DIETHYLAMINO HYDROXYBENZOYL HEXYL BENZOATE

Selected organic sunscreens from different chemical families were investigated in the context of their ability to inhibit butyrylcholinesterase using novel Multiple Linear Regression, Artificial Neural Network, and Support Vector Regression models based on a set of six independent variables commonly associated with compounds' absorption and distribution properties. It was established that the descriptors that have a particularly strong, positive influence on the ability of compounds to inhibit BChE expressed as p IC 50 are the count of rotatable bonds ( nRot ) and lipophilicity (log D ); p IC 50 is negatively correlated with flexibility ( Flex ), fraction of sp 3 carbon atoms ( F sp3 ), caco-2 permeability ( caco2 ), and plasma protein binding ability ( PPB ). The sunscreens that are likely to be particularly strong BChE inhibitors are Ethylhexyl Triazone (ET), Diethylhexyl Butamido Triazone (DOBT), Octocrylene (OCR), and Diethylamino Hydroxybenzoyl Hexyl Benzoate (DHHB). However, it must be stressed that ET and DOBT lie outside the chemical space of the reference compounds, so predictions for these two compounds should be treated with caution.

The increasing utilization of novel triazine-based UV filters (UVFs) has drawn significant attention regarding their potential toxicity to aquatic organisms. However, there is limited toxicity data for these emerging UVFs. Herein, we evaluated acute toxicities of triazine-based UVFs including bis-ethylhexyloxyphenol methoxyphenol triazine (BEMT), diethylhexyl butamido triazone (DBT), and ethylhexyl triazone (EHT), towards Chlorella vulgaris and Daphnia magna. For comparison, the acute toxicities of three commonly used non-triazine-based UVFs, namely diethylamino hydroxybenzoyl hexyl benzoate (DHHB), avobenzone (AVB), and octocrylene (OCR) were also assessed. Simultaneously, we investigated the acute mixture toxicity of these compounds on Daphnia. Under single-compound exposure (≤15 mg/L), BEMT, DBT, and EHT demonstrated less than 10 % growth inhibition in Chlorella. In contrast, DHHB, AVB, and OCR exhibited concentration-dependent inhibition. Based on 48-hours EC 50 values for Daphnia, the triazine-based UVFs were markedly less toxic than the non-triazine counterparts. Mixture exposure experiments revealed an antagonistic effect for combinations such as BEMT+EHT, BEMT+EHT+DHHB, and DHHB+EHT, whereas the mixture AVB + OCR+ BEMT exhibited primarily synergistic effects, likely attributed to distinct modes of action among its components. This study suggests that triazine-based UVFs exhibit lower acute toxicity under the conditions tested to Chlorella growth inhibition and Daphnia immobilization than the conventional non-triazine UVFs tested, providing essential data for the environmental risk assessment of these emerging contaminants.

