{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T16:25:01Z","timestamp":1787934301141,"version":"build-2784847793"},"reference-count":68,"publisher":"American Chemical Society (ACS)","issue":"12","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":1920,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background: Bis-(2-ethylhexyl) tetrabromophthalate (TBPH) is widely used as a replacement for polybrominated diphenyl ethers (PBDEs) in commercial flame retardant mixtures such as Firemaster 550. It is also used in a commercial mixture called DP 45. Mono-(2-ethyhexyl) tetrabromophthalate (TBMEHP) is a potentially toxic metabolite.<\/jats:p>\n                  <jats:p>Objectives: We used in vitro and rodent in vivo models to evaluate human exposure and the potential metabolism and toxicity of TBPH.<\/jats:p>\n                  <jats:p>Methods: Dust collected from homes, offices, and cars was measured for TBPH by gas chromatography followed by mass spectrometry. Pregnant rats were gavaged with TBMEHP (200 or 500 mg\/kg) or corn oil on gestational days 18 and 19, and dams and fetuses were evaluated histologically for toxicity. We also assessed TBMEHP for deiodinase inhibition using rat liver microsomes and for peroxisome proliferator-activated receptor (PPAR) \u03b1 and \u03b3 activation using murine FAO cells and NIH 3T3 L1 cells.<\/jats:p>\n                  <jats:p>Results: TBPH concentrations in dust from office buildings (median, 410 ng\/g) were higher than in main living areas in homes (median, 150 ng\/g). TBPH was metabolized by purified porcine esterases to TBMEHP. Two days of TBMEHP exposure in the rat produced maternal hypothyroidism with markedly decreased serum T3 (3,3\u00b4,5-triiodo-l-thyronine), maternal hepatotoxicity, and increased multinucleated germ cells (MNGs) in fetal testes without antiandrogenic effects. In vitro, TBMEHP inhibited deiodinase activity, induced adipocyte differentiation in NIH 3T3 L1 cells, and activated PPAR\u03b1- and PPAR\u03b3-mediated gene transcription in NIH 3T3 L1 cells and FAO cells, respectively.<\/jats:p>\n                  <jats:p>Conclusions: TBPH a) is present in dust from indoor environments (implying human exposure) and b) can be metabolized by porcine esterases to TBMEHP, which c) elicited maternal thyrotoxic and hepatotoxic effects and d) induced MNGs in the fetal testes in a rat model. In mouse NIH 3T3 L1 preadipocyte cells, TBMEHP inhibited rat hepatic microsome deiodinase activity and was an agonist for PPARs in murine FAO and NIH 3T3 L1 cells.<\/jats:p>","DOI":"10.1289\/ehp.1204932","type":"journal-article","created":{"date-parts":[[2012,11,19]],"date-time":"2012-11-19T14:42:43Z","timestamp":1353336163000},"page":"1711-1719","source":"Crossref","is-referenced-by-count":80,"title":["Rodent Thyroid, Liver, and Fetal Testis Toxicity of the Monoester Metabolite of Bis-(2-ethylhexyl) Tetrabromophthalate (TBPH), a Novel Brominated Flame Retardant Present in Indoor Dust"],"prefix":"10.1021","volume":"120","author":[{"given":"Cecilia","family":"Springer","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Dere","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island, USA"},{"name":"Division of Urology, Rhode Island Hospital, Providence, Rhode Island, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan J.","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth V.","family":"McDonnell","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon C.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Nicholas School of the Environment, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig M.","family":"Butt","sequence":"additional","affiliation":[{"name":"Nicholas School of the Environment, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather M.","family":"Stapleton","sequence":"additional","affiliation":[{"name":"Nicholas School of the Environment, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah J.","family":"Watkins","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts, USA"},{"name":"Center for Environmental Health and Technology, Brown University, Providence, Rhode Island, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"McClean","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas F.","family":"Webster","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer J.","family":"Schlezinger","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Boekelheide","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2012,9,26]]},"reference":[{"key":"2026080610060631600_micit1","unstructured":"Agency for Toxic Substances and Disease Registry\n          . 2002. Toxicological Profile for Di(2-ethylhexyl)phthalate (DEHP). Atlanta, GA:Agency for Toxic Substances and Disease Registry.Available: http:\/\/www.atsdr.cdc.gov\/toxprofiles\/tp9.pdf [accessed 2 November 2012]."},{"key":"2026080610060631600_micit2","first-page":"293","article-title":"Absorption, metabolism, and excretion of di(2-ethylhexyl) phthalate by rats and mice.","volume":"65","author":"Albro","year":"1986","journal-title":"Environ Health Perspect"},{"issue":"6","key":"2026080610060631600_micit3","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1080\/03601238209372351","article-title":"Applications of isotope differentiation for metabolic studies with di-(2-ethylhexyl) phthalate.","volume":"17","author":"Albro","year":"1982","journal-title":"J Environ Sci Health B"},{"issue":"8","key":"2026080610060631600_micit4","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/j.envint.2008.03.006","article-title":"Critical factors in assessing exposure to PBDEs via house 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phthalate monoesters.","volume":"82","author":"Bility","year":"2004","journal-title":"Toxicol Sci"},{"key":"2026080610060631600_micit8","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1289\/ehp.6559","article-title":"Brominated flame retardants: cause for concern?","volume":"112","author":"Birnbaum","year":"2004","journal-title":"Environ Health Perspect"},{"issue":"3","key":"2026080610060631600_micit9","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.etap.2007.12.004","article-title":"Environmental exposure to PBDEs and thyroid function among New York anglers.","volume":"25","author":"Bloom","year":"2008","journal-title":"Environ Toxicol Pharmacol"},{"issue":"8","key":"2026080610060631600_micit10","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1002\/jemt.20684","article-title":"Dose-dependent effects on cell proliferation, seminiferous tubules, and male germ cells in the fetal rat testis following exposure to di(n-butyl) 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resistant to phthalate-induced endocrine disruption.","volume":"120","author":"Heger","year":"2012","journal-title":"Environ Health Perspect"},{"issue":"2","key":"2026080610060631600_micit29","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.envres.2008.08.009","article-title":"Mechanisms of action of phthalate esters, individually and in combination, to induce abnormal reproductive development in male laboratory rats.","volume":"108","author":"Howdeshell","year":"2008","journal-title":"Environ Res"},{"issue":"2","key":"2026080610060631600_micit30","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1093\/toxsci\/kfg145","article-title":"Activation of PPAR\u03b1 and PPAR\u03b3 by environmental phthalate monoesters.","volume":"74","author":"Hurst","year":"2003","journal-title":"Toxicol Sci"},{"issue":"3","key":"2026080610060631600_micit31","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1006\/exmp.1993.1016","article-title":"The influence of phthalate 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