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To provide an up-to-date synopsis of the literature on the safety of sunscreen active ingredients in humans and the environment and highlight regulatory changes in the USA. Currently, as per the US Food and Drug Administration, the only ultraviolet filters generally recognized as safe and effective are inorganic zinc oxide (ZnO) and titanium dioxide (TiO2). In vivo human systemic absorption studies found that common organic filters attain sufficient plasma concentrations to require carcinogenicity and reproductive studies. In vivo human skin penetration studies showed ZnO nanoparticles (ZnO-NP) did not penetrate the stratum corneum. Limited quantities of TiO2-NP may be absorbed systemically. In laboratory settings, corals exposed to oxybenzone manifested concentration-dependent toxicity and bleaching. In response, bills passed in Hawaii and elsewhere ban sales of oxybenzone-containing sunscreens. ZnO-NP, but not TiO2-NP, caused coral bleaching under controlled conditions. The collective knowledge on sunscreen safety is continually evolving, with many preliminary findings. Studies on the effects of systemic absorption of organic filters in humans are forthcoming; importantly, there has been no evidence of harm over decades of use. Organic (less so inorganic) filters caused coral bleaching in controlled environments, but filter concentrations may not have been realistic, and bleaching is predominantly driven by other factors. No present evidence suggests any marketed sunscreens should be avoided. For consumers with concerns, inorganic ZnO and TiO2 are supported by the most reassuring data at the time of writing.

Background: Lack of established criteria for sunscreen product recommendations and potentially allergenic ingredients in sunscreens pose an issue for physicians and patients with autoimmune skin conditions. Objective: We reviewed popular sunscreens for effectiveness and potential allergenicity for recommendation and use in the autoimmune skin condition population. Methods: In this cohort study, we selected sunscreens from the bestseller lists of Amazon, Target, and CVS. Of those, sunscreens with sun protection factor of 50 to 99 and 100 that met our effectiveness criteria (52 sunscreens) were analyzed for allergenic ingredients. An allergen list was developed from the North American Contact Dermatitis Group core data and stratified into low-prevalence and high-prevalence allergens. Results: The allergenicity of popular sunscreens that met our effectiveness criteria are organized in a table by number of tiered potential allergens. Although no sunscreen was allergen-free, several products contained a minimal number of low-prevalence allergens. The most common low-prevalence allergens were chemical sunscreen ingredients avobenzone, octocrylene, and oxybenzone, and the most common high-prevalence allergen was fragrance. A limitation is that not all U.S. sunscreens were analyzed. Conclusion: With the wide range of sunscreens available, physicians and patients should be aware of the effectiveness and potential allergenicity of sunscreens and make recommendations and consumption choices accordingly. Keywords: dermatology, sunscreen, photosensitivity, allergens, contact dermatitis, autoimmune skin

Sunscreens have now been around for decades to mitigate the Sun’s damaging ultraviolet (UV) radiation which, although essential for the existence of life, is a recognized prime carcinogen. Accordingly, have suncreams achieved their intended purposes towards protection against sunburns, skin photo-ageing and the like? Most importantly, however, have they provided the expected protection against skin cancers that current sunscreen products claim to do? In the last two decades, there have been tens, if not hundreds of studies on sunscreens with respect to skin protection against UVB (280‒320 nm)—traditionally sunscreens with rather low sun protection factors (SPF) were intended to protect against this type of radiation—and UVA (320‒400 nm) radiation; a distinction between SPF and UVA protection factor (UVA-PF) is made. Many of the studies of the last two decades have focused on protection against the more skin-penetrating UVA radiation. This non-exhaustive article reviews some of the important facets of what is currently known about sunscreens with regard (i) to the physical UV filters titanium dioxide (TiO2) and zinc oxide (ZnO) and the mostly photo-unstable chemical UVB/UVA filters (e.g., octinoxate (OMC) and avobenzone (AVO), among others), (ii) to novel chemical sunscreen agents, (iii) to means that minimize the breakdown of chemical filters and improve their stability when exposed to UV sunlight, (iv) to SPF factors, and (v) to a short discussion on non-melanoma skin cancers and melanoma. Importantly, throughout the article we allude to the safety aspects of sunscreens and at the end ask the question: do active ingredients in sunscreen products pose a risk to human health, and what else can be done to enhance protection? Significant loss of skin protection from two well-known commercial suncreams when exposed to simulated UV sunlight. Cream I: titanium dioxide, ethylhexyl triazone, avobenzone, and octinoxate; Cream II: octyl salicylate, oxybenzone, avobenzone, and octinoxate.

BACKGROUND: Recent evidence of high systemic absorption of sunscreen ingredients has raised concerns regarding the safety of sunscreen products. Oxybenzone (BP-3) and octinoxate (OMC), two common sunscreen ingredients, were recently banned in Key West and Hawaii due to their toxic effects on marine ecosystems. Their impact on human health requires a careful assessment. OBJECTIVE: To summarize the current evidence on the association between the systemic level of BP-3 or OMC and its health impact. METHODS: A primary literature search was conducted using PubMed database in February 2019. RESULTS: There are 29 studies that address the impact of these ingredients on human health. Studies show that elevated systemic level of BP-3 has no adverse effect on male and female fertility, female reproductive hormone level, adiposity, fetal growth, child’s neurodevelopment and sexual maturation. However, the association of BP-3 level on thyroid hormone, testosterone level, kidney function and pubertal timing has been reported and prompts further investigations to validate a true association. The systemic absorption of OMC has no reported effect on thyroid and reproductive hormone levels. CONCLUSIONS: Current evidence is not sufficient to support the causal relationship between the elevated systemic level of BP-3 or OMC and adverse health outcomes. There are either contradictory findings among different studies or insufficient number of studies to corroborate the observed association. To accurately evaluate the long-term risk of exposure to BP-3 and OMC from sunscreen, a well-designed longitudinal randomized controlled trial needs to be conducted.

