Organic UV filters: Occurrence, risks and (anti-)progestogenic activities in samples from the Czech aquatic environment and their bioaccumulation in fish.

The occurrence, environmental risks and contribution of organic UV filters to detected (anti-)progestogenic activities were examined in samples of wastewater treatment plant influents and effluents, various surface waters and fish from the Czech Republic. Of the 20 targeted UV filters, 15 were detected in the WWTP influent samples, 11 in the effluents, and 13 in the surface water samples. Benzophenone-3, benzophenone-4, and phenyl benzimidazole sulfonic acid (PBSA) were found in all water samples. Octocrylene, UV-327 and 4-methylbenzylidene camphor exceeded the risk quotient of 1 at some sites. In the anti-progestogenic CALUX assay, 10 out of the 20 targeted UV filters were active. Anti-progestogenic activities reaching up to 7.7 ng/L, 3.8 ng/L, and 4.5 ng/L mifepristone equivalents were detected in influents, effluents, and surface waters, respectively. UV filters were responsible for up to 37 % of anti-progestogenic activities in influents. Anti-progestogenic activities were also measured in fish tissues from the control pond and Podrouzek (pond with the highest number of detected UV filters) and ranged from 2.2 to 9.5 and 1.9 to 8.6 ng/g dw mifepristone equivalents, respectively. However, only benzophenone was found in fish, but it does not display anti-progestogenic activity and thus could not explain the observed activities.

Concentrations, compositional profiles, and health risks of benzophenones among the Taiwanese population based on analysis of 23 daily consumed foods.

In this study, we analyzed the occurrence and distribution of 11 benzophenone-type ultraviolet filters (BPs) in 893 food samples spanning 7 food categories in Taiwan. We conducted a Monte Carlo simulation to determine the carcinogenic and noncarcinogenic risks of BPs. The results indicated that cornflakes had the highest mean level of BPs (103 ng/g), followed by bread (101 ng/g) and pastries (59 ng/g). BP was the most prevalent category, followed by 4-methylbenzophenone (4-MBP), 2-hydroxybenzophenone, and benzophenone-3. Estimation of the lifetime cancer risk (LTCR) of BP (average life expectancy of 80 years) placed them in the 50th and 97.5th percentiles [P50 (P97.5)] LTCR of 1.9 × 10-7 (5.7 × 10-6), indicating that BP in food poses a low renal hazard to the Taiwanese population. The noncarcinogenic risk of BPs was evaluated using a hazard quotient and combined margin of exposure (MOET), revealing a P50 (P97.5) hazard index of < 1 for BP, 4-MBP, and methyl-2-benzoylbenzoate. Although the P50 MOET values for all age groups were within the moderate range of concern, with a more conservative extreme (P2.5), the MOET values for the 0-3, 3-6, and 6-12 age groups fell below 100, indicating a high concern for renal degeneration and hyperplasia.

UV-filter benzophenones suppress human, pig, rat, and mouse 11ß-hydroxysteroid dehydrogenase 1: Structure-activity relationship and in silico docking analysis.

Benzophenone chemicals (BPs) have been developed to prevent the adverse effects of UV radiation and they are widely contaminated. 11ß-Hydroxysteroid dehydrogenase 1 (11ß-HSD1) catalyze the conversion of inactive glucocorticoid to active glucocorticoid, playing critical role in many physiological function. However, the direct effect of BPs on human, pig, rat, and mouse 11ß-HSD1 remains unclear. In this study, we screened the inhibitory strength of 12 BPs on 4 species, and performed the structure-activity relationship (SAR) and in silico docking analysis. The inhibitory potency of BPs was: for human 11ß-HSD1, BP6 (IC50 = 18.76 µM) > BP8 (40.84 µM) > BP (88.89 µM) > other BPs; for pig 11ß-HSD1, BP8 (45.57 µM) > BP6 (59.44 µM) > BP2 (65.12 µM) > BP (135.56 µM) > other BPs; for rat 11ß-HSD1, BP7 (67.17 µM) > BP (68.83 µM) > BP8 (133.04 µM) > other BPs; and for mouse 11ß-HSD1, BP8 (41.41 µM) > BP (50.61 µM) > other BPs. These BP chemicals were mixed/competitive inhibitors of these 11ß-HSD1 enzymes. The 2,2'-dihydroxy substitutions in two benzene rings play a key role in enhancing the effectiveness of inhibiting 11ß-HSD1, possibly via increasing hydrogen bond interactions. Docking analysis shows that these BPs bind to NADPH/glucocorticoid binding sites and forms hydrogen bonds with catalytic residues Ser and/or Tyr. In conclusion, this study demonstrates that BP chemicals can inhibit 11ß-HSD1 from 4 species, and there are subtle species-dependent difference in the inhibitory strength and structural variations of BPs.

