In vitro safety evaluation of (6-methoxy-9-oxo-9H-xanthen-2-yl)methyl (E)-3-(2,4-dimethoxyphenyl)acrylate (K-116) - the novel potential UV filter designed by means of a double chromophore strategy.

The use of topical photoprotection is necessary to reduce adverse effects caused by excessive exposure to ultraviolet radiation. Despite the high standards set for UV filters, many of them may contribute to the occurrence of adverse effects. The newly synthesised compound K-116, the (E)-cinnamoyl xanthone derivative, could be an alternative. We conducted extended in vitro safety evaluation of compound K-116. The research included assessment of irritation potential on skin tissue, evaluation of penetration through the epidermis, and assessment of phototoxicity, and mutagenicity. Additionally, the eco-safety of compound K-116 was evaluated, including an examination of its degradation pathway in the Cunninghamella echinulata model, as well as in silico simulation of the toxicity of both the parent compound and its degradation products. The research showed that compound K-116 tested in future application conditions is deprived of skin irritant potential additionally it does not penetrate through the epidermis. Results showed that K-116 concentrate is not phototoxic and not mutagenic. The eco-safety studies showed that it undergoes biodegradation in 27% in Cunninghamella echinulata model. The parent compound and formed metabolite are less toxic than reference UV filters (octinoxate and octocrylene).

Ecotoxicological assessment of UV filters benzophenone-3 and TiO2 nanoparticles, isolated and in a mixture, in developing zebrafish (Danio rerio).

The increasing use of UV filters, such as benzophenone-3 (BP-3) and titanium dioxide nanoparticles (TiO2 NPs), has raised concerns regarding their ecotoxicological effects on the aquatic environment. The aim of the present study was to examine the embryo-larval toxicity attributed to BP-3 or TiO2 NPs, either alone or in a mixture, utilizing zebrafish (Danio rerio) as a model after exposure to environmentally relevant concentrations of these compounds. Zebrafish embryos were exposed to BP-3 (10, 100, or 1000 ng/L) or TiO2 NPs (1000 ng/L) alone or in a mixture (BP-3 10, 100, or 1000 ng/L plus 1000 ng/L of TiO2 NPs) under static conditions for 144 hr. After exposure, BP-3 levels were determined by high-performance liquid chromatography (HPLC). BP-3 levels increased in the presence of TiO2 NPs, indicating that the BP-3 degradation decreased in the presence of the NPs. In addition, in the presence of zebrafish, BP-3 levels in water decreased, indicating that zebrafish embryos and larvae might absorb BP-3. Data demonstrated that, in general, environmentally relevant concentrations of BP-3 and TiO2 NPs, either alone or in a mixture, did not significantly induce changes in heart and spontaneous contractions frequencies, levels of reactive oxygen species (ROS), morphological and morphometric parameters as well as mortality rates during 144 hr exposure. However, the groups exposed to TiO2 NPs alone and in a mixture with BP-3 at 10 ng/L exhibited an earlier significant hatching rate than the controls. Altogether, the data indicates that a potential ecotoxicological impact on the aquatic environment exists.

Use of in vitro ADME methods to identify suitable analogs of homosalate and octisalate for use in a read-across safety assessment.

Case studies are needed to demonstrate the use of human-relevant New Approach Methodologies in cosmetics ingredient safety assessments. For read-across assessments, it is crucial to compare the target chemical with the most appropriate analog; therefore, reliable analog selection should consider physicochemical properties, bioavailability, metabolism, as well as the bioactivity of potential analogs. To complement in vitro bioactivity assays, we evaluated the suitability of three potential analogs for the UV filters, homosalate and octisalate, according to their in vitro ADME properties. We describe how technical aspects of conducting assays for these highly lipophilic chemicals were addressed and interpreted. There were several properties that were common to all five chemicals: they all had similar stability in gastrointestinal fluids (in which no hydrolysis to salicylic occurred); were not substrates of the P-glycoprotein efflux transporter; were highly protein bound; and were hydrolyzed to salicylic acid (which was also a major metabolite). The main properties differentiating the chemicals were their permeability in Caco-2 cells, plasma stability, clearance in hepatic models, and the extent of hydrolysis to salicylic acid. Cyclohexyl salicylate, octisalate, and homosalate were identified suitable analogs for each other, whereas butyloctyl salicylate exhibited ADME properties that were markedly different, indicating it is unsuitable. Isoamyl salicylate can be a suitable analog with interpretation for octisalate. In conclusion, in vitro ADME properties of five chemicals were measured and used to pair target and potential analogs. This study demonstrates the importance of robust ADME data for the selection of analogs in a read-across safety assessment.

Human exposure risk of organic UV filters: A comprehensive analysis based on primary exposure pathways.

