An expert-driven literature review of “negative” chemicals for developmental neurotoxicity (DNT) in vitro assay evaluation

Martin, Melissa M.; Baker, Nancy C.; Boyes, William K.; Carstens, Kelly E.; Culbreth, Megan E.; Gilbert, Mary E.; Harrill, Joshua A.; Nyffeler, Johanna; Padilla, Stephanie; Friedman, Katie Paul; Shafer, Timothy J.

doi:10.1016/j.ntt.2022.107117

Title: An expert-driven literature review of “negative” chemicals for developmental neurotoxicity (DNT) in vitro assay evaluation

Journal Article · Fri Jul 29 00:00:00 EDT 2022 · Neurotoxicology and Teratology

DOI:https://doi.org/10.1016/j.ntt.2022.107117· OSTI ID:1981723

Martin, Melissa M. ^[1]; Baker, Nancy C. ^[2]; Boyes, William K. ^[3]; Carstens, Kelly E. ^[1]; Culbreth, Megan E. ^[1]; Gilbert, Mary E. ^[3]; Harrill, Joshua A. ^[1]; Nyffeler, Johanna ^[4]; Padilla, Stephanie ^[1]; Friedman, Katie Paul ^[1]; Shafer, Timothy J. ^[1]

US Environmental Protection Agency (EPA), Research Triangle Park, NC (United States). Center for Computational Toxicology and Exposure (CCTE)
Leidos, Inc., Research Triangle Park, NC (United States)
US Environmental Protection Agency (EPA), Research Triangle Park, NC (United States). Center for Public Health and Environmental Assessment (CPHEA)
US Environmental Protection Agency (EPA), Research Triangle Park, NC (United States). Center for Computational Toxicology and Exposure (CCTE); Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)

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. Further, the panel determined that 10, 22, and 7 chemicals met the criteria for “Favorable”, “Not Favorable”, and “Indeterminate”, for use as negatives in a DNT NAM evaluation set. Ultimately, this approach not only supports DNT NAM performance evaluation but also highlights challenges in identifying large numbers of negative DNT chemicals.

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Research Organization:: Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: SC0014664

OSTI ID:: 1981723

Alternate ID(s):: OSTI ID: 1960938

Journal Information:: Neurotoxicology and Teratology, Vol. 93, Issue C; ISSN 0892-0362

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
Neurosciences & Neurology
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Reference chemicals

Title: An expert-driven literature review of “negative” chemicals for developmental neurotoxicity (DNT) in vitro assay evaluation

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References (53)

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