Abstract
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.
Highlights
The involvement of endocrine-disrupting chemicals (EDCs) in the onset of adverse developmental and reproductive health effects in human and wildlife has been extensively documented, underlining the necessity to characterize the risk related to these compounds [1,2]
Zebrafish has been found to be useful in studies related to EDCs, with important research efforts conducted over the past few years
Using 3H-labeled molecules, we investigated in the current study the comparative fate of BP2 and bisphenol S (BPS) in larvae versus adult zebrafish
Summary
The involvement of endocrine-disrupting chemicals (EDCs) in the onset of adverse developmental and reproductive health effects in human and wildlife has been extensively documented, underlining the necessity to characterize the risk related to these compounds [1,2] In this context, mammalian and non-mammalian in vitro and in vivo species-specific bioassays have been developed and implemented for the screening and testing of the endocrine activity of chemical substances, with both research and regulatory perspectives [3]. Zebrafish has been found to be useful in studies related to EDCs, with important research efforts conducted over the past few years This led to significant advances in the understanding of the mode of action of EDCs on steroid receptor-regulated pathways, and of the development of both in vitro and in vivo biological models and assays used to assess the endocrine disrupting (ED) potency of chemicals [4]. The combined use of these in vitro and in vivo methods in a tiered-approach is quite promising for the assessment of the estrogenic activity of chemicals in fish, since they provide reliable and accurate information on the molecular mode of action and the effect of substances on the endocrine system
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