The exposure of organic UV filters has been increasingly confirmed to induce adverse effects on humans. However, the critical exposure pathway and the vulnerable population of organic UV filters are not clearly identified. This paper attempts to evaluate the health risk of commonly used organic UV filters from various exposure routes based on comprehensive analysis strategy. The estimated daily intakes (EDI) and hazard quotient (HQ) values of organic UV filters through four pathways (dermal exposure, indoor dust, indoor air, and drinking water) for various age groups were determined. Although the total HQ values (0.01-0.4) from comprehensive exposure of organic UV filters were below risk threshold (1.0), infants were identified as the most vulnerable population, with EDI (75.71 ng/kg-bw/day) of 2-3 times higher than that of adults. Additionally, the total EDI values of individual exposure pathways were estimated and ranked as follows: indoor air (138.44 ng/kg-bw/day) > sunscreen application (37.2 ng/kg-bw/day) > drinking water (21.87 ng/kg-bw/day) > indoor dust (9.24 ng/kg-bw/day). Moreover, we successfully tailored the Sankey diagram to depict the EDI proportion of individual organic UV filters from four exposure pathways. It was noted that EHMC (ethylhexyl methoxycinnamate) and EHS (ethylhexyl salicylate) dominated the contribution of EDI (72 %) via indoor air exposure routes. This study serves as a crucial reference for enhancing public health risk awareness concerning organic UV filters, with a special focus on the vulnerable populations such as infants and children.

Prevalence of selected UV filter compounds in Biscayne National Park.

This research was carried out in order to assess a baseline occurrence in Biscayne National Park, Florida, of four organic contaminants: the UV filters oxybenzone, dioxybenzone, and benzophenone, as well as the topical pain reliever benzocaine. A total of 35 samples were taken from five locations within the park, four near barrier islands, and one at a coral reef. Analyses were carried out using liquid chromatography coupled to high-resolution mass spectrometry. Oxybenzone was detected in 26% of samples from the park at concentrations up to 31 ng/L. Benzophenone was detected in 49% of samples from the park at concentrations up to 131 ng/L. Benzocaine and dioxybenzone were not detected in any of the samples.

The effects of UV filters on health and the environment.

Sunscreens are an important means of protection against sunburns, dyspigmentation, photoaging, and photocarcinogenesis. Sunscreens come in a variety of formulations that can protect against ultraviolet B (UVB) radiation, both UVB and ultraviolet A (UVA) radiation (broad-spectrum sunscreens), and UVB, UVA, and visible light (tinted broad-spectrum sunscreens). In the USA, there is currently a paucity of FDA-approved broad-spectrum filters on the market. Studies have identified the presence of multiple UV filters in water sources globally. Many laboratory studies have implicated the potential impact of UV filters on coral reef bleaching, the food chain, and human health. However, many of these studies are performed at concentrations that are much higher than those present in the natural environment. With increasing discussion surrounding the role of organic and inorganic UV filters as potential environmental pollutants over the past decade, approval of additional broad-spectrum filters would be an important means of alleviating the use of more controversial filters. The aim of this article is to review the effects of UV filters on health and the environment and explore potential adjunctive agents for photoprotection.

Spectra and photorelaxation of tris-biphenyl-triazine-type UV absorbers: from monomers to nanoparticles.

Water-insoluble organic UV filters like tris-biphenyl-triazine (TBPT) can be prepared as aqueous dispersions of nanoparticles. The particles consist of the respective UV absorber molecules and show strong UV absorbance. Since there is a certain solubility of such UV absorbers in organic solvents, it is possible to measure the absorbance spectrum also in solution, for instance in ethanol or dioxane. The UV spectrum of the aqueous dispersion shows a slight hypsochromic shift of the original band with an additional shoulder at longer wavelengths. For the understanding of the observed changes of UV-Vis spectra of this UV absorber, either dissolved in an organic solvent or dispersed as nanoparticles in water, DFT calculations were carried out with the respective monomer and aggregates of TBPT molecules in the different media. The calculated UV-Vis spectra of isolated, that means dissolved, TBPT molecules in ethanol and in dioxane agree well with experimentally observed ones. The observed changes in the shape of experimental UV-Vis spectra in aqueous dispersion cannot be explained with a solvent effect only. It was found that the studied molecules could form stable energetically favorable π-stacked aggregates, which show UV-Vis spectra in reasonable agreement with those experimentally observed in aqueous dispersion. Such aggregates of TBPT are most likely the reason for the observed additional shoulder in the UV/vis absorbance spectrum. In addition, the mechanism of the photochemical deactivation of excited TBPT molecules was studied in detail with TD DFT in dioxane and in water.

Ultraviolet filters in the United States and European Union: A review of safety and implications for the future of US sunscreens.

