Gradient, Cambridge, MA, USA.
Gradient, Cambridge, MA, USA.
Regul Toxicol Pharmacol. 2019 Aug;106:239-250. doi: 10.1016/j.yrtph.2019.05.008. Epub 2019 May 9.
Toxicokinetics are important for extrapolating health effects and effect levels observed in laboratory animals to humans for purposes of establishing health-based criteria. We conducted a comprehensive review of key absorption, distribution, metabolism, and excretion (ADME) parameters across different mammalian species for five perfluoroalkyl substances (PFAS) and discussed how these data can be used to inform human health risk assessment of these substances. Our analysis revealed several notable differences among the different PFAS regarding species- and substance-specific tissue partitioning, half-life, and transfer to developing offspring via the placenta or lactation, as well as highlighted data gaps for certain substances. We incorporated these observations in an analysis of whether health-based values for specific PFAS can be applied to other PFAS of differing chain length or toxicological mode of action. Overall, our analysis provides one of the first syntheses of available empirical PFAS toxicokinetic data to facilitate interpreting human relevance of animal study findings and developing health-based criteria for PFAS from such studies.
毒代动力学对于将实验室动物中观察到的健康影响和效应水平外推到人类，以便为基于健康的标准建立提供重要依据。我们对五种全氟烷基物质（PFAS）在不同哺乳动物物种中的关键吸收、分布、代谢和排泄（ADME）参数进行了全面审查，并讨论了如何利用这些数据为这些物质的人类健康风险评估提供信息。我们的分析揭示了不同 PFAS 在物种和物质特异性组织分配、半衰期以及通过胎盘或哺乳向发育中的后代转移方面存在一些显著差异，并突出了某些物质的数据空白。我们将这些观察结果纳入了对特定 PFAS 的基于健康的数值是否可应用于不同链长或毒理学作用模式的其他 PFAS 的分析中。总的来说，我们的分析提供了对现有 PFAS 毒代动力学数据的综合评估之一，以促进解释动物研究结果与人类的相关性，并为基于此类研究的 PFAS 制定基于健康的标准。
