Interspecies differences in perfluoroalkyl substances (PFAS) toxicokinetics and application to health-based criteria

Toxicokinetics are important for extrapolating health effects and effect levels observed in laboratory animals to humans for purposes of establishing health-based criteria. We conducted a comprehensive review of key absorption, distribution, metabolism, and excretion (ADME) parameters across different mammalian species for five perfluoroalkyl substances (PFAS) and discussed how these data can be used to inform human health risk assessment of these substances. Our analysis revealed several notable differences among the different PFAS regarding species- and substance-specific tissue partitioning, half-life, and transfer to developing offspring via the placenta or lactation, as well as highlighted data gaps for certain substances. We incorporated these observations in an analysis of whether health-based values for specific PFAS can be applied to other PFAS of differing chain length or toxicological mode of action. Overall, our analysis provides one of the first syntheses of available empirical PFAS toxicokinetic data to facilitate interpreting human relevance of animal study findings and developing health-based criteria for PFAS from such studies.