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Developmental Neurotoxicity (DNT) Health Effect Research Publications

DOI: https://doi.org/10.22427/NTP-DATA-500-105-001-000-2

Publication

Abstract

Humans are exposed to thousands of chemicals with unknown DNT potential, making efficient chemical evaluation crucial. The DNT Health Effect Research is actively working to generate screening-level information for these compounds using new approach methodologies. This effort aims to assess potential hazards and prioritize chemicals for further detailed evaluation. You can learn more about this initiative on the NIEHS DNT Health Effects Research page.

The DNT screening process consists of four phases—Pilot and Phases 1-3—each evaluating approximately 100 compounds. The DNT-DIVER platform was specifically developed to analyze, compare, and visualize the results from these screenings through an interactive web application.

Below, you'll find publications associated with each phase of the DNT screening.

Pilot

References

Behl, M. et al. (2019). Screening for Developmental Neurotoxicity at the National Toxicology Program: The Future Is Here. Toxicological sciences : an official journal of the Society of Toxicology, 167(1), 6–14. https://doi.org/10.1093/toxsci/kfy278

Hagstrom, D. et al. (2019). Comparative Analysis of Zebrafish and Planarian Model Systems for Developmental Neurotoxicity Screens Using an 87-Compound Library. Toxicological sciences : an official journal of the Society of Toxicology, 167(1), 15–25. https://doi.org/10.1093/toxsci/kfy180

Zhang, S. et al. (2019). Multi-Behavioral Endpoint Testing of an 87-Chemical Compound Library in Freshwater Planarians. Toxicological sciences : an official journal of the Society of Toxicology, 167(1), 26–44. https://doi.org/10.1093/toxsci/kfy145

Sirenko, O. et al. (2019). Functional and Mechanistic Neurotoxicity Profiling Using Human iPSC-Derived Neural 3D Cultures. Toxicological sciences : an official journal of the Society of Toxicology, 167(1), 58–76. https://doi.org/10.1093/toxsci/kfy218

Dach, K. et al. (2019). Teratological and Behavioral Screening of the National Toxicology Program 91-Compound Library in Zebrafish (Danio rerio). Toxicological sciences : an official journal of the Society of Toxicology, 167(1), 77–91. https://doi.org/10.1093/toxsci/kfy266

Hiseh, J.H. et al. (2019). Application of Benchmark Concentration (BMC) Analysis on Zebrafish Data: A New Perspective for Quantifying Toxicity in Alternative Animal Models. Toxicological sciences : an official journal of the Society of Toxicology, 167(1), 92–104. https://doi.org/10.1093/toxsci/kfy258

Ash, P.E.A. et al. (2019). Heavy Metal Neurotoxicants Induce ALS-Linked TDP-43 Pathology. Toxicological sciences : an official journal of the Society of Toxicology, 167(1), 105–115. https://doi.org/10.1093/toxsci/kfy267

Quevedo, C. et al. (2019). Detection and Prioritization of Developmentally Neurotoxic and/or Neurotoxic Compounds Using Zebrafish. Toxicological sciences : an official journal of the Society of Toxicology, 168(1), 225–240. https://doi.org/10.1093/toxsci/kfy291

Sachana, M. et al. (2019). International regulatory and scientific effort for improved developmental neurotoxicity testing. Toxicological Sciences, 167(1), 9-21. https://doi.org/10.1093/toxsci/kfy244

Delp, J. et al. (2018). A high-throughput approach to identify specific neurotoxicants/ developmental toxicants in human neuronal cell function assays. ALTEX, 35(2), 235–253. https://doi.org/10.14573/altex.1712182

Nyffeler, J. et al. (2017). Combination of multiple neural crest migration assays to identify environmental toxicants from a proof-of-concept chemical library. Archives of toxicology, 91(11), 3613–3632. https://doi.org/10.1007/s00204-017-1977-y

Pei, Y. et al. (2016). Comparative neurotoxicity screening in human iPSC-derived neural stem cells, neurons, and astrocytes. Brain Research, 1638(Pt A), 57-73. https://doi.org/10.1016/j.brainres.2015.11.015

Phase 1

References

Hall, L.A. et al. (2026). Prioritizing chemicals for developmental neurotoxicity by integrating data from a new approach methods (NAMs) battery covering key cellular events in neurodevelopment. 115, 103485. https://doi.org/10.1016/j.neuro.2026.103485

Massri, A.J. et al. (2026). Differential gene expression profiling implicates altered network development in rat postnatal day 4 cortex following 4-Methylimidazole (4-MeI) induced maternal seizures. Neurotoxicology and Teratology. 100, 107301. https://doi.org/10.1016/j.ntt.2023.107301

Carstens, K.E. et al. (2025). A comparative study of biostatistical pipelines for benchmark concentration modeling of in vitro screening assays. Computational Toxicology, 34. 100360. https://doi.org/10.1016/j.comtox.2025.100360

Celardo I. et al. (2025). Developmental neurotoxicity (DNT): A call for implementation of new approach methodologies for regulatory purposes: Summary of the 5th International Conference on DNT Testing. Altex, 42(2), 323-349. https://doi.org/10.14573/altex.2503191

Cöllen, E. et al. (2025). Mapping out strategies to further develop human-relevant, new approach methodology (NAM)-based developmental neurotoxicity (DNT) testing. Altex, 42(2), 308-322. https://doi.org/10.14573/altex.2501091

Kendricks, D.R. et al. (2025). Neurobehavioral and metabolic effects of prenatal low-dose chlorpyrifos in C57BL/6J mice. Neurotoxicity. 110, 132-144. https://doi.org/10.1016/j.neuro.2025.08.001

Bernstein, BJ. et al. (2024). Sex differences in spontaneous behavior and cognition in mice using an automated behavior monitoring system. Physiology & Behavior. 283, 114595. https://doi.org/10.1016/j.physbeh.2024.114595

Kreutz, A. et al. (2024). Integrated Approach for Testing and Assessment for Developmental Neurotoxicity (DNT) to Prioritize Aromatic Organophosphorus Flame Retardants. Toxics. 12(6), https://doi.org/10.3390/toxics12060437