BACKGROUND: Availability of new UV filters in the United States lags behind the European Union (EU), partly due to differing approval processes. OBJECTIVE: To review available human safety data of all US- and EU-approved UV filters. METHODS: Data from Food and Drug Administration and EU regulatory guidelines, federal governmental documentation, databases, reviews, and opinions for approval and ongoing safety evaluation were analyzed. RESULTS: Currently, there are 17 US UV filters and 29 EU UV filters (18 EU-approved only filters). Almost all US filters possessed sensitization data (94%, 16/17) with the majority (76%, 13/17) showing minimal skin sensitization. The minority of EU-approved only filters (33%, 6/18) possessed sensitization data, all showing no sensitization. Some filters possessed dermal absorption data (US: 76%, 13/17; EU: 44%, 8/18). Oxybenzone, octinoxate, octisalate, homosalate, and octocrylene, approved in the US and EU, were shown to have plasma levels exceeding the Food and Drug Administration exposure threshold. LIMITATIONS: Proprietary manufacturer human data were unavailable. CONCLUSIONS: Many new UV filters are available in the EU, but not yet in the United States. Rigorous US and EU guidelines ensure that UV filters provide adequate photoprotection assuming consumers follow American Academy of Dermatology SPF (sun protection factor) and broad-spectrum recommendations. Human data are limited, but known human risks of sunscreen appear minimal.

Binding of common organic UV-filters to the thyroid hormone transport protein transthyretin using in vitro and in silico studies: Potential implications in health.

Several anthropogenic contaminants have been identified as competing with the thyroid hormone thyroxine (T4) for binding to transport proteins as transthyretin (TTR). This binding can potentially create toxicity mechanisms posing a threat to human health. Many organic UV filters (UVFs) and paraben preservatives (PBs), widely used in personal care products, are chemicals of emerging concern due to their adverse effects as potential thyroid-disrupting compounds. Recently, organic UVFs have been found in paired maternal and fetal samples and PBs have been detected in placenta, which opens the possibility of the involvement of TTR in the transfer of these chemicals across physiological barriers. We aimed to investigate a discrete set of organic UVFs and PBs to identify novel TTR binders. The binding affinities of target UVFs towards TTR were evaluated using in vitro T4 competitive binding assays. The ligand-TTR affinities were determined by isothermal titration calorimetry (ITC) and compared with known TTR ligands. In parallel, computational studies were used to predict the 3-D structures of the binding modes of these chemicals to TTR. Some organic UVFs, compounds 2,2',4,4'-tetrahydroxybenzophenone (BP2, Kd = 0.43 µM); 2,4-dihydroxybenzophenone (BP1, Kd = 0.60 µM); 4,4'-dihydroxybenzophenone (4DHB, Kd = 0.83 µM), and 4-hydroxybenzophenone (4HB, Kd = 0.93 µM), were found to display a high affinity to TTR, being BP2 the strongest TTR binder (ΔH = -14.93 Kcal/mol). Finally, a correlation was found between the experimental ITC data and the TTR-ligand docking scores obtained by computational studies. The approach integrating in vitro assays and in silico methods constituted a useful tool to find TTR binders among common organic UVFs. Further studies on the involvement of the transporter protein TTR in assisting the transplacental transfer of these chemicals across physiological barriers and the long-term consequences of prenatal exposure to them should be pursued.

A time trend of urinary 4-methylbenzylidene camphor metabolites in young adults from Germany.

4-methylbenzylidene camphor (4-MBC) is used as a UV-B filter in cosmetics. Two oxidized metabolites of 4-MBC - 3-(4-carboxybenzylidene)camphor (cx-MBC) and 3-(4-carboxybenzylidene)-6-hydroxycamphor (cx-MBC-OH) - were analyzed in 250 24-h urine samples from young adults in Germany. The samples were from the German Environmental Specimen Bank (ESB) and represented exposure in the years 1995, 2005, 2010, 2015 and 2019. A UHPLC-MS/MS method enabled the sensitive determination of both metabolites, with limits of quantification at 0.15 µg L-1 (cx-MBC) and 0.30 µg L-1 (cx-MBC-OH), respectively. A temporal trend of the internal exposure to 4-MBC was clearly noticeable. The metabolite cx-MBC was frequently quantifiable at the beginning of the period: in 70% of the samples in 1995, and 56% in 2005. After 2005, urinary concentrations and detection rates of cx-MBC dropped to reach very low levels. In 2015 and 2019, the detection rate was only 2% and 0%, respectively. A similar trend was observed for cx-MBC-OH, though overall, this metabolite was detected less often and at lower concentration levels than cx-MBC. Nowadays, measurable levels of urinary 4-MBC metabolites are an extremely rare occurrence in Germany. These trends are consistent with the history of 4-MBC use by the cosmetic industry. The highest measured individual concentration of 16.20 µg L-1 (in a sample of the year 2005) was still more than 30 times below the health-based guidance value (HBM-I). An investigation of the ratios between both metabolites uncovered several features of the 4-MBC metabolism which have been essentially overlooked until now. In particular, stereochemical aspects should be explored in future studies. As urine was collected in autumn/winter in Northwestern Germany, the 4-MBC metabolites measured probably do not arise from sunscreen products in a narrow sense. They rather may reveal the use of other skin care products containing 4-MBC for UV protection as an added feature.

