Data-driven modeling of PFAA substances in serum as basis for setting limit values for drinking water and food

Per- and polyfluoroalkyl substances (PFAS) are man-made chemicals causing world-wide pollution of food and drinking water (DW) and some may be precursors of the very persistent perfluoroalkyl acids (PFAA).

PFAA will represent a significant exposure source for humans from DW and edible fish for the coming decades despite future legislative banning.

A large fraction of the Swedish population exceeds EU’s tolerable weekly intake (TWI) for the sum of four PFAA (PFAA4), based on decreased vaccination antibody response in toddlers after in utero/breastfeeding exposure.

We plan to (1) develop toxicokinetic (TK) models that describe the relation between lifetime PFAA4 exposures from DW and food and PFAA4 concentrations in serum for both genders.

Using the validated TK model, we will then (2) translate the TWI to health-based guidance values (HBGV) for PFAA4 substances at different ages and for both genders, and (3) back calculate the HBGVs to safe PFAA4 concentrations in DW and fish.

We further aim to (4) apply the TK models for translating in vitro testing data of critical immunotoxic effects underlying the reduced antibody response for more PFAA than just PFAA4 to serum concentrations.

The results from the previous steps will be used (5) to develop a user-friendly calculator for end-users not familiar with toxicokinetics.

Overall, the project is expected to result in refined cumulative PFAA exposure assessment and will serve as a valuable tool in risk management of PFAA.