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

Chemico-biological Interactions
J G FilserG A Csanády

Abstract

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 6-8h 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 micromol/l (rat) and 23.5 ...Continue Reading

References

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Citations

Aug 17, 2010·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·Roberta L GrantMichael Honeycutt
Jan 8, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Johannes G FilserGyörgy A Csanády
Dec 17, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Johannes G FilserGyörgy A Csanády
May 24, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Igor KoturbashIgor P Pogribny
Sep 27, 2013·Toxicological Sciences : an Official Journal of the Society of Toxicology·Johannes Georg FilserGyörgy András Csanády
Dec 15, 2010·Environmental Health Perspectives·Igor KoturbashIvan Rusyn
Feb 25, 2014·Toxicology·Jessica H HartmanGunnar Boysen
Dec 23, 2011·Drug and Chemical Toxicology·Constantinos PistosSotiris Athanaselis
Jan 21, 2012·Journal of Pharmaceutical and Biomedical Analysis·Franciszek K GłówkaTomasz Wróbel
Nov 7, 2006·Chemico-biological Interactions·Gunnar BoysenJames A Swenberg
Mar 6, 2007·Chemico-biological Interactions·Matthew W HimmelsteinR Jeffrey Lewis
Oct 11, 2011·Toxicology Letters·György András CsanádyJohannes Georg Filser
Nov 22, 2011·Regulatory Toxicology and Pharmacology : RTP·C R Kirman, R L Grant
Sep 28, 2010·Critical Reviews in Toxicology·Christopher R KirmanMichael L Gargas
Apr 26, 2007·Chemical Research in Toxicology·Melissa GogginNatalia Tretyakova

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