期刊
ENVIRONMENT INTERNATIONAL
卷 129, 期 -, 页码 408-422出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.envint.2019.03.058
关键词
Interspecies extrapolation; Markov chain Monte Carlo (MCMC); Perfluoroalkyl substances (PFAS); Perfluorooctane sulfonate (PFOS); Physiologically based pharmacokinetic (PBPK) modeling; Risk assessment
资金
- Kansas State University College of Veterinary Medicine New Faculty Startup funds
A challenge in the risk assessment of perfluorooctane sulfonate (PFOS) is the large interspecies differences in its toxicokinetics that results in substantial uncertainty in the dosimetry and toxicity extrapolation from animals to humans. To address this challenge, the objective of this study was to develop an open-source physiologically based pharmacokinetic (PBPK) model accounting for species-specific toxicokinetic parameters of PFOS. Considering available knowledge about the toxicokinetic properties of PFOS, a PBPK model for PFOS in mice, rats, monkeys, and humans after intravenous and oral administrations was created. Available species-specific toxicokinetic data were used for model calibration and optimization, and independent datasets were used for model evaluation. Bayesian statistical analysis using Markov chain Monte Carlo (MCMC) simulation was performed to optimize the model and to characterize the uncertainty and interspecies variability of chemical-specific parameters. The model predictions well correlated with the majority of datasets for all four species, and the model was validated with independent data in rats, monkeys, and humans. The model was applied to predict human equivalent doses (HEDs) based on reported points of departure in selected critical toxicity studies in rats and monkeys following U.S. EPA's guidelines. The lower bounds of the model-derived HEDs were overall lower than the HEDs estimated by U.S. EPA (e.g., 0.2 vs. 1.3 mu g/kg/day based on the rat plasma data). This integrated and comparative analysis provides an important step towards improving interspecies extrapolation and quantitative risk assessment of PFOS, and this open-source model provides a foundation for developing models for other perfluoroalkyl substances.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据