6:2クロロポリフルオロアルキルエーテルスルホン酸のヒト健康リスク評価を改善するための生理学的薬物動態モデルの開発

The pervasive detection of 6:2 chlorinated polyfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA, commercial name: F-53B), a commonly utilized alternative for perfluorooctane sulfonate (PFOS), has raised concern. However, the lack of comprehensive toxicokinetic information poses a significant challenge in estimating associated human risk. This study aimed to develop a physiologically based pharmacokinetic (PBPK) model for 6:2 Cl-PFESA in male mice, derive a human-equivalent reference dose (RfD) using toxicokinetic data, and assess associated health risks based on measured serum concentrations. Results revealed that 6:2 Cl-PFESA exhibited tissue-specific accumulation in male mice following oral and intravenous administration, with the distribution ranked as liver > blood > fat > kidney > other tissues. The bioavailability of 6:2 Cl-PFESA was approximately 65 %. Based on these toxicokinetic data, the newly developed PBPK model estimated a half-life of up to 46.5 days at low exposure levels and a volume of distribution between 0.592 and 0.604 L/kg. The resulting RfD was 0.02 ng/kg/day, indicating higher toxicity and greater human health risks than PFOS. The population-weighted hazard quotient (HQ) for 6:2 Cl-PFESA was 1.95, suggesting a significant health risk in China. These findings highlight the urgent need for stringent regulatory measures targeting PFOS alternatives, including 6:2 Cl-PFESA.