Application of PBK models for long-chain PFAS to short-chain PFAS: a proposal for toxicokinetic evaluation and in vitro to in vivo extrapolation

This study explored the possibility to adapt the physiologically based kinetic (PBK) model, originally developed for long-chain and long half-life per- and polyfluoroalkyl substances (PFASs) by the European Food Safety Authority (EFSA), to assess three short-chain and short half-life PFASs namely perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA) and perfluorobutanesulfonic acid (PFBS). The aim was to estimate the plasma concentration of short-chain PFASs following repeated oral exposure and use this data to inform the Universal Immune System Simulator (UISS) model to predict effect on antibody response. In parallel, in vitro to in vivo extrapolation (QIVIVE) was conducted using values obtained from in vitro experiments. Results show the feasibility of applying established long-chain PFASs kinetic models to short-chain PFASs and to investigate their potential health impacts.