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Advancing Translational Applications of Human Organotypic Thyroid Assays
Citation:
Deisenroth, C. Advancing Translational Applications of Human Organotypic Thyroid Assays. Society of Toxicology Risk Assessment Specialty Section webinar series, N/A, NC, April 12, 2023. https://doi.org/10.23645/epacomptox.22669999
Impact/Purpose:
This is a joint presentation to the Society of Toxicology Risk Assessment Specialty Section webinar series in April 2023 covering virtual and complex tissue modeling entitled “Engineering Complex Systems for Predictive Toxicology in the Animal-free Zone”. Dr. Chad Deisenroth of the EPA’s Computational Center for Toxicology and Exposure (CCTE) will first present “Advancing Translational Applications of Human Organotypic Thyroid Assays”. Dr. Tom Knudsen, also of EPA’s CCTE, will then present “Computational Integration of ToxCast In vitro Bioactivity Data with In silico Agent-based Models of Complex Biological Systems to Predict Cellular Dynamics in Developmental Toxicity”. Both presentations will provide state of the science examples of virtual and complex tissue modeling.
Description:
Altered maternal thyroid hormones present an increased risk for child neurodevelopmental impairment, thus evaluating the potential impact of chemical exposures on thyroid hormone imbalance is of key regulatory concern. Thyroid new approach methods (NAMs) are being developed and applied to increase data coverage across the ToxCast/Tox21 chemical inventories using a tiered testing strategy. Interpreting the biological effect of chemicals identified in mechanistic high-throughput screening (HTS) assays remains a considerable challenge. Advancements in complex in vitro culture systems comprised of primary cells from human donors has enabled reconfiguration of the cellular architecture and microenvironment that more closely simulates the natural structure and function of in vivo tissues and organs. Ongoing work will address development of a human thyroid microtissue model to address data gaps in screening and prioritization of thyroid disrupting chemicals, efforts to increase confidence in the model by setting appropriate qualification standards and expectations for the context of use, and demonstrate orthogonal screening of prioritized chemicals in thyroid microtissues for mechanistic and functional relevance to thyroid disruption. DISCAIMER: The views expressed are those of the author and do not necessarily reflect the views or policies of the U.S. Environmental Protection Agency.
URLs/Downloads:
DOI: Advancing Translational Applications of Human Organotypic Thyroid Assays
2023APRIL12_EPA_DEISENROTH_SOT RASS_V2.PDF (PDF, NA pp, 4010.184 KB, about PDF)