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Evaluating the applicability of read-across tools and high throughput screening data for food relevant chemicals (ASCCT)
Citation:
Wynder, J., J. Ovesen, A. Maier, R. Judson, N. Kleinstreuer, AND M. Krishan. Evaluating the applicability of read-across tools and high throughput screening data for food relevant chemicals (ASCCT). Presented at American Society for Cellular and Computational Toxicology (ASCCT), Gaithersburg, MD, September 21 - 22, 2017. https://doi.org/10.23645/epacomptox.7017119
Impact/Purpose:
Poster presented at American Society for Cellular and Computational Toxicology (ASCCT) Sep 2017
Description:
Alternative toxicity assessment methods to characterize the hazards of chemical substances have been proposed to improve animal welfare and screen thousands of chemicals in an efficient manner. Resources to accomplish this goal include utilizing large in vitro chemical screening data from efforts such as the high-throughput (HT) Tox21/ToxCast programs and read-across tools such as the Organization for Economic and Development (OECD) QSAR toolbox. The goal of this study is to compare the results from traditional toxicity studies with predictions from these proposed alternative testing methods. More specifically, we evaluated the utility of these emerging methods by using data from ToxCast combined with read-across tools to evaluate the hazards of current use food relevant chemicals. Briefly, computational models developed using Tox21/ToxCast HT data were used to predict estrogenic and/or androgenic activity of food-relevant chemicals. We identified 104 putatively estrogen-or androgen-active food-relevant chemicals in ToxCast. To reduce possible confounding cytotoxicity and cell stress effects, the ER and AR model results were filtered for any observed in vitro cytotoxicity, which resulted in confirmation of 89 putatively active, non-cytotoxic food chemicals. To conduct our proof of concept study, we further shortlisted these putatively active, noncytotoxic food relevant chemicals based on the availability of in vivo data related to developmental and reproductive toxicity (DART). This resulted in 10 putatively active, non-cytotoxic, endocrine disrupting chemicals. More specifically we identified 3 ER agonists, 1 ER antagonist, 1 AR agonist, and 9 AR antagonists. Read-across methods were used to identify potential analogues for each of the 10 chemicals. The pattern and potency of developmental and reproductive toxicity for the analogues identified using read-across approaches was compared to the known endocrine-disrupting potential of the target chemical to evaluate the utility of these alternative methods to assess the safety of food relevant chemicals in ToxCast. Using structural similarity and similar mode of actions as our primary criteria, we identified 8 target chemicals for which the analogue approach successfully predicted the putative endocrine disrupting potential of current use food relevant chemicals. This study demonstrates that HT assay data and read-across tools can be used together to characterize the hazards of chemical substances.
URLs/Downloads:
DOI: Evaluating the applicability of read-across tools and high throughput screening data for food relevant chemicals (ASCCT)
JLN ILSI ASCCT POSTER.PDF (PDF, NA pp, 1213.689 KB, about PDF)