title: Detection of carboxylic acids and inhibition of hippuric acid formation in rats treated with 3-butene-1,2-diol, a major metabolite of 1,3-butadiene.
abstract: Epidemiological studies have indicated that 1,3-butadiene exposure is associated with an increased risk of leukemia. In human liver microsomes, 1,3-butadiene is rapidly oxidized to butadiene monoxide, which can then be hydrolyzed to 3-butene-1,2-diol (BDD). In this study, BDD and several potential metabolites were characterized in the urine of male B6C3F1 mice and Sprague-Dawley rats after BDD administration (i.p.). Rats given 1420 micromol kg(-1) BDD excreted significantly greater amounts of BDD relative to rats administered 710 micromol kg(-1) BDD. Rats administered 1420 or 2840 micromol kg(-1) BDD excreted significantly greater amounts of BDD per kilogram of body weight than mice given an equivalent dose. Trace amounts of 1-hydroxy-2-butanone and the carboxylic acid metabolites, crotonic acid, propionic acid, and 2-ketobutyric acid, were detected in mouse and rat urine after BDD administration. Because of the identification of the carboxylic acid metabolites and because of the known ability of carboxylic acids to conjugate coenzyme A, which is critical for hippuric acid formation, the effect of BDD treatment on hippuric acid concentrations was investigated. Rats given 1420 or 2272 micromol kg(-1) BDD had significantly elevated ratios of benzoic acid to hippuric acid in the urine after treatment compared with control urine. However, this effect was not observed in mice administered 1420 or 2840 micromol kg(-1) BDD. Collectively, the results demonstrate species differences in the urinary excretion of BDD and show that BDD administration in rats inhibits hippuric acid formation. The detection of 1-hydroxy-2-butanone and the carboxylic acids also provides insight regarding pathways of BDD metabolism in vivo.
authors.affiliation: School of Veterinary Medicine, 2015 Linden Drive, Madison, WI 53706, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Sprague
authors.forename: Adnan A
authors.initials: AA
authors.lastname: Elfarra
mesh_terms: D000818:Animals; D019817:Benzoic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000652:urine; D002070:Butadienes / Q000737:chemistry*; D002074:Butanones / Q000652:urine; D002087:Butyrates / Q000652:urine; D002264:Carboxylic Acids / Q000652:urine*; D003437:Crotonates / Q000652:urine; D004305:Dose-Response Relationship, Drug; D006018:Glycols / Q000008:administration & dosage* / Q000378:metabolism*; D006626:Hippurates / Q000037:antagonists & inhibitors* / Q000652:urine; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver; D015394:Molecular Structure; D011422:Propionates / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
chemical_list: D002070:Butadienes; D002074:Butanones; D002087:Butyrates; D002264:Carboxylic Acids; D003437:Crotonates; D006018:Glycols; D006626:Hippurates; D011422:Propionates; C005087:alpha-ketobutyric acid; D019817:Benzoic Acid; C029658:propionic acid; C031763:1,3-butadiene; C487002:1-hydroxy-2-butanone; C034598:3-butene-1,2-diol; C030514:hippuric acid