Development of a\nPhysiologically Based Pharmacokinetic\n(PBPK) Model for F‑53B in Pregnant Mice and Its Extrapolation\nto Humans

Chlorinated polyfluorinated ether sulfonic acid (F-53B),\na commonly\nutilized alternative for perfluorooctane sulfonate, was detected in\npregnant women and cord blood recently. However, the lack of detailed\ntoxicokinetic information poses a significant challenge in assessing\nthe human risk assessment for F-53B exposure. Our study aimed to develop\na physiologically based pharmacokinetic (PBPK) model for pregnant\nmice, based on toxicokinetic experiments, and extrapolating it to\nhumans. Pregnant mice were administered 80 μg/kg F-53B orally\nand intravenously on gestational day 13. F-53B concentrations in biological\nsamples were analyzed via ultraperformance liquid chromatography–mass\nspectrometry. Results showed the highest F-53B accumulation in the\nbrain, followed by the placenta, amniotic fluid, and liver in fetal\nmice. These toxicokinetic data were applied to F-53B PBPK model development\nand evaluation, and Monte Carlo simulations were used to characterize\nthe variability and uncertainty in the human population. Most of the\npredictive values were within a 2-fold range of experimental data\n(>72%) and had a coefficient of determination (R<sup>2</sup>) greater\nthan 0.68. The developed mouse model was then extrapolated to the\nhuman and evaluated with human biomonitoring data. Our study provides\nan important step toward improving the understanding of toxicokinetics\nof F-53B and enhancing the quantitative risk assessments in sensitive\npopulations, particularly in pregnant women and fetuses.