The pharmacokinetics of perfluorobutanoic acid in female rats

Perfluorobutanoic acid (PFBA) is of increasing concern due to its widespread occurrence, high environmental mobility, and potential for human exposure. This study investigated the toxicokinetics of PFBA in female Sprague Dawley rats and assessed implications for human exposure. Under repeated oral exposure (0.2 mg/kg/day for 16 days), concentrations of PFBA in blood increased rapidly and stabilized within the range of 230-300 ng/mL. Owing to its large tissue mass, muscle served as the major reservoir for the overall body burden of PFBA. Among the various organs, kidney, stomach, liver and gut exhibited the highest proportions of PFBA, with peak concentrations of 675 ng/g, 514 ng/g, 256 ng/g and 250 ng/g. During the elimination phase, PFBA concentrations in all tissues declined sharply, with clearance ranging from 71.2% to 95.5% relative to peak levels. The gastrointestinal tract showed the greatest reduction among these tissues. The multiphasic kinetics were effectively captured by a three-compartment pharmacokinetic model that features parallel first-order and Michaelis-Menten elimination, with RMSE of 2.56 × 10³ and 1.65 × 10⁴ for the central and peripheral compartments, respectively. The estimated terminal half-life (68.7 h) and central volume of distribution (323 mL/kg) suggest limited interspecies differences compared to humans. These findings provide quantitative toxicokinetic parameters under repeated exposure, offering a foundation for human exposure assessment, mechanistic interpretation of tissue distribution, and risk evaluation of short-chain PFAS.