Comparison of blood concentrations of 1,3-butadiene and butadiene epoxides in mice and rats exposed to 1,3-butadiene by inhalation |
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| Authors: | Himmelstein, Matthew W. Turner, Max J. Asgharian, Bahman Bond, James A. |
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| Affiliation: | Chemical Industry Institute of Toxicology PO Box 12137, Research Triangle Park, NC 27709, USA |
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| Abstract: | 1,3Butadiene (BD), an important commodity chemical usedin the production of synthetic rubber, is carcinogenic in B6C3F1mice and Sprague-Dawley rats, raising concern for potentialcarcinogenicity in humans. Mice are more sensitive than ratsto the carcinogenic effects of BD. Metabolic activation of BDto form the putative DNAreactive metabolites, butadiene monoxide(BMO) and butadiene diepoxide (BDE), is mediated by cytochromeP450. Detoxication of the epoxides occurs by glutathione Stransferase-catalyzedconjugation with glutathione and hydrolysis by epoxide hydrolase.Species differences in metabolic activation and detoxicationmost likely contribute to the difference in carcinogenic potencyof BD by modulating the circulating blood levels of the epoxides.This study measured the in vivo concentrations of BD, BMO andBDE in the blood of male Sprague-Dawley rats and B6C3F1 miceduring and following 6 h nose-only exposure to inhaled BD at62.5, 625 or 1250 p.p.m. BD. Blood samples for BD and BMO ( |
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