Skin contact has been hypothesized to contribute to human exposure to bisphenol A (BPA). We examined the diffusion and metabolism of BPA using viable skin models: human skin explants and short-term cultures of pig ear skin, an alternative model for the study of the fate of xenobiotics following contact exposure. 14C-BPA [50-800 nmol] was applied on the surface of skin models. Radioactivity distribution was measured in all skin compartments and in the diffusion cells of static cells diffusion systems. BPA and metabolites were further quantified by radio-HPLC. BPA was efficiently absorbed in short-term cultures, with no major difference between the models used in the study [viable pig ear skin: 65%; viable human explants: 46%; non-viable (previously frozen) pig skin: 58%]. BPA was extensively metabolized in viable systems only. Major BPA metabolites produced by the skin were BPA mono-glucuronide and BPA mono-sulfate, accounting together for 73% and 27% of the dose, in pig and human, respectively. In conclusion, experiments with viable skin models unequivocally demonstrate that BPA is readily absorbed and metabolized by the skin. The trans-dermal route is expected to contribute substantially to BPA exposure in human, when direct contact with BPA (free monomer) occurs.

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Zebrafish embryo assays are increasingly used in the toxicological assessment of endocrine disruptors. Among other advantages, these models are 3R-compliant and are fit for screening purposes. Biotransformation processes are well-recognized as a critical factor influencing toxic response, but major gaps of knowledge exist regarding the characterization of functional metabolic capacities expressed in zebrafish. Comparative metabolic studies between embryos and adults are even scarcer. Using 3H-labeled chemicals, we examined the fate of two estrogenic emerging contaminants, benzophenone-2 (BP2) and bisphenol S (BPS), in 4-day embryos and adult zebrafish. BPS and BP2 were exclusively metabolized through phase II pathways, with no major qualitative difference between larvae and adults except the occurrence of a BP2-di-glucuronide in adults. Quantitatively, the biotransformation of both molecules was more extensive in adults. For BPS, glucuronidation was the predominant pathway in adults and larvae. For BP2, glucuronidation was the major pathway in larvae, but sulfation predominated in adults, with ca. 40% conversion of parent BP2 and an extensive release of several conjugates into water. Further larvae/adults quantitative differences were demonstrated for both molecules, with higher residue concentrations measured in larvae. The study contributes novel data regarding the metabolism of BPS and BP2 in a fish model and shows that phase II conjugation pathways are already functional in 4-dpf-old zebrafish. Comparative analysis of BP2 and BPS metabolic profiles in zebrafish larvae and adults further supports the use of zebrafish embryo as a relevant model in which toxicity and estrogenic activity can be assessed, while taking into account the absorption and fate of tested substances.