A Simple Pharmacokinetic Model of Prenatal and Postnatal Exposure to Perfluoroalkyl Substances (PFASs)

Abstract

Most children are exposed to perfluoroalkyl substances (PFASs) through placental transfer, breastfeeding, and other environmental sources. To date, there are no validated tools to estimate exposure and body burden during infancy and childhood. In this study, we aimed to (i) develop a two-generation pharmacokinetic model of prenatal and postnatal exposure to perfluorooctanoic acid (PFOA), perfluorooctanesulfonate (PFOS), and perfluorohexanesulfonate (PFHxS); and to (ii) evaluate it against measured children's levels in two studies. We developed a pharmacokinetic model consisting of a maternal and a child compartment to simulate lifetime exposure in women and transfer to the child across the placenta and through breastfeeding. To evaluate the model, we performed simulations for each mother-child dyad from two studies in which maternal PFAS levels at delivery and children's PFAS levels were available. Model predictions based on maternal PFAS levels, sex of child, body weight, and duration of breastfeeding explained between 52% and 60% of the variability in measured children's levels at 6 months of age and between 52% and 62% at 36 months. Monte Carlo simulations showed that the daily intake through breastfeeding and resulting internal PFAS levels can be much higher in nursing infants than in mothers. This pharmacokinetic model shows potential for postnatal exposure assessment in the context of epidemiological studies and risk assessment.

Estimated exposures to perfluorinated compounds in infancy predict attenuated vaccine antibody concentrations at age 5-years

“…In order to estimate PFAS concentrations over time, single-compartment toxicokinetic models have been successfully applied, e.g., to calculate past serum-PFOA concentrations after cessation of exposure (Seals et al 2011) and serum-PFAS profiles in children exposed from breastfeeding (Verner et al 2016). Thus, the present study included both PFAS concentrations measured in age 18-month blood samples, and the study also utilized information on the duration of exclusive breastfeeding to calculate profiles of serum-PFAS concentrations during infancy.…”

Per- and polyfluoroalkyl substances in human serum and urine samples from a residentially exposed community

“…Volume of distribution ( VdC ) was scaled to bodyweight and assigned values of 170 mL/kg bodyweight (PFOA), 230 mL/kg bodyweight (PFOS) (Thompson et al, 2010), and 213 mL/kg bodyweight (PFHxS) (Verner et al, 2016). …”

Perfluoroalkyl Acids (PFAAs) in Serum from 2–4-Month-Old Infants: Influence of Maternal Serum Concentration, Gestational Age, Breast-Feeding, and Contaminated Drinking Water

“…[9][10][11] Modeling of infant exposure to some PFAAs suggests that in utero exposure and breastfeeding are important determinants of blood concentrations. 12,13 Food, drinking water, dust and air contribute to exposure when the child gets older. 4,[14][15][16][17] High early life exposure to some PFAAs is related to lower birth weight and immune toxicity, [18][19][20] and knowledge of determinants of PFAS concentrations in infant blood is urgently needed for identification of infant exposure sources.…”