{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T02:40:05Z","timestamp":1784169605965,"version":"3.55.0"},"reference-count":32,"publisher":"Wiley","issue":"3-4","license":[{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"vor","delay-in-days":68,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chronic exposure to high (20,000\u2009ppm) concentrations of <jats:italic>tert<\/jats:italic>\u2010butyl alcohol (TBA) in drinking water, equivalent to ~2100\u2009mg\/kg bodyweight per day, is associated with slight increases in the incidence of thyroid follicular cell adenomas and carcinomas in mice, with no other indications of carcinogenicity. In a recent toxicological review of TBA, the U.S. EPA determined that the genotoxic potential of TBA was inconclusive, largely based on non\u2010standard studies such as in vitro comet assays. As such, the potential role of genotoxicity in the mode of action of thyroid tumors and therefore human relevance was considered uncertain. To address the potential role of genotoxicity in TBA\u2010associated thyroid tumor formation, CD\u20101 mice were exposed up to a maximum tolerated dose of 1500\u2009mg\/kg\u2010day via oral gavage for two consecutive days and DNA damage was assessed with the comet assay in the thyroid. Blood TBA levels were analyzed by headspace GC\u2013MS to confirm systemic tissue exposure. At study termination, no significant increases (DNA breakage) or decreases (DNA crosslinks) in %DNA tail were observed in TBA exposed mice. In contrast, oral gavage of the positive control ethyl methanesulfonate significantly increased %DNA tail in the thyroid. These findings are consistent with most genotoxicity studies on TBA and provide mechanistic support for non\u2010linear, threshold toxicity criteria for TBA. While the mode of action for the thyroid tumors remains unclear, linear low dose extrapolation methods for TBA appear more a matter of policy than science.<\/jats:p>","DOI":"10.1002\/em.22601","type":"journal-article","created":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T12:28:39Z","timestamp":1715171319000},"page":"129-136","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Assessment of the genotoxicity of tert\u2010butyl alcohol in an in vivo thyroid comet assay"],"prefix":"10.1002","volume":"65","author":[{"given":"Chad M.","family":"Thompson","sequence":"first","affiliation":[{"name":"ToxStrategies, LLC  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Dewhurst","sequence":"additional","affiliation":[{"name":"Helix3, Inc.  Morrisville North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitri","family":"Moundous","sequence":"additional","affiliation":[{"name":"Alera Labs  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan J.","family":"Borghoff","sequence":"additional","affiliation":[{"name":"ToxStrategies, LLC  North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie C.","family":"Haws","sequence":"additional","affiliation":[{"name":"ToxStrategies, LLC  Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie Z.","family":"Vasquez","sequence":"additional","affiliation":[{"name":"Helix3, Inc.  Morrisville North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3412"},{"issue":"1","key":"e_1_2_10_3_1","first-page":"31","article-title":"The pharmacokinetics of tertiary butanol in c57bl\/6j mice","volume":"64","author":"Faulkner T.P.","year":"1989","journal-title":"Research Communications in Chemical Pathology and Pharmacology"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(89)90573-0"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.21727"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.22535"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.22338"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.21870"},{"issue":"1","key":"e_1_2_10_9_1","first-page":"75","article-title":"Acute toxicology of butyl nitrites and butyl alcohols","volume":"26","author":"Maickel R.P.","year":"1979","journal-title":"Research Communications in Chemical Pathology and Pharmacology"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3109\/10408444.2010.494249"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.2850110110"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrgentox.2004.10.002"},{"key":"e_1_2_10_13_1","unstructured":"National Research Council. 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