An expert-driven literature review of “negative” chemicals for developmental neurotoxicity (DNT) in vitro assay evaluation
Abstract
To date, approximately 200 chemicals have been tested in US Environmental Protection Agency (EPA) or Organization for Economic Co-operation and Development (OECD) developmental neurotoxicity (DNT) guideline studies, leaving thousands of chemicals without traditional animal information on DNT hazard potential. To address this data gap, a battery of in vitro DNT new approach methodologies (NAMs) has been proposed. Evaluation of the performance of this battery will increase the confidence in its use to determine DNT chemical hazards. One approach to evaluate DNT NAM performance is to use a set of chemicals to evaluate sensitivity and specificity. Since a list of chemicals with potential evidence of in vivo DNT has been established, this study aims to develop a curated list of "negative" chemicals for inclusion in a "DNT NAM evaluation set". A workflow, including a literature search followed by an expert-driven literature review, was used to systematically screen 39 chemicals for lack of DNT effect. Expert panel members evaluated the scientific robustness of relevant studies to inform chemical categorizations. Following review, the panel discussed each chemical and made categorical determinations of "Favorable", "Not Favorable", or "Indeterminate" reflecting acceptance, lack of suitability, or uncertainty given specific limitations and considerations, respectively. The panel determined that 10, 22, and 7 chemicals met the criteria for "Favorable", "Not Favorable", and "Indetermin…
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Only around 200 chemicals have been systematically assessed for DNT in vivo studies by the US EPA or within the OECD TG, severely limiting capacity for the thousands of chemicals in commerce.
“Consequently, only around 200 chemicals have been systematically assessed for DNT in vivo studies by the US EPA or within the OECD TG, severely limiting capacity for the thousands of chemicals in commerce (Martin et al., 2022).”
From Challenges and solutions in transitioning to animal-free standards: a comprehensive analysis of components in human cell-based developmental neurotoxicity assays (2026) · cites this paper as Martin et al., 2022
Cites
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Bridging imaging-based in vitro methods from biomedical research to regulatory toxicology
Piergiovanni, M., Mennecozzi, M., Barale-Thomas, E., Danovi, D., Dunst, S., Egan, D., Fassi, A., Hartley, M., Kainz, P., Koch, K., et al. (2025) · Archives of Toxicology · doi:10.1007/s00204-024-03922-z · Cited by 7 · see citing works
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- Authors
- Martin, M. M., Baker, N. C., Boyes, W. K., Carstens, K. E., Culbreth, M. E., Gilbert, M. E., Harrill, J. A., Nyffeler, J., Padilla, S., Friedman, K. P., & Shafer, T. J.
- Venue
- Neurotoxicology and Teratology
- Publisher
- Elsevier BV
- Published
- 2022-09
- Volume
- 93
- Pages
- 107117
- ISSN
- 0892-0362
- Cited by
- 29
- References
- 6
- Language
- en
- Licence
- Funders
- Oak Ridge Institute for Science and Education
- Office of Research and Development
- U.S. Department of Energy
- U.S. Environmental Protection Agency
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