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吸入的 3,3'-二氯联苯的消除和 4-羟基代谢物的形成。

Elimination of inhaled 3,3'-dichlorobiphenyl and the formation of the 4-hydroxylated metabolite.

机构信息

Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, Iowa 52242, USA.

出版信息

Environ Sci Technol. 2013 May 7;47(9):4743-51. doi: 10.1021/es3049114. Epub 2013 Apr 25.

Abstract

The recent discovery of 3,3'-dichlorobiphenyl (CB11) as a byproduct of pigment manufacturing underscores the urgency to investigate its biological fate. The high level and ubiquity of atmospheric CB11 indicates that inhalation is the major route of exposure. However, few data on its uptake and elimination exist. A time course study was performed exposing male Sprague-Dawley rats to CB11 via nose-only inhalation with necropsy at 0, 4, and 8 h post exposure. An analytical method for CB11 and monohydroxylated metabolites employing pressurized liquid extraction and gas chromatography-mass spectrometry yielded efficient recovery of CB11 (73 ± 9%) and its metabolite 3,3'-dichlorobiphenyl-4-ol (4-OH-CB11) (82 ± 12%). Each rat was exposed to 106 μg/m(3) vapor-phase CB11 for 2 h and received an estimated dose of 1.8 μg. Rapid apparent first-order elimination of CB11 was found in lung, serum, and liver with half-lives of 1.9, 1.8, and 2.1 h, respectively. 4-OH-CB11 was detected in the liver but not the lung or serum of exposed animals and displayed apparent first-order elimination with a 2.4 h half-life. This study demonstrates rapid metabolism of CB11 and elimination of 4-OH-CB11 and suggests that the metabolite is not retained in the body but is susceptible to further biotransformation.

摘要

最近发现 3,3'-二氯联苯 (CB11) 是颜料制造的副产品,这突显出调查其生物命运的紧迫性。大气中 CB11 的高浓度和普遍存在表明,吸入是主要的暴露途径。然而,关于其吸收和消除的数据很少。一项时间进程研究通过鼻吸入仅暴露雄性 Sprague-Dawley 大鼠 CB11,在暴露后 0、4 和 8 小时进行尸检。采用加压液体提取和气相色谱-质谱联用的方法,对 CB11 和单羟基化代谢物进行分析,可有效回收 CB11(73±9%)和其代谢物 3,3'-二氯联苯-4-醇(4-OH-CB11)(82±12%)。每只大鼠暴露于 106μg/m3 气相 CB11 2 小时,估计剂量为 1.8μg。在肺、血清和肝脏中发现 CB11 的快速表观一级消除,半衰期分别为 1.9、1.8 和 2.1 小时。在暴露动物的肝脏中检测到 4-OH-CB11,但在肺或血清中未检测到,其表观一级消除半衰期为 2.4 小时。这项研究表明 CB11 的代谢迅速,4-OH-CB11 的消除迅速,并表明代谢物不会在体内蓄积,而是容易进一步生物转化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d7d/3962796/7466a963deb4/nihms472698f1.jpg

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