Enhanced Elimination of Perfluorooctane Sulfonic Acid by Menstruating Women: Evidence from Population-Based Pharmacokinetic Modeling

Human biomonitoring studies have shown that concentrations of perfluorooctane sulfonic acid (PFOS) in men are higher than in women. We investigate sex differences in elimination of PFOS by fitting a population-based pharmacokinetic model to six cross-sectional data sets from 1999 to 2012 from the US National Health and Nutrition Examination Survey (NHANES) and derive human first-order elimination rate constants (k(E)) and corresponding elimination half-lives (t(1/2)) for PFOS, where t(1/2) = In 2/k(E). We use a modified version of the Ritter population-based pharmacokinetic model and derive elimination rate constants separately for men and women. The model accounts for population-average lifetime changes in PFOS intake, body weight, and menstruation rate. We compare the model-derived elimination rate constant for hypothetical nonmenstruating women to the elimination rate constant for men and women when menstruation is included as a loss process to evaluate the hypothesis that loss of PFOS by menstruation is an important process for women. The modeled elimination half-life for men is 4.7 years, and the modeled elimination half-life for women when excluding losses from menstruation is 3.7 years. The elimination half-life for women when menstruation is included in the model is 4.0 years. Thus, menstruation accounts for 3096 of the discrepancy in elimination of PFOS between men and women. The remaining discrepancy is likely due to other sex-specific elimination routes that are not considered in our modeling.