Estimating the early-life exposure to two perfluorinated compounds (PFOS and PFOA) using PBPK modelling and biomarker measurements

Children exposure to per- and polyfluoroalkyl acids substances (PFAS) is a major concern in health risk assessment as early-life exposures are suspected to induce adverse effects such as cardiometabolic, neurodevelopmental, or impact on immune response. Our work aims to estimate children exposure to PFOA and PFOS using a Physiologically-Based Pharmacokinetic (PBPK) modelling approach.

A lifetime model for PFAS was updated to simulate the internal PFAS exposures during the in utero life and childhood, and to include individual characteristics and exposure scenarios. Our approach was applied on the HELIX cohort, involving 1,239 mother-child pairs with measured PFOA and PFOS plasma concentrations at two sampling times: during pregnancy and in childhood (6 to 10 y.o).

Our model predicted an increase of the plasma concentrations during fetal development and childhood until 2 y.o when the maximum concentrations were reached. Higher PFOA plasma concentrations than PFOS ones were predicted until 2 y.o, and then PFOS levels gradually became higher than PFOA ones. From 2 to 8 y.o, mean concentrations decrease from 3.09 to 1.88 µg/L (PFOA) and from 4.77 to 3.56 µg/L (PFOS). The concentration-time profiles vary with the age and were mostly influenced by in utero exposure (0-4 months), breastfeeding (5 months – 2 (PFOA) or 5 (PFOS) y.o), and food intake (after 3 (PFOA) or 6 (PFOS) y.o). Similar measured biomarker levels can correspond to large differences in the simulated internal exposures, highlighting the importance to investigate the child exposure over the early life to improve exposure classification of the child. The simulated internal concentrations in several infants and toddlers exceeded the HBM-I value threshold compared to the ones in older children, especially for PFOA.

Our approach based on PBPK modelling and HBM data demonstrates the possibility to simulate individualized internal exposures, that could be accounted to refine risk assessment in early life.