Evaluation of issues relating to the carcinogen risk assessment of chromium

Important issues in the carcinogenic risk assessment of chromium compounds are whether both trivalent and hexavalent chromium compounds are carcinogenic, the role of solubility in the carcinogenic response, and the carcinogenicity of ingested chromium. Hexavalent chromium compounds are carcinogenic to animals via several routes of exposure, while trivalent chromium compounds, although they demonstrate evidence of genotoxicity, have not been shown in animal studies to be carcinogenic. Workers in chromate production plants, where the risk of lung cancer is elevated, are exposed to both trivalent and hexavalent chromium compounds. A cancer unit risk estimate for Wistar rats exposed to a hexavalent chromium aerosol (sodium dichromate) is less than the risk estimate for workers in chromate production. If this difference is biologically real, a possible explanation may be that trivalent compounds also have a carcinogenic effect. For hexavalent chromium compounds, it is contended that only sparingly soluble hexavalent chromium compounds are carcinogenic. Recent evidence, however, indicates that highly soluble hexavalent chromium compounds are also carcinogenic. Animal ingestion studies have not found trivalent chromium compounds to be carcinogenic by ingestion; hexavalent compounds have not been studied. Research by EPA to address the issue of valence state and solubility with respect to carcinogenicity is currently being conducted.