Physiologically based pharmacokinetic (PBPK) modeling of perfluorohexane sulfonate (PFHxS) in humans

Per- and polyfluoroalkyl substances (PFAS) are persistent, man-made compounds prevalent in the environment and consistently identified in human biomonitoring samples. In particular, perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonic acid (PFHxS) have been identified at U.S. Air Force installations. The study of human toxicokinetics and physiologically based pharmacokinetic (PBPK) modeling of PFHxS has been less robust and has been limited in scope and application as compared to PFOS and PFOA. The primary goal of the current effort was to develop a PBPK model describing PFHxS disposition in humans that can be applied to retrospective, current, and future human health risk assessment of PFHxS. An existing model developed for PFOS and PFOA was modified and key parameter values for exposure and toxicokinetics were calibrated for PFHxS prediction based on human biomonitoring data, particularly general population serum levels from the U.S. Centers for Disease Prevention and Control (CDC) National Health and Nutrition Examination Survey (NHANES). Agreement between the model and the calibration and evaluation data was excellent and recapitulated observed trends across sex, age, and calendar years. Confidence in the model is greatest for application to adults in the 2000-2018 time frame and for shorter-term future projections.