{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:03:27Z","timestamp":1790831007828,"version":"4.1.0"},"reference-count":113,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T00:00:00Z","timestamp":1626393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Many xenobiotics are identified as potential thyroid disruptors due to their action to reduce circulating levels of thyroid hormone, most notably thyroxine (T4). Developmental neurotoxicity is a primary concern for thyroid disrupting chemicals yet correlating the impact of chemically induced changes in serum T4 to perturbed brain development remains elusive. A number of thyroid-specific neurodevelopmental assays have been proposed, based largely on the model thyroid hormone synthesis inhibitor propylthiouracil (PTU). This study examined whether thyroid disrupting chemicals acting distinct from synthesis inhibition would result in the same alterations in brain as expected with PTU. The perfluoroalkyl substance perfluorohexane sulfonate (50\u2009mg\/kg\/day) and the antimicrobial Triclosan (300\u2009mg\/kg\/day) were administered to pregnant rats from gestational day 6 to postnatal day (PN) 21, and a number of PTU-defined assays for neurotoxicity evaluated. Both chemicals reduced serum T4 but did not increase thyroid stimulating hormone. Both chemicals increased expression of hepatic metabolism genes, while thyroid hormone-responsive genes in the liver, thyroid gland, and brain were largely unchanged. Brain tissue T4 was reduced in newborns, but despite persistent T4 reductions in serum, had recovered in the PN6 pup brain. Neither treatment resulted in a low dose PTU-like phenotype in either brain morphology or neurobehavior, raising questions for the interpretation of serum biomarkers in regulatory toxicology. They further suggest that reliance on serum hormones as prescriptive of specific neurodevelopmental outcomes may be too simplistic and to understand thyroid-mediated neurotoxicity we must expand our thinking beyond that which follows thyroid hormone synthesis inhibition.<\/jats:p>","DOI":"10.1093\/toxsci\/kfab080","type":"journal-article","created":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T19:11:31Z","timestamp":1626376291000},"page":"195-213","source":"Crossref","is-referenced-by-count":45,"title":["Thyroid Disruptors: Extrathyroidal Sites of Chemical Action and Neurodevelopmental Outcome\u2014An Examination Using Triclosan and Perfluorohexane Sulfonate"],"prefix":"10.1093","volume":"183","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8916-8851","authenticated-orcid":false,"given":"Mary E","family":"Gilbert","sequence":"first","affiliation":[{"name":"Center for Public Health and Environmental Assessment, Public Health Integrated Toxicology Division, US Environmental Protection Agency, Research Triangle Park, North Carolina 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5167-8554","authenticated-orcid":false,"given":"Katherine L","family":"O\u2019Shaughnessy","sequence":"additional","affiliation":[{"name":"Center for Public Health and Environmental Assessment, Public Health Integrated Toxicology Division, US Environmental Protection Agency, Research Triangle Park, North Carolina 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan E","family":"Thomas","sequence":"additional","affiliation":[{"name":"Oak Ridge Institute for Science Education, Oak Ridge, Tennesse 37830, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cal","family":"Riutta","sequence":"additional","affiliation":[{"name":"Oak Ridge Institute for Science Education, Oak Ridge, Tennesse 37830, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen R","family":"Wood","sequence":"additional","affiliation":[{"name":"Center for Public Health and Environmental Assessment, Public Health Integrated Toxicology Division, US Environmental Protection Agency, Research Triangle Park, North Carolina 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Smith","sequence":"additional","affiliation":[{"name":"Oak Ridge Institute for Science Education, Oak Ridge, Tennesse 37830, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy O","family":"Oshiro","sequence":"additional","affiliation":[{"name":"Center for Public Health and Environmental Assessment, Public Health Integrated Toxicology Division, US Environmental Protection Agency, Research Triangle Park, North Carolina 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard L","family":"Ford","sequence":"additional","affiliation":[{"name":"Oak Ridge Institute for Science Education, Oak Ridge, Tennesse 37830, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle Gatien","family":"Hotchkiss","sequence":"additional","affiliation":[{"name":"Center for Public Health and Environmental Assessment, Public Health Integrated Toxicology Division, US Environmental Protection Agency, Research Triangle Park, North Carolina 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6031-3891","authenticated-orcid":false,"given":"Iman","family":"Hassan","sequence":"additional","affiliation":[{"name":"Center for Public Health and Environmental Assessment, Public Health Integrated Toxicology Division, US Environmental Protection Agency, Research Triangle Park, North Carolina 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jermaine L","family":"Ford","sequence":"additional","affiliation":[{"name":"Center for Computational Toxicology and Exposure, Chemical Characterization and Exposure Division, US Environmental Protection Agency, Research Triangle Park, North Carolina 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,7,16]]},"reference":[{"key":"2022030408164099500_kfab080-B1","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1093\/aje\/kwt141","article-title":"Maternal and cord-blood thyroid hormone levels and exposure to polybrominated diphenyl ethers and polychlorinated biphenyls during early pregnancy","volume":"178","author":"Abdelouahab","year":"2013","journal-title":"Am. 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