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ToxCast Embryonic Stem Cell (H9) Profiling for Predicting Developmental Toxicity
Citation:
Knudsen, T., T. Zurlinden, K. Saili, AND N. Baker. ToxCast Embryonic Stem Cell (H9) Profiling for Predicting Developmental Toxicity. Presented at Teratology Society's 59th Annual Meeting, San Diego, CA, June 22 - 26, 2019. https://doi.org/10.23645/epacomptox.8862287
Impact/Purpose:
Poster presented at the Teratology Society's 59th Annual Meeting in June 2019
Description:
The protocol commonly used to test for prenatal developmental toxicity (i.e., OECD TG 414) is based on observation of fetal malformations, usually in pregnant rats and/or rabbits. EPA is evaluating new approach methodologies (NAMs) that can be used to quickly evaluate the human toxicity potential of chemicals with less reliance on animal testing. ToxCast generates in vitro data on thousands of chemicals utilizing high-throughput screening (HTS) methods. To increase the assay space for predicting human developmental toxicity, we profiled ToxCast chemicals in the devTOXqP assay. The assay measures a critical drop in the ornithine/cystine ratio H9 hESC culture medium. Data for 1062 chemicals was pipelined in ToxCast to generate the STM dataset (pending release); a positive signal for developmental toxicity was elicited by 183 (17%). Here, we assessed the predictive value of the STM data with a subset of 432 ToxCast chemicals tested for prenatal developmental toxicity. Specific aims were binary classification to correlate STM responses with animal models of human prenatal developmental toxicity captured from ToxRefDB and other sources of in vivo data; and recursive partitioning: mining in vitro bioactivity profiles of >800 ToxCast in vitro assays to assess the value of the STM dataset for predicting human developmental toxicity. The views expressed in this poster are those of the presenters and do not reflect the views or policies of the US EPA.
URLs/Downloads:
DOI: ToxCast Embryonic Stem Cell (H9) Profiling for Predicting Developmental Toxicity
KNUDSEN_2019-06-05_DEVTOX_TS_POSTER_FINAL_M.PDF (PDF, NA pp, 892.75 KB, about PDF)