Thanaka (H. crenulata, N. crenulata, L. acidissima L.) is a common tree in Southeast Asia used by the people of Myanmar to create their distinctive face makeup meant for daily sun protection and skincare. Moreover, it is used as a traditional remedy to treat various diseases since it can also be applied as an insect repellent. In this systematic review, the chemical and biological properties of Thanaka have been summarised from 18 articles obtained from the Scopus database. Various extracts of Thanaka comprise a significant number of bioactive compounds that include antioxidant, anti-ageing, anti-inflammatory, anti-melanogenic and anti-microbial properties. More importantly, Thanaka exhibits low cytotoxicity towards human cell lines. The use of natural plant materials with various beneficial biological activities have been commonly replacing artificial and synthetic chemicals for health and environmental reasons as natural plant materials offer advantages such as antioxidant, antibacterial qualities while providing essential nourishment to the skin. This review serves as a reference for the research, development and commercialisation of Thanaka skincare products, in particular, sunscreen. Natural sunscreens have attracted enormous interests as a potential replacement for sun protection products made using synthetic chemicals such as oxybenzone that would cause health issues and damage to the environment.

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.

With increasing awareness regarding the risks of sunburn, photoaging, and skin cancer, the use of sunscreens has increased. Organic and inorganic filters are used in sunscreen products worldwide. Concerns have been raised regarding the environmental effects of commonly used organic ultraviolet (UV) filters, including oxybenzone (benzophenone-3), 4-methylbenzylidene camphor, octocrylene, and octinoxate (ethylhexyl methoxycinnamate). Studies have identified UV filters such as oxybenzone, octocrylene, octinoxate, and ethylhexyl salicylate in almost all water sources around the world and have commented that these filters are not easily removed by common wastewater treatment plant techniques. Additionally, in laboratory settings, oxybenzone has been implicated specifically as a possible contributor to coral reef bleaching. Furthermore, UV filters such as 4-methylbenzylidene camphor, oxybenzone, octocrylene, and octinoxate have been identified in various species of fish worldwide, which has possible consequences for the food chain. As dermatologists, it is important for us to continue to emphasize the public health impact of excessive sun exposure and advise our patients about proper photoprotection practice, which consists of seeking shade, wearing photoprotective clothing (including hats and sunglasses), and applying appropriate sunscreens.

Sunscreens have been widely used by the general public for their photoprotective properties, including prevention of photocarcinogenesis and photoaging and management of photodermatoses. It is important to emphasize to consumers the necessity of broad-spectrum protection, with coverage of both ultraviolet A (320-400 nm) and ultraviolet B (290-320 nm) radiation. This review discusses the benefits of sunscreen, different ultraviolet filters, sunscreen regulations and controversies, the importance of broad-spectrum protection, issues of photostability and formulation, and patient education and compliance.

Importance The US Food and Drug Administration (FDA) has provided guidance that sunscreen active ingredients with systemic absorption greater than 0.5 ng/mL or with safety concerns should undergo nonclinical toxicology assessment including systemic carcinogenicity and additional developmental and reproductive studies. Objective To determine whether the active ingredients (avobenzone, oxybenzone, octocrylene, and ecamsule) of 4 commercially available sunscreens are absorbed into systemic circulation. Design, Setting, and Participants Randomized clinical trial conducted at a phase 1 clinical pharmacology unit in the United States and enrolling 24 healthy volunteers. Enrollment started in July 2018 and ended in August 2018. Interventions Participants were randomized to 1 of 4 sunscreens: spray 1 (n = 6 participants), spray 2 (n = 6), a lotion (n = 6), and a cream (n = 6). Two milligrams of sunscreen per 1 cm2was applied to 75% of body surface area 4 times per day for 4 days, and 30 blood samples were collected over 7 days from each participant. Main Outcomes and Measures The primary outcome was the maximum plasma concentration of avobenzone. Secondary outcomes were the maximum plasma concentrations of oxybenzone, octocrylene, and ecamsule. Results Among 24 participants randomized (mean age, 35.5 [SD, 1.5] years; 12 (50%] women; 14 [58%] black or African American; 14 [58%]), 23 (96%) completed the trial. For avobenzone, geometric mean maximum plasma concentrations were 4.0 ng/mL (coefficient of variation, 6.9%) for spray 1; 3.4 ng/mL (coefficient of variation, 77.3%) for spray 2; 4.3 ng/mL (coefficient of variation, 46.1%) for lotion; and 1.8 ng/mL (coefficient of variation, 32.1%). For oxybenzone, the corresponding values were 209.6 ng/mL (66.8%) for spray 1, 194.9 ng/mL (52.4%) for spray 2, and 169.3 ng/mL (44.5%) for lotion; for octocrylene, 2.9 ng/mL (102%) for spray 1, 7.8 ng/mL (113.3%) for spray 2, 5.7 ng/mL (66.3%) for lotion, and 5.7 ng/mL (47.1%) for cream; and for ecamsule, 1.5 ng/mL (166.1%) for cream. Systemic concentrations greater than 0.5 ng/mL were reached for all 4 products after 4 applications on day 1. The most common adverse event was rash, which developed in 1 participant with each sunscreen. Conclusions and Relevance In this preliminary study involving healthy volunteers, application of 4 commercially available sunscreens under maximal use conditions resulted in plasma concentrations that exceeded the threshold established by the FDA for potentially waiving some nonclinical toxicology studies for sunscreens. The systemic absorption of sunscreen ingredients supports the need for further studies to determine the clinical significance of these findings. These results do not indicate that individuals should refrain from the use of sunscreen. Trial Registration ClinicalTrials.gov Identifier:NCT03582215

