You are here:
Development of Novel In Vitro Assay Technologies for Human Thyroid Screening
Citation:
Deisenroth, C. Development of Novel In Vitro Assay Technologies for Human Thyroid Screening. The Society of Toxicology Annual Meeting (2021), Durham, North Carolina, March 12 - 26, 2021. https://doi.org/10.23645/epacomptox.19773106
Impact/Purpose:
This presentation is part of a continuing education course for the Society of Toxicology Annual Meeting in March 2021. Course Title: Applications of In Vitro and In Silico New Approach Methodologies for Predictive and Mechanistic Thyroid Toxicity Testing. Course Description: Understanding disruption of thyroid signaling pathways and thyroid homeostasis following exposure to environmental, agricultural, and industrial chemicals is both an evolving and increasingly important challenge in the global regulatory community. This session will focus on innovative new approach methodologies (NAMs), such as 3D microtissues, organ-on-a-chip, hepatic thyroxine clearance models, and computational approaches that are being developed for predictive and mechanistic thyroid toxicology testing approaches. There is currently a heavy reliance on traditional animal testing approaches to evaluate the potential for a chemical to induce adverse thyroid effects, which are time and resource intensive. In fact, several in vivo guideline studies were recently updated to include additional thyroid-related apical endpoints, such as thyroxine and thyroid stimulating hormone measurements. There is an opportunity to harness new transformative approaches, such as in silico screening and organotypic in vitro models to replace animal intensive testing programs to identify thyroid disrupting toxicants and elucidate the mode of action and human relevance. Embracing NAMs can both provide valuable information to aid in molecule design from a predictive safety standpoint and provide guidance for targeted toxicological testing strategies. With continual progress in screening assays for thyroid hormone disruption as demonstrated by recent publications and new releases of data, and with endocrine disruptor identification in the EU being dependent on such assays to identify points of chemical interaction with the thyroid pathway, this session provides a timely update on the data and tools available for rapidly evaluating in vitro activity relevant to the thyroid adverse outcome pathway network. To this end, experts from industry, the United States government, and the European Commission will discuss the current state of the science and how these approaches are being utilized for predictive and mechanistic studies as well as regulatory toxicology applications. Each speaker will discuss opportunities for NAMs to be integrated in chemical safety evaluation. Following the presentations, a Q&A will engage attendees to enable deeper understanding of the current state-of-the-art approaches for addressing chemical-induced thyroid-related bioactivities. The targeted audience would be those interested in understanding how these tools are being leveraged in real-world regulatory testing paradigms. They will also gain insight into the strengths, limitations, and future development opportunities of in vitro, in silico, and alternative models for predictive and mechanistic thyroid toxicity assessments.
Description:
The US EPA Endocrine Disruptor Screening Program has identified several molecular thyroid targets relevant to hormone synthesis dynamics that have been adapted to high-throughput screening assays to rapidly evaluate the ToxCast/Tox21 chemical inventories for potential thyroid disrupting chemicals (TDCs). The uncertainty regarding the specificity of active chemicals identified in these screens and the relevance to phenotypic effects on in vivo human thyroid hormone synthesis are notable data gaps for hazard identification and prioritization of TDCs. 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 development of an organotypic screening assay using human 3D thyroid microtissues to evaluate chemical effects on thyroid hormone synthesis. In addition, efforts to develop and characterize a novel immortalized human thyrocyte cell line will be discussed. Applications of both primary and immortalized thyroid models to evaluate thyroid-specific targets in more physiological and human relevant models will be discussed. This abstract does not necessarily reflect U.S. EPA policy.
URLs/Downloads:
DOI: Development of Novel In Vitro Assay Technologies for Human Thyroid Screening
2021_SOT_THYROID CE COURSE_DEISENROTH_V2.PDF (PDF, NA pp, 4722.125 KB, about PDF)