Integrating Data FromIn VitroNew Approach Methodologies for Developmental Neurotoxicity

• DOI: 10.1093/toxsci/kfac018
• Publication Date: 2022-02-12T04:18:37Z
• Authors: Kelly E Carstens; Amy F Carpenter; Melissa M Martin; Joshua A Harrill; Timothy J Shafer; Katie Paul Friedman
• Keywords: Neurotoxicity; Multielectrode array; In vitro toxicology; High-Content Screening; Synaptogenesis

In vivo developmental neurotoxicity (DNT) testing is resource intensive and lacks information on cellular processes affected by chemicals. To address this, DNT new approach methodologies (NAMs) are being evaluated, including: the microelectrode array neuronal network formation assay; high-content imaging to evaluate proliferation, apoptosis, neurite outgrowth, synaptogenesis. This work addresses 3 hypotheses: (1) a broad screening battery provides sensitive marker of bioactivity; (2) selective bioactivity (occurring at noncytotoxic concentrations) may indicate functional disrupted; and, (3) subset endpoints optimally classify chemicals with in evidence for DNT. The dataset was comprised 92 screened all 57 assay sourced from publicly available data, including set NAM evaluation putative positives (53) negatives (13). bioactivity, particularly cytotoxicity connectivity parameters. Hierarchical clustering suggested potency (including cytotoxicity) important classifying positive high sensitivity (93%) but failed distinguish patterns disrupted processes. contrast, values revealed informative differential activity demonstrated lower (74%). false were associated several limitations, such as maximal concentration tested or gaps biology captured current battery. demonstrates that this multi-dimensional suite biomarker providing possible insight into specific chemical exposure basis further research.