Effects of benzophenone-3 and its metabolites on the marine diatom Chaetoceros neogracilis: Underlying mechanisms and environmental implications.

The wide application of benzophenones (BPs), such as benzophenone-3 (BP3), as an ingredient in sunscreens, cosmetics, coatings, and plastics, has led to their global contamination in aquatic environments. Using the marine diatom Chaetoceros neogracilis as a model, this study assessed the toxic effects and mechanisms of BP3 and its two major metabolites (BP8 and BP1). The results showed that BP3 exhibited higher toxicity on C. neogracilis than BP8 and BP1, with their 72-h median effective concentrations being 0.4, 0.8 and 4 mg/L, respectively. Photosynthesis efficiencies were significantly reduced after exposure to environmentally relevant concentrations of the three benzophenones, while cell viability, membrane integrity, membrane potential, and metabolic activities could be further impaired at their higher concentrations. Comparative transcriptomic analysis, followed by gene ontology and KEGG pathway enrichment analyses unraveled that all the three tested benzophenones disrupted photosynthesis and nitrogen metabolism of the diatom through alteration of similar pathways. The toxic effect of BP3 was also attributable to its unique inhibitory effects on eukaryotic ribosome biosynthesis and DNA replication. Taken together, our findings underscore that benzophenones may pose a significant threat to photosynthesis, oxygen production, primary productivity, carbon fixation, and the nitrogen cycle of diatom in coastal waters worldwide.

In vitro blastocyst implantation and trophoblast migration are disrupted by the UV filter benzophenone-3 (BP3).

Benzophenone-3 (BP3) is a common ingredient in personal care products (PCPs) due to its well-established effectiveness in absorbing UV radiation. Sunscreen products are among the most widely used PCPs-containing BP3 applied to the skin, resulting in significant human exposure to BP3 primarily through a dermal application. In the present work, we have tested the action of three environmentally relevant concentrations of BP3 (2, 20 and 200 µg/L) on an in vitro model of implantation of murine blastocysts and on migration ability of the human trophoblast cell line Swan 71. We showed that BP3 caused a significant reduction of blastocyst expansion and a delayed hatching in a non-monotonic way. Besides, embryos displayed a delayed attachment in the three BP3 groups, resulting in a smaller implantation area on the 6th day of culture: BP3(2) (0.32 ± 0.07 mm2); BP3(20) (0.30 ± 0.08 mm2) and BP3(200) (0.25 ± 0.06 mm2) in comparison to the control (0.42 ± 0.07 mm2). We also found a reduced migration capacity of the human first-trimester trophoblast cell line Swan 71 in a scratch assay when exposed to BP3: the lowest dose displayed a higher uncovered area (UA) at 6h when compared to the control, whereas a higher UA of the wound was observed for the three BP3 concentrations at 18 and 24 h of exposure. The changes in UA provoked by BP3 restored to normal values in the presence of flutamide, an androgen receptor (AR) inhibitor. These results indicate that a direct impairment on early embryo implantation and a defective migration of extravillous trophoblast cells through the androgen receptor pathway can be postulated as mechanisms of BP3-action on early gestation with potential impact on fetal growth.

