| Hexavalent Chromium Is Carcinogenic to F344/N Rats and B6C3F1 Mice
after Chronic Oral Exposure Matthew D. Stout, Ronald A. Herbert, Grace E. Kissling, Bradley J. Collins, Gregory S. Travlos, Kristine L. Witt, Ronald L. Melnick, Kamal M. Abdo, David E. Malarkey, and Michelle J. Hooth National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA Abstract
Background: Hexavalent chromium [Cr(VI) ] is a human carcinogen after inhalation exposure. Humans also ingest Cr(VI) from contaminated drinking water and soil ; however, limited data exist on the oral toxicity and carcinogenicity of Cr(VI) . Objective: We characterized the chronic oral toxicity and carcinogenicity of Cr(VI) in rodents. Methods: The National Toxicology Program (NTP) conducted 2-year drinking water studies of Cr(VI) (as sodium dichromate dihydrate) in male and female F344/N rats and B6C3F1 mice. Results: Cr(VI) exposure resulted in increased incidences of rare neoplasms of the squamous epithelium that lines the oral cavity (oral mucosa and tongue) in male and female rats, and of the epithelium lining the small intestine in male and female mice. Cr(VI) exposure did not affect survival but resulted in reduced mean body weights and water consumption, due at least in part to poor palatability of the dosed water. Cr(VI) exposure resulted in transient microcytic hypochromic anemia in rats and microcytosis in mice. Nonneoplastic lesions included diffuse epithelial hyperplasia in the duodenum and jejunum of mice and histiocytic cell infiltration in the duodenum, liver, and mesenteric and pancreatic lymph nodes of rats and mice. Conclusions: Cr(VI) was carcinogenic after administration in drinking water to male and female rats and mice. Key words: anemia, cancer, hexavalent chromium, histiocytic cellular infiltration, National Toxicology Program, oral cavity, small intestine. Environ Health Perspect 117:716–722(2009) . doi:10.1289/ehp.0800208 available via http://dx.doi.org/ [Online 31 December 2008]
Address correspondence to M.J. Hooth, NIEHS, P.O. Box 12233, MD K2-13, Research Triangle Park, NC 27709 USA. Telephone: (919) 316-4643. Fax: (919) 541-4255. E-mail: hooth@niehs.nih.gov We thank P. Foster and S. Masten for critical review of the manuscript. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences, under research project 1 Z01 ES045004-11 BB. The authors declare they have no competing financial interests. Received 19 September 2008 ; accepted 31 December 2008.
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