Tests suggest air pollutant may not be as toxic as once thought.
Different species react to chemical exposure in different ways. Butadiene, a compound widely used in the production of synthetic rubber and other resins, causes cancer in many organs in both rats and mice, but mice are about 1,000 times more sensitive to its carcinogenic effects than rats. This difference in cancer formation in two closely related species (rats and mice) creates a serious dilemma for predicting risk for butadiene-exposed humans.
The cancer-causing effects of butadiene are thought to result from the conversion of butadiene in the body to one or more toxic metabolites, primarily butadiene monoepoxide. This metabolite is believed to react with DNA, the genetic material in cells, to begin the carcinogenic process. Therefore, CIIT scientists compared the rates at which the liver tissues from humans, rats and mice metabolize butadiene to butadiene monoepoxide, as well as the rates at which each species detoxified the metabolite. These comparisons provided clues as to the differences among humans, mice and rats in the capability of butadiene to initiate cancer by producing the monoepoxide.
Two findings from these experiments are noteworthy. First, human and rat liver tissues produce far less butadiene monoepoxide than liver tissue of mice, an animal species that is particularly sensitive to butadiene exposure. Second, human liver tissue rapidly detoxifies the relatively low amount of butadiene monoepoxide produced to other nontoxic metabolites. In contrast, mouse liver tissue very slow degrades butadiene monoepoxide to nontoxic products.
Human risk assessments for butadiene require knowledge of how people metabolize this chemical following exposure. Since human liver tissues appears to metabolize butadiene more like that of rats, an animal species relatively resistant to the carcinogenic effects of the chemical, human cancer risks may be more like those of low-risk rats than high-risk mice. Similar studies invoking this strategy of interspecies comparison of chemical metabolism are currently underway at CIIT for other chemicals identified as hazardous air pollutants, such as styrene, acrylonitrile, ethylene oxide and benzene.
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|Publication:||Journal of Environmental Health|
|Date:||Dec 1, 1993|
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