The ablative fractional laser is a new modality used for surgical resurfacing. It is expected that laser treatment can generally deliver drugs into and across the skin, which is toxicologically relevant. The aim of this study was to establish skin absorption characteristics of antibiotics, sunscreens, and macromolecules via laser-treated skin and during postoperative periods. Nude mice were employed as the animal model. The skin received a single irradiation of a fractional CO2 laser, using fluences of 4-10 mJ with spot densities of 100-400 spots/cm(2). In vitro skin permeation using Franz cells was performed. Levels of skin water loss and erythema were evaluated, and histological examinations with staining by hematoxylin and eosin, cyclooxygenase-2, and claudin-1 were carried out. Significant signs of erythema, edema, and scaling of the skin treated with the fractional laser were evident. Inflammatory infiltration and a reduction in tight junctions were also observed. Laser treatment at 6 mJ increased tetracycline and tretinoin fluxes by 70- and 9-fold, respectively. A higher fluence resulted in a greater tetracycline flux, but lower skin deposition. On the other hand, tretinoin skin deposition increased following an increase in the laser fluence. The fractional laser exhibited a negligible effect on modulating oxybenzone absorption. Dextrans with molecular weights of 4 and 10 kDa showed increased fluxes from 0.05 to 11.05 and 38.54 μg/cm(2)/h, respectively. The optimized drug dose for skin treated with the fractional laser was 1/70-1/60 of the regular dose. The skin histology and drug absorption had recovered to a normal status within 2-3 days. Our findings provide the first report on risk assessment of excessive skin absorption after fractional laser resurfacing.

Background Ultraviolet (UV) exposure is the predominant cause of skin aging. A systematic evaluation of drug skin permeation via photoaged skin is lacking. Objectives The aim of this work was to investigate whether UVA and UVB affect absorption by the skin of drugs and sunscreens, including tetracycline, quercetin, and oxybenzone. Methods The dorsal skin of nude mice was subjected to UVA (24 and 39 J/cm2) or UVB (150, 200, and 250 mJ/cm2) irradiation. Levels of skin water loss, erythema, and sebum were evaluated, and histological examinations of COX-2 and claudin-1 expressions were carried out. Permeation of the permeants into and through the skin was determined in vitro using a Franz cell. In vivo skin uptake was also evaluated. Senescent skin (24 weeks old) was used for comparison. Results Wrinkling and scaling were significant signs of skin treated with UVA and UVB, respectively. The level of claudin-1, an indicator of tight junctions (TJs), was reduced by UVA and UVB irradiation. UVA enhanced tetracycline and quercetin skin deposition by 11- and 2-fold, respectively. A similar enhancement was shown for flux profiles. Surprisingly, a lower UVA dose revealed greater enhancement compared to the higher dose. The skin deposition and flux of tetracycline both decreased with UVB exposure. UVB also significantly reduced quercetin flux. The skin absorption behavior of chronologically aged skin approximated that of the UVA group, with photoaged skin showing higher enhancement. UV generally exhibited a negligible effect on modulating oxybenzone permeation. Conclusions Skin disruption produced by UV does not necessarily result in enhanced skin absorption. It depends on the UV wavelength, irradiated energy, and physicochemical properties of the permeant. To the best of our knowledge, this is the first report establishing drug permeation profiles for UV-irradiated skin.

Electromagnetic radiation in the ultraviolet, visible, and infrared ranges all produce biologic effects. Ultraviolet filters are the most well-studied photoprotective measure for the adverse effects of ultraviolet radiation. Because of the reported endocrinologic effects of oxybenzone in animal studies, its effects on coral reefs, and its photocontact allergy potential, its use has been minimized in many countries worldwide. New developments in topical antioxidants and oral and subcutaneous agents (eg, Polypodium leucotomos extract, afamelanotide, nicotinamide) with photoprotective and antiphotocarcinogenic properties could potentially provide addition modalities for protection against the effects of visible light and infrared radiation.

