Hexavalent chromium is carcinogenic to F344/N rats and B6C3F1 mice after chronic oral exposure.
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.
Stout
Matthew D
MD
National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709 , USA. hooth@niehs.nih.gov
Herbert
Ronald A
RA
Kissling
Grace E
GE
Collins
Bradley J
BJ
Travlos
Gregory S
GS
Witt
Kristine L
KL
Melnick
Ronald L
RL
Abdo
Kamal M
KM
Malarkey
David E
DE
Hooth
Michelle J
MJ
D000284:Administration, Oral; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000473:pathology; D002857:Chromium / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D008297:Male; D051379:Mice; D009055:Mouth / Q000187:drug effects* / Q000473:pathology*; D009062:Mouth Neoplasms / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D002857:Chromium; C074702:chromium hexavalent ion