The effects of acute and chronic exposure to bisphenols and PFAS on neuronal activity and network development.

Exposure to bisphenols and perfluoroalkyl substances (PFAS) is linked to various health impairments, including (developmental) neurotoxicity. Evidence indicates that bisphenols and PFAS can impact early neurodevelopmental processes such as proliferation, migration, and differentiation, although little is known about the effects of these compounds on neuronal activity and network development. Therefore, we assessed the effects of acute and chronic exposure to different bisphenols (bisphenol-A (BPA), bisphenol-F (BPF), and bisphenol-S (BPS)) and PFAS (perfluorooctanoate (PFOA), perfluorooctanesulfonate (PFOS), and perfluorohexanesulfonate (PFHxS)) on neuronal activity and network development in rat primary cortical cultures using micro-electrode array recordings. Acute exposure to BPA and BPF decreased neuronal activity, while BPS had no effect. Chronic exposure to 100 μM BPA decreased network development, while chronic exposure to 10 μM BPA, 100 μM BPF, and 100 μM BPS induced a hyperexcitation. Thus, differences in the molecular structure of bisphenols and exposure duration influence the effects of these compounds on neuronal activity and network development. In contrast, both acute and chronic exposure to PFOS, PFOA, and PFHxS had limited effects on neuronal activity and network development. Since bisphenols and PFAS are known endocrine-disrupting compounds, we also evaluated the possible involvement of estrogen, glucocorticoid, thyroid hormone, and aryl hydrocarbon receptor pathways in the observed neurotoxic effects. Our cortical cultures appeared insensitive to endocrine-mediated effects of (ant)agonists of these pathways, making it unlikely that the observed neurotoxic effects are endocrine-mediated. These findings contribute to hazard assessment for toxicological risk assessments and emphasize the need to consider molecular structure in evaluating neurotoxicity.