Shedding a light on the importance of photopatch testing: A 12-year experience in a dermatology unit.

BACKGROUND: Photopatch testing has been standardized for diagnosing photoallergic contact dermatitis but is still infrequently used. OBJECTIVES: To characterize photopatch test (PPT) results and their clinical relevance. METHODS: We collected retrospective data from patients photopatch tested in our Dermatology Unit (2010-2021), using the European PPT 'baseline' series, other allergens, and patient's own products, when appropriate. RESULTS: Out of 223 patients, 75 patients (33.6%) were reactive with 124 positive PPT reactions, considered relevant in 56/223 patients (25.1%) and in 72/124 reactions (58.1%). Most reactions were caused by topical drugs (n = 33; 45.8%), such as ketoprofen or promethazine, and 7 (9.8%) by systemic drugs, such as hydrochlorothiazide and fenofibrate. 'Classical' ultraviolet filters were responsible for six positive PPT reactions whereas there was only three relevant PPT to the 'newer' UV filters. Patients' sunscreens/cosmetics or plant extracts caused 10 positive PPT each. Additional patch test reactions were observed, mostly to Tinosorb® M. CONCLUSION: Contrary to the trend in ACD, most positive PPT reactions were caused by topical drugs, outweighing ultraviolet filters and cosmetics. We stress the low reactivity to the 'newer' UV filters included in the PPT series. PPT was occasionally positive in systemic drug photosensitivity, but overall PPT reactivity was low.

Insights on the UV-Screening Potential of Marine-Inspired Thiol Compounds.

One of the major threats to skin aging and the risk of developing skin cancer is excessive exposure to the sun's ultraviolet radiation (UVR). The use of sunscreens containing different synthetic, organic, and inorganic UVR filters is one of the most widespread defensive measures. However, increasing evidence suggests that some of these compounds are potentially eco-toxic, causing subtle damage to the environment and to marine ecosystems. Resorting to natural products produced in a wide range of marine species to counteract UVR-mediated damage could be an alternative strategy. The present work investigates marine-inspired thiol compounds, derivatives of ovothiol A, isolated from marine invertebrates and known to exhibit unique antioxidant properties. However, their potential use as photoprotective molecules for biocompatible sunscreens and anti-photo aging formulations has not yet been investigated. Here, we report on the UVR absorption properties, photostability, and in vitro UVA shielding activities of two synthetic ovothiol derivatives, 5-thiohistidine and iso-ovothiol A, by spectrophotometric and fluorimetric analysis. We found that the UVA properties of these compounds increase upon exposure to UVA and that their absorption activity is able to screen UVA rays, thus reducing the oxidative damage induced to proteins and lipids. The results of this work demonstrate that these novel marine-inspired compounds could represent an alternative eco-friendly approach for UVR skin protection.

A Comparative Study between Onion Peel Extracts, Free and Complexed with ß-Cyclodextrin, as a Natural UV Filter to Cosmetic Formulations.

The growing concern regarding the adverse effects of synthetic UV filters found in sunscreens has spurred significant attention due to their potential harm to aquatic ecosystems and human health. To address this, the present study aimed to extract and microencapsulate sensitive bioactive compounds derived from by-product onion peel (OP) by molecular inclusion using ß-cyclodextrin as the wall material. Identification and quantification of bioactive compounds within the extract were conducted through high-performance liquid chromatography (HPLC-DAD) analysis, revealing quercetin and resveratrol as the primary constituents. The photoprotection capacity, evaluated by the sun protection factor (SPF), revealed a protection factor comparable to the value for a synthetic UV filter. The produced microparticles presented high antioxidant capacity, significant photoprotection capacity, encapsulation efficiency of 91.8%, mean diameter of 31 µm, and polydispersity of 2.09. Furthermore, to comprehensively evaluate the performance of OP extract and its potential as a natural UV filter, five O/W emulsions were produced. Results demonstrated that microparticles displayed superior ability in maintaining SPF values over a five-week period. Photoprotection evaluation-skin reactivity tests revealed that both extract and microparticles absorb UV radiation in other regions of UV radiation, revealing their potential to be used as a natural UV filter to produce a sustainable and eco-friendly value-added sunscreen.

First In Vivo Insights on the Effects of Tempol-Methoxycinnamate, a New UV Filter, as Alternative to Octyl Methoxycinnamate, on Zebrafish Early Development.

