Screening of PFAS for potential developmental neurotoxicity using NAMs
PFAS are a distinct set of commercial chemicals widely found in humans and the environment. However, only a small number of PFAS have epidemiological or experimental data to characterize any potential hazard they might pose. Using in vitro new approach methodologies (NAMs), EPA scientists tested 160 PFAS to characterize their potential to induce developmental neurotoxicity (DNT) (Carstens et al. 2023). The DNT NAMs battery used evaluated proliferation, apoptosis, neurite outgrowth, and neural network formation. While most of the PFAS tested were inactive or equivocal in the DNT NAMs, specific chemical structures were identified that appeared to correlate with PFAS bioactivity in the NAMs. These data demonstrate that a subset of PFAS perturb neurodevelopmental processes in vitro and suggest focusing future studies of DNT on PFAS with specific structural features. Analytical quality control indicated that significant numbers of both inactive PFAS and active PFAS samples were degraded. This indicates a need for careful interpretation of test results of these substances, as some negatives may have been due to loss of the parent PFAS and some active results may have been caused by PFAS degradants.