USDA Agriculture Research Service, 1605 Albrecht Blvd Biosciences Research Laboratory, Fargo, North Dakota 58102-2765, United States.
Environ Sci Technol. 2016 Jan 5;50(1):89-96. doi: 10.1021/acs.est.5b04510. Epub 2015 Dec 17.
Male Sprague-Dawley rats were dosed orally with 3 mg/kg of one of three hexabromocyclododecane (HBCD) diastereomers. Each diastereomer was well absorbed (73-83%), and distributed preferentially to lipophilic tissues. Feces were the major route of excretion; cumulatively accounting for 42% of dose for α-HBCD, 59% for ß-HBCD, and 53% for γ-HBCD. Urine was also an important route of HBCD excretion, accounting for 13% of dose for α-HBCD, 30% for ß-HBCD, and 21% for γ-HBCD. Total metabolism of HBCD diastereomers followed the rank order ß > γ > α, and was >65% of that administered. The metabolites formed were distinct in male rats: α-HBCD did not debrominate or stereoisomerize, but formed two hydroxylated metabolites; ß- and γ-HBCD were both extensively metabolized via pathways of stereoisomerization, oxidation, dehydrogenation, reductive debromination, and ring opening. ß-HBCD was biotransformed to two mercapturic acid pathway metabolites. The metabolites of ß- and γ-HBCD were largely distinct, and could possibly be used as markers of exposure. These isomer-specific data suggest that α-HBCD would be the most dominant HBCD diastereomer in biological tissues because it was metabolized to the lowest degree and also accumulated from the stereoisomerization of the β- and γ- diastereomers.
雄性 Sprague-Dawley 大鼠经口给予 3 毫克/千克的三种六溴环十二烷（HBCD）非对映异构体之一。每个非对映异构体均被很好地吸收（73-83%），并优先分布于亲脂性组织。粪便为主要排泄途径；α-HBCD 累积占剂量的 42%，β-HBCD 累积占剂量的 59%，γ-HBCD 累积占剂量的 53%。尿液也是 HBCD 排泄的重要途径，α-HBCD 累积占剂量的 13%，β-HBCD 累积占剂量的 30%，γ-HBCD 累积占剂量的 21%。HBCD 非对映异构体的总代谢遵循 β>γ>α 的顺序，且代谢量大于给予的剂量。在雄性大鼠中形成的代谢物是不同的：α-HBCD 既不脱溴也不发生立体异构化，但形成两种羟基化代谢物；β-和 γ-HBCD 均通过立体异构化、氧化、脱氢、还原脱溴和开环途径广泛代谢。β-HBCD 被生物转化为两种巯基尿酸途径代谢物。β-和 γ-HBCD 的代谢物在很大程度上是不同的，并且可能被用作暴露的标志物。这些异构体特异性数据表明，α-HBCD 将是生物组织中最主要的 HBCD 非对映异构体，因为它的代谢程度最低，并且还可以从β-和γ-非对映异构体的立体异构化中积累。
