United States Environmental Protection Agency, Office of Research and Development, National Health Effects and Exposure Research Laboratory, Integrated Systems Toxicology Division, Mail Drop B143-01, 109 T.W. Alexander Drive, Research Triangle Park, NC 27711, USA.
Toxicol Sci. 2011 Jun;121(2):234-44. doi: 10.1093/toxsci/kfr059. Epub 2011 Mar 25.
Alpha-hexabromocyclododecane (α-HBCD) is an emerging persistent organic pollutant present in the hexabromocyclododecane (HBCD) commercial mixture. HBCD is used as an additive flame retardant in a wide variety of household consumer products. Three main stereoisomers, alpha (α), beta (β), and gamma (γ), comprise roughly 10, 10, and 80% of the mixture, respectively. Despite its small contribution to HBCD global production and usage, α-HBCD is the major stereoisomer found in wildlife and human tissues including breast milk and blood in North America, European Union, and Asia. No mammalian or human data are currently available regarding the toxicokinetics of α-HBCD. This study was conducted in an effort to fully characterize the absorption, distribution, metabolism, and elimination of α-HBCD following a single and repeated exposure with respect to dose, time, and route of administration in female C57BL/6 mice. Results indicate that ∼90% of the administered dose (3 mg/kg) was absorbed after oral exposure. Disposition was (1) dictated by lipophilicity, as adipose, liver, muscle, and skin were major depots and (2) was dose dependent with nonlinear accumulation at higher doses. Elimination, both whole-body and from individual tissues, was biphasic. α-HBCD-derived radioactivity was excreted in the feces as parent and metabolites, whereas urine only contained metabolites. Presence of polar metabolites in the blood and urine were a major factor in determining the rapid initial whole-body half-life after a single oral exposure. Initial half-lives were ∼1-3 days and much longer terminal half-lives of 17 days were observed, suggesting the potential for α-HBCD bioaccumulation. A 10-day repeated study supports α-HBCD bioaccumulation potential. Stereoisomerization previously observed after exposure to γ-HBCD was not seen after exposure of α-HBCD. The toxicokinetic behavior reported here has important implications for the extrapolation of toxicological studies of the commercial HBCD mixture to the assessment of risk of α-HBCD which is the major stereoisomer found in wildlife and people.
α-六溴环十二烷（α-HBCD）是一种新兴的持久性有机污染物，存在于六溴环十二烷（HBCD）商业混合物中。HBCD 用作各种家用消费品的添加剂阻燃剂。三种主要的立体异构体，α（α）、β（β）和γ（γ），分别约占混合物的 10%、10%和 80%。尽管 α-HBCD 在 HBCD 的全球生产和使用中所占比例很小，但它是北美的野生动物和人体组织（包括母乳和血液）以及欧洲联盟和亚洲地区发现的主要立体异构体。目前尚无关于哺乳动物或人类体内 α-HBCD 的毒代动力学数据。这项研究的目的是在雌性 C57BL/6 小鼠中，通过单次和重复接触，全面描述 α-HBCD 在吸收、分布、代谢和消除方面的特征，涉及剂量、时间和给药途径。结果表明，经口暴露后约 90%的给予剂量（3mg/kg）被吸收。处置方式（1）由亲脂性决定，因为脂肪、肝脏、肌肉和皮肤是主要的蓄积部位，（2）与剂量有关，高剂量时呈非线性蓄积。全身和各组织的消除均呈双相。α-HBCD 衍生的放射性以母体和代谢物的形式从粪便中排出，而尿液中仅含有代谢物。血液和尿液中极性代谢物的存在是决定单次口服暴露后快速初始全身半衰期的主要因素。初始半衰期约为 1-3 天，观察到更长的终末半衰期为 17 天，表明 α-HBCD 具有生物蓄积潜力。为期 10 天的重复研究支持 α-HBCD 生物蓄积潜力。以前在接触 γ-HBCD 后观察到的立体异构化在接触 α-HBCD 后没有出现。这里报道的毒代动力学行为对将商业 HBCD 混合物的毒理学研究外推到评估 α-HBCD 的风险具有重要意义，α-HBCD 是在野生动物和人群中发现的主要立体异构体。
