Quantitative Assessment of the Risk of Cancer Associated with Exposure to 1, 3-Butadiene, Based on a Low Dose Inhalation Study in B6C3F1 Mice

摘要

The cancer risk associated with exposure to 1,3-butadiene (106990) was evaluated,based on inhalation studies conducted on B6C3F1-mice as part of the NTP bioassay program. Male and female mice were exposed at concentrations from 6.25 to 625 parts per million (ppm) for 6 hours/day, 5 days/week for up to 104 weeks. Mice showed significant increases in lymphomas, heart hemangiosarcomas, and tumors of the lung, liver forestomach and Harderian gland. There were significant increases in mammary and ovarian tumors in females and preputial gland tumors in males. The time of tumor onset for each tissue was modeled, using the one stage, two stage and three stage Weibull time to tumor models. The results for mice were extrapolated to humans using body weight to the three fourths power. Based on maximum likelihood estimates for the most sensitive site, the authors note the excess risk of lung cancer resulting from lifetime occupational exposure to 1,3-butadiene at the proposed permissible exposure limit of 2ppm is 597 cases per 10,000 workers, or approximately 6.0%. They estimate that the lifetime occupational exposure to 0.032ppm would be consistent with a lifetime excess risk of 1 in 1000.