While laser skin resurfacing is expected to result in reduced barrier function and increased risk of drug absorption, the extent of the increment has not yet been systematically investigated. We aimed to establish the skin permeation profiles of tetracycline and sunscreens after exposure to the erbium:yttrium-aluminum-garnet (Er:YAG) laser during postoperative periods. Physiological and histopathological examinations were carried out for 5 days after laser treatment on nude mice. Percutaneous absorption of the permeants was determined by an in vitro Franz cell. Ablation depths varied in reaching the stratum corneum (10 μm, 2.5 J/cm 2 ) to approach the epidermis (25 μm, 6.25 J/cm 2 ) and upper dermis (40 μm, 10 J/cm 2 ). Reepithelialization evaluated by transepidermal water loss was complete within 2–4 days and depended on the ablation depth. Epidermal hyperplasia was observed in the 40-μm-treated group. The laser was sufficient to disrupt the skin barrier and allow the transport of the permeants into and across the skin. The laser fluence was found to play an important role in modulating skin absorption. A 25-μm ablation depth increased tetracycline flux 84-fold. A much smaller enhancement (3.3-fold) was detected for tetracycline accumulation within the skin. The laser with different fluences produced enhancement of oxybenzone skin deposition of 3.4–6.4-fold relative to the untreated group. No penetration across the skin was shown regardless of whether titanium dioxide was applied to intact or laser-treated skin. However, laser resurfacing increased the skin deposition of titanium dioxide from 46 to 109–188 ng/g. Tetracycline absorption had recovered to the level of intact skin after 5 days, while more time was required for oxybenzone absorption. The in vivo skin accumulation and plasma concentration revealed that the laser could increase tetracycline absorption 2–3-fold. The experimental results indicated that clinicians should be cautious when determining the dose for postoperative treatment.

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.

Summary Background Benzophenone-3 (BZ-3; 2-hydroxy-4-methoxybenzophenone, oxybenzone) is commonly used to absorb ultraviolet (UV) radiation. BZ-3 penetrates the skin and can be found in the urine. The amount varies between 0·4% and 2%. This seems to be the main metabolic pathway in rats. Objectives To investigate the total amount of BZ-3 excreted in the urine after repeated topical whole-body applications of a sunscreen and to see if UV radiation has any effect on the amount excreted. Methods Twenty-five volunteers applied a commercially available sunscreen containing 4% BZ-3 morning and night for 5 days. Their urine was measured during those 5 days and during a further 5 days after the last application. They were divided into groups A (unirradiated) and B. Group B received UV radiation according to skin type: UVA between 400 and 707 J cm−2, and UVB between 0·46 and 2·0 J cm−2. BZ-3 in urine was analysed with a high-performance liquid chromatography method. Results The volunteers excreted 1·2–8·7% (mean 3·7%) of the total amount of BZ-3 applied. There was no significant difference between the two groups (P

It is well established that sun exposure is the main cause for the development of skin cancer. Chronic continuous UV radiation is believed to induce malignant melanoma, whereas intermittent high-dose UV exposure contributes to the occurrence of actinic keratosis as precursor lesions of squamous cell carcinoma as well as basal cell carcinoma. Not only photocarcinogenesis but also the mechanisms of photoaging have recently become apparent. In this respect the use of sunscreens seemed to prove to be more and more important and popular within the last decades. However, there is still inconsistency about the usefulness of sunscreens. Several studies show that inadequate use and incomplete UV spectrum efficacy may compromise protection more than previously expected. The sunscreen market is crowded by numerous products. Inorganic sunscreens such as zinc oxide and titanium oxide have a wide spectral range of activity compared to most of the organic sunscreen products. It is not uncommon for organic sunscreens to cause photocontact allergy, but their cosmetic acceptability is still superior to the one given by inorganic sunscreens. Recently, modern galenic approaches such as micronization and encapsulation allow the development of high-quality inorganic sunscreens. The potential systemic toxicity of organic sunscreens has lately primarily been discussed controversially in public, and several studies show contradictory results. Although a matter of debate, at present the sun protection factor (SPF) is the most reliable information for the consumer as a measure of sunscreen filter efficacy. In this context additional tests have been introduced for the evaluation of not only the protective effect against erythema but also protection against UV-induced immunological and mutational effects. Recently, combinations of UV filters with agents active in DNA repair have been introduced in order to improve photoprotection. This article reviews the efficacy of sunscreens in the prevention of epithelial and nonepithelial skin cancer, the effect on immunosuppression and the value of the SPF as well as new developments on the sunscreen market.

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.

1 to 14 days after exposure. Photoallergic reactions are clinically similar to allergic contact dermatitis but require light to chemically alter the medication or chemical to render it allergenic. They occur more frequently with topically applied agents, such as oxybenzone, than with systemic medications. The histopathologic changes of photoallergic reactions are identical to contact dermatitis with spongiosis in the epidermis and perivascular infiltrate of lymphocytes in the dermis. Many drugs induce photosensitivity. Examples include quinolones, tetracyclines, diuretics, nonsteroidal antiinflammatory drugs (NSAIDs), and others. The ability of a drug to act as a photosensitizer depends on its physical, chemical, pharmacokinetic, and pharmacodynamic properties. These include a low molecular weight (200-500 Daltons), planar, tricyclic, or polycyclic configurations, heteroatoms in their structure to enable resonance stabilization, and aromatic halogen substituents. The absorption maximum refers to the ability of the chemical to absorb light. The lipophilicity of a drug is an important factor in its ability to reach the skin. Doxycycline has a molecular weight of 444.4 Daltons, a tetracyclic configuration, and does not contain heteroatoms or aromatic halogen atoms. Its absorption maximum is 352 nm, which is in the UVA spectrum. The photosensitivity effect created by doxycycline is dependent on the medication dose, UVA intensity, and the skin phenotype. Demeclocycline is the strongest photosensitizer of the tetracycline group; however, it is rarely used. Tetracycline is also known to cause phototoxic reactions, but less so than doxycycline. Minocycline is minimally phototoxic. Like sunburn, phototoxic reactions usually subside within a week. Treatment is symptomatic. Avoiding the offending agent and excessive sunlight exposure is required. It is important to apply sunscreen 15 minutes before exposure and repeat at least every 2 hours. If excessive sun is difficult to avoid—as in a wintertime cruise to a high UV-light destination—discontinue the medication for several days and restart. Of note, window glass transmits sunlight above 330 nm, which is in the UVA range, and artificial room lighting contains wavelengths above 370 nm. For this series, the recommended choices are: 1, d; 2, c; 3, a.

