Species differences in the metabolism of 1,3-butadiene in vivo.
The metabolism of 1,3-butadiene in vivo was studied in mice, rats and primates. The percentage of inhaled butadiene that is absorbed by exposed animals depends in large part on its rate of metabolism. Uptake of inhaled butadiene was 20% in B6C3F1 mice but only 4% in Sprague-Dawley rats and 3% in cynomolgus monkeys exposed to low levels (10 ppm 14C-butadiene or less). The routes of excretion of the carbon-14 retained after completion of the exposures were similar in rats and mice, one-half of the material being excreted in urine, 5-10% in faeces, 5-10% exhaled as carbon dioxide, 15-20% exhaled as volatile metabolites and 10-20% retained in the body. Monkeys, however, appeared to metabolize the retained 14C-butadiene more completely, as one-half of the internal dose of butadiene was exhaled as 14C-carbon dioxide. With equivalent exposures, blood metabolite levels were much higher in mice than in monkeys. In mice, the only species examined thus far, bone marrow was found to have much higher levels of butadiene monoepoxide per gram of tissue than did the blood, suggesting formation of the butadiene monoepoxide in the marrow in situ. The major urinary metabolites were two mercapturic acids (called M-I and M-II), formed from the glutathione conjugates of either butadiene monoepoxide (M-II) or the butenediol hydrolysis product of butadiene monoepoxide (M-I). Mice excrete three times as much M-II as M-I, corroborating the finding in vitro that mice are more efficient at forming the glutathione conjugate of butadiene monoepoxide than in hydrolysing it to the butenediol.(ABSTRACT TRUNCATED AT 250 WORDS)
Henderson
R F
RF
Inhalation Toxicology Research Institute, Albuquerque, NM.
Bechtold
W E
WE
Sabourin
P J
PJ
Maples
K R
KR
Dahl
A R
AR
D000280:Administration, Inhalation; D000818:Animals; D002070:Butadienes / Q000493:pharmacokinetics*; D004852:Epoxy Compounds / Q000493:pharmacokinetics; D008252:Macaca fascicularis; D051379:Mice; D008815:Mice, Inbred Strains; D009153:Mutagens / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D002070:Butadienes; D004852:Epoxy Compounds; D009153:Mutagens; C024370:3,4-epoxy-1-butene; C031763:1,3-butadiene