Comparison and evaluation of pharmacokinetics of PFOA and PFOS in the adult rat using a physiologically based pharmacokinetic model

Perfluoroalkyl acid carboxylates and sulfonates (PFAAs) have many consumer and industrial applications. The persistence and widespread distribution of PFAAs have brought them under intense scrutiny. Limited PK data for PFAAs is available for humans; however, toxicological and pharmacokinetic data exist for rats, which can be useful for cross-species extrapolation. In this work, PBPK models were developed for adult male and female rats to describe the pharmacokinetics of PFOA and PFOS. The models contain a description of saturable renal resorption, free fraction of chemical in plasma, and saturable binding in liver. Both male and female rat models for each chemical were consistent with available PK data resulting from IV, oral, and dietary dosing regimens. Predicted plasma concentration curves followed trends observed in experimental data, and model predictions were within a factor of two of experimental values. PFOA and PFOS rat model output is sensitive to parameters governing renal resorption, indicating that renal resorption is responsible for the long-half life. These models, along with the PFAA gestation and lactation models published in this issue, will help address concerns about possible health effects due to PFAA exposure in the fetus and neonate and will be useful in comparing PK across life stages.