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A systematic literature review for the determination of “negative” chemical compounds for developmental neurotoxicity (DNT) assay evaluation
Citation:
Martin, M., Nancy C. Baker, W. Boyes, K. Carstens, M. Culbreth, Mary E. Gilbert, J. Harrill, J. Nyffeler, S. Padilla, K. Paul-Friedman, AND T. Shafer. A systematic literature review for the determination of “negative” chemical compounds for developmental neurotoxicity (DNT) assay evaluation. Summer School on Innovative Approaches in Science (Online), RTP, North Carolina, June 22 - 25, 2020. https://doi.org/10.23645/epacomptox.12933248
Impact/Purpose:
Presentation given to the Summer School on Innovative Approaches in Science Webinar June 2020. This is relevant to work supporting TSCA and FIFRA, and is designed to help evaluate the performance of new alternative methodologies (NAMs) for developmental neurotoxicity.
Description:
A diverse range of chemicals have been associated with cognitive deficits following prenatal and/or postnatal exposure in humans and animal models. To date, however, less than 200 chemicals have been tested in EPA or OECD guideline DNT studies. To address this gap, a battery of in vitro assays has been proposed for the screening and prioritization of DNT hazard potential. One measure of this DNT assay battery performance should include the evaluation of reference chemicals, including chemicals with evidence of DNT effect (defined as “positive” compounds) and chemicals with a lack of DNT effect (defined as “negative” compounds) following in vivo exposure. To accomplish this, curation of these reference chemicals is critically important. Therefore, the aim of this study was to develop a curated list of negative DNT reference chemicals. Using a systematic approach, 38 potential negative chemicals were subjected to a literature search and the number of query results for each chemical were narrowed down by reading the title, abstract, and main text of those articles. For those relevant articles, expert panel members were asked to answer a series of questions related to experimental design and outcomes. After completion, the expert panel reviewed each chemical to decide whether there was substantial scientific evidence to support a lack of DNT effect. By utilizing this workflow, the panel was able to determine which compounds met strict criteria as a “negative”. (Disclaimer: This abstract does not necessarily reflect EPA policy. Mention of trade names is not an endorsement or recommendation for use)
URLs/Downloads:
DOI: A systematic literature review for the determination of “negative” chemical compounds for developmental neurotoxicity (DNT) assay evaluation
MMARTIN_SUMMERSCHOOL2020_FINAL.PDF (PDF, NA pp, 647.765 KB, about PDF)