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大鼠体内1,4,7,8-四氯二苯并对二噁英的代谢与处置

Metabolism and disposition of 1,4,7,8-tetrachlorodibenzo-p-dioxin in rats.

作者信息

Huwe J K, Feil V J, Larsen G L, Wiener C

机构信息

USDA Biosciences Research Laboratory, Fargo, ND 58105, USA.

出版信息

Chemosphere. 1998 Oct-Nov;37(9-12):1885-93. doi: 10.1016/s0045-6535(98)00255-0.

DOI:10.1016/s0045-6535(98)00255-0
PMID:9828317
Abstract

Metabolism studies of 1,4,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a relatively nontoxic dioxin congener, were undertaken to gain a better understanding of mammalian metabolism of dioxins without the problems associated with the use of the most toxic congener, 2,3,7,8-TCDD. 14C-1,4,7,8-TCDD was dosed to conventional and bile-cannulated rats at a level of 8 mg/kg. The 14C was excreted almost entirely in 72 hours with the major routes of excretion feces and bile. Metabolites were identified from the feces, bile, and urine by GC-MS or negative ion FAB MS and 1H NMR. The two major fecal metabolites were hydroxylated tetra- and triCDDs. Glucuronide and sulfate conjugates of these hydroxyl metabolites were found in the urine and bile. Minor metabolites included dichlorocatechol, dihydroxylated tetra- and triCDDs, and conjugates of these compounds.

摘要

对相对无毒的二噁英同系物1,4,7,8-四氯二苯并对二噁英(TCDD)进行了代谢研究,目的是在不涉及使用毒性最强的同系物2,3,7,8-TCDD相关问题的情况下,更好地了解二噁英在哺乳动物体内的代谢情况。将14C-1,4,7,8-TCDD以8毫克/千克的剂量给予常规大鼠和胆管插管大鼠。14C几乎在72小时内全部排出,主要排泄途径为粪便和胆汁。通过气相色谱-质谱联用仪(GC-MS)或负离子快原子轰击质谱(negative ion FAB MS)以及1H核磁共振(1H NMR)从粪便、胆汁和尿液中鉴定出代谢产物。两种主要的粪便代谢产物是羟基化的四氯和三氯二噁英。在尿液和胆汁中发现了这些羟基代谢产物的葡萄糖醛酸和硫酸盐结合物。次要代谢产物包括二氯儿茶酚、二羟基化的四氯和三氯二噁英以及这些化合物的结合物。

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