Screening-level information for developmental neurotoxicity using new approach methodologies
In 2023, the OECD published the guidance document “Initial Recommendations on Evaluation of Data from the Developmental Neurotoxicity (DNT) In-Vitro Testing Battery” (OECD 2023). The DNT in vitro battery consists of multiple new approach methodologies (NAMs) that evaluate key processes of neurodevelopment such as proliferation, migration, differentiation, neuronal network formation, and function and locomotor activity in zebrafish (Danio rerio) embryos.
To explore a broader chemical space and increase the applicability domain, there is a need to screen additional compounds. The DNT Health Effects Innovation program within the NIEHS Division of Translational Toxicology is generating screening-level information on chemicals using the DNT in vitro battery and behavioral assays in small model organisms. Currently about 220 chemicals have been selected and distributed for testing with half of them being finalized and analyzed using a unified data analysis pipeline to combine data from the individual assays. To further build confidence in using the DNT in vitro battery for regulatory applications, the screening level information is being used to develop specific case studies of integrated approaches to testing and assessment.