Screening methods for thyroid hormone disruptors.
Publication: Environmental Health Perspectives
Volume 107, Issue 5
Pages 407 - 415
Abstract
The U.S. Congress has passed legislation requiring the EPA to implement screening tests for identifying endocrine-disrupting chemicals. A series of workshops was sponsored by the EPA, the Chemical Manufacturers Association, and the World Wildlife Fund; one workshop focused on screens for chemicals that alter thyroid hormone function and homeostasis. Participants at this meeting identified and examined methods to detect alterations in thyroid hormone synthesis, transport, and catabolism. In addition, some methods to detect chemicals that bind to the thyroid hormone receptors acting as either agonists or antagonists were also identified. Screening methods used in mammals as well as other vertebrate classes were examined. There was a general consensus that all known chemicals which interfere with thyroid hormone function and homeostasis act by either inhibiting synthesis, altering serum transport proteins, or by increasing catabolism of thyroid hormones. There are no direct data to support the assertion that certain environmental chemicals bind and activate the thyroid hormone receptors; further research is indicated. In light of this, screening methods should reflect known mechanisms of action. Most methods examined, albeit useful for mechanistic studies, were thought to be too specific and therefore would not be applicable for broad-based screening. Determination of serum thyroid hormone concentrations following chemical exposure in rodents was thought to be a reasonable initial screen. Concurrent histologic evaluation of the thyroid would strengthen this screen. Similar methods in teleosts may be useful as screens, but would require indicators of tissue production of thyroid hormones. The use of tadpole metamorphosis as a screen may also be useful; however, this method requires validation and standardization prior to use as a broad-based screen.
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EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted.
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Published online: 1 May 1999
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- Suto H, Ogata K, Minami K, Sato A, Tomiyama N, Kosaka T, Hojo H, Takahashi N, Aoyama H, Yamada T, Perinatal maternal exposure to high-dose sodium phenobarbital in the modified Comparative Thyroid Assay: no significant reduction in thyroid hormones in pups despite notable effects in dams, The Journal of Toxicological Sciences, 10.2131/jts.49.509, 49, 11, (509-529), (2024).
- Minami K, Sato A, Tomiyama N, Ogata K, Kosaka T, Hojo H, Takahashi N, Suto H, Aoyama H, Yamada T, Prenatal test cohort of a modified rat comparative thyroid assay adding brain thyroid hormone measurements and histology but lowering group size appears able to detect disruption by sodium phenobarbital, Current Research in Toxicology, 10.1016/j.crtox.2024.100168, 6, (100168), (2024).
- Fair P, Houde M, Environmental endocrine-disrupting chemicals and their effects in marine mammals, Environmental Contaminants and Endocrine Health, 10.1016/B978-0-12-824464-7.00017-9, (283-306), (2023).
- Li J, Li Y, Zhu M, Song S, Qin Z, A Multiwell-Based Assay for Screening Thyroid Hormone Signaling Disruptors Using thibz Expression as a Sensitive Endpoint in Xenopus laevis, Molecules, 10.3390/molecules27030798, 27, 3, (798), (2022).
- Barra N, Kwon Y, Morrison K, Steinberg G, Wade M, Khan W, Vijayan M, Schertzer J, Holloway A, Increased gut serotonin production in response to bisphenol A structural analogs may contribute to their obesogenic effects, American Journal of Physiology-Endocrinology and Metabolism, 10.1152/ajpendo.00049.2022, 323, 1, (E80-E091), (2022).
- Odum J, Disrupters of Thyroid Hormone Action and Synthesis, Endocrine Disruption and Human Health, 10.1016/B978-0-12-821985-0.00004-9, (105-126), (2022).
- Gadaleta D, d’Alessandro L, Marzo M, Benfenati E, Roncaglioni A, Quantitative Structure-Activity Relationship Modeling of the Amplex Ultrared Assay to Predict Thyroperoxidase Inhibitory Activity, Frontiers in Pharmacology, 10.3389/fphar.2021.713037, 12, (2021).
- Marty S, Beekhuijzen M, Charlton A, Hallmark N, Hannas B, Jacobi S, Melching-Kollmuss S, Sauer U, Sheets L, Strauss V, Urbisch D, Botham P, van Ravenzwaay B, Towards a science-based testing strategy to identify maternal thyroid hormone imbalance and neurodevelopmental effects in the progeny – part II: how can key events of relevant adverse outcome pathways be addressed in toxicological assessments?, Critical Reviews in Toxicology, 10.1080/10408444.2021.1910625, 51, 4, (328-358), (2021).
- Olker J, Korte J, Denny J, Haselman J, Hartig P, Cardon M, Hornung M, Degitz S, In vitro screening for chemical inhibition of the iodide recycling enzyme, iodotyrosine deiodinase, Toxicology in Vitro, 10.1016/j.tiv.2020.105073, 71, (105073), (2021).
- Paul-Friedman K, Martin M, Crofton K, Hsu C, Sakamuru S, Zhao J, Xia M, Huang R, Stavreva D, Soni V, Varticovski L, Raziuddin R, Hager G, Houck K, Limited Chemical Structural Diversity Found to Modulate Thyroid Hormone Receptor in the Tox21 Chemical Library, Environmental Health Perspectives, 10.1289/EHP5314, 127, 9, (2019).