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%.

Background Ambient particulate matters (PMs) are known as inducers that adversely affect a variety of human organs. Objectives In this study, we aimed to evaluate the influence of PMs on the permeation of drugs and sunscreens via the skin. The role of skin-barrier properties such as the stratum corneum (SC) and tight junctions (TJs) during the delivery process was explored. Methods This work was conducted using both in vitro and in vivo experiments in pigs to check the responses of the skin to PMs. PMs primarily containing heavy metals (1648a) and polycyclic aromatic hydrocarbons (PAHs, 1649b) were employed to treat the skin. Results According to the transepidermal water loss (TEWL), 1649b but not 1648a significantly disrupted the SC integrity by 2-fold compared to the PBS control. The immunohistochemistry (IHC) of cytokeratin, filaggrin, and E-cadherin exhibited that 1649b mildly damaged TJs. The cytotoxicity of keratinocytes and skin fibroblasts caused by 1649b was stronger than that caused by 1648a. The 1649b elicited apoptosis via caspase-3 activation. The proteomic profiles showed that PMs upregulated Annexin A2 by >5-fold, which can be a biomarker of PM-induced barrier disruption. We found that the skin uptake of ascorbic acid, an extremely hydrophilic drug, was increased from 74 to 112 μg/g by 1649b treatment. The extremely lipophilic drug tretinoin also showed a 2.6-fold increase of skin accumulation. Oxybenzone and dextran absorption was not affected by PMs. The in vivo dye distribution visualized by fluorescence microscopy had indicated that 1649b intervention promoted permeant partitioning into SC. Conclusions Caution should be taken in exposing the skin to airborne dust due to its ability to reduce barrier function and increase the risk of drug overabsorption, although this effect was not very marked.

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.

Background: There are considerable data to suggest that protection from solar ultraviolet (UV) radiation will reduce the risk of acute and chronic skin damage in humans. Whereas the sun protection factor (SPF) provides an index of protection against erythemally effective solar UV, largely confined to the UVB (290-320 nm) and short-wavelength UVA (320-340 nm) region, there is currently no agreed-upon method to measure broad-spectrum protection against long-wavelength UVA (340-400 nm). Objective: The objective of these studies was to assess the potential of in vitro UV substrate spectrophotometry and subsequent calculation of the "critical wavelength" value as a measure of broad-spectrum UV protection and as a routine, practical procedure for classification of sunscreen products. Methods: The spectral absorption of 59 commercially available sunscreen products and multiple experimental formulas with one or more UV filters was measured. Sunscreen product, 1 mg/cm 2 , was applied to a hydrated synthetic collagen substrate, preirradiated with a solar simulator, and then subjected to UV substrate spectrophotometry. Multiple determinations from 5 independent samples per product were used to calculate the critical wavelength value, defined as the wavelength at which the integral of the spectral absorbance curve reached 90% of the integral from 290 to 400 nm. Results: We found that a recognized long-wave UVA active ingredient such as titanium dioxide, zinc oxide, or avobenzone is a necessary but insufficient product requirement for achieving the highest proposed broad-spectrum classification, that is, critical wavelength of 370 nm or more. Although SPF and critical wavelength are largely independent of each other, UVA absorbance must increase commensurate with SPF to maintain the same critical wavelength value. Substrate spectrophotometry and the calculation of critical wavelength can readily account for sunscreen photostability by UV preirradiation. Finally, there is also a strong positive relationship between critical wavelength and a currently available in vivo measure of UVA protection. Conclusion: Determination of critical wavelength by means of UV substrate spectrophotometry provides a rapid, inexpensive, and reliable measure of broad-spectrum protection, which is largely independent of SPF, yet ensures long-wavelength UVA protection commensurate with SPF. The procedure provides a routine, sensitive means of differentiating and classifying sunscreen products and, importantly, obviates the need to subject volunteers to acute exposures of high-dose, nonterrestrial UV, the health risks of which are still poorly understood. (J Am Acad Dermatol 2000;43:1024-35.)

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.

