title: Mechanistic insights from the NTP studies of chromium.
abstract: Hexavalent chromium (Cr(VI)) is a contaminant of water and soil and is a human lung carcinogen. Trivalent chromium (Cr(III)), a proposed essential element, is ingested by humans in the diet and in dietary supplements such as chromium picolinate (CP). The National Toxicology Program (NTP) demonstrated that Cr(VI) is also carcinogenic in rodents when administered in drinking water as sodium dichromate dihydrate (SDD), inducing neoplasms of the oral cavity and small intestine in rats and mice, respectively. In contrast, there was no definitive evidence of toxicity or carcinogenicity following exposure to Cr(III) administered in feed as CP monohydrate (CPM). Cr(VI) readily enters cells via nonspecific anion channels, in contrast to Cr(III), which cannot easily pass through the cell membrane. Extracellular reduction of Cr(VI) to Cr(III), which occurs primarily in the stomach, is considered a mechanism of detoxification, while intracellular reduction is thought to be a mechanism of genotoxicity and carcinogenicity. Tissue distribution studies in additional groups of male rats and female mice demonstrated higher Cr concentrations in tissues following exposure to Cr(VI) compared to controls and Cr(III) exposure at a similar external dose, indicating that some of the Cr(VI) escaped gastric reduction and was distributed systemically. The multiple potential pathways of Cr-induced genotoxicity will be discussed.
authors: Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
authors: Kristine L
authors: KL
authors: Witt
authors: Matthew D
authors: MD
authors: Stout
authors: Ronald A
authors: RA
authors: Herbert
authors: Gregory S
authors: GS
authors: Travlos
authors: Grace E
authors: GE
authors: Kissling
authors: Bradley J
authors: BJ
authors: Collins
authors: Michelle J
authors: MJ
authors: Hooth
mesh_terms: D000818:Animals; D015197:Carcinogenicity Tests; D002857:Chromium / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D004386:Duodenum / Q000187:drug effects / Q000473:pathology; D005260:Female; D006644:Histiocytes; D006965:Hyperplasia / Q000139:chemically induced; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D009061:Mouth Mucosa / Q000187:drug effects / Q000473:pathology; D009152:Mutagenicity Tests; D009369:Neoplasms / Q000139:chemically induced; D051381:Rats; D014018:Tissue Distribution; D014059:Tongue / Q000187:drug effects / Q000473:pathology; D014874:Water Pollutants, Chemical / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D014874:Water Pollutants, Chemical; D002857:Chromium; C074702:chromium hexavalent ion