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双(2-氯乙基)醚和双(2-氯异丙基)醚在大鼠体内的代谢

Metabolism of bis(2-chloroethyl)ether and bis(2-chloroisopropyl)ether in the rat.

作者信息

Lingg R D, Kaylor W H, Pyle S M, Domino M M, Smith C C, Wolfe G F

出版信息

Arch Environ Contam Toxicol. 1982;11(2):173-83. doi: 10.1007/BF01054894.

DOI:10.1007/BF01054894
PMID:6807217
Abstract

Male rats were given single peroral doses of bis(1-14C-2-chloroethyl)ether ([1-14C]BCEE) (40 mg/kg) and of bis(1-14C-2-chloroisopropyl)ether ([1-14C]BCIE) (90 mg/kg). Excretion of 14CO2 and urinary 14C was followed for 48 hr. The time required to eliminate one half of the dose was 12 hr for [1-14C]BCEE and 19 hr for [1-14C]BCIE. In the case of [1-14C]BCEE, expired 14CO2 accounted for 11.5 +/- 5.6(SD)% of the dose, urinary 14C accounted for 64.7 +/- 14.8%, and 2.4 +/- 1.3% was found in the feces. The figures for [1-14C]BCIE were 20.3 +/- 9.4% expired as 14CO2, 47.5 +/- 8.1% as urinary 14C, and 3.8 +/- 0.3% as fecal 14C. Thiodiglycolic acid (TDGA) accounted for roughly 75% of the total urinary 14C collected after the [1-14C]BCEE dose. Lesser metabolites of BCEE were 2-chloroethoxyacetic acid (CEAA) (5%), and N-acetyl-S-[2-(2-chloroethoxy)ethyl]-L-cysteine (ACEEC) (7%). Metabolites of [1-14C]BCIE identified in rat urine were 2-(2-chloro-1-methylethoxy)propanoic acid (CMEPA), roughly 36% of the total urinary 14C, and N-acetyl-S-(2-hydroxypropyl)-L-cysteine (AHPC) at 19%.

摘要

给雄性大鼠经口单次给予双(1-¹⁴C-2-氯乙基)醚([1-¹⁴C]BCEE)(40毫克/千克)和双(1-¹⁴C-2-氯异丙基)醚([1-¹⁴C]BCIE)(90毫克/千克)。跟踪48小时内¹⁴CO₂的排泄和尿中¹⁴C的情况。[1-¹⁴C]BCEE消除一半剂量所需时间为12小时,[1-¹⁴C]BCIE为19小时。对于[1-¹⁴C]BCEE,呼出的¹⁴CO₂占剂量的11.5±5.6(标准差)%,尿中¹⁴C占64.7±14.8%,粪便中为2.4±1.3%。[1-¹⁴C]BCIE的相应数据为:以¹⁴CO₂形式呼出的占20.3±9.4%,尿中¹⁴C占47.5±8.1%,粪便中¹⁴C占3.8±0.3%。硫代二甘醇酸(TDGA)约占[1-¹⁴C]BCEE剂量后收集的尿中总¹⁴C的75%。BCEE的次要代谢产物是2-氯乙氧基乙酸(CEAA)(5%)和N-乙酰-S-[2-(2-氯乙氧基)乙基]-L-半胱氨酸(ACEEC)(7%)。在大鼠尿液中鉴定出的[1-¹⁴C]BCIE的代谢产物是2-(2-氯-1-甲基乙氧基)丙酸(CMEPA),约占尿中总¹⁴C的36%,N-乙酰-S-(2-羟丙基)-L-半胱氨酸(AHPC)占19%。

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本文引用的文献

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Bioassay of Technical Grade Bis(2-chloro-1-methylethyl) ether for Possible Carcinogenicity (CAS No. 108-60-1).工业级双(2-氯-1-甲基乙基)醚潜在致癌性的生物测定(化学物质登记号:108-60-1)
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Bioassay of pesticides and industrial chemicals for tumorigenicity in mice: a preliminary note.用于小鼠致癌性的农药和工业化学品生物测定:初步报告。
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Metabolism of volatile anesthetics.
Int Anesthesiol Clin. 1971 Fall;9(3):145-69. doi: 10.1097/00004311-197100930-00009.
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Fate of (14C)vinyl chloride after single oral administration in rats.大鼠单次口服给予(14C)氯乙烯后的命运。
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The metabolism of 3-chloro,- 3-bromo- and 3-iodoprpan-1,2-diol in rats and mice.
Xenobiotica. 1975 Mar;5(3):155-65. doi: 10.3109/00498257509056101.
6
Quantitative metabolic profiling of urinary organic acids by gas chromatography-mass spectrometry: comparison of isolation methods.气相色谱-质谱联用法定量分析尿液有机酸的代谢谱:分离方法比较
Anal Chem. 1975 Jul;47(8):1313-21. doi: 10.1021/ac60358a074.
7
Alkylation and carbamoylation intermediates from the carcinostatic 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU)-1.来自抗癌药物1-(2-氯乙基)-3-环己基-1-亚硝基脲(CCNU)的烷基化和氨基甲酰化中间体-1 。
Life Sci. 1975 Apr 15;16(8):1263-70. doi: 10.1016/0024-3205(75)90311-2.
8
The oxidative metabolism of 1-bromopropane in the rat.大鼠体内1-溴丙烷的氧化代谢
Xenobiotica. 1979 Dec;9(12):763-72. doi: 10.3109/00498257909042344.
9
Identification of S-(carboxymethyl)-L-cysteine and thiodiglycolic acid, urinary metabolites of 2,2'-bis-(chloroethyl)-ether in the rat.大鼠体内2,2'-双(氯乙基)醚的尿液代谢产物S-(羧甲基)-L-半胱氨酸和硫代二甘醇酸的鉴定。
Cancer Lett. 1979 Sep;7(5):299-305. doi: 10.1016/s0304-3835(79)80057-9.
10
Thiodiglycolic acid: a major metabolite of bis(2-chloroethyl)ether.硫代二乙醇酸:双(2-氯乙基)醚的主要代谢产物。
Toxicol Appl Pharmacol. 1979 Jan;47(1):23-34. doi: 10.1016/0041-008x(79)90067-x.