{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:09:03Z","timestamp":1788865743756,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2007,12,28]],"date-time":"2007-12-28T00:00:00Z","timestamp":1198800000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2008,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In this study, the endocrine\u2010disrupting (ED) potency of metabolites from brominated flame retardants (BFRs) was determined. Metabolites were obtained by incubating single\u2010parent compound BFRs with phenobarbital\u2010induced rat liver microsomes. Incubation extracts were tested in seven<jats:italic> in vitro<\/jats:italic> bioassays for their potency to compete with thyroxine for binding to transthyretin (TTR), to inhibit estradiol\u2010sulfotransferase (E2SULT), to interact with thyroid hormone\u2010mediated cell proliferation, and to (in\u2010)activate the androgen, progesterone, estrogen, or aryl hydrocarbon receptor. For most BFRs, TTR\u2010binding potencies, and to a lesser extent E2SULT\u2010inhibiting potencies, significantly increased after biotransformation. Microsomal incubation had less pronounced effects on other ED modes of action, due to low biotransformation efficiency and background activities determined in control incubations without BFRs. Moreover, cell\u2010based bioassays suffered from cytotoxicity from metabolites of lower\u2010brominated polybrominated diphenyl ethers. For the environmentally relevant 2,2\u2032,4,4\u2032\u2010tetrabromodiphenyl ether (BDE\u201047), six hydroxylated metabolites were identified. Individual metabolites had TTR\u2010binding and E2SULT\u2010inhibiting potencies 160\u20131600 and 2.2\u2013220 times higher than BDE\u201047 itself, whereas their combined potencies in a realistic mixture were well predicted<jats:italic> via<\/jats:italic> concentration addition. In combination with other environmentally relevant hydroxylated organohalogens acting on TTR\u2010binding and E2SULT inhibition, internal exposure to BFR metabolites may significantly contribute to the overall risk of endocrine disruption.<\/jats:p>","DOI":"10.1002\/mnfr.200700104","type":"journal-article","created":{"date-parts":[[2007,12,28]],"date-time":"2007-12-28T12:48:11Z","timestamp":1198846091000},"page":"284-298","source":"Crossref","is-referenced-by-count":214,"title":["Biotransformation of brominated flame retardants into potentially endocrine\u2010disrupting metabolites, with special attention to 2,2\u2032,4,4\u2032\u2010tetrabromodiphenyl ether (BDE\u201047)"],"prefix":"10.1002","volume":"52","author":[{"given":"Timo","family":"Hamers","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorke H.","family":"Kamstra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin","family":"Sonneveld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albertinka J.","family":"Murk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo J.","family":"Visser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J. 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