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Investigation of species differences in isobutene (2-methylpropene) metabolism between mice and rats
Authors:G. A. Csanády  D. Freise  B. Denk  J. G. Filser  M. Cornet  V. Rogiers  R. J. Laib
Affiliation:(1) Institut für Arbeitsphysiologie an der Universität Dortmund, Ardeystrasse 67, W-4600 Dortmund, FRG;(2) Institut für Toxikologie, GSF, Ingolstädter Landstrasse 1, W-8042 Neuherberg, FRG;(3) Department of Toxicology, Free University of Brussels, Belgium;(4) Present address: CIIT, 6 Davis Drive, PO Box 12137, 27 709 Research Triangle Park, NC, USA;(5) Present address: c/o Ministerium für Umwelt und Gesundheit, Kaiser-Friedrich-Strasse 7, W-6500 Mainz 1, FRG
Abstract:
Metabolism of isobutene (2-methylpropene) in rats (Sprague Dawley) and mice (B6C3F1) follows kinetics according to Michaelis-Menten. The maximal metabolic elimination rates are 340 mgrmol/kg/h for rats and 560 mgrmol/kg/h for mice. The atmospheric concentration at which Vmax/2 is reached is 1200 ppm for rats and 1800 ppm for mice. At steady state, below atmospheric concentrations of about 500 ppm the rate of metabolism of isobutene is direct proportional to its concentration. 1,1-Dimethyloxirane is formed as a primary reactive intermediate during metabolism of isobutene in rats and can be detected in the exhaled air of the animals. Under conditions of saturation of isobutene metabolism the concentration of 1,1-dimethyloxirane in the atmosphere of a closed exposure system is only about 1/15 of that observed for ethene oxide and about 1/100 of that observed for 1,2-epoxy-3-butene as intermediates in the metabolism of ethene or 1,3-butadiene.On leave from: Central Research Institute of Chemistry, Hungarian Academy of Sciences, Budapest, Hungary.
Keywords:Isobutene (2-methylpropene)  1,1-Dimethyloxirane  Pharmacokinetics  Inhalation  Epoxide formation  Species differences
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