Toxicokinetic Modeling for Intermittent Dietary Uptake of Per- and Polyfluoroalkyl Substances by Zebrafish

Dietary uptake plays an important role in fish bioaccumulation of per- and polyfluoroalkyl substances (PFAS). However, the existing toxicokinetic modeling for dietary uptake of PFAS is limited. In this study, adult zebrafish were exposed to diet-borne PFAS with diverse structures for 3 days, followed by a 12 day depuration. The PFAS levels in zebrafish were monitored and predicted by toxicokinetic models. The experimental results showed intermittent feeding caused a peak PFAS level during feeding intervals. A two-compartment model considering intermittent feeding can accurately describe the dietary uptake kinetics of PFAS and provide a robust estimation of assimilation efficiency. The extent of PFAS level fluctuation is determined by the elimination rate constant in the whole body. Subsequently, a physiologically based toxicokinetic (PBTK) model considering intermittent dietary uptake was developed to predict the internal body burden and tissue distribution of PFAS in zebrafish. The incorporation of intermittent feeding into the PBTK model significantly enhanced the model performance and provided PFAS level estimates within a factor of 2 for most of the experimental measurements during exposure. This study underscores the significant influence of intermittent dietary uptake on the internal body burden of PFAS in fish and advocates for its integration within the toxicokinetic model framework.