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大鼠体内二氯丙醇尿液代谢物的鉴定与定量分析

Identification and quantitative analysis of urinary metabolites of dichloropropanols in rats.

作者信息

Koga M, Inoue N, Imazu K, Yamada N, Shinoki Y

机构信息

Research Center for Common Use, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.

出版信息

J UOEH. 1992 Mar 1;14(1):13-22. doi: 10.7888/juoeh.14.13.

DOI:10.7888/juoeh.14.13
PMID:1509208
Abstract

Urinary metabolites of dichloropropanols in rats were analyzed by gas chromatography-mass spectrometry (GC/MS). Solutions of dichloropropanols consisting of 1, 3-dichloro-2-propanol (DC2P) and 2, 3-dichloro-1-propanol (DC1P) were diluted in a saline at the concentration of 100 mg/ml, and 0.1 ml of the solutions were subcutaneously injected into male Wistar rats weighing about 160g. The urine samples were collected over a period of 24 hours after the injections. DC2P and DC1P in the urine were extracted with ethylacetate and analyzed by a GC/MS. The derivatization procedure with 4-bromophenylboric acid after acetonitril extraction was applied for the analyses of diols in the urine. By the GC/MS analysis, 3-chloro-1, 2-propanediol (3CPD), 2-chloro-1, 3-propanediol (2CPD) and 1, 2-propanediol (PPD) were identified as the hydroxylated metabolites of dichlorpropanols. Based on the analytical results, the metabolic pathways of dichlorpropanols forming 3CPD and 2CPD, and then hydroxylating to PPD were elucidated.

摘要

采用气相色谱-质谱联用仪(GC/MS)分析大鼠体内二氯丙醇的尿液代谢产物。将由1,3-二氯-2-丙醇(DC2P)和2,3-二氯-1-丙醇(DC1P)组成的二氯丙醇溶液用生理盐水稀释至浓度为100mg/ml,取0.1ml该溶液皮下注射到体重约160g的雄性Wistar大鼠体内。注射后24小时内收集尿液样本。尿液中的DC2P和DC1P用乙酸乙酯萃取,并用GC/MS进行分析。采用乙腈萃取后用4-溴苯硼酸进行衍生化处理的方法分析尿液中的二醇。通过GC/MS分析,鉴定出3-氯-1,2-丙二醇(3CPD)、2-氯-1,3-丙二醇(2CPD)和1,2-丙二醇(PPD)为二氯丙醇的羟基化代谢产物。根据分析结果,阐明了二氯丙醇形成3CPD和2CPD,然后羟基化生成PPD的代谢途径。

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引用本文的文献

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Formation of epichlorohydrin, a known rodent carcinogen, following oral administration of 1,3-dichloro-2-propanol in rats.大鼠口服1,3-二氯-2-丙醇后形成环氧氯丙烷,一种已知的啮齿动物致癌物。
Chem Res Toxicol. 2014 Oct 20;27(10):1787-95. doi: 10.1021/tx500239q. Epub 2014 Oct 9.
2
Comparative testicular toxicities of two isomers of dichloropropanol, 2,3-dichloro-1-propanol, and 1,3-dichloro-2-propanol, and their metabolites alpha-chlorohydrin and epichlorohydrin, and the potent testicular toxicant 1,2-dibromo-3-chloropropane.二氯丙醇的两种异构体(2,3-二氯-1-丙醇和1,3-二氯-2-丙醇)及其代谢产物α-氯醇和环氧氯丙烷,以及强效睾丸毒物1,2-二溴-3-氯丙烷的比较性睾丸毒性。
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