The demand for organic UV filters as active components in sunscreen products has rapidly risen over the last century, as people have gradually realized the hazards of overexposure to UV radiation. Their extensive usage has resulted in their ubiquitous presence in different aquatic matrices, representing a potential threat to living organisms. In this context, the need to replace classic UV filters such as octyl methoxycinnamate (OMC), one of the most popular UV filters reported to be a potential pollutant of aquatic ecosystems, with more environmentally friendly ones has emerged. In this study, using zebrafish, the first in vivo results regarding the effect of exposure to tempol-methoxycinnamate (TMC), a derivative of OMC, are reported. A comparative study between TMC and OMC was performed, analyzing embryos exposed to similar TMC and OMC concentrations, focusing on morphological and molecular changes. While both compounds seemed not to affect hatching and embryogenesis, OMC exposure caused an increase in endoplasmic reticulum (ER) stress response genes, according to increased eif2ak3, ddit3, nrf2, and nkap mRNA levels and in oxidative stress genes, as observed from modulation of the sod1, sod2, gpr, and trx mRNA levels. On the contrary, exposure to TMC led to reduced toxicity, probably due to the presence of the nitroxide group in the compound's molecular structure responsible for antioxidant activity. In addition, both UV filters were docked with estrogen and androgen receptors where they acted differently, in agreement with the molecular analysis that showed a hormone-like activity for OMC but not for TMC. Overall, the results indicate the suitability of TMC as an alternative, environmentally safer UV filter.

Novelty Cosmetic Filters Based on Nanomaterials Composed of Titanium Dioxide Nanoparticles.

The following work describes the synthesis of new physical filters based on TiO2/SiO2 and TiO2/Ag nanostructures. Titanium dioxide nanoparticles (TiO2 NPs) were applied as control material and a popular physical UV filter. The advantage of using materials on the nanometer scale is the elimination of the skin whitening effect that occurs when using photoprotective cosmetics containing titanium dioxide on a macro scale. In addition, the silica coating makes the material less harmful, and the silver coating enriches the material with antibacterial properties. Nanoparticles and nanostructures have been characterized by Energy Dispersive X-Ray Analysis (EDX), the Scanning Electron Microscope (SEM), Transmission Electron Microscopy (TEM), and Fourier-Transform Infrared Spectroscopy (FT-IR) methods. Due to the use of physical filters in anti-radiation protection cosmetics, water-in-oil (W/O) emulsion has been prepared. All cosmetic formulations have been tested for stability. The sun protection research with the Sun Protection Diagnostic SP37 was carried out. These studies made it possible to determine the natural sun protection time and to compare the synthesized materials. Furthermore, one of the most important parameters when describing this type of cosmetic is water resistance, which has also been measured. The results show that the new type of material of TiO2/Ag used as a new physical filter in emulsion W/O shows the best sun protection compared with other obtained nanomaterials. It is most likely due to the improved optical properties of the combination of noble metals, for example, silver with TiO2.

A Novel Approach in Skin Care: By-Product Extracts as Natural UV Filters and an Alternative to Synthetic Ones.

The cosmetic industry has been focusing on replacing synthetic ingredients with natural ones, taking advantage of their bioactive compounds. This work assessed the biological properties of onion peel (OP) and passion fruit peel (PFP) extracts in topical formulations as an alternative to synthetic antioxidants and UV filters. The extracts were characterized regarding their antioxidant capacity, antibacterial capacity and sun protection factor (SPF) value. Results revealed that the OP extract exhibited better results, which can result from the high concentrations of quercetin, as identified and quantified in HPLC analysis. Afterward, nine formulations of O/W creams were produced with minor changes in the quantity of additives: OP and PFP extract (natural antioxidants and UV filters), BHT (synthetic antioxidant) and oxybenzone (synthetic UV filter). The stability of the formulations was determined for 28 days; it was verified that they remained stable throughout the study period. The assays of the formulations' antioxidant capacity and SPF value revealed that OP and PFP extracts have some photoprotective properties and are excellent sources of antioxidants. As a result, they can be incorporated in daily moisturizers with SPF and sunscreens replacing and/or diminishing the quantities of synthetic ingredients, reducing their negative effects on human health and the environment.

Cosmetic UV filters in the environment-state of the art in EU regulations, science and possible knowledge gaps.

