title: Potential carcinogenicity of foundry fumes: a comparative in vivo-in vitro study.
abstract: Epidemiological studies of workers exposed to fumes in the iron and steel foundry industry have consistently demonstrated an increased relative risk of lung cancer of approximately 1.4. Foundry fume is a complex mixture of gases and fine particles generated during the casting process when molten metal is poured into sand moulds bound together with organic binders. The chemical composition of fume varies according to foundry process and, specifically, binder composition. Previous in vitro studies have demonstrated that some fumes have mutagenic activity and that this varies with fume type. The current study has examined the potential carcinogenicity of three fumes in a 2-yr in vivo rodent bioassay using an intrabronchial pellet implantation technique. The toxicity and genotoxicity of the fumes were tested concurrently in a number of in vitro assays including those identifying mutagenicity, unscheduled DNA synthesis, free radical DNA damage and micronucleus induction. The rodent bioassay failed to demonstrate a carcinogenic response, although an increase in preneoplastic lesions was seen in all fume-treated groups relative to controls. When tested in vitro, the fumes were positive in many assays and activity correlated with the polycyclic aromatic hydrocarbon content of the fumes. The employment of a combination of in vitro assays for different genotoxic endpoints, such as those presented in the current study, provides information useful for the overall assessment of carcinogenicity of complex mixtures such as foundry fume.
authors.affiliation: Medical Research Council, Institute for Environment and Health, University of Leicester, UK.
authors.forename: C D
authors.initials: CD
authors.lastname: Humfrey
authors.forename: L S
authors.initials: LS
authors.lastname: Levy
authors.forename: S P
authors.initials: SP
authors.lastname: Faux
mesh_terms: D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000473:pathology; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects*; D005260:Female; D015386:Hazardous Substances / Q000633:toxicity*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008175:Lung Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D008297:Male; D008669:Metallurgy; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity; D016273:Occupational Exposure; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis / Q000633:toxicity*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013232:Steel; D014132:Trachea / Q000187:drug effects* / Q000473:pathology
chemical_list: D002273:Carcinogens; D015386:Hazardous Substances; D009153:Mutagens; D011084:Polycyclic Aromatic Hydrocarbons; D013232:Steel; D004247:DNA