The exposure to UV filters: Prevalence, effects, possible molecular mechanisms of action and interactions within mixtures.

Substances that can absorb sunlight and harmful UV radiation such as organic UV filters are widely used in cosmetics and other personal care products. Since humans use a wide variety of chemicals for multiple purposes it is common for UV filters to co-occur with other substances either in human originating specimens or in the environment. There is increasing interest in understanding such co-occurrence in form of potential synergy, antagonist, or additive effects of biological systems. This review focuses on the collection of data about the simultaneous occurrence of UV filters oxybenzone (OXYB), ethylexyl-methoxycinnamate (EMC) and 4-methylbenzylidene camphor (4-MBC) as well as other classes of chemicals (such as pesticides, bisphenols, and parabens) to understand better any such interactions considering synergy, additive effect and antagonism. Our analysis identified >20 different confirmed synergies in 11 papers involving 16 compounds. We also highlight pathways (such as transcriptional activation of estrogen receptor, promotion of estradiol synthesis, hypothalamic-pituitary-gonadal (HPG) axis, and upregulation of thyroid-hormone synthesis) and proteins (such as Membrane Associated Progesterone Receptor (MAPR), cytochrome P450, and heat shock protein 70 (Hsp70)) that can act as important key nodes for such potential interactions. This article aims to provide insight into the molecular mechanisms on how commonly used UV filters act and may interact with other chemicals.

In vitro Safety Assessment of Extracts and Compounds From Plants as Sunscreen Ingredients.

This work investigated the safety of extracts obtained from plants growing in Colombia, which have previously shown UV-filter/antigenotoxic properties. The compounds in plant extracts obtained by the supercritical fluid (CO2) extraction method were identified using gas chromatography coupled to mass spectrometry (GC/MS) analysis. Cytotoxicity measured as cytotoxic concentration 50% (CC50) and genotoxicity of the plant extracts and some compounds were studied in human fibroblasts using the trypan blue exclusion assay and the Comet assay, respectively. The extracts from Pipper eriopodon and Salvia aratocensis species and the compound trans-ß-caryophyllene were clearly cytotoxic to human fibroblasts. Conversely, Achyrocline satureioides, Chromolaena pellia, and Lippia origanoides extracts were relatively less cytotoxic with CC50 values of 173, 184, and 89 µg/mL, respectively. The C. pellia and L. origanoides extracts produced some degree of DNA breaks at cytotoxic concentrations. The cytotoxicity of the studied compounds was as follows, with lower CC50 values representing the most cytotoxic compounds: resveratrol (91 µM) > pinocembrin (144 µM) > quercetin (222 µM) > titanium dioxide (704 µM). Quercetin was unique among the compounds assayed in being genotoxic to human fibroblasts. Our work indicates that phytochemicals can be cytotoxic and genotoxic, demonstrating the need to establish safe concentrations of these extracts for their potential use in cosmetics.

Bioconcentration, biotransformation, and transcriptomic impact of the UV-filter 4-MBC in the manila clam Ruditapes philippinarum.

Ultraviolet filters (UV-filters) are compounds extensively used in personal care products. These compounds are produced at increasing rates and discharged into marine ecosystems in unknown quantities and with no regulation, making them emerging contaminants. Among those, the UV-filter 4-Methylbenzylidene camphor (4-MBC) is used in a variety of personal care products such as sunscreens, soaps, or lipsticks. This high consumption has resulted in its presence in various environmental matrices at in concentrations ranging from ng to µg L-1. Very little is known, however, about the possible adverse effects in exposed non-target organisms. Our study presents novel data on the bioconcentration, toxicokinetics, and molecular effects of 4-MBC in a marine bivalve species of commercial interest, Ruditapes philippinarum (Manila clam). Organisms were exposed at two different concentrations (1.34 and 10.79 µg L-1) of 4-MBC for 7 days, followed by a 3-day depuration period (clean sea waters). Bioconcentration factors (BCF) were 3562 and 2229 L kg-1 for the low and high exposure concentrations, respectively, making this pollutant bioaccumulative according to REACH criteria. Up to six 4-MBC biotransformation products (BTPs)were identified, 2 of them for the first time. Transcriptomic analysis revealed between 658 and 1310 differently expressed genes (DEGs) after 4-MBC exposure. Functional and enrichment analysis of the DEGs showed the activation of the detoxification pathway to metabolize and excrete the bioconcentrated 4-MBC, which also involved energy depletion and caused an impact on the metabolism of carbohydrates and lipids and in the oxidative phosphorylation pathways. Oxidative stress and immune response were also evidenced through the activation of cathepsins and the complement system. Such elucidation of the mode of action of a ubiquitous pollutant such as 4-MBC at the molecular level is valuable both from an environmental point of view and for the sustainable production of Manila clam, one of the most cultivated mollusk species worldwide.

