Estimating drinking water PFAS exposures associated with serum clinical action levels using a probabilistic toxicokinetic model

Abstract

Consumption of drinking water is a major and actionable human exposure pathway for per- and polyfluoroalkyl substances (PFAS), making it a focus of regulatory efforts. Population-based clinical guidelines recently established serum PFAS levels associated with health risk, but translating these into corresponding external drinking water exposure concentrations remains a data gap. Toxicokinetic (TK) models that relate drinking water PFAS concentrations to population serum levels provide a framework to link clinical guidelines with environmental exposure. In this study, we expand and evaluate a probabilistic, one-compartment TK model to estimate population serum PFAS concentrations for six regulated PFAS. We implement the model to estimate drinking water PFAS concentrations that maintain serum concentrations in sensitive populations below a clinical action level recommended by the National Academies of Sciences, Engineering and Medicine. Model revisions include incorporating population variability distributions for exposure factors, implementing continuous modeling from birth to account for transgenerational transfer, improving computational efficiency, and adding two additional PFAS. Distributions of modifiable parameters are combined using Monte Carlo simulations to predict the distribution of serum PFAS concentrations across defined populations. Model predictions reproduced empirical serum concentrations for populations of infants, children, and adults within two-fold error of observed central tendencies and upper percentiles for six PFAS. Drinking water concentrations that maintain serum concentrations below the National Academies of Sciences, Engineering, and Medicine clinical action level for breastfed infants range from 19 to 162 ng/L for the six PFAS, individually. These drinking water concentrations can inform regulatory, policy, and clinical decision-making, although they are not appropriate as health-protective drinking water standards.