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DOI | 10.1289/EHP7671 |
Development of a Gestational and Lactational Physiologically Based Pharmacokinetic (PBPK) Model for Perfluorooctane Sulfonate (PFOS) in Rats and Humans and Its Implications in the Derivation of Health-Based Toxicity Values | |
Wei-Chun Chou; Zhoumeng Lin | |
2021-03-17 | |
发表期刊 | Environmental Health Perspectives |
出版年 | 2021 |
英文摘要 | AbstractBackground:There is a great concern on potential adverse effects of exposure to perfluorooctane sulfonate (PFOS) in sensitive subpopulations, such as pregnant women, fetuses, and neonates, due to its reported transplacental and lactational transfer and reproductive and developmental toxicities in animals and humans. Objectives:This study aimed to develop a gestational and lactational physiologically based pharmacokinetic (PBPK) model in rats and humans for PFOS to aid risk assessment in sensitive human subpopulations. Methods:Based upon existing PBPK models for PFOS, the present model addressed a data gap of including a physiologically based description of basolateral and apical membrane transporter–mediated renal reabsorption and excretion in kidneys during gestation and lactation. The model was calibrated with published rat toxicokinetic and human biomonitoring data and was independently evaluated with separate data. Monte Carlo simulation was used to address the interindividual variability. Results:Model simulations were generally within 2-fold of observed PFOS concentrations in maternal/fetal/neonatal plasma and liver in rats and humans. Estimated fifth percentile human equivalent doses (HEDs) based on selected critical toxicity studies in rats following U.S. Environmental Protection Agency (EPA) guidelines ranged from 0.08 to . These values are lower than the HEDs estimated in U.S. EPA guidance () using an empirical toxicokinetic model in adults. Conclusions:The results support the importance of renal reabsorption/excretion during pregnancy and lactation in PFOS dosimetry and suggest that the derivation of health-based toxicity values based on developmental toxicity studies should consider gestational/lactational dosimetry estimated from a life stage-appropriate PBPK model. This study provides a quantitative tool to aid risk reevaluation of PFOS, especially in sensitive human subpopulations, and it provides a basis for extrapolating to other per- and polyfluoroalkyl substances (PFAS). All model codes and detailed tutorials are provided in the Supplemental Materials to allow readers to reproduce our results and to use this model. https://doi.org/10.1289/EHP7671 |
领域 | 资源环境 |
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文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/319813 |
专题 | 资源环境科学 |
推荐引用方式 GB/T 7714 | Wei-Chun Chou,Zhoumeng Lin. Development of a Gestational and Lactational Physiologically Based Pharmacokinetic (PBPK) Model for Perfluorooctane Sulfonate (PFOS) in Rats and Humans and Its Implications in the Derivation of Health-Based Toxicity Values[J]. Environmental Health Perspectives,2021. |
APA | Wei-Chun Chou,&Zhoumeng Lin.(2021).Development of a Gestational and Lactational Physiologically Based Pharmacokinetic (PBPK) Model for Perfluorooctane Sulfonate (PFOS) in Rats and Humans and Its Implications in the Derivation of Health-Based Toxicity Values.Environmental Health Perspectives. |
MLA | Wei-Chun Chou,et al."Development of a Gestational and Lactational Physiologically Based Pharmacokinetic (PBPK) Model for Perfluorooctane Sulfonate (PFOS) in Rats and Humans and Its Implications in the Derivation of Health-Based Toxicity Values".Environmental Health Perspectives (2021). |
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