To the Editor: Recently 2 very interesting, stimulating articles about sunscreens appeared. The first from Ou-Yang et al reports sun-protection factors (SPFs) of 6 sunscreens, SPF 30 to 100, tested at 4 application rates from 0.5 to 2.0 mg/cm. They suggest that because sunscreen users may apply much less than the prescribed 2 mg/cm, SPFs as high as 100 are valuable because at 0.5 mg/cm at least SPF 30 protection remains. The other by Chouteau et al, testing both sunscreen products and active ingredients, reported that 13 of 21 showed antiinflammatory activity, including, interestingly, all ingredients in the SPF 100 products in the study of Ou-Yang et al. Table I shows sunscreen product amount applied over 0.5, 1, and 2 m body surface areas based on several of the application densities reported by Ou-Yang et al, and the corresponding topically applied amount of potential anti-inflammatory sunscreen agents. Because today’s sunscreen products are very water resistant, applied sunscreen is very efficiently absorbed into the body potentially at levels with pharmacologic significance. The SPF 100 products contained 5 sunscreens comprising 39% of their total weight, over half of which are salicylates, relatives of aspirin, reasonably expected to exhibit some degree of analogous antiinflammatory activity. Following this aspirin analogy, the amount of anti-inflammatory sunscreen agent applied to the skin is comparable to 2.5 to more than 40 tablets, not trivial levels of potent drugs. The sunscreens oxybenzone and dioxybenzone have in fact been patented as anti-inflammatory agents shown to be effective in attenuating ultraviolet-induced erythema when applied following exposure. In addition, several sunscreen agents were also reported as inhibiting the inflammatory mediator, inducible nitric oxide synthase. On the basis of these data, particularly that oxybenzone present in each of the products reported by Ou-Yang et al independently reduces ultraviolet erythema via anti-inflammatory mechanism(s) rather than the inherent optical attenuation of ultraviolet, the conclusions reached by Ou-Yang et al must be reconsidered. Robert M. Sayre, PhD, John C. Dowdy, PhD, and E. William Rosenberg, MD Rapid Precision Testing Laboratories, Cordova; Division of Dermatology, Department of Medicine, University of Tennessee Health Science Center, Memphis; and Department of Physics, University of Memphis

We used noninvasive Fourier transform (FT) Raman spectroscopy to follow the fate of the broadly used ultraviolet UVA sun blocker, oxybenzone, after topical application to the skin. Our results showed that oxybenzone is rapidly photo-oxidized, yielding oxybenzone semiquinone, a potent electrophile, which reacts with thiol groups on important anti-oxidant enzymes and substrates, such as thioredoxin reductase and reduced glutathione, respectively. Although oxybenzone is an excellent broad spectrum UVA filter, its rapid oxidation followed by the inactivation of important antioxidant systems indicates that this substance may be rather harmful to the homeostasis of the epidermis. Furthermore, these results demonstrate that ET-Raman spectroscopy is a useful method for studying the transport and metabolism of active ingredients in topical preparations.

Purpose. In order to improve our knowledge on the efficacy and safety of sunscreen products, we measured the skin penetration profiles of ultra-violet (UV) filters in vitro and in vivo, and the corresponding sun protection factors (SPF) from two vehicles (an O/W emulsion-gel and petroleum jelly). Methods. The UV filters tested were oxybenzone (5%, A), 2-ethylhexyl 4-methoxycinnamate (7.5%, B), and 2-ethylhexylsalicylate (3%, C). Two mg/cm2 were applied for 2 min to 6 h. In vitro penetration measurements were performed with static diffusion cells. In vivo, horny layer concentrations were measured after stripping and the SPF evaluated as recommended by the COLIPA-guidelines. Results. Significant differences between vehicles were noticed in vitro as well as in vivo. In vitro, the emulsion-gel generated higher epidermal concentrations than petroleum jelly. Values at 6 h, expressed as percent of the applied dose for A, B, and C were 4, 9, and 7% for the emulsion-gel and 2, 1, and 2% for petroleum jelly. An opposite trend was noticed, mainly for A, in the deeper skin layers with concentrations of 2% in the dermis and 5% in the receptor fluid for petroleum jelly and 0.6% and 1% for the emulsion-gel respectively. In vivo, for each UV filter, maximal stratum corneum levels (15 strips) were obtained at 0.5 h with percentages of the applied doses of 50% for the emulsion-gel and 15% for petroleum jelly. SPFs, measured 0.5 h after application amounted to 14 for the emulsion-gel and 5 for petroleum jelly, and decreased in both cases by a factor 2.2 after removal of non penetrated product. Conclusions. These preliminary results demonstrated that UV filters penetration and retention as well as expected SPF could be optimized by a suitable vehicle.

Summary A 21-year-old woman developed an erythematous papulovesicular eruption of photo-exposed sites, following the use of an oxybenzone-containing sunscreen. Patch testing, photopatch testing, phototesting, and histology produced findings strongly suggestive of oxybenzone photoallergy. Photopatch testing with a monochromator source showed abnormal UVA responses, with evidence of immediate urticaria, and delayed-onset dermatitis. Sun-barrier use is associated with a risk of the development of contact or photocontact allergic reactions. The benzophenones are frequently used in high-protection factor sun-barrier preparations, and appear to have a particular ability to induce such responses.

