Developmental neurotoxicity (DNT): A call for implementation of new approach methodologies for regulatory purposes: Summary of the 5th International Conference on DNT Testing

The 5th 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 appli-cation 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.

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ALTEX
Published
2025-01-01
DOI
https://doi.org/10.14573/altex.2503191
Citations
2
Primary Topic
Pharmaceutical studies and practices
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article
Field-Weighted Citation Impact
6.99

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article

Developmental neurotoxicity (DNT): A call for implementation of new approach methodologies for regulatory purposes: Summary of the 5th International Conference on DNT Testing

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2 citations
ALTEX
Pharmaceutical studies and practices
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article

Developmental neurotoxicity (DNT): A call for implementation of new approach methodologies for regulatory purposes: Summary of the 5th International Conference on DNT Testing

Ellen V.S. Hessel, Randolph S. Ashton, Sebastian Gutsfeld, Maurice Whelan, Barry Hardy, Jui‐Hua Hsieh, Andrea Cediel-Ulloa, Katharina Koch, Anna‐Katharina Ückert, Eliška Kuchovská, Marcel Leist, Yasunari Kanda, Tamara Tal, Nadine Dreser, Anna Bal‐Price, Oddvar Myhre, Timothy J. Shafer, Ivana Celardo, Thomas B. Knudsen, Martin Paparella, Ellen Fritsche, Gavin Knight, Michael Aschner, M. Sue Marty, Harm J. Heusinkveld, Lena Smirnova, Iris Mangas, Iris Müller, Patrick Müller, Helena T. Högberg, K. Schlüppmann, Emily M. Pitzer, Jasmin Schäfer, Stephanie Melching‐Kollmuss, Giuseppe Testa, Kevin M. Crofton, Thomas Härtung, Eike Cöllen, Silvia Tangianu, Yaroslav Tanaskov, Kelly E Carstens, Magdalini Sachana, Susan J. Debad, Suzanne Fitzpatrick
article en
2 citations

Abstract

The 5th 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 appli-cation 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.

ALTEXVol. 42(2)
Albert Einstein College of Medicine (US), Environmental Protection Agency (US), Norwegian Institute of Public Health (NO), Innsbruck Medical University (AT), University of Basel (CH), University of Konstanz (DE), National Institute of Environmental Health Sciences (US), Leibniz Institute of Environmental Medicine (DE), National Institute for Public Health and the Environment (NL), Natural and Medical Sciences Institute (DE), Human Technopole (IT), Joint Research Centre (IT), Dow Chemical (United States) (US), National Institute of Health Sciences (JP), Edelweiss Connect (Switzerland) (CH), University of Tübingen (DE)
National Science Foundation, U.S. Department of Health and Human Services, U.S. Environmental Protection Agency, University of Wisconsin-Madison, European Commission, Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Ministry of Health, Labour and Welfare, National Institutes of Health, National Institute of Environmental Health Sciences
Openalex Percentile: Top 5%
Pharmaceutical studies and practices
6.99
DOIOpen Access PDFOpenAlex
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