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Time-to-Tumour Risk Assessment for 1,3-Butadiene Based on Exposure of Mice to Low Doses by Inhalation.

Authors
Dankovic-DA; Smith-RJ; Stayner-LT; Bailer-AJ
Source
Butadiene and Styrene: Assessment of Health Hazards 1993:335-344
Link
NIOSHTIC No.
00227592
Abstract
A quantitative risk assessment of 1,3-butadiene (106990) carcinogenicity based on data obtained in a study of mice exposed to low butadiene concentrations was performed. Data were taken from the second National Toxicology Program bioassay of butadiene in mice. In that study, B6C3F1-mice were exposed by inhalation to 0, 6.25, 20, 62.5, 200, or 625 parts per million (ppm) butadiene vapor for 2 years. Butadiene induced dose related increases in the incidence of lymphoma, heart hemangiosarcomas, and lung, liver, forestomach, and Harderian tumors in both male and female mice. Female mice also had dose related increases in the incidence of mammary and ovary tumors. Male mice also developed tumors of the preputial gland. The excess risk for cancer due to lifetime occupational exposure, 8 hours per day, 5 days a week, 50 weeks per year for 45 years, to butadiene at the proposed OSHA standard of 2ppm was estimated by fitting the bioassay data to a multistage Weibull time to tumor model and applying various mouse to human scaling factors. The excess cancer risk was expressed as a function of tumor site and derived from mice to humans based on body weights raised to the three fourths power. The risk ranges from 0.2 tumor/10,000 workers when based on female heart hemangiosarcomas to 600 tumors/10,000 when based on female mouse lung tumors. Assuming that lung tumors were rapidly fatal and excluding the 625ppm dose group increased the lifetime risk to 1,600 tumors/10,000. If it was assumed that the occurrence of lung tumors was incidental to survival of the animal, inclusion or exclusion of the 625ppm dose group did not significantly affect the risk estimate. The authors conclude that when based on the most sensitive site (the female mouse lung) the excess risk for cancer resulting from lifetime occupational exposure to 2ppm butadiene would be approximately 600 tumors/10,000. Although varying the assumptions and considering other tumor sites can lower the estimated risks, the results suggest that prolonged exposure to 2ppm butadiene may present a significant cancer risk and that work related butadiene exposures should be reduced to the lowest feasible level.
Keywords
NIOSH-Author; Olefins; In-vivo-studies; Laboratory-animals; Long-term-study; Carcinogenesis; Inhalation-studies; Risk-analysis; Mathematical-models; Malignant-neoplasms; Exposure-limits;
CODEN
IARCCD
CAS No.
106-99-0;
Publication Date
19930101
Document Type
Journal Article;
Editors
Sorsa-M; Peltonen-K; Vainio-H; Hemminki-K;
Fiscal Year
1993
NTIS Accession No.
NTIS Price
Source Name
Butadiene and Styrene: Assessment of Health Hazards
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