Review of the Evidence Regarding the Carcinogenicity of Hexavalent Chromium in Drinking Water

Recent analyses have revealed that 38% of municipal sources of drinking water in California have detectable levels of hexavalent chromium. This observation provided new impetus to characterize the carcinogenic risk associated with oral exposure to hexavalent chromium in drinking water. Notwithstanding the well-characterized increases in cancer associated with inhalation exposure to this chemical, the marked reduction of hexavalent chromium to trivalent chromium in the stomach suggests that exposure to hexavalent chromium in drinking water may not pose a carcinogenic risk. A reevaluation of studies that investigated the toxicokinetics, the genotoxicity, and the mechanism of carcinogenicity of hexavalent chromium, as well as the available human and animal cancer studies, was undertaken to determine if there is evidence that exposure to this chemical in drinking water may pose a carcinogenic risk. Mechanistic studies suggest the potential for a carcinogenic response if hexavalent chromium enters cells. Both toxicokinetic and genotoxicity studies indicate that a portion of an orally administered dose of hexavalent chromium is absorbed and gets into cells of several tissues, causing DNA damage. The only lifetime oral study of hexavalent chromium in animals conducted thus far yielded a statistically significant increase in stomach tumors compared to controls. Also, in a limited-term cancer study, co-exposure to hexavalent chromium in drinking water and ultraviolet light produced skin tumors in mice. The only available cancer study of humans exposed to hexavalent chromium in drinking water revealed a statistically significant increase in stomach tumors. Moreover, a meta-analysis of occupational studies also revealed a statistically significant increase in stomach cancers. The increases in stomach tumors in both human and animal studies, along with the toxicokinetic, genotoxic, and mechanistic data, suggest that oral exposure to this agent appears to pose a carcinogenic risk.

Keywords:

• Chromium 6+
• chromium 3+
• Risk Assessment
• Drinking Water
• Cancer
• Hexavalent Chromium
• Trivalent Chromium

Acknowledgments

We thank Martha Sandy for her valuable suggestions in preparing this manuscript.

The views expressed are those of the authors and do not necessarily represent those of the Office of Environmental Health Hazard Assessment, the California Environmental Protection Agency, or the State of California.

Notes

¹It is important to note that no group has looked for genotoxicity of the oral cavity or gastrointestinal tract following oral administration of hexavalent chromium.

²In the Bigaliev et al. (87) study, for this dose group only, the methods translated from Russian state that the rats were chronically administered with a “… dosage 1 mg per 1 kg of live weight orally or inside trachea with 0.2 mL of 5% solution of K₂Cr₂O₇.” It is difficult to interpret this statement, but it appears that the authors were not sure to what extent the dosing tube was passed into the stomach or the trachea over the year-long dosing period.

^a Rate ratio, 95% confidence interval.

^b Statistically significant (p < 0.05).