Metabolism of 1,3-butadiene: inhalation pharmacokinetics and tissue dosimetry of butadiene epoxides in rats and mice.
Significant species differences exist in the susceptibility to butadiene (BD)-induced cancer in rats and mice, and metabolism is likely a critical determinant for species sensitivity. This study measured the in vivo concentrations of, (1) BD in blood; (2) epoxybutene (EB) and diepoxybutane (DEB) in blood, lung and liver; and (3) glutathione (GSH) in lung and liver of male B6C3F1 mice and Sprague-Dawley rats during and after 6-h exposure to 62.5, 625, 1250, and 8000 (rat only) ppm BD. Mice had higher concentrations of EB and DEB in blood and tissues than did rats, DEB could not be detected in blood or tissues of rats, and the greatest depletion of GSH occurred in the lungs of mice. During exposure, the peak concentrations of EB in mice compared with rats were 4- to 8-fold higher in blood, 13- to 15-fold higher in lung, and 5- to 8-fold higher in liver. These data suggest that higher levels of BD epoxides in blood and tissues of mice compared with rats may explain, in part, the greater sensitivity of mice than rats to BD-induced carcinogenicity.
Himmelstein
M W
MW
Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709, USA.
Turner
M J
MJ
Asgharian
B
B
Bond
J A
JA
D000280:Administration, Inhalation; D000818:Animals; D002070:Butadienes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D002273:Carcinogens / Q000493:pharmacokinetics*; D004852:Epoxy Compounds / Q000493:pharmacokinetics*; D005978:Glutathione / Q000378:metabolism; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D002070:Butadienes; D002273:Carcinogens; D004852:Epoxy Compounds; C024370:3,4-epoxy-1-butene; C007366:diepoxybutane; D005978:Glutathione; C031763:1,3-butadiene