Abstract
A major challenge facing toxicologists is the development of improved human risk assessment methods based on understanding the mechanisms of chemical carcinogenesis in animal and human cells. Such methods will enable us to close the gap between experimental toxicity data and their relevance to human health. We have used 1,3-butadiene (BD), a potent mouse carcinogen but weak oncogen in the rat, as a model compound to determine if genetic toxicity results from animal and human cells can aid in extrapolating animal toxicity data to man. Sister chromatid exchange and micronucleus induction data for BD parallel the chemical's carcinogenicity in the mouse and rat. Effort is underway to determine BD's genotoxic effects in human cells in vitro and to compare these effects in corresponding cultured rodent cells. This approach will help identify which species is a better predictor of the human response. If the BD research proves useful in assessing its hazard to man, similar methods can be extended to other major chemicals.
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