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0090-9556/03/3108-986-992$20.00
DMD 31:986-992, 2003

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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

Christopher L. Sprague, and Adnan A. Elfarra

Department of Comparative Biosciences and the Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, Madison, Wisconsin

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 µmol kg-1 BDD excreted significantly greater amounts of BDD relative to rats administered 710 µmol kg-1 BDD. Rats administered 1420 or 2840 µmol 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 µmol 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 µmol 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.

Address correspondence to: Dr. Adnan A. Elfarra, 3154 School of Veterinary Medicine, 2015 Linden Drive, Madison, WI 53706. E-mail: elfarraa{at}svm.vetmed.wisc.edu




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C. L. Sprague, L. A. Phillips, K. M. Young, and A. A. Elfarra
Species and Tissue Differences in the Toxicity of 3-Butene-1,2-diol in Male Sprague-Dawley Rats and B6C3F1 Mice
Toxicol. Sci., July 1, 2004; 80(1): 3 - 13.
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