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

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

Index: Arch. Environ. Contam. Toxicol. 11(2) , 173-83, (1982)

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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%.