Degradation of organic UV filters in the water environment: A concise review on the mechanism, toxicity, and technologies.

Organic ultraviolet filters (OUVFs) have been used globally for the past 20 years. Given that OUVFs can be quickly released from sunscreens applied on human skins, they have been frequently detected in aquatic environments and organisms. Some byproducts of OUVFs might be more recalcitrant and toxic than their parent compounds. To further assess the toxicity and potential risk of OUVFs' byproducts, it is necessary to determine the fate of OUVFs and identify their transformation products. This review summarizes and analyzes pertinent literature and reports in the field of OUVFs research. These published research works majorly focus on the degradation mechanisms of OUVFs in aquatic environments, their intermediates/byproducts, and chlorination reaction. Photodegradation (direct photolysis, self-sensitive photolysis and indirect photolysis) and biodegradation are the main transformation pathways of OUVFs through natural degradation. To remove residual OUVFs' pollutants from aqueous environments, novel physicochemical and biological approaches have been developed in recent years. Advanced oxidation, ultrasound, and bio-based technologies have been proven to eliminate OUVFs from wastewaters. In addition, the disinfection mechanism and the byproducts (DBPs) of various OUVFs in swimming pools are discussed in this review. Besides, knowledge gaps and future research directions in this field of study are also mentioned.

Fish gut and skin microbiota dysbiosis induced by exposure to commercial sunscreen formulations.

UV filters (organic or mineral) present in sunscreen products are emerging contaminants of coastal aquatic environments. There is an urgent need to understand marine organisms responses to these compounds. In this study, we investigated the effect of exposure to dilutions of commercial sunscreen formulations on bacterial communities of mullet (Chelon sp.). The gut and skin mucus microbial communities were characterized using a metabarcoding approach targeting the 16S rRNA gene. Our results revealed that mullets had its own bacterial communities that differ from their surrounding habitats and specific to tissue. The dilutions of commercial sunscreens modified the relative abundance of Actinobacteroita, Bacteriodota and Proteobacteria for both gut and skin microbiota. They also allowed to bacteria affiliated to Mycobacterium, Nocardia and Tenacibaculum genera, known to house pathogenic species, to colonize the epithelium which may have implications for fish host health.

Effects associated with exposure to the emerging contaminant octyl-methoxycinnamate (a UV-B filter) in the aquatic environment: a review.

Given the increasing concern surrounding ultraviolet (UV) radiation-induced skin damage, there has been a rise in demand for UV filters. Currently, UV-filters are considered emerging contaminants. The extensive production and use of UV filters have led to their widespread release into the aquatic environment. Thus, there is growing concern that UV filters may bioaccumulate and exhibit persistent properties within the environment, raising several safety health concerns. Octyl-methoxycinnamate (OMC) is extensively employed as a UV-B filter in the cosmetic industry. While initially designed to mitigate the adverse photobiological effects attributed to UV radiation, the safety of OMC has been questioned with some studies reporting toxic effects on environment. The aim of this review to provide an overview of the scientific information regarding the most widely used organic UV-filter (OMC), and its effects on biodiversity and aquatic environment.

