Advance-CTR

Advance RI-CTR Pilot Projects Program (Cycle 9)

"Guarding Innocence: Unraveling the Transfer of PFAS from Mother to Child via Breastmilk"

Per- and polyfluoroalkyl substances (PFAS) are a class of highly persistent and anthropogenic neurotoxins that have been associated with behavioral issues and reduced IQ scores in young children. The presence of PFAS in human breast milk suggests PFAS transmission via breastfeeding during early childhood when the immature blood-brain barrier renders the developing brain more vulnerable to neurotoxins. 

PFAS are known to be neurotoxic, particularly concerning during early childhood when the immature blood-brain barrier heightens susceptibility. Higher PFAS concentrations in children's serum have been linked to behavioral difficulties and lower IQ scores. Breastfeeding, a vital source of infant nutrition, also presents a potential route for maternal PFAS transmission. Understanding the factors influencing PFAS transfer via breastfeeding is crucial to assess the risk for PFAS-related toxicity in children.

This project aims to investigate the toxicokinetic (TK) mechanisms underlying the transfer of PFAS from maternal blood to breast milk. A list of 50 priority PFAS that cover the physicochemical diversity relevant to human exposure will be categorized according to their potential to accumulate in breast milk. TK parameters including partition coefficients, permeabilities, and active transporters (BCRP) will be measured in in vitro cell-based bioassays and binding assays and implemented into a two-compartment TK model to simulate PFAS accumulation in breast milk in women during lactation following intake of contaminated drinking water. 

A follow-up translational clinical study is suggested that will enable TK simulations with Bayesian inference methods to derive probabilistic distributions of PFAS levels in human breast milk considering variabilities in PFAS blood concentrations, human physiology, and toxicokinetics. The project will help prioritize efforts to regulate and mitigate PFAS exposure risks during infancy using a combination of new approach methods (NAMs), in accordance with recent guidelines to reduce, refine, and replace animal testing.

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