Background: Currently there is no consensus on a test method to determine the protectiveness of sunscreens in the UVA region alone. Objective: The protection factor in UVA (PFA) test method was evaluated to determine its ability to detect dose-response, specificity for UVA protection only, and repeatability between laboratories, and to detect whether the protection factors depended on the skin response observed (erythema or tanning). Methods: Sunscreens containing 0%, 2%, or 5% oxybenzone, or 7% octyl dimethyl para-aminobenzoic acid were tested by the PFA protocol in five laboratories. Results: The test method demonstrated ability to distinguish differences between the protection in the oxybenzone formulations but not between the placebo (0%) and the 7% octyl dimethyl para-aminobenzoic acid formula. The protection factors were independent of the type of skin response. Conclusion: These data support the utility and validity of the PFA method for determining the UVA protection provided by sunscreen products.

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

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.

Lack of recognition and regulation is having serious medical consequences Skin lightening (bleaching) cosmetics and toiletries are used to lighten the colour of darker skin. The practice, which is fuelled by racial prejudice, stems from the misconceptions that black skin is inferior and that someone with a fair skin is more attractive⇓. Seyllou/AFP/Getty Images By definition, cosmetics are meant to improve the appearance of the skin or enhance the attractiveness of users, not to alter the basic structure of the skin. Skin lightening creams alter the chemical structure of the skin by inhibiting the synthesis of melanin and should therefore be regulated as drugs not cosmetics. The active ingredients include hydroquinone, mercury, and highly potent fluorinated corticosteroid ointments and creams such as fluocinonide, betamethasone valerate, and clobetasol propionate. The list of ingredients has expanded because some manufacturers have introduced new chemicals of unknown safety—such as niacinamide, oxybenzone, and triethanolamine—to circumvent the efforts of government regulatory agencies that prohibited the use of the above chemicals in cosmetics and toiletries.1 Some products do not have ingredient labelling or place of manufacture,2 3 and inadequate regulation has provided users with easy access to cheap, substandard, and misbranded toxic products. These products are associated with serious and life threatening complications because they are used for long periods on a large body surface area and often under hot and humid tropical conditions, which promote percutaneous absorption. Complications such as exogenous ochronosis and colloid milium were initially reported in people with coloured …

The purpose of this study was to evaluate the prevalence of sunscreen contact allergy and/or contact photoallergy in 370 patients with suspected photodermatitis. Patch and photopatch tests were performed using the French Society of Photodermatology (SFPD) standard series. A total of 57 cases of contact allergy and/or photocontact allergy to sunscreens were diagnosed (15.4%). Amongst these, 27 reactions were related to oxybenzone and 14 to isopropyl dibenzoylmethane. These results, obtained from January 1990 to December 1994, confirm that, given the high frequency of photosensitization cases, a large part of the battery of photopatch tests should be dedicated to sunblocks.

About 15 min after applying a sunscreen (Sunspray SPF 15 water resistant; Hegron Cosmetics , Purmerend, the Netherlands) all over her body and before sun exposure, a 44-year-old woman fainted with generalized wheals, an inspiratory stridor, low blood pressure (74/46 mmHg), and increased heart rate. She required resuscitation with epinephrine, dexamethasone, clemastine, and saline and was transferred to a hospital. Some months before, she had experienced pruritus, erythema, and nausea within 30 min of putting on her bathing suit, which she had also worn earlier while she applied the sunscreen. She had used the sunscreen previously without apparent problem. She had no relevant past history. Patch testing with benzophenone-3 (10%pet.;Trolab ,Hermal,Reinbek, Germany) resulted in an urticarial reaction at the test site within 20 min. Patch tests with the European baseline series (TRUE test; Mekos, Hillerod, Denmark) and textile, cosmetic, and perfume series were negative. Photo patch tests (without benzophenone-3) were negative. No specific immunoglobulin E (IgE) antibodies were found against inhalation allergens or latex. An assay for detection of IgE to benzophenone-3 was explored by incubating benzophenone-3 with human serum albumin immobilized to caps followed by specific IgE measurement (ImmunoCap; Phadia, Uppsala, Sweden), but no specific IgE to benzophenone-3 could be detected.

Background/purpose: Oxybenzone is an active ingredient found in sunscreen products that absorbs a broad spectrum of ultraviolet (UV) light, with absorbance peaking in the UVB region and extending into the UVA region. Although the overall incidence of sensitization and irritation associated with oxybenzone in the general population remains unclear, a few studies have reported on the incidence in specific circumstances. However, the relevance of these studies to the general population is limited, because the sample populations reported in these papers generally have consisted of individuals who sought medical attention for pre-existing skin conditions. Therefore, the reported incidence of allergic reactions to oxybenzone in these studies may be overestimated as related to the general population. The objective of this meta-analysis was to determine the safety of oxybenzone in participants recruited from the general population. Methods: The data from 64 unpublished exaggerated use human repeat insult patch tests (HRIPT) and photoallergy (PA) studies sponsored by Schering-Plough HealthCare Products Inc. between 1992 and 2006 were aggregated and analyzed to evaluate the irritancy and sensitization potential of sunscreen products containing oxybenzone at concentrations between 1% and 6%. Results: Forty-eight of 19 570 possible dermal responses were considered to be suggestive of irritation or sensitization; the mean rate of responses across all formulations was 0.26%. Sensitization rates did not correlate significantly with oxybenzone concentration. The available re-challenge data indicated that only eight of these responses were contact allergies from oxybenzone, and the mean rate of contact allergy to oxybenzone was 0.07%. The source of the skin responses was not confirmed for 15 subjects who were lost to follow-up. However, all subjects were given the opportunity to participate in follow-up testing. Conclusion: Our data indicate that sunscreen products formulated with 1–6% oxybenzone do not possess a significant sensitization or irritation potential for the general public. Furthermore, these data suggest that the incidence rate implied in the published literature overestimates the actual incidence of sensitization/irritation due to oxybenzone-containing sunscreen products in the general population.