Are Physical Sunscreens Safe for Marine Life? A Study on a Coral-Zooxanthellae Symbiotic System.

Limited toxic and ecological studies were focused on physical sunscreen that is considered to have "safer performance", in which nanosize zinc oxide (nZnO) and nanosize titanium dioxide (nTiO2) generally are added as ultraviolet filters. Herein, the common button coral Zoanthus sp. was newly used to assess the toxic effects and underlying mechanisms of physical sunscreen. Results showed that physical sunscreen induced severe growth inhibition effects and largely compelled the symbiotic zooxanthellae, indicating that their symbiotic systems were threatened and, also, that neural and photosynthesis functions were influenced. Zn2+ toxicity and bioaccumulation were identified as the main toxic mechanisms, and nTiO2 particles released from physical sunscreen also displayed limited bioattachment and toxicity. Oxidative stress, determined by increased reactive oxygen species, superoxide dismutase, and malondialdehyde content, was indicated as another important toxic mechanism. Furthermore, when Zoanthus sp. was restored, the inhibited individual coral could be largely recovered after a short (3 d) exposure time; however, a longer exposure time damaged the coral irretrievably, which revealed the latent environmental risks of physical sunscreen. This study investigated the toxic effect of physical sunscreen on Zoanthus sp. in a relatively comprehensive manner, thus providing new insights into the toxic response of sunscreen on marine organisms.

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.

Single and mixture toxicity evaluation of avobenzone and homosalate to male zebrafish and H295R cells.

Avobenzone and homosalate are widely used in sunscreens to provide ultraviolet (UV) protection, either as single compounds or in combination. Some UV filters exhibit estrogenic or anti-androgenic activities, however, studies regarding their interactions and toxicity in mixtures are limited. In this study, the effect of the toxicity of a binary mixture comprising avobenzone (0.72 µg L-1) and homosalate (1.02 and 103 µg L-1) on steroid hormone biosynthesis were investigated using male zebrafish and human adrenocortical carcinoma (H295R) cells. In fish exposed to homosalate, a significant decrease in the gonadosomatic index, testosterone level, and transcription of several genes (e.g, hsd3b2, cyp17a1, and hsd17b1) and a significant increase in the hepatosomatic index, liver steatosis, 17ß-estradiol level, and transcription of vtg gene were observed. These results suggest that estrogenic and anti-androgenic effects of homosalate were mediated by the steroidogenic pathway. The presence of 0.72 µg L-1 of avobenzone augmented the anti-androgenic responses in male fish. The testosterone level in the H295R cells were significantly decreased after they were exposed to homosalate alone or in combination with avobenzone, which is consistent with observations in male zebrafish. Further studies need to be conducted to understand the endocrine disrupting properties of long-term exposure to substances typically used in sunscreens.

Inorganic nanoparticles in dermopharmaceutical and cosmetic products: Properties, formulation development, toxicity, and regulatory issues.

The use of nanotechnology strategies is a current hot topic, and research in this field has been growing significantly in the cosmetics industry. Inorganic nanoparticles stand out in this context for their distinctive physicochemical properties, leading in particular to an increased refractive index and absorption capacity giving them a broad potential for cutaneous applications and making them of special interest in research for dermopharmaceutical and cosmetic purposes. This performance is responsible for its heavy inclusion in the manufacture of skin health products such as sunscreens, lotions, beauty creams, skin ointments, makeup, and others. In particular, their suitable bandgap energy characteristics allow them to be used as photocatalytic semiconductors. They provide excellent UV absorption, commonly known as UV filters, and are responsible for their wide worldwide use in sunscreen formulations without the undesirable white residue after consumer application. In addition, cosmetics based on inorganic nanoparticles have several additional characteristics relevant to formulation development, such as being less expensive compared to other nanomaterials, having greater stability, and ensuring less irritation, itching, and propensity for skin allergies. This review will address in detail the main inorganic nanoparticles used in dermopharmaceutical and cosmetic products, such as titanium dioxide, zinc oxide, silicon dioxide, silver, gold, copper, and aluminum nanoparticles, nanocrystals, and quantum dots, reporting their physicochemical characteristics, but also their additional intrinsic properties that contribute to their use in this type of formulations. Safety issues regarding inorganic nanoparticles, based on toxicity studies, both to humans and the environment, as well as regulatory affairs associated with their use in dermopharmaceuticals and cosmetics, will be addressed.

