. Cell survival following exposure to UVC or unfiltered UVB was not altered by preincubation with 25 μg/mL of octyl p-dimethylaminobenzoate (o-PABA), 2-ethylhexyl p-methoxycinnamate (EHMC) or oxybenzone. However, UVA or UVB filtered to reproduce the solar UV spectrum penetrating to the basal layer of the epidermis, highly sensitized cells to killing by o-PABA but not by its hydrolysis product, 4-dimethylaminobenzoic acid. Sensitization was found in all cell types tested, except normal keratinocytes, and could be prevented by certain antioxidants particularly pyruvate and the hydroxyl radical scavenger mannitol. o-PABA and EHMC applied without UV reduced the adherence of cells. The results indicate that sunscreens may increase cell mobility and the combination of o-PABA...