1,2-Dichloropropane: investigation of the mechanism of mercapturic acid formation in the rat.
1. Three mercapturic acid metabolites were identified in the urine of male and female Fischer 344 rats given 1,2-dichloropropane (DCP) orally (100 mg/kg) or by inhalation exposure (100 ppm, 6 h). 2. These compounds (N-acetyl-S-(2-hydroxypropyl)-L-cysteine, N-acetyl-S-(2-oxopropyl)-L-cysteine and N-acetyl-S-(1-carboxyethyl)-L-cysteine) were isolated from the urine following acidification and extraction with ethyl acetate. The extracts were derivatized with diazomethane and N,O-bis(trimethylsilyl)trifluoroacetamide and analysed by chemical ionization g.l.c.-mass spectrometry. 3. Further mechanistic studies were carried out with the stable isotope-labelled analogue, D6-DCP (105 mg/kg, orally). Analysis of the resulting mass spectra indicated retention of primarily three deuterium atoms in the 2-hydroxypropyl-mercapturic acid formed from D6-DCP. Similar isotope retention was observed for the 2-oxopropyl-mercapturic acid metabolite. 4. These results do not support a sulphonium ion intermediate in the formation of the 2-hydroxypropyl-mercapturic acid metabolite of DCP. Instead, this metabolite is thought to arise via direct oxidation of DCP, either prior to or following conjugation with glutathione.
Bartels
M J
MJ
Dow Chemical Company, Midland, Michigan 48674.
Timchalk
C
C
D000111:Acetylcysteine / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D000818:Animals; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D008297:Male; D011407:Propane / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000652:urine; D051381:Rats; D011916:Rats, Inbred F344
C004765:propylene dichloride; D011407:Propane; D000111:Acetylcysteine