title: 1,2:3,4-Diepoxybutane in blood of male B6C3F1 mice and male Sprague-Dawley rats exposed to 1,3-butadiene.
abstract: The important industrial chemical 1,3-butadiene (BD; CAS Registry Number: 106-99-0) is a potent carcinogen in B6C3F1 mice and a weak one in Sprague-Dawley rats. This difference is mainly attributed to the species-specific burden by the metabolically formed 1,2:3,4-diepoxybutane (DEB). However, only limited data exist on the DEB blood burden of rodents at BD concentrations below 100 ppm. Considering this, DEB concentrations were determined in the blood of mice and rats immediately after 6h exposures to various constant concentrations of BD of between about 1 and 1200 ppm. Immediately after its collection, blood was injected into a vial that contained perdeuterated DEB (DEB-D(6)) as internal standard. Plasma samples were prepared and treated with sodium diethyldithiocarbamate that derivatized metabolically produced DEB and DEB-D(6) to their bis(dithiocarbamoyl) esters, which were then analyzed by high performance liquid chromatography coupled with an electrospray ionization tandem mass spectrometer. DEB concentrations in blood versus BD exposure concentrations in air could be described by one-phase exponential association functions. Herewith calculated (±)-DEB concentrations in blood increased in mice from 5.4 nmol/l at 1 ppm BD to 1860 nmol/l at 1250 ppm BD and in rats from 1.2 nmol/l at 1 ppm BD to 92 nmol/l at 200 ppm BD, at which exposure concentration 91% of the calculated DEB plateau concentration in rat blood was reached. This information on the species-specific blood burden by the highly mutagenic DEB helps to explain why the carcinogenic potency of BD in rats is low compared to that in mice.
authors: Institute of Toxicology, German Research Center for Environmental Health, Helmholtz Zentrum München, D-85764 Neuherberg, Germany.
authors: György András
authors: GA
authors: Csanády
authors: Robert
authors: R
authors: Steinhoff
authors: Martin Bernhard
authors: MB
authors: Riester
authors: Brigitte
authors: B
authors: Semder
authors: Christian
authors: C
authors: Pütz
authors: Qiang
authors: Q
authors: Li
authors: Nadine
authors: N
authors: Richter
authors: Winfried
authors: W
authors: Kessler
authors: Dominik
authors: D
authors: Klein
authors: Johannes Georg
authors: JG
authors: Filser
mesh_terms: D000818:Animals; D002070:Butadienes / Q000493:pharmacokinetics*; D002273:Carcinogens / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000097:blood*; D019570:Inhalation Exposure / Q000009:adverse effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D053719:Tandem Mass Spectrometry
chemical_list: D002070:Butadienes; D002273:Carcinogens; D004852:Epoxy Compounds; C007366:diepoxybutane; C031763:1,3-butadiene