The objective of this work is to investigate different sunscreens and Viscogel group organoclays for the preparation of new intercalated sunscreens to improve the effectiveness and safety in photoprotection using new approach methodology (NAMs). For this study, we examined Diethylamino hydroxybenzoyl hexyl benzoate (DHHB), octyl methoxycinnamate (OMC), Bemotrizinol (BEMT) and Viscogel S4®, S7®, and B8® using a set of Saccharomyces cerevisiae mutant strains that are sensitive to UVA, UVB and Solar Simulated Light (SSL) to evaluate their photoprotective and mutagenic potential. Additionally, we developed delaminated nanocomposites by chemical intercalation reactions followed by ultrasonic treatment to enhance clay exfoliation. These nanocomposites were then characterized using X-ray Powder Diffraction (XRPD), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA) and Dynamic Light Scattering (DLS). As a function of photoprotective action and safety, the combination of Viscogel S4® and OMC filter was chosen for nanocomposite development. Our results evidenced the intercalation of the OMC in the organoclay (S4 + OMC-NC). Survival and mutagenesis tests indicated a positive effect of the formulation, as it increased cell survival to SSL, even without reducing mutagenesis, while its respective physical mixture was unable to provide antimutagenic protection. S4 + OMC-NC showed promising results for photoprotection, offering cellular protection combined with antimutagenic effects upon SSL exposure. This formulation enables prospects for the preparation of new, effective and safe photoprotective formulations. L'objectif de ce travail de recherche est d'étudier différents écrans solaires et organo‐argiles du groupe Viscogel pour la préparation de nouveaux écrans solaires intercalés, afin d'améliorer l'efficacité et la sécurité de la photoprotection à l'aide d'une nouvelle approche méthodologique (NAM). MÉTHODES: Pour cette étude, nous avons examiné le benzoate d'hexyle hydroxybenzoyle diéthylamino (DHHB), le méthoxycinnamate d'octyle (OMC), le bémotrizinol (BEMT), et le Viscogel S4®, S7® et B8® à l'aide d'un ensemble de souches mutantes S. cerevisiae sensibles aux UVA, UVB et à la lumière simulée (Solar Simulated Light, SSL), afin d'évaluer leur potentiel photoprotecteur et mutagène. De plus, nous avons développé des nanocomposites délaminés par des réactions d'intercalation chimique suivies d'un traitement par ultrasons pour améliorer l'exfoliation de l'argile. Ces nanocomposites ont ensuite été caractérisés à l'aide de la diffraction des rayons X sur poudre (X‐ray Powder Diffraction, XRPD), de la calorimétrie à balayage différentiel (Differential Scanning Calorimetry, DSC), de l'analyse thermogravimétrique (Thermogravimetric Analysis, TGA) et de la diffusion dynamique de la lumière (Dynamic Light Scattering, DLS). RÉSULTATS: En fonction de l'action photoprotectrice et de la sécurité, l'association du filtre Viscogel S4® et de l'OMC a été choisie pour le développement des nanocomposites. Nos résultats ont mis en évidence l'intercalation de l'OMC dans l'organo‐argile (S4 + OMC NC). Les tests de survie et de mutagenèse ont indiqué un effet positif de la formulation, car elle augmentait la survie cellulaire à la SSL, sans pour autant réduire la mutagenèse, tandis que son mélange physique respectif n'était pas en mesure de fournir une protection antimutagène. S4 + OMC NC a montré des résultats prometteurs pour la photoprotection, offrant une protection cellulaire associée à des effets antimutagènes lo

Understanding the processes that organic UV filters undergo in coastal and marine environments is crucial for assessing their long-term environmental risks. One key process is degradation by microorganisms in sediments. This study aimed to determine whether coastal marine sediments harbor microorganisms capable of degrading organic UV filters. Sediment from Toulon Harbor was tested for its degradation potential with respect to 12 different organic UV filters. Sediment microcosms showed degradation activity towards benzophenone-3 (BP3), 2-ethylhexyl salicylate (ES), and homosalate (HS) after 12 days. However, no degradation was observed for butyl methoxydibenzoylmethane (BM), octocrylene (OC), diethylamino hydroxybenzoyl hexyl benzoate (DHHB), drometrizole trisiloxane (DTS), phenylene bis-diphenyltriazine (TriAsorB), bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT), methylene bis-benzotriazolyl tetramethylbutylphenol (MBBT), diethylhexyl butamido triazone (DBT), or ethylhexyl triazone (ET), even after 100 days of incubation. Two degrading strains were isolated from the microcosms: a Rhodococcus strain degrading ES and a Microbacterium strain capable of degrading HS. Despite substantial efforts, the microorganism thought to be responsible for BP3 degradation could not be isolated. This work demonstrates that microorganisms in coastal sediments can degrade a limited range of organic UV filters.

