Time-to-tumour risk assessment for 1,3-butadiene based on exposure of mice to low doses by inhalation. 1993

D A Dankovic, and R J Smith, and L T Stayner, and A J Bailer
National Institute for Occupational Safety and Health, Cincinnati, OH.

The excess risk for cancer due to lifetime occupational exposure to 1,3-butadiene at the proposed US Occupational Safety and Health Administration standard of 2 ppm was estimated on the basis of a quantitative risk assessment. The risk assessment was based on a recent study by the US National Toxicology Program of the carcinogenicity of butadiene in B6C3F1 mice, using exposure concentrations ranging from 6.25 to 625 ppm butadiene and controls. Cancer risks were estimated using a multistage Weibull time-to-tumour model; the dose was based on the external butadiene concentration, owing to the low-dose linearity of butadiene metabolism. The parameters of the time-to-tumour model were estimated for seven tumour sites in male mice and nine in female mice. The risk estimates were extrapolated from mice to humans on the basis of body weight raised to the three-fourths power, and the median lifespan of mice was equated to a human lifespan of 74 years. Estimates of excess risk for lifetime occupational exposure (8 h/day, 5 days/week, 50 weeks/year, for 45 years) to 2 ppm butadiene ranged from 0.2 per 10,000 workers, based on female mouse heart haemangiosarcomas, to 600 per 10,000 workers, based on female mouse lung tumours. An analysis was performed to assess the effects of varying the modelling assumptions (incidental versus fatal tumours, inclusion or exclusion of the 625-ppm dose group, and basis for interspecies scaling) on the risk estimates from the female mouse lung tumour model. Depending on the assumptions, estimates of lifetime excess risk derived from the female mouse lung model ranged from 60 per 10,000 to 1600 per 10,000. These results suggest that exposures to butadiene in the work place should be reduced to the lowest feasible level.

UI MeSH Term Description Entries
D008297 Male Males
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D009784 Occupational Diseases Diseases caused by factors involved in one's employment. Diseases, Occupational,Occupational Illnesses,Disease, Occupational,Illnesse, Occupational,Illnesses, Occupational,Occupational Disease,Occupational Illnesse
D002070 Butadienes Four carbon unsaturated hydrocarbons containing two double bonds. Butadiene Derivative,Butadiene Derivatives,Derivative, Butadiene,Derivatives, Butadiene
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000280 Administration, Inhalation The administration of drugs by the respiratory route. It includes insufflation into the respiratory tract. Drug Administration, Inhalation,Drug Administration, Respiratory,Drug Aerosol Therapy,Inhalation Drug Administration,Inhalation of Drugs,Respiratory Drug Administration,Aerosol Drug Therapy,Aerosol Therapy, Drug,Drug Therapy, Aerosol,Inhalation Administration,Administration, Inhalation Drug,Administration, Respiratory Drug,Therapy, Aerosol Drug,Therapy, Drug Aerosol
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012307 Risk Factors An aspect of personal behavior or lifestyle, environmental exposure, inborn or inherited characteristic, which, based on epidemiological evidence, is known to be associated with a health-related condition considered important to prevent. Health Correlates,Risk Factor Scores,Risk Scores,Social Risk Factors,Population at Risk,Populations at Risk,Correlates, Health,Factor, Risk,Factor, Social Risk,Factors, Social Risk,Risk Factor,Risk Factor Score,Risk Factor, Social,Risk Factors, Social,Risk Score,Score, Risk,Score, Risk Factor,Social Risk Factor

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