OBJECTIVE: The aim of this work was to review the principals of environmental hazard and risk assessment (ERA) of cosmetic UV filters registered under EU REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals). Furthermore, effects as obtained from non-standardized testing methods and organisms from scientific literature were compared against the predicted no effect concentrations (PNECs) as derived based on standardized test methods for the various environmental compartments under REACH. METHODS: The REACH dossiers at the ECHA webpage were screened for available information related to basic physico-chemical data (i.e. water solubility, octanol-water partitioning coefficient), PNECs and associated data (data basis, assessment factors (AFs)). Scientific literature was screened for available ecotoxicity data and the adverse effect levels were compared against the derived PNECs under REACH. Current approaches for environmental risk assessments of UV filters were evaluated for its applicability for a direct release scenario. RESULTS: Under REACH, PNECs were derived for all hazardous UV filters. Although, PNECs were often derived for various environmental compartments (i.e. freshwater, marine water, sediment, soil), results from literature focused on aquatic data. Effects as observed within scientific literature matches in principle with the hazardous profile of the UV filters. Effects levels both on the acute and the chronic toxicity as retrieved from the non-standardized test organisms (literature) were above the derived PNECs under REACH. Currently, ERAs performed for cosmetic UV filters under REACH are solely tonnage driven and thus do not fully capture the use in sunscreens and associated leisure activities. CONCLUSION: Existing EU REACH regulation is considered as sufficient to evaluate the environmental safety of UV filters used in sunscreens. To cover the direct release of UV filters due to various leisure activities into the aquatic freshwater and marine environment, an additional application-based ERA is considered necessary.

OBJECTIF: L'objectif de ce travail était d'examiner les principes de l'évaluation des dangers et des risques environnementaux des filtres UV cosmétiques enregistrés dans le cadre du règlement REACH de l'Union européenne. En outre, les effets obtenus à partir de méthodes de test non normalisées et d'organismes issus de la littérature scientifique ont été comparés aux concentrations prédites sans effet (PNECs) dérivées des méthodes de test normalisées pour les différents compartiments environnementaux du règlement REACH. MÉTHODES: Les dossiers REACH de la page web de l'ECHA ont été examinés pour rechercher des informations disponibles concernant les données physico-chimiques de base (c'est-à-dire la solubilité dans l'eau, le coefficient de partage octanol-eau), les PNECs et les données associées (base de données, facteurs d'évaluation). Un filtrage de la littérature scientifique a permis d'obtenir les données d'écotoxicité disponibles, et les niveaux d'effets indésirables ont été comparés aux PNECs dérivées en vertu du règlement REACH. Les approches actuelles des évaluations des risques environnementaux des filtres UV consistaient en l'évaluation de leur applicabilité à un scénario de libération directe. RÉSULTATS: En vertu du règlement REACH, les PNECs ont été dérivées pour tous les filtres UV dangereux. Cependant, les PNECs ont souvent été dérivées pour différents compartiments environnementaux (c'est-à-dire eau douce, eau marine, sédiment, sol), les résultats de la littérature se concentrant sur les données aquatiques. Les effets observés dans la littérature scientifique correspondent en principe au profil dangereux des filtres UV. Les niveaux d'effets à la fois sur la toxicité aiguë et sur la toxicité chronique, extraits des organismes de test non normalisés (littérature), étaient supérieurs aux PNECs dérivées en vertu du règlement REACH. Actuellement, les évaluations des dangers et des risques environnementaux des filtres UV cosmétiques en vertu du règlement REACH sont uniquement axées sur le tonnage et ne reflètent donc pas entièrement l'utilisation des protections solaires et des activités de loisirs associées. CONCLUSION: Le règlement REACH de l'UE existant est considéré comme suffisant pour évaluer la sécurité environnementale des filtres UV utilisés dans les protections solaires. Pour couvrir la libération directe de filtres UV en raison de différentes activités de loisirs dans un environnement aquatique d'eau douce et d'eau de mer, une évaluation des dangers et des risques environnementaux supplémentaire basée sur l'application est considérée comme nécessaire.

New formulation technology to boost sun protection.

OBJECTIVE: As every skin type worldwide is concerned by photoprotection, with consumers preferring cosmetic elegant and efficient sunscreen products, we aim at developing the most performant and desirable sun care products. METHODS: We selected an interesting polymer, abbreviated AAHCP and designed scanning electron cryomicroscopy (cryoSEM), small angle and wide angle X-ray scattering and confocal laser scanning microscopy studies to understand its behaviour in solution and in simplex sun care formulations. This allowed us to develop innovative sunscreen formulation technology that was demonstrated by in vitro and in vivo photoprotection methods. Comprehensive photoprotection evaluations were made on the fully developed sun protection product. RESULTS: We observed the polymer oil structuring properties as well as its ability to form small and stable droplets in simplex emulsions. In vitro and in vivo sun protection factor (SPF) measurements demonstrated the sun protection boosting efficacy of AAHCP polymer in several emulsions or as a stand-alone emulsifier. This formulation technology also allowed to filtering system concentration optimization. Use-test performed on a fully developed AAHCP-based sunscreen validated its optimal performances as well as its ideal cosmetic features, with non-sticky, non-greasy perception and invisible skin result. CONCLUSION: For the first time, thanks to a new specific polymer creating a new type of emulsion, we succeed in reconciliate in a single sun care product maximal SPF efficacy, resistance to numerous stresses and optimal sensoriality.