Human biomonitoring (HBM) has become a crucial tool for assessing exposure to emerging chemicals. We analyzed 250 24-h urine samples from the German Environmental Specimen Bank (ESB), collected between 2000 and 2021, for exposure to diethylamino hydroxybenzoyl hexyl benzoate (DHHB), a UV filter increasingly used in sunscreens. Three major metabolites were examined: 2-(4-diethylamino)-, 2-(4-ethylamino)-, and 2-(4-amino)-2-hydroxybenzoyl)benzoic acid (DHB, EHB, AHB), with detection rates of 18°%, 13°%, and 87°%, respectively. While EHB and DHB were specific to DHHB, AHB suggested other exposure sources, making it unreliable for assessing DHHB exposure. DHB and EHB were first detected in 2012, with increased detection rates thereafter. The median daily intake of 37 ng/kg bw/d was much lower than the derived no-effect level of 2900 mg/kg bw/d, indicating low risk from DHHB exposure. However, since the analyzed ESB samples were collected in winter, they likely reflect exposure from other products and the environment rather than sunscreen-related exposure. Recently, concerns have emerged regarding the DHHB impurity di-n-hexylphthalate (DnHexP), a reproductive toxicant not authorized in the EU. Retrospective analysis of oral DHHB dosing experiments indeed revealed impurity related dose-dependent excretion of DnHexP metabolites (MnHexP, oxidized 5-OH-MnHexP, and 5-oxo-MnHexP). Due to uncertainties in dose allocation, only a rough excretion fraction of 45°% for MnHexP was derived. Our findings suggest that the DHHB impurity DnHexP may contribute to DnHexP exposure in sunscreen users applying products with contaminated DHHB. Given DnHexP's toxicity, this warrants re-assessment of DHHB's safety in cosmetics and enhanced surveillance of both DHHB and DnHexP in HBM studies.

Recently, the cosmetic and pharmaceutical industries have aimed to reduce the concentration of EU-approved organic filters in their products by incorporating more natural ingredients. The goal is to find effective SPF boosters from plants while maintaining high protection levels and adhering to ecological and public health standards. This study focuses on developing a sunscreen formulation that replaces the organic filter EHMC (2-ethylhexyl-4-meth-oxycinnamate) with extracts from Echinacea purpurea and/or Propolis oil. The new formulation, which includes Ethylhexyltriazone (EHT), Octocrylene (OCR), Diethylamino hydroxybenzoyl hexyl benzoate (DHHB), and Methylene bis -benzotriazol-yltetramethylbutylphenol (MBBT), was compared with a control formulation containing EHMC. The results showed that the plant-based combination significantly enhanced the in vitro SPF and UVAPF by over 80% and 60%, respectively.

Marine ecosystems, particularly coastal areas, are becoming increasingly vulnerable to pollution from human activities. Persistent organic pollutants and contaminants of emerging concern (CECs) are recognized as significant threats to both human and environmental health. Our study aimed to identify the molecules present in the seawater of two bathing areas in the Western Mediterranean Sea. Polar Organic Chemical Integrative Samplers were employed for passive sampling of UV filters and other contaminants in the seawater. The concentrations of UV filters bemotrizinol (BEMT), benzophenone-3 (BP3), diethylamino hydroxybenzoyl hexyl benzoate (DHHB), octyl triazone (ET), and octocrylene (OC) were measured at these bathing sites during the summer of 2022. In addition, non-targeted chemical analysis was used to complement the list of pollutants in the sampling areas, leading to the identification of 53 contaminants and three natural products. Dodecyltrimethylammonium (DTA) and tetradecyltrimethylammonium (TTA) ions, 1,3-diphenylguanidine (DPG), N,N-diethyl-m-toluamide (DEET), and crystal violet (CV) were successfully quantified. Risk assessments showed that DEET, DPG, and BP3 present low environmental risks at the detected concentrations, while CV, DTA, and TTA pose medium to high risks, warranting further investigation. OC was found to pose a significant risk to marine biodiversity, as its environmental concentrations exceeded predicted no-effect concentration values. Overall, this study highlights the complexity of environmental pollution in coastal bathing areas and underscores the urgent need for comprehensive risk assessments to safeguard marine life and public health.

