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State of the Science: ToxCast and Tox21 assays and approaches to screening for potential thyroid hormone disruption (SOT 2021)
Citation:
Paul-Friedman, K. State of the Science: ToxCast and Tox21 assays and approaches to screening for potential thyroid hormone disruption (SOT 2021). Society of Toxicology Annual Meeting (Virtual), NA, Virtual, March 12 - 26, 2021. https://doi.org/10.23645/epacomptox.17897870
Impact/Purpose:
This presentation is for a SOT 2021 Continuing Education class on screening for thyroid-related bioactivity with new approach methodologies. This presentation covers only publicly available information in ToxCast/Tox21 about the assays available and is intended to give a general overview of data that might inform prediction of thyroid-related bioactivity.
Description:
The ToxCast and Tox21 programs have developed a series of medium and high-throughput screening assays (MTS/HTS) for multiple molecular-initiating event (MIE) and key event targets in an adverse outcome pathway (AOP) network for thyroid hormone (TH) disruption. Assays for receptors involved in hypothalamic-pituitary-thyroid axis regulation including the thyroid hormone receptor (TR), thyroid stimulating hormone receptor, and thyrotropin-releasing hormone receptor are available, but only data for TRs in orthogonal and confirmatory assays have been used to demonstrate that a limited chemical structural feature space would represent true actives for TR activation or inactivation. Ongoing work to contextualize high-throughput screening data for these other receptor targets using new MTS approaches as well as in silico approaches will be discussed. Additionally, HTS assays for MIEs involved in TH synthesis (sodium-iodide symporter, thyroperoxidase, and deiodinases) in the latest release of the ToxCast database, invitrodb, will be reviewed, along with the ToxCast/Tox21 assays currently available to evaluate hypotheses regarding activation of hepatic catabolism by xenobiotics, an AOP relevant to TH clearance. This abstract does not necessarily reflect U.S. EPA policy.
URLs/Downloads:
DOI: State of the Science: ToxCast and Tox21 assays and approaches to screening for potential thyroid hormone disruption (SOT 2021)
SOT2021-CE-TOXCAST&THYROID_KPF.PDF (PDF, NA pp, 4276.149 KB, about PDF)