OBJECTIF: Tous les types de peau du monde étant concernés par la photoprotection, avec des consommateurs qui préfèrent des produits solaires élégants et efficaces, nous nous sommes donné pour mission de développer les produits de protection solaire les plus performants et les plus agréables. MÉTHODES: Nous avons sélectionné un polymère intéressant, l'« AAHCP ¼ dans sa forme abrégée, et avons conçu les études de cryomicroscopie électronique à balayage (CryoSEM), de diffusion des rayons X et de microscopie confocale à balayage laser (Confocal Laser Scanning Microscopy) pour comprendre son comportement en solution et dans des formulations de protection solaire simples. Cela nous a permis de développer une technologie innovante de formulation de protection solaire, qui a été démontrée par des méthodes de photoprotection in vitro et in vivo. Le produit de protection solaire a fait l'objet d'évaluations exhaustives de la photoprotection à la fin de sa phase de développement. RÉSULTATS: Nous avons observé les propriétés de structuration de l'huile polymère, ainsi que sa capacité à former de petites gouttelettes stables dans les émulsions de simplex. Les mesures du facteur de protection solaire (sun protection factor, SPF) in vitro et in vivo ont montré que la présence du polymère AAHCP dans plusieurs émulsions ou comme émulsifiant autonome optimise le niveau de protection solaire obtenu. Cette technologie de formulation a également permis d'ajuster la concentration du système de filtration. Le test en conditions réelles d'utilisation effectué sur une protection solaire à base d'AAHCP à la fin de la phase de développement a permis de valider ses performances optimales, ainsi que ses caractéristiques cosmétiques idéales, avec une sensation non collante et non grasse, et un résultat invisible sur la peau. CONCLUSION: Pour la première fois, grâce à un nouveau polymère spécifique créant un nouveau type d'émulsion, nous avons réussi à développer un produit de protection solaire simple à l'efficacité SPF maximale, qui résiste à de nombreuses contraintes et possède une sensibilité optimale.

Nanomaterials in sunscreens: Potential human and ecological health implications.

Inorganic nanomaterials such as TiO2 and ZnO provide significant benefits in terms of UV protection, and their use generally has increased in commercial sunscreens. However, more recently there have been concerns about their potential human and ecological health implications, mostly driven by perception rather than by formal assessments. The large and increasing body of literature on these nanomaterials indicates that in most circumstances their risk are minimal. Penetration of the human epidermis is minimal for these nanomaterials, significantly reducing the potential effects that these nanomaterials may pose to internal organs. The excess Zn ion dose is very small compared to normal dietary consumption of Zn, which is a necessary element. The levels of residual nanomaterials or released ions in public swimming pools is also low, with minimal effect in case this water is ingested during swimming or bathing. In natural environments with significant water flow due to wind and water currents, the concentrations of nanomaterials and released ions are generally well below levels that would cause effects in aquatic organisms. However, sensitive habitats with slow currents, such as coral reefs, may accumulate these nanomaterials. The number of studies of the levels and effects of nanomaterials in these sensitive habitats is very small; more research is needed to determine if there is an elevated risk to these ecosystems from the use of sunscreens with these nanomaterials.

Les nanomatériaux inorganiques, comme le dioxyde de titane (TiO2 ) et l'oxyde de zinc (ZnO), offrent des avantages significatifs en ce qui concerne la protection UV, et leur utilisation a généralement augmenté dans les protections solaires commerciales. Cependant, plus récemment, il y a eu des préoccupations concernant leurs implications potentielles sur la santé humaine et écologique, motivées principalement par la perception plutôt que par des évaluations formelles. L'importante quantité croissante de littérature sur ces nanomatériaux indique que dans la plupart des circonstances, leur risque est minime. La pénétration dans l'épiderme humain est minimale pour ces nanomatériaux, ce qui réduit significativement les effets potentiels de ces nanomatériaux sur les organes internes. La dose d'ions Zn en excès est très faible par rapport à la consommation alimentaire normale de Zn, qui est un élément nécessaire. Les niveaux de nanomatériaux résiduels ou d'ions libérés dans les piscines publiques sont également faibles, avec un effet minime dans le cas où cette eau est ingérée pendant la natation ou la baignade. Dans les environnements naturels caractérisés par un flux d'eau important en raison de courants éoliens et de courants aquatiques, les concentrations de nanomatériaux et d'ions libérés sont généralement nettement inférieures aux niveaux qui pourraient avoir des effets sur les organismes aquatiques. En revanche, des habitats sensibles à courants lents, comme les récifs coralliens, peuvent accumuler ces nanomatériaux. Le nombre d'études sur les niveaux et les effets des nanomatériaux dans ces habitats sensibles est très faible. Des recherches supplémentaires sont nécessaires pour déterminer s'il existe un risque élevé pour ces écosystèmes lié à l'utilisation de crèmes solaires comportant ces nanomatériaux.

