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.