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ICCVAM Biennial Report 2018-2019

Biennial Progress Report 2018-2019 Interagency Coordinating Committee on the Validation of Alternative Methods

High-throughput Transcriptomic Profiling of a Diverse Subset of Tox21 10K Library Chemicals

High-throughput transcriptomics generates gene expression profiles to rapidly evaluate the effects of large numbers of chemicals on in vitro cell culture systems (Harrill et al. 2019). To provide a basis for characterizing the toxicity potential of chemicals with limited or no available data, scientists at NIEHS and EPA are building a common reference chemical dataset to enhance interpretation of high-throughput transcriptomics screening data. The project systematically identified a robust set of reference chemicals with direct interactions to specific biological targets (e.g., nuclear receptors, enzymes, kinases, ion channels). A subset of approximately 300 of these reference chemicals has been acquired by Tox21 chemistry collaborators for evaluation in two human cell culture models: MCF-7 cells, derived from breast cells, and HepaRG, derived from liver cells (Ramaiahgari et al. 2019). The next stage of the project is to create the reference chemical dataset, analyze both gene-level and pathway-level responses that enable improved interpretation of transcriptomic data with test chemicals, and identify the most efficient conditions to expand coverage to thousands of reference chemicals.