Developmental Neurotoxicity (DNT): A Call for Implementation of New Approach Methodologies for Regulatory Purposes: Summary of the 5th International Conference on DNT Testing

The 5^th International Conference on Developmental Neurotoxicity (DNT) Testing (DNT5) took place in April 2024 in Konstanz, Germany, organized by CAAT-Europe, the University of Konstanz, and scientists from the US EPA, SCAHT, and CAAT at Johns Hopkins University Bloomberg School of Public Health. The conference convened experts from regulatory agencies, industry, and academia to explore the latest advancements in DNT testing and the integration of animal-free new approach methodologies (NAMs) into next-generation risk assessment (NGRA). The key topic was the application and further development of the recently established DNT in vitro test battery (DNT-IVB). To support this, OECD held a satellite meeting to discuss necessary next steps for further implementation of the DNT-IVB in regulatory contexts. Validation of new DNT test methods and use of their data for in-vitro-to-in-vivo extrapolations in physiologically based kinetic models were also important themes of the main meeting. In this context, the question was raised when a comprehensive biological and chemical coverage by the DNT-IVB would be reached. A need for additional testing data was recognized. Context-specific validation approaches for the entire DNT-IVB and the potential for intelligent combinations of assays to enhance the predictive power of the test battery were also addressed. Many presentations demonstrated the field’s embrace of novel developments, including the use of multi-endpoint embryonic zebrafish tests, the development of artificial intelligence-driven computational approaches, and the establishment of complex, electrically active brain organoids and other self-organizing structures. Through its highly interactive format, DNT5 promoted extensive collaborative efforts in advancing the field toward more human-relevant, scientifically reliable, and ethical toxicological assessments.