Experimental Toxicology and Modeling Unit, INERIS, UMR-I 02 SEBIO, Verneuil en Halatte 65550, France; Ecotoxicology of Substances and Fields Unit, INERIS, UMR-I 02 SEBIO, Verneuil en Halatte 65550, France.
Ecotoxicology of Substances and Fields Unit, INERIS, UMR-I 02 SEBIO, Verneuil en Halatte 65550, France.
Aquat Toxicol. 2022 Jun;247:106174. doi: 10.1016/j.aquatox.2022.106174. Epub 2022 Apr 18.
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.
双酚 A（BPA）是一种具有重大关注意义的化学物质，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，鱼类等生物会受到 BPA 的慢性暴露。然而，生理基础毒代动力学（PBTK）模型是一种有价值的工具，可以帮助我们更好地了解化学物质在生物体中的命运，但从未专门针对鱼类的 BPA 毒代动力学（TK）进行过适应性建模。在我们的工作中，对现有的针对四种不同鱼类的 PBTK 模型进行了修改，以模拟 BPA 的吸收、分布、代谢和排泄过程。模型中还考虑了 BPA 代谢为 BPA-单葡萄糖醛酸苷（BPA gluc）和 BPA-单硫酸盐（BPA sulf）以及它们在各种器官中的 TK。在通常用于生态毒理学的模式物种棘鱼中进行了实验以生成 BPA TK 数据。模型结构必须包括两个代谢部位，以便在棘鱼器官中准确模拟 BPA TK。因此，鱼类肝脏可能不是 BPA 代谢的唯一部位：血浆或鳃也可能在 BPA 代谢中发挥作用。在斑马鱼和虹鳟鱼的文献数据上评估的 PBTK 模型预测性能与这一结论一致。最后，将来自三个物种的校准混合数据与仅在棘鱼数据上的校准进行了比较。
