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Evaluating the Human Relevance of Potential Thyroid-Disrupting Chemicals Using In vitro New Approach Methods.
Citation:
Deisenroth, C. Evaluating the Human Relevance of Potential Thyroid-Disrupting Chemicals Using In vitro New Approach Methods. Society of Toxicology (SOT) 2023 62nd Annual Meeting and ToxExpo, Nashville, TN, March 19 - 23, 2023. https://doi.org/10.23645/epacomptox.22704652
Impact/Purpose:
This presentation is part of a symposium session entitled 'Tackling the Challenge of Assessing Human-Relevant Thyroid Disruption' to take place at the Society of Toxicology (SOT) 2023 annual meeting in March 2023. Description: Exposure to chemicals may result in an interaction with the thyroid hormone axis causing a disruption of the normal physiological thyroid hormone activities that could result in adverse effects, particularly neurodevelopmental adversity, in exposed offspring. Toxicological evaluation of potential thyroid disrupting chemicals, including pesticidal active ingredients, is primarily based on data derived from animal models. Establishing new approach methods to effectively assess thyroid hormone disruption in available test systems to determine possible adverse outcomes is critical to protecting human health. This session will begin by reviewing current research in rodent thyroid hormone physiology with a focus on informing adversity in humans as well as species similarities and differences. Next an introduction to new methodologies for assessing human relevant thyroid hormone disruption including a human 3D microtissue will be followed by a discussion of a novel physiologically based biokinetic (PBK) model for thyroid hormone homeostasis and the effect of PXR/CAR inducers in rat and humans. An overview about facilitating the transition from qualitative to quantitative AOPs will be given with a case study of a quantitative adverse outcome pathway for neurodegeneration. The session will end with a presentation about a proposed testing and assessment scheme for thyroid hormone disruption.
Description:
There is significant regulatory need to identify and evaluate chemicals that may disrupt the thyroid endocrine system. 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 thyroid high-throughput screening (HTS) assays remains a considerable challenge. Continued efforts to build new in vitro and in silico approach methods are necessary for evaluating the potential health impacts of thyroid-related toxicity. Ongoing work will address the application of human organotypic thyroid screening assays to evaluate chemical effects on thyroid hormone synthesis to determine mechanistic and biological relevance. The impact of these efforts may enable more robust assessments of thyroid disrupting chemicals using a human-based NAM approach. This abstract does not necessarily reflect U.S. EPA policy.
URLs/Downloads:
DOI: Evaluating the Human Relevance of Potential Thyroid-Disrupting Chemicals Using In vitro New Approach Methods.
2023MARCH22_EPA_DEISENROTH_SOT SEMINAR_V2.PDF (PDF, NA pp, 3882.311 KB, about PDF)