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Development and Human Extrapolation of Physiologically Based Toxicokinetic Models for Chlorinated Polyfluoroalkyl
Jing Zhang1,2, Huihui Bao2, Wen-Hui Zhao1
1Joint International Research Laboratory of Environment and Health, Ministry of Education, Guangdong Provincial Engineering Technology Research Center of Environmental Pollution and Health Risk Assessment, Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
None:
Chlorinated polyfluoroalkyl ether sulfonates (F-53B, including 6:2 Cl-PFESA and 8:2 Cl-PFESA) are typical alternatives to perfluorooctanesulfonate in China. However, they are persistent and frequently detected in the environment and humans and pose bioaccumulation and health risks. The limited understanding of F-53B's toxicokinetic data hinders its risk assessment. This study aimed to develop physiologically based toxicokinetic (PBTK) models for 6:2 Cl-PFESA and 8:2 Cl-PFESA in rats and to extrapolate the models to humans. Male rats were administered a single 100 μg/kg dose of F-53B (with a 6:2 Cl-PFESA to 8:2 Cl-PFESA ratio of about 9:1) via gavage and intravenous injection, and biosample concentrations were quantified using ultrahigh-performance liquid chromatography-mass spectrometry. Results showed that 6:2 Cl-PFESA was mainly distributed to the liver and plasma, while 8:2 Cl-PFESA was primarily distributed to the liver and lung. The developed PBTK models successfully predicted 100% of 6:2 Cl-PFESA and 92% of 8:2 Cl-PFESA concentrations within a 2-fold range of the observed values. These models were subsequently extrapolated to humans and validated with human biomonitoring data. This study establishes PBTK models for F-53B in the general adult population, enhancing quantitative risk assessments under real-world scenarios.
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