Previous risk assessments of 1,3-butadiene have been based on studies using 625 and 1250 ppm exposures for mice, and 1000 and 8000 ppm exposures for rats. We have re-assessed the low-dose carcinogenicity of BD, based on a new study in B6C3F1 mice using exposures of 6.25 to 625 ppm BD. Maximum likelihood estimates of excess risk based on tumors observed at 6 sites in male mice, and 8 sites in females, were calculated using a multistage Weibull time-to-tumor model, with chamber concentration as "dose." Mouse to human extrapolation was based on (body weight )3/4, equating a human age of 74 years to an age of 900 days in mice. Lifetime occupational exposure to 2 ppm BD was estimated to result in an excess cancer risk of 6.0%, based on lung tumors in female mice (the most sensitive site). A risk estimate of 1.1% was derived from lymphomas in male mice, which are of interest due to the epidemiological association of BD with hematopoietic tumors. Discrepancies between these estimates and prior risk estimates for BD are partially attributable to the use of external exposure concentration, rather than an "internal" measure of dose, and to the use of allometric scaling relationships for interspecies extrapolation, as well as to the availability of the new data. The results support the previous NIOSH recommendation that occupational exposures to 1,3-butadiene should be reduced to the lowest feasible level.
The Toxicologist. Society of Toxicology 31st Annual Meeting, February 23-27,1992, Seattle, Washingtion