A total of 16 organic sunscreens and over 160 products of their degradation in biotic and abiotic conditions were investigated in the context of their safety during pregnancy. Drug-likeness and the ability of the studied compounds to be absorbed from the gastrointestinal tract and cross the human placenta were predicted in silico using the SwissADME software (for drug-likeness and oral absorption) and multiple linear regression and "ARKA" models (for placenta permeability expressed as fetus-to-mother blood concentration in the state of equilibrium), with the latter outperforming the MLR models. It was established that most of the studied compounds can be absorbed from the gastrointestinal tract. The drug-likeness of the studied compounds (expressed as a binary descriptor, Lipinski ) is closely related to their ability to cross the placenta (most likely by a passive diffusion mechanism). The organic sunscreens and their degradation products are likely to cross the placenta, except for very bulky and highly lipophilic 1,3,5-triazine derivatives; an avobenzone degradation product, 1,2-bis(4-tert-butylphenyl)ethane-1,2-dione; diethylamino hydroxybenzoyl hexyl benzoate; and dimerization products of sunscreens from the 4-methoxycinnamate group.

Although the negative effects of inorganic UV filters have been documented on several marine organisms, sunscreen products containing such filters are available in the market and proposed as eco-friendly substitutes for harmful, and already banned, organic UV filters (e.g. octinoxate and oxybenzone). In the present study, we investigated the effects of four sunscreen products, labelled by cosmetic companies as "eco-friendly", on the early developmental stages of the sea urchin Paracentrotus lividus, a keystone species occurring in vulnerable coastal habitats. Among sunscreens tested, those containing ZnO and TiO 2 or their mix caused severe impacts on sea urchin embryos. We show that inorganic UV filters were incorporated by larvae during their development and, despite the activation of defence strategies (e.g. phagocytosis by coelomocytes), generated anomalies such as skeletal malformations and tissue necrosis. Conversely, the sunscreen product containing only new-generation organic UV filters (e.g. methylene bis-benzotriazolyl tetramethyl, ethylhexyl triazone, butylphenol diethylamino hydroxybenzoyl hexyl benzoate) did not affect sea urchins, thus resulting actually eco-compatible. Our findings expand information on the impact of inorganic UV filters on marine life, corroborate the need to improve the eco-friendliness assessment of sunscreen products and warn of the risk of bioaccumulation and potential biomagnification of inorganic UV filters along the marine food chain.

Organic UV filters are important ingredients in many personal care products, including sunscreens. Evaluating the biodegradability of organic UV filters is key to estimate their recalcitrance and environmental fate and thus central to their overall environmental risk assessment. In order to further understand the degradation process, the aim was to investigate whether specific consortia could degrade certain UV filters. Several bacterial strains were isolated from enrichment cultures actively degrading octocrylene (OC), butyl methoxydibenzoylmethane (BM), homosalate (HS), and 2-ethylhexyl salicylate (ES) and were utilized to construct an in-house consortium. This synthetic consortium contained 27 bacterial strains and degraded OC, BM, HS, and ES 60-80% after 12 days, but not benzophenone-3 (BP3), methoxyphenyl triazine (BEMT), methylene bis-benzotriazolyl tetramethylbutylphenol (MBBT), diethylhexyl butamido triazone (DBT), ethylhexyl triazone (EHT), or diethylamino hydroxybenzoyl hexyl benzoate (DHHB). Furthermore, several commercial microbial mixtures from Greencell were tested to assess their degradation activity toward the same organic UV filters. ES and HS were degraded by some of the commercial consortia, but to a lesser extent. The rest of the tested UV filters were not degraded by any of the commercial bacterial mixes. These results confirm that some organic UV filters are recalcitrant to biodegradation, while others are degraded by a specific set of microorganisms.