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Carcinogenicity and mutagenicity of chromium compounds: the association between bronchial metaplasia and neoplasia.

Over the last 40 years, experiments with animals and epidemiology of exposed human populations have established that certain hexavalent chromium-containing compounds are capable of causing cancer whilst trivalent materials are not. More recently, a variety of short-term genotoxicity tests (predictive of carcinogenicity) have clearly demonstrated that Cr[VI] is genotoxic per se, and that all Cr[VI]-containing materials which have been tested are genotoxic. What experiments have failed to demonstrate clearly, however, is which of the myriad of industrially available hexavalent materials are carcinogenic and which are not. In this long-term study we have looked at the incidence of squamous metaplasia in the bronchial epithelium of rats exposed to a range of chromium-containing materials by intrabronchial implantation. Squamous metaplasia is generally considered to be a transformed state from which squamous carcinoma may arise. We have shown that its incidence is increased in all groups exposed to Cr[VI]-materials, and in rats exposed to the reference carcinogen 20-methylcholanthrene. Squamous metaplasia was not increased in rats exposed to Cr[III] materials. Of rats exposed to Cr[VI], only those receiving materials of sparing aqueous solubility developed bronchial squamous carcinoma at statistically significant levels. These results strongly support the hypothesis that although Cr[VI] per se is biologically active, producing genotoxic effects and pathological changes which may predispose to the development of cancer, only Cr[VI] materials of sparing aqueous solubility seem to be capable of evoking a carcinogenic response.