The complex composition of lipstick formulations usually needs the use of organic solvents for sample dissolution. A treatment based on dissolution of cosmetic samples in ethanol-water (70 : 30, v/v) by use of ultrasonic irradiation is proposed. A C(18) stationary phase and an isocratic mobile phase of ethanol:water:acetic acid (70 : 29.5 : 0.5, v/v/v) with a flow rate of 1 mL min(-1) and an injection volume of 20 microL is proposed for the high-pressure liquid chromatography (HPLC) determination of four UV-filters, and detection was carried out at 309 nm. The limit of the chromatographic detection was 7.0 microg mL(-1) for butyl methoxydibenzoylmethane, 1.5 microg mL(-1) for benzophenone-3, 1.4 microg mL(-1) for octyl dimethyl p-aminobenzoic acid (octyl dimethyl PABA) and 2.7 microg mL(-1) for octyl methoxycinnamate. The relative standard deviations of the results were between 1.8 and 2.4%. The results were comparable to those obtained by a procedure based on the use of tetrahydrofuran. The method can be considered as a green analytical procedure because it only requires the use of small quantities of ethanol.

Defence against oxidative damage by UV-generated free radicals in both guinea pig and human skin has been found to be mediated by the ubiquitous thioprotein, thioredoxin reductase. Human keratinocytes contain approximately 5% thioredoxin reductase in their total acidic protein fraction and also express membrane-associated enzyme activity in cells cultured in synthetic medium. The thioredoxin reductase/thioredoxin system has been shown to reduce superoxide anion radicals through hydrogen peroxide to water. However, both UVA and UVB radiation, below the minimal erythemal dose, generate a sufficiently high concentration of oxygen radicals to deactivate thioredoxin reductase considerably. In albino guinea pigs, enzyme deactivation was up to 70% for UVA and 66% for UVB (n = 10 animals/protocol). The application of sun blockers SPF4, SPF8 and SPF15 to albino guinea pig skin offered no significant protection for the deactivation of thioredoxin reductase by either UVA or UVB radiation. In the human population (n = 15), thioredoxin reductase was deactivated by 54% with UVA and 36% with UVB radiation, although the degree of enzyme inhibition depended on skin phototype (I-VI, Fitzpatrick Classification). SPF24 offered considerable protection for thioredoxin reductase against both UVA and UVB for skin types I and II. However, SPF24 yielded no significant protection with UVA for skin types III-VI, and enhanced the enzyme inhibition with UVB additively. These results indicate that UVB photo-oxidation of oxybenzone (the UVA filter in SPF24) may deactivate thioredoxin reductase in more pigmented members of the population by Michael addition of oxybenzone semiquinone to the thiolate active site of this enzyme.

We report the epidemiology of sunscreen allergy over a period of 5 years at the National Skin Centre. A total of 61 patients with suspected allergy to sunscreen underwent patch or photopatch testing to our sunscreen series from 1992 to 1996. The results were retrospectively analysed and evaluated. Out of these 61 patients, 5 were found to have positive patch test reactions to sunscreens. 2 were photoallergic, and 3 were allergic to active ingredients in sunscreens. The main causative allergens were 2-ethylhexyl-4-methoxycinnamate (Parsol MCX) and 2-hydroxy-4-methoxybenzophenone (oxybenzone). We conclude that sunscreen contact allergy is uncommon in our practice.

Summary Background Insect repellents and sunscreens are over-the-counter products extensively used by the general public. Concurrent application of these products has become widespread in many regions across North America, because of concerns about West Nile virus and skin cancers. Objectives We investigated whether formulation type, application amount, and sequence would affect the percutaneous absorption profiles of the active repellent and sunscreen ingredients. Methods In vitro percutaneous permeation of the repellent N,N-diethyl-m-toluamide (DEET) and the sunscreen oxybenzone from concurrent application of five commercially available products (A, repellent spray; B, repellent lotion; C, sunscreen lotion; D and E, combined repellent/sunscreen lotions) was measured and compared using Franz-style diffusion cells with piglet skin at 37 °C. Results Penetration of DEET in A and B increased by 1640% and 282%, respectively, when C was applied concurrently. Penetration of DEET in D and E was 53% and 79% higher than that in B. Permeation of DEET from A + C (2 : 1) and A + C (1 : 2) increased by 530% and 278%, respectively. Permeation of oxybenzone was 189% and 280% higher in A + C and B + C than in C. Permeation of oxybenzone in D and E was also 221% and 296% higher than that in C. Permeation of oxybenzone was 196% greater when A was applied on top of C than when C was applied on top of A, while oxybenzone in A + C (1 : 2) permeated 171% more than that in A + C (2 : 1). Conclusions Concurrent application of commercially available repellent and sunscreen products resulted in significant synergistic percutaneous permeation of the repellent DEET and the sunscreen oxybenzone in vitro. The percutaneous penetration profiles were dependent upon the type of formulation, application sequence and application proportion.