Hexavalent Chromium Is Carcinogenic to F344/N Rats and B6C3F1 Mice after Chronic Oral Exposure

• Published in: Environmental health perspectives Vol. 117; no. 5; pp. 716 - 722
• Main Authors: Stout, Matthew D., Herbert, Ronald A., Kissling, Grace E., Collins, Bradley J., Travlos, Gregory S., Witt, Kristine L., Melnick, Ronald L., Abdo, Kamal M., Malarkey, David E., Hooth, Michelle J.
• Format: Journal Article
• Language: English
• Published: United States National Institute of Environmental Health Sciences. National Institutes of Health. Department of Health and Human Services 01.05.2009; National Institute of Environmental Health Sciences
• Subjects: Adenoma; Administration, Oral; Animals; Carcinogenesis; Carcinogenicity; Carcinogens; Carcinogens - administration & dosage; Carcinogens - toxicity; Carcinoma, Squamous Cell - chemically induced; Carcinoma, Squamous Cell - pathology; Chemical hazards; Chromates; Chromium; Chromium - administration & dosage; Chromium - toxicity; Chromium compounds; Contamination; Diffusion; Dosage; Drinking water; Duodenum; Environmental aspects; Epithelium; Female; Females; Health; Hexavalent chromium; Human; Infiltration; Lymph; Male; Males; Mice; Mouth; Mouth - drug effects; Mouth - pathology; Mouth Neoplasms - chemically induced; Mouth Neoplasms - pathology; Neoplasia; Neoplasms; Physiological aspects; Potable water; Rats; Rats, Inbred F344; Risk factors; Sodium; Toxicity; Water consumption; United States; hexavalent chromium; National Toxicology Program; histiocytic cellular infiltration; oral cavity; cancer; small intestine; anemia
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.0800208

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.