Development and Human Extrapolation of Physiologically Based Toxicokinetic Models for Chlorinated Polyfluoroalkyl Ether Sulfonates from Rats

Chlorinated
polyfluoroalkyl ether sulfonates (F-53B, including
6:2 Cl-PFESA and 8:2 Cl-PFESA) are typical alternatives to perfluorooctanesulfonate
in China. However, they are persistent and frequently detected in
the environment and humans and pose bioaccumulation and health risks.
The limited understanding of F-53B’s toxicokinetic data hinders
its risk assessment. This study aimed to develop physiologically based
toxicokinetic (PBTK) models for 6:2 Cl-PFESA and 8:2 Cl-PFESA in rats
and to extrapolate the models to humans. Male rats were administered
a single 100 μg/kg dose of F-53B (with a 6:2 Cl-PFESA to 8:2
Cl-PFESA ratio of about 9:1) via gavage and intravenous injection,
and biosample concentrations were quantified using ultrahigh-performance
liquid chromatography–mass spectrometry. Results showed that
6:2 Cl-PFESA was mainly distributed to the liver and plasma, while
8:2 Cl-PFESA was primarily distributed to the liver and lung. The
developed PBTK models successfully predicted 100% of 6:2 Cl-PFESA
and 92% of 8:2 Cl-PFESA concentrations within a 2-fold range of the
observed values. These models were subsequently extrapolated to humans
and validated with human biomonitoring data. This study establishes
PBTK models for F-53B in the general adult population, enhancing quantitative
risk assessments under real-world scenarios.