Identifying possible neurodevelopmental effects of per- and polyfluoroalkyl substances (PFAS) through an adverse outcome pathway (AOP) network for human developmental neurotoxicology.
📄 Abstract
Human studies have reported inconsistent associations between early-life exposure to per- and polyfluoroalkyl substances (PFAS), particularly during critical windows of brain development, and neurodevelopmental outcomes. To address the lack of clarity regarding how PFAS affect neurodevelopment, this study developed the first unified adverse outcome pathway (AOP) network to explore the mechanisms involved in developmental neurotoxicity (DNT). Of 343 AOPs retrieved from AOP-Wiki, 19 linear AOPs associated with DNT satisfied the inclusion criteria. To pinpoint critical nodes and relationships, the constructed DNT-AOP network was examined using topological metrics. Through a combination of qualitative weight of evidence (WoE) assessment and network topology analysis, two critical paths were identified: one based on thyroid hormone disruption and the other on the intracellular calcium (Ca