Toxicokinetics of inhaled 1,3-butadiene in monkeys: comparison to toxicokinetics in rats and mice.
1,3-Butadiene is a potent carcinogen in mice and a weaker carcinogen in rats. People are exposed to butadiene through its industrial use--largely in rubber production (over 3 billion pounds of butadiene were produced in 1989)--and because it is common in the environment, occurring in cigarette smoke, gasoline vapor and in the effluents from fossil fuel incineration. Epidemiological studies have provided some evidence for butadiene carcinogenicity in people. Differences in the uptake and metabolism of inhaled butadiene between rodents and primates, including people, might be reflected in differences in its toxicity. In order to compare uptake and metabolism in primates to that in rodents--for which data were already available--we exposed cynomolgus monkeys (Macaca fascicularis) to 14C-labeled butadiene at concentrations of 10.1, 310 or 7760 ppm for 2 hr. Exhaled air and excreta were collected during exposure and for 96 hr after exposure. The uptake of butadiene as a result of metabolism was much lower in monkeys than in rodents. For equivalent inhalation exposures, the concentrations of total butadiene metabolites in the blood were 5-50 times lower in monkey than in the mouse, the more sensitive rodent species, and 4-14 times lower than in the rat. If the toxicokinetics of butadiene in people is more like that of the monkey than that of rodents, then our data suggest that people will receive lower doses of butadiene and its metabolites than rodents following equivalent inhalation exposures to butadiene. This has important implications for assessing the risk to humans of butadiene exposure based on animal studies.
Dahl
A R
AR
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico 87185.
Sun
J D
JD
Birnbaum
L S
LS
Bond
J A
JA
Griffith
W C
WC
Mauderly
J L
JL
Muggenburg
B A
BA
Sabourin
P J
PJ
Henderson
R F
RF
D000280:Administration, Inhalation; D000818:Animals; D001944:Breath Tests; D002070:Butadienes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D002245:Carbon Dioxide / Q000032:analysis / Q000652:urine; D002250:Carbon Radioisotopes; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D008956:Models, Chemical; D012119:Respiration
D002070:Butadienes; D002250:Carbon Radioisotopes; D002245:Carbon Dioxide; C031763:1,3-butadiene