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The toxicokinetics of bisphenol A and its metabolites in fish elucidated by a PBTK model
Aquatic Toxicology ( IF 4.5 ) Pub Date : 2022-04-18 , DOI: 10.1016/j.aquatox.2022.106174
Corentin Mit 1 , Anne Bado-Nilles 2 , Gaëlle Daniele 3 , Barbara Giroud 3 , Emmanuelle Vulliet 3 , Rémy Beaudouin 4
Affiliation  

Bisphenol A (BPA) is a chemical of major concern due to its endocrine disrupting function, high production volume, and persistence in the aquatic environment. Consequently, organisms such as fish are subject to chronic exposure to BPA. However, physiologically-based toxicokinetic (PBTK) models, which are valuable tools to improve the understanding of a chemical's fate in an organism, have never been specifically adapted to model BPA toxicokinetics (TK) in fish. In our work, an existing PBTK developed for four different fish species was modified to model BPA ADME processes (absorption, distribution, metabolization and excretion). The metabolization of BPA into BPA-monoglucuronide (BPA gluc) and BPA-monosulfate (BPA sulf) and their TK in various organs was taking into account in the model. Experiments were performed to generate BPA TK data in a model species commonly used in ecotoxicology, the stickleback. The model structure had to include two sites of metabolization to simulate BPA TK accurately in stickleback organs. Thus, the fish liver may not be the only site of the metabolization of BPA: plasma or gills could also play a role in BPA metabolization. The PBTK model predictive performance evaluated on literature data in zebrafish and rainbow trout concurs with this conclusion. Finally, a calibration mixing data from the three species was compared to the calibration on stickleback data only.



中文翻译:

PBTK模型阐明鱼体内双酚A及其代谢物的毒代动力学

双酚 A (BPA) 是一种备受关注的化学品,因为它具有内分泌干扰功能、高产量和在水生环境中的持久性。因此,鱼类等生物体长期接触 BPA。然而,基于生理的毒代动力学 (PBTK) 模型是提高对生物体中化学物质归宿的理解的宝贵工具,但从未专门适用于模拟鱼类中的 BPA 毒代动力学 (TK)。在我们的工作中,针对四种不同鱼类开发的现有 PBTK 进行了修改,以模拟 BPA ADME 过程(吸收、分布、代谢和排泄)。模型中考虑了 BPA 代谢为 BPA-单葡糖苷酸 (BPA gluc) 和 BPA-单硫酸盐 (BPA sulf) 及其在各个器官中的 TK。进行了实验以在生态毒理学中常用的模型物种棘鱼中生成 BPA TK 数据。模型结构必须包括两个代谢位点,以准确模拟刺鱼器官中的 BPA TK。因此,鱼肝可能不是 BPA 代谢的唯一场所:血浆或鱼鳃也可能在 BPA 代谢中发挥作用。根据斑马鱼和虹鳟鱼文献数据评估的 PBTK 模型预测性能与此结论一致。最后,将三种物种的混合校准数据与仅刺鱼数据的校准进行了比较。鱼肝可能不是 BPA 代谢的唯一场所:血浆或鱼鳃也可能在 BPA 代谢中发挥作用。根据斑马鱼和虹鳟鱼文献数据评估的 PBTK 模型预测性能与此结论一致。最后,将三种物种的混合校准数据与仅刺鱼数据的校准进行了比较。鱼肝可能不是 BPA 代谢的唯一场所:血浆或鱼鳃也可能在 BPA 代谢中发挥作用。根据斑马鱼和虹鳟鱼文献数据评估的 PBTK 模型预测性能与此结论一致。最后,将三种物种的混合校准数据与仅刺鱼数据的校准进行了比较。

更新日期:2022-04-18
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