1,3-Butadiene induces cancer in experimental animals at all concentrations from 6.25 to 8000 parts per million

1,3-Butadiene, a chemical produced in large volumes, induces cancer in many organs in rats (at 1000 and 8000 ppm) and mice (at 6.25 to 1250 ppm); however, the sites of tumour induction (seven in rats and nine in mice) and the magnitudes of response differ between the two species. Particularly noteworthy in the studies of mice exposed by inhalation were the early, extensive induction of malignant lymphomas, the induction of uncommon haemangiosarcomas of the heart and the development of malignant lung tumours at 6.25 ppm, the lowest concentration ever used in a long-term carcinogenicity study of this gas. In order to account for the impact of early mortality on the expression of late development of tumours, survival-adjusted tumour rates were computed for mice exposed to butadiene at 6.25-625 ppm. The results provide a more accurate characterization of concentration-dependent responses for butadiene-induced cancers. Stop-exposure studies revealed that the atmospheric concentration of butadiene was a greater contributing factor to the development of lymphomas than was duration of exposure. The studies in mice show a good correspondence with the reported associations between occupational exposure to butadiene and excess mortality from lymphatic and haematopoietic cancers; mice are thus a better experimental surrogate for humans. Although further work is needed to improve our understanding of the mechanisms of tumour induction by butadiene, pursuit of that research must not delay reduction of human exposure to this carcinogenic chemical.