Assessing developmental neurotoxicity of emerging environmental chemicals using multiple in vitro models: A comparative analysis.

Newly synthesized chemicals are being introduced into the environment without undergoing proper toxicological evaluation, particularly in terms of their effects on the vulnerable neurodevelopment. Thus, it is important to carefully assess the developmental neurotoxicity of these novel environmental contaminants using methods that are closely relevant to human physiology. This study comparatively evaluated the potential developmental neurotoxicity of 19 prevalent environmental chemicals including neonicotinoids (NEOs), organophosphate esters (OPEs), and synthetic phenolic antioxidants (SPAs) at environment-relevant doses (100 nM and 1 μM), using three commonly employed in vitro neurotoxicity models: human neural stem cells (NSCs), as well as the SK-N-SH and PC12 cell lines. Our results showed that NSCs were more sensitive than SK-N-SH and PC12 cell lines. Among all the chemicals tested, the two NEOs imidaclothiz (IMZ) and cycloxaprid (CYC), as well as the OPE tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), generated the most noticeable perturbation by impairing NSC maintenance and neuronal differentiation, as well as promoting the epithelial-mesenchymal transition process, likely via activating NF-κB signaling. Our data indicate that novel NEOs and OPEs, particularly IMZ, CYC, and TDCIPP, may not be safe alternatives as they can affect NSC maintenance and differentiation, potentially leading to neural tube defects and neuronal differentiation dysplasia in fetuses. [Display omitted] • The developmental neurotoxicity of 19 emerging environmental chemicals was assessed. • Neural stem cells were more sensitive to the chemicals than the SK-N-SH and PC12 cell lines. • Among the chemicals tested, IMZ, CYC, and TDCIPP exhibited the most adverse effects. • IMZ, CYC, and TDCIPP impaired NSC maintenance and differentiation, likely via NF-κB. • This study provides valuable insights for the safe use of emerging environmental chemicals. [ABSTRACT FROM AUTHOR]