Comparison between endocrine activity assessed using ToxCast/Tox21 database and human plasma concentration of sunscreen active ingredients/UV filters.

Sunscreen products are composed of ultraviolet (UV) filters and formulated to reduce exposure to sunlight thereby lessening skin damage. Concerns have been raised regarding the toxicity and potential endocrine disrupting (ED) effects of UV filters. The ToxCast/Tox21 program, that is, CompTox, is a high-throughput in vitro screening database of chemicals that identify adverse outcome pathways, key events, and ED potential of chemicals. Using the ToxCast/Tox21 database, octisalate, homosalate, octocrylene, oxybenzone, octinoxate, and avobenzone, 6 commonly used organic UV filters, were found to have been evaluated. These UV filters showed low potency in these bioassays with most activity detected above the range of the cytotoxic burst. The pathways that were most affected were the cell cycle and the nuclear receptor pathways. Most activity was observed in liver and kidney-based bioassays. These organic filters and their metabolites showed relatively weak ED activity when tested in bioassays measuring estrogen receptor (ER), androgen receptor (AR), thyroid receptor, and steroidogenesis activity. Except for oxybenzone, all activity in the endocrine assays occurred at concentrations greater than the cytotoxic burst. Moreover, except for oxybenzone, plasma concentrations (Cmax) measured in humans were at least 100× lower than bioactive (AC50/ACC) concentrations that produced a response in ToxCast/Tox21 assays. These data are consistent with in vivo animal/human studies showing weak or negligible endocrine activity. In sum, when considered as part of a weight-of-evidence assessment and compared with measured plasma concentrations, the results show these organic UV filters have low intrinsic biological activity and risk of toxicity including endocrine disruption in humans.

Health risks posed by environmental benzophenone-type ultraviolet filters (BP-UVFs): An investigation into the binding of BP-UVFs to trypsin and their adverse effects.

Benzophenone-type ultraviolet filters (BP-UVFs) are ubiquitous in the environment, and people frequently ingest them via food chain and drinking water. However, there is no clear information about whether BP-UVFs are detrimental to human health. Herein, experiments using multi-spectroscopy revealed typical BP-UVFs, i.e., benzophenone (BP), 2-hydroxybenzophenone (2-OHBP), 4-hydroxybenzophenone (4-OHBP), 2,2'-dihydroxybenzophenone (2,2'-OHBP), 2,4-dihydroxybenzophenone (2,4-OHBP), 4,4'-dihydroxybenzophenone (4,4'-OHBP), 2,4,4'-trihydroxybenzophenone (2,4,4'-OHBP), 2,2',4,4'-tetraphydroxybenzophenone (2,2',4,4'-OHBP), 2-hydroxy-4-methoxybenzophenone (2-OH-4-MeOBP) and 2,2'-dihydroxy-4-methoxybenzophenone (2,2'-OH-4-MeOBP), could bind to the active site of trypsin with different binding constants (2.69 × 104-1.07 × 106 L/mol), cause structural abnormalities and inhibit the enzymatic activity in varying degrees, indicating that the BP-UVFs ingestion poses a risk to human health. In contrast to previous research, this study systematically analysed the binding mechanism using an innovative combination of molecular docking and advanced quantum chemistry calculations, including molecular dynamics simulations, energy calculations, etc. The results revealed that most amino acids that make up trypsin have a greater positive electrostatic surface potential (ESP). Therefore, the greater the area and distribution of negative ESP in a particular BP-UVFs, the more easily it will bind to trypsin. This provides new insight into the binding of pollutants to proteins. This study suggests a need for better monitoring and control of environmental BP-UVFs.