A simple and reliable isocratic high-performance chromatographic assay for the simultaneous determination of hydrophilic benzophenone-4 and lipophilic octocrylene in sunscreens.

OBJECTIVE: This work aimed to develop a simple HPLC method for the simultaneous quantitative determination of the ultraviolet (UV) filters, hydrophilic benzophenone-4 and lipophilic octocrylene, in the presence of three other commonly used UV filters, avobenzone, octisalate and homosalate. METHODS: Reverse-phased HPLC was performed on a C18 column. A scouting gradient was initially used to determine the approximate mobile phase composition required for efficient analyte elution and separation before further optimization. The assay was validated with regard to specificity, linearity, intra- and inter-day accuracy and precision, limits of detection and limits of quantification. An ultrasound dispersion extraction method for the UV filters from a commercial sunscreen was developed, and the extraction efficiencies from spiked samples were calculated. RESULTS: An acetonitrile-methanol-water mixture (20:67:13, v/v/v), where the water component contained 0.2% trifluoroacetic acid (v/v), was found to be the optimal mobile phase at a flow rate of 1.0 mL/min. The assay was linear between 1.0-100 µg/mL for both benzophenone-4 and octocrylene (both correlation coefficients were above 0.999). There was no interference from the excipients of the sunscreen nor from the three other UV filters. The intra- and inter-day accuracy was between 90.0-104.6% for both analytes. Extraction recoveries from a spiked commercial sunscreen were between 95.4 ± 2.1% to 98.5 ± 2.1% for benzophenone-4, and between 87.3 ± 2.3% and 98.9 ± 3.1% for octocrylene. All validation parameters were within the acceptance criteria set out in the International Council for Harmonization (ICH) guidelines. The HPLC assay showed the extracted quantities of benzophenone-4 and octocrylene from the commercial sunscreen closely matched claimed quantities. CONCLUSION: The developed isocratic HPLC method was suitable for simultaneously determining the hydrophilic benzophenone-4 and lipophilic octocrylene in the presence of other commonly used UV filters. Additionally, the extraction method was simple and effective for accurately quantifying the UV filters in a commercial sunscreen.

OBJECTIF: Ces travaux visaient à développer une méthode de chromatographie en phase liquide à haute performance simple pour la détermination quantitative simultanée de la benzophénone-4 hydrophile et de l'octocrylène lipophile, des filtres ultraviolets (UV), en présence de trois autres filtres UV couramment utilisés, l'avobenzone, l'octisalate et l'homosalate. MÉTHODES: Une chromatographie en phase liquide à haute performance en phase inverse a été réalisée sur une colonne C18. Un gradient de référence a été initialement utilisé pour déterminer la composition approximative de la phase mobile requise pour une élution et une séparation efficace de l'analyte avant une optimisation plus poussée. Le dosage a été validé en termes de spécificité, de linéarité, d'exactitude et de précision intra- et inter-journalières, de limites de détection et de limites de quantification. Une méthode d'extraction par dispersion ultrasonique des filtres UV d'une crème solaire commerciale a été mise au point, et les efficacités d'extraction des échantillons artificiellement traités ont été calculées. RÉSULTATS: Un mélange acétonitrile-méthanol-eau (20:67:13, v/v/v), où la composante eau contenait 0,2 % d'acide trifluoroacétique (v/v), s'est avéré être la phase mobile optimale à un débit de 1,0 ml/min. Le dosage était linéaire entre 1,0 et 100 µg/ml pour la benzophénone-4 et l'octocrylène (les deux coefficients de corrélation étaient supérieurs à 0,999). Aucune interférence n'a été observée entre les excipients de l'écran solaire et les trois autres filtres UV. La précision intra et inter-journalière était comprise entre 90,0 et 104,6 % pour les deux analytes. Les récupérations par extraction à partir d'une crème solaire commerciale artificiellement traitée étaient comprises entre 95,4 % ± 2,1 % et 98,5 % ± 2,1 % pour la benzophénone-4, et entre 87,3 % ± 2,3 % et 98,9 % ± 3,1 % pour l'octocrylène. Tous les paramètres de validation étaient conformes aux critères d'acceptation définis dans les lignes directrices du Conseil international d'harmonisation (ICH). Le dosage par chromatographie en phase liquide à haute performance a montré que les quantités extraites de benzophénone-4 et d'octocrylène de la crème solaire commerciale correspondaient étroitement aux quantités revendiquées. CONCLUSION: La méthode de chromatographie en phase liquide à haute performance isocratique mise au point a permis de déterminer simultanément la benzophénone-4 hydrophile et l'octocrylène lipophile en présence d'autres filtres UV couramment utilisés. En outre, la méthode d'extraction était simple et efficace pour quantifier avec précision les filtres UV dans une crème solaire commerciale.