Biotransformation of 1,2-dibromopropane in rats into four mercapturic acid derivatives.
1,2-Dibromopropane was administered orally in doses of 50-350 mg/kg to male Wistar rats. Four mercapturic acids were identified in urine by GC/MS, viz. N-acetyl-S-(2-oxopropyl)-L-cysteine (I), N-acetyl-S-(2-hydroxypropyl)-L-cysteine (II), N-acetyl-S-(1-carboxyethyl)-L-cysteine (III), and N-acetyl-S-(2-bromo-2-propenyl)-L-cysteine (IV). Mercapturic acid IV was a minor metabolite which could only be measured at doses of 200 mg/kg or higher. In 24 hr, urinary excretion of mercapturic acids amounted to about 36% of the dose (11% I, 21% II, 4% III, 0.2% IV). No dose dependency was found up to the highest dose. A unified scheme is proposed for the metabolism of 1,2-dibromopropane in the rat, which accounts for the identified mercapturic acids. The role of direct glutathione conjugation in the route leading to the major metabolite II, presumably involving thiiranium ion formation, is discussed. This route probably is biologically not very important because of the absence of detectable activity of 1,2-dibromopropane toward glutathione S-transferases in vitro, the very low mutagenicity of 1,2-dibromopropane, and the high mutagenic activity of N-acetyl-S-(2-bromopropyl)-L-cysteine methyl ester which was studied as a model compound for direct conjugation.
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D000818:Animals; D001711:Biotransformation; D002849:Chromatography, Gas; D008401:Gas Chromatography-Mass Spectrometry; D006842:Hydrocarbons, Brominated / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D006842:Hydrocarbons, Brominated; C050753:1,2-dibromopropane; D000111:Acetylcysteine