Reliability of toxicokinetic modelling for PFAS exposure assessment in contaminated water in northern Italy

Introduction: Long-term contamination of tap water and groundwater by perfluoroalkyl and polyfluoroalkyl substances (PFASs) has been documented in the Veneto region of northern Italy. This study aimed to assess the exposure of individuals residing in the contaminated area and to test several toxicokinetic (TK) models of varying complexities to identify an efficient method for predicting perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) concentrations in human serum using observed data. The ultimate goal is to provide public health officials with guidance on selecting the appropriate TK model for specific contexts, a reliable and rapid tool to support human bio-monitoring (HBM) studies. Methods: Two simpler empirical TK models and a more complex multi-compartment physiologically based toxicokinetic (PBTK) model were compared with individual and aggregate data from an HBM study. In addition, the PBPK model was modified by adjusting input parameters and introducing new terms into the equations within the original model code. These modifications aimed to optimize the results compared to the original model, with some versions incorporating adjustments to account for the influence of menstruation in women. All models were evaluated to understand their strengths and weaknesses, providing guidance on the appropriate model to use according to specific scenarios. Results: The results obtained from the tested models were quite similar, with significant improvements observed only in the modified models. Simpler models also provided satisfactory results in scenarios involving low PFOS serum concentrations and recent exposure cessation. In many cases, predictions demonstrated high accuracy, particularly at the aggregate level and for women. Conclusions: These findings suggest that environmental protection agencies and health authorities may benefit from employing the tested models at the aggregate level as an initial step in HBM studies, rather than conducting more invasive and expensive screening campaigns.