US EPA

4822351 

Journal Article 

Metabolites of (3-13C)1,2-Dibromo-3-chloropropane in Male Rats Studied by 13C and 1H-13C Correlated Two-Dimensional NMR Spectroscopy 

Dohn, DR; Graziano, MJ; Casida, JE 

1988 

Yes 

Biochemical Pharmacology
ISSN: 0006-2952
EISSN: 1873-2968 

37 

18 

3485-3495 

http://www.sciencedirect.com/science/article/pii/0006295288907010
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Several metabolites of carbon-13 (C-13) labeled 1,2-dibromo-3-chloropropane (96128) (DBCP) were identified in the bile and urine of male rats by direct C-13 and two dimensional (2D) NMR spectroscopy. The mechanisms of formation of these metabolites and their toxicological implications are considered. Male Sprague-Dawley-rats were treated intraperitoneally with 81mg/kg C-13 labeled or unlabeled DBCP. Both DBCP solutions contained tracer amounts of carbon-14. Urine and bile were collected for 48 hours after dosing or until the animals died. Fifteen C-13 NMR signals were observed for biliary metabolites and 12 for urinary metabolites. Nine of the biliary metabolite signals were very similar or identical to those for nine urinary metabolites. DBCP derived radiocarbon was extensively excreted and appeared more rapidly in the bile following intraperitoneal than oral administration. Possible mechanisms for production of carbon-dioxide include metabolism of DBCP either to a tricarboxylic-acid cycle intermediate or to an alpha keto acid such as 3-chloropyruvate or 3-bromopyruvate which undergoes oxidative decarboxylation. Four metabolites of DBCP were identified and were found to be sulfur based conjugates; one was labeled in two positions. The metabolites identified were S-(3-chloro-2-hydroxypropyl) and S-(2,3-dihydroxypropyl) derivatives and S-(E-chloropropenyl) and S-(Z-1-chloropropenyl) derivatives. Direct glutathione conjugation, radical processes, and oxidative pathways were discussed a as possible mechanisms for the formation of these metabolites. The authors conclude that the specificity of the NMR techniques in identifying a series of very polar metabolites in the bile and urine without separation or potential degradation will prove very helpful in future studies of the unidentified metabolites and aid in determining the causes of the diverse toxic effects of such compounds as DBCP. 

Animals; Bile/metabolism; Carbon Isotopes; Glutathione/metabolism; Magnetic Resonance Spectroscopy; Oxidation-Reduction; Propane/analogs & derivatives; Propane/metabolism; Propane/toxicity; Inbred Strains; Index Medicus/