In vitro test battery for developmental neurotoxicity
Developmental neurotoxicity (DNT) testing is traditionally done using animals, which is resource-intensive and fails to provide information on cellular processes affected by chemicals. EPA scientists have been evaluating use of new approach methodologies (NAMs) to assess DNT potential (Carstens et al. 2022), focusing on the microelectrode array neuronal network formation assay and high-content imaging to evaluate proliferation, apoptosis, neurite outgrowth, and synapse formation. Data for 92 chemicals with a range of potential DNT activities screened in 57 assay endpoints were sourced from publicly available data. From these data, a proposed DNT NAM battery was constructed that provides a sensitive marker of DNT bioactivity, particularly for evaluating cytotoxicity and network connectivity. This multi-dimensional assay suite may also provide insight into specific functional processes affected by chemical exposure.