title: Quantitative assessment of the risk of lung cancer associated with occupational exposure to refractory ceramic fibers.
abstract: We present the results of a quantitative assessment of the lung cancer risk associated with occupational exposure to refractory ceramic fibers (RCF). The primary sources of data for our risk assessment were two long-term oncogenicity studies in male Fischer rats conducted to assess the potential pathogenic effects associated with prolonged inhalation of RCF. An interesting feature of the data was the availability of the temporal profile of fiber burden in the lungs of experimental animals. Because of this information, we were able to conduct both exposure-response and dose-response analyses. Our risk assessment was conducted within the framework of a biologically based model for carcinogenesis, the two-stage clonal expansion model, which allows for the explicit incorporation of the concepts of initiation and promotion in the analyses. We found that a model positing that RCF was an initiator had the highest likelihood. We proposed an approach based on biological considerations for the extrapolation of risk to humans. This approach requires estimation of human lung burdens for specific exposure scenarios, which we did by using an extension of a model due to Yu. Our approach acknowledges that the risk associated with exposure to RCF depends on exposure to other lung carcinogens. We present estimates of risk in two populations: (1) a population of nonsmokers and (2) an occupational cohort of steelworkers not exposed to coke oven emissions, a mixed population that includes both smokers and nonsmokers.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Moolgavkar
authors.forename: E G
authors.initials: EG
authors.lastname: Luebeck
authors.forename: J
authors.initials: J
authors.lastname: Turim
authors.forename: L
authors.initials: L
authors.lastname: Hanna
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D002273:Carcinogens / Q000009:adverse effects; D002516:Ceramics / Q000009:adverse effects*; D003043:Cocarcinogenesis; D015331:Cohort Studies; D006801:Humans; D016013:Likelihood Functions; D008175:Lung Neoplasms / Q000209:etiology*; D008297:Male; D008954:Models, Biological; D009784:Occupational Diseases / Q000209:etiology*; D016273:Occupational Exposure; D051381:Rats; D011916:Rats, Inbred F344; D018570:Risk Assessment; D012907:Smoking / Q000009:adverse effects
chemical_list: D002273:Carcinogens