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.

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%。