Portier played a key role in the development of biologically based dose-response models for dioxin's effects. Lucier also prepared the chapter on animal carcinogenicity. The dose-response models and animal carcinogenicity chapters received favorable reviews from the EPA Peer Review process in September 1992. The Scientific Advisory Board will review the background papers and the risk characterization in late 1993. Species Differences in Butadiene Carcinogenesis 1,3-Butadiene, a gaseous hydrocarbon used in the production of synthetic rubber and other resins, is a carcinogen in rodents and is associated with leukemia and lymphoma in humans.
Mice develop tumors at lower exposures to butadiene than rats.
Some investigators have concluded that species differences in tumor development are due to differences in metabolic activation of butadiene and detoxification of expoxide intermediates. In addition, the model predicts that, because of these physiological differences, butadiene accumulates in the fat of humans, but not mice, on repeated exposure. According to the model, butadiene released from fat during the periods between exposures continues to be converted into epoxybutene, adding to the carcinogenic risk. In a recent editorial in Science , it was stated that after exposure to 10 ppm butadiene in the ambient air, blood epoxybutene levels are 590 times higher in mice than in monkeys. Yet, in Kohn and Melnick's models, mice produce only 5.5 times as much epoxybutene as humans at exposures that result in equivalent amounts of butadiene absorbed into the body.