Avoidance behaviour and toxicological impact of sunscreens in the teleost Chelon auratus.

There is increasing evidence that sunscreen, more specifically the organic ultra-violet filters (O-UVFs), are toxic for aquatic organisms. In the present study, we simulated an environmental sunscreen exposure on the teleost fish, Chelon auratus. The first objective was to assess their spatial avoidance of environmental concentrations of sunscreen products (i.e. a few µg.L-1 of O-UVFs). Our results showed that the fish did not avoid the contaminated area. Therefore, the second objective was to evaluate the toxicological impacts of such pollutants after 35 days exposure to concentrations of a few µg.L-1 of O-UVFs. At the individual level, O-UVFs increased the hepatosomatic index which could suggest pathological alterations of the liver or the initiation of the detoxification processes. At the cellular level, a significant increase of malondialdehyde was measured in the muscle of fish exposed to O-UVFs which suggests a failure of antioxidant defences and/or an excess of reactive oxygen species.

4-Methylbenzylidene camphor triggers estrogenic effects via the brain-liver-gonad axis in zebrafish larvae.

4-Methylbenzylidene camphor (4-MBC), an emerging contaminant, is a widely-used ultraviolet (UV) filter incorporated into cosmetics because it protects the skin from UV rays and counters photo-oxidation. Despite the well-established estrogenic activity of 4-MBC, the link between this activity and its effects on neurobehavior and the liver remains unknown. Thus, we exposed zebrafish larvae to environmentally relevant concentrations of 4-MBC with 1.39, 4.17, 12.5 and 15.4 µg/mL from 3 to 5 days postfertilization. We found that 4-MBC produced an estrogenic effect by intensifying fluorescence in the transgenic zebrafish, which was counteracted by co-exposure with estrogen receptor antagonist. 4-MBC-upregulated estrogen receptor alpha (erα) mRNA, and an interaction between 4-MBC and ERα suggested ERα's involvement in the 4-MBC-induced estrogenic activity. RNA sequencing unearthed 4-MBC-triggered responses in estrogen stimulus and lipid metabolism. Additionally, 4-MBC-induced hypoactivity and behavioral phenotypes were dependent on the estrogen receptor (ER) pathway. This may have been associated with the disruption of acetylcholinesterase and acetylcholine activities. As a result, 4-MBC increased vitellogenin expression and caused lipid accumulation in the liver of zebrafish larvae. Collectively, this is the first study to report 4-MBC-caused estrogenic effects through the brain-liver-gonad axis. It provides novel insight into how 4-MBC perturbs the brain and liver development.

Toxicity assessment of binary mixtures of BP3 with 4-MBC (UV-filters), and BP3 with DEET (insect repellent) using the aquatic midge Chironomus riparius.

Personal care products have various organic ultraviolet filters (UV filters) in their composition to increase protection against ultraviolet radiation. Some of these products also contain insect repellents in their formulations. Consequently, these compounds reach freshwater ecosystems, exposing aquatic organisms to a cocktail of anthropogenic contaminants. In this study, the joint effects of two most frequently detected UV filters (Benzophenone - 3 (BP3) and Enzacamene (4-MBC)) and joint effects of BP3 combined with an insect repellent (N, N diethyl-3-methylbenzamide - DEET) were evaluated using life-history traits of the aquatic midge Chironomus riparius such as emergence rate, time to emergence and imagoes body weight. The results showed synergistic effects between BP3 and 4-MBC for C. riparius emergence rate. Regarding the effects of BP3 and DEET mixture, our analysis suggests synergism in the case of males but antagonism in the case of females' time to emergence. Our results imply that the effects of UV filters present in sediments within chemical mixtures are complex and that the evaluation of effects using different life-history traits can yield different patterns of responses. This study demonstrates the importance of assessing the combined effects of pollutants used/found concomitantly in aquatic systems for a more accurate risk assessment, as individual chemical testing can underestimate the toxicity of organic UV filters.