{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T23:22:30Z","timestamp":1780096950547,"version":"3.54.0"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Thyroid hormones (THs) are highly iodinated molecules that regulate many aspects of mammalian physiology and are essential for normal growth and development. Deiodinases (Dio) are a family of metabolizing enzymes controlling systemic and local availability of the major TH secreted from the thyroid gland. Despite their critical role in TH regulation, the toxicological characterization of the effects of chemical interference of Dios in mammalian models has remained relatively underexplored. Here, we investigated the effects of exposure to iopanoic acid (IOP), a potent in vitro inhibitor of Dio enzymes. Adult rats administered IOP (0, 1, 5, 10, and 50\u2009mg\/kg\/day, oral gavage) for 14\u2009days exhibited an increase in serum thyroxine (T4) and reverse T3 (rT3), consistent with an inhibition of deiodinase 1 (Dio1). To verify these serum TH effects were induced by IOP action on deiodination pathways, we examined Dio activity ex vivo in liver from exposed animals. TH metabolites quantified by liquid chromatography mass spectrometry (LC\/MS\/MS) were used as the readout of Dio activity. Dose-dependent reductions in Dio1 and Dio3 activity were confirmed in hepatic microsomes prepared from IOP-exposed animals. The findings provide a signature pattern for serum TH change to assist translation of in vitro assays for this mode of action of environmental contaminants and interpretation of regulatory reports of serum TH profiles. By elucidating the mechanistic underpinning of chemical-induced perturbations of this critical TH metabolic pathway, the findings may inform risk-based decision making and serve to help to refine regulatory strategies for TH system-disrupting compounds.<\/jats:p>","DOI":"10.1093\/toxsci\/kfaf141","type":"journal-article","created":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T11:56:30Z","timestamp":1760183790000},"page":"330-342","source":"Crossref","is-referenced-by-count":5,"title":["Toxicological profile of chemical interference of thyroid hormone metabolism via deiodinase enzymes in a rodent model"],"prefix":"10.1093","volume":"208","author":[{"given":"Ryne","family":"Thomas","sequence":"first","affiliation":[{"name":"US Environmental Protection Agency, Office of Research and Development , Research Triangle Park, NC 27711,","place":["United States"]},{"name":"Centre for Public Health and Environmental Assessment, US Environmental Protection Agency , Research Triangle Park, NC 27709,","place":["United States"]},{"name":"Oak Ridge Institute for Science and Education , Oak Ridge, TN 37830,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jermaine","family":"Ford","sequence":"additional","affiliation":[{"name":"US Environmental Protection Agency, Office of Research and Development , Research Triangle Park, NC 27711,","place":["United States"]},{"name":"Center for Computational Toxicology and Exposure, US Environmental Protection Agency , Research Triangle Park, NC, 27709,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carter","family":"Kuehn","sequence":"additional","affiliation":[{"name":"US Environmental Protection Agency, Office of Research and Development , Research Triangle Park, NC 27711,","place":["United States"]},{"name":"Oak Ridge Institute for Science and Education , Oak Ridge, TN 37830,","place":["United States"]},{"name":"Center for Computational Toxicology and Exposure, US Environmental Protection Agency , Research Triangle Park, NC, 27709,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Wood","sequence":"additional","affiliation":[{"name":"US Environmental Protection Agency, Office of Research and Development , Research Triangle Park, NC 27711,","place":["United States"]},{"name":"Centre for Public Health and Environmental Assessment, US Environmental Protection Agency , Research Triangle Park, NC 27709,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4304-4527","authenticated-orcid":false,"given":"MaryAnn","family":"Hawks","sequence":"additional","affiliation":[{"name":"US Environmental Protection Agency, Office of Research and Development , Research Triangle Park, NC 27711,","place":["United States"]},{"name":"Centre for Public Health and Environmental Assessment, US Environmental Protection Agency , Research Triangle Park, NC 27709,","place":["United States"]},{"name":"Oak Ridge Institute for Science and Education , Oak Ridge, TN 37830,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigmund","family":"Degitz","sequence":"additional","affiliation":[{"name":"US Environmental Protection Agency, Office of Research and Development , Research Triangle Park, NC 27711,","place":["United States"]},{"name":"Center for Computational Toxicology and Exposure, US Environmental Protection Agency , Duluth, MN 55804,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8916-8851","authenticated-orcid":false,"given":"Mary","family":"Gilbert","sequence":"additional","affiliation":[{"name":"US Environmental Protection Agency, Office of Research and Development , Research Triangle Park, NC 27711,","place":["United States"]},{"name":"Centre for Public Health and Environmental Assessment, US Environmental Protection Agency , Research Triangle Park, NC 27709,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"2025112517264672100_kfaf141-B1","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1507\/endocrj.EJ24-0723","article-title":"Effects of excessive iodine intake during the perinatal period on thyroid function and higher brain functions in mouse offspring","volume":"72","author":"Amano","year":"2025","journal-title":"Endocrine J"},{"key":"2025112517264672100_kfaf141-B2","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/978-1-4939-7902-8_8","article-title":"The deiodinase trio and thyroid hormone signaling","volume":"1801","author":"Bianco","year":"2018","journal-title":"Methods Mol 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tissue specific. 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