Estimating the early life exposure to PFAS using PBPK modelling and Human biomarker data

In 2020, EFSA established a tolerable weekly intake (TWI) of 4.4 ng/kg bw/week for PFOA, PFNA, PFHxS and PFOS based on a sum value approach.

Our work aims to estimate the exposure of children to these compounds using a physiologically based pharmacokinetic (PBPK) modelling approach and to determine the contribution of each exposure source ( in utero, breastfeeding and diet). A PFAS lifetime model was updated to simulate internal PFAS exposures during prenatal and childhood and to include individual characteristics and exposure scenarios. Our approach was applied to the HELIX cohort which contains more than a thousand mother-child pairs from six European countries with measured plasma concentrations of the four PFAS at two sampling times: during pregnancy and in childhood (6 to 10 years).

Our first results show that the model predicted an increase in plasma concentrations during fetal development and childhood up to the age of 2 years, when maximum concentrations are reached. The estimated total daily intakes (DI) of several infants aged of one year exposed to the four PFAS exceed the EFSA threshold, although the average for all children remains below. The highest DI appear to be found in children from France and Norway for PFOS and in France, England and Norway for PFOA.

Furthermore, we observed that similar measured biomarker levels can correspond to large differences in simulated internal exposures, highlighting the importance of studying the child's exposure in early life to refine early life risk assessment.