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Filser, J.G. ; Hutzler, C.* ; Meischner, V. ; Veereshwarayya, V. ; Csanády, G.A.

Metabolism of 1,3-butadiene to toxicologically relevant metabolites in single-exposed mice and rats.

Chem. Biol. Interact. 166, 93-103 (2007)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
1,3-Butadiene (BD) was carcinogenic in rodents. This effect is related to reactive metabolites such as 1,2-epoxy-3-butene (EB) and especially 1,2:3,4-diepoxybutane (DEB). A third mutagenic epoxide, 3,4-epoxy-1,2-butanediol (EBD), can be formed from DEB and from 3-butene-1,2-diol (B-diol), the hydrolysis product of EB. In BD exposed rodents, only blood concentrations of EB and DEB have been published. Direct determinations of EBD and B-diol in blood are missing. In order to investigate the BD-dependent blood burden by all of these metabolites, we exposed male B6C3F1 mice and male Sprague-Dawley rats in closed chambers over 6–8 h to constant atmospheric BD concentrations. BD and exhaled EB were measured in chamber atmospheres during the BD exposures. EB blood concentrations were obtained as the product of the atmospheric EB concentration at steady state with the EB blood-to-air partition coefficient. B-diol, EBD, and DEB were determined in blood collected immediately at the end of BD exposures up to 1200 ppm (B-diol, EBD) and 1280 ppm (DEB). Analysis of BD was done by GC/FID, of EB, DEB, and B-diol by GC/MS, and of EBD by LC/MS/MS. EB blood concentrations increased with BD concentrations amounting to 2.6 ?mol/l (rat) and 23.5 ?mol/l (mouse) at 2000 ppm BD and to 4.6 ?mol/l in rats exposed to 10000 ppm BD. DEB (detection limit 0.01 ?mol/l) was found only in blood of mice rising to 3.2 ?mol/l at 1280 ppm BD. B-diol and EBD were quantitatively predominant in both species. B-diol increased in both species with the BD exposure concentration reaching 60 ?mol/l at 1200 ppm BD. EBD reached maximum concentrations of 9.5 ?mol/l at 150 ppm BD (rat) and of 42 ?mol/l at 300 ppm BD (mouse). At higher BD concentrations EBD blood concentrations decreased again. This picture probably results from a competitive inhibition of the EBD producing CYP450 by BD, which occurs in both species.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords 1;3-Butadiene; 1;2-Epoxy-3-butene; 3-Butene-1;2-diol; 3;4-Epoxy-1;2-butanediol; 1;2:3;4-Diepoxybutane; Mouse; Rat; Inhalation
ISSN (print) / ISBN 0009-2797
e-ISSN 1872-7786
Journal Chemico-Biological Interactions
Quellenangaben Volume: 166, Issue: 1-3, Pages: 93-103 Article Number: , Supplement: ,
Publisher Elsevier
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Toxicology and Pharmacology (TOXI)