U.S. Environmental Protection Agency, Office of Pesticide Programs, Health Effects Division, 109 TW Alexander Dr, Research Triangle Park, NC, 27709, USA.
Corteva Agriscience, Haskell R&D Center, 1090 Elkton Road, Newark, DE, 19714, USA.
Regul Toxicol Pharmacol. 2020 Aug;115:104691. doi: 10.1016/j.yrtph.2020.104691. Epub 2020 Jun 2.
Physiologically-based pharmacokinetic (PBPK) modeling analysis does not stand on its own for regulatory purposes but is a robust tool to support drug/chemical safety assessment. While the development of PBPK models have grown steadily since their emergence, only a handful of models have been accepted to support regulatory purposes due to obstacles such as the lack of a standardized template for reporting PBPK analysis. Here, we expand the existing guidances designed for pharmaceutical applications by recommending additional elements that are relevant to environmental chemicals. This harmonized reporting template can be adopted and customized by public health agencies receiving PBPK model submission, and it can also serve as general guidance for submitting PBPK-related studies for publication in journals or other modeling sharing purposes. The current effort represents one of several ongoing collaborations among the PBPK modeling and risk assessment communities to promote, when appropriate, incorporating PBPK modeling to characterize the influence of pharmacokinetics on safety decisions made by regulatory agencies.
基于生理学的药代动力学（PBPK）建模分析本身不适用于监管目的，但它是支持药物/化学物质安全评估的强大工具。虽然自出现以来，PBPK 模型的开发一直在稳步增长，但由于缺乏标准化的 PBPK 分析报告模板等障碍，只有少数模型被接受用于支持监管目的。在这里，我们通过推荐与环境化学物质相关的其他元素，扩展了现有的专为制药应用而设计的指南。公共卫生机构在收到 PBPK 模型提交时可以采用和定制这个统一的报告模板，它也可以作为在期刊上发表或其他模型共享目的提交与 PBPK 相关研究的一般指南。目前的工作是 PBPK 建模和风险评估社区之间正在进行的几项合作之一，旨在在适当的情况下，纳入 PBPK 建模以描述药代动力学对监管机构做出的安全决策的影响。
