Exposure to hexavalent chromium resulted in significantly higher tissue chromium burden compared with trivalent chromium following similar oral doses to male F344/N rats and female B6C3F1 mice.
In National Toxicology Program 2-year studies, hexavalent chromium [Cr(VI)] administered in drinking water was clearly carcinogenic in male and female rats and mice, resulting in small intestine epithelial neoplasms in mice at a dose equivalent to or within an order of magnitude of human doses that could result from consumption of chromium-contaminated drinking water, assuming that dose scales by body weight(3/4) (body weight raised to the 3/4 power). In contrast, exposure to trivalent chromium [Cr(III)] at much higher concentrations may have been carcinogenic in male rats but was not carcinogenic in mice or female rats. As part of these studies, total chromium was measured in tissues and excreta of additional groups of male rats and female mice. These data were used to infer the uptake and distribution of Cr(VI) because Cr(VI) is reduced to Cr(III) in vivo, and no methods are available to speciate tissue chromium. Comparable external doses resulted in much higher tissue chromium concentrations following exposure to Cr(VI) compared with Cr(III), indicating that a portion of the Cr(VI) escaped gastric reduction and was distributed systemically. Linear or supralinear dose responses of total chromium in tissues were observed following exposure to Cr(VI), indicating that these exposures did not saturate gastric reduction capacity. When Cr(VI) exposure was normalized to ingested dose, chromium concentrations in the liver and glandular stomach were higher in mice, whereas kidney concentrations were higher in rats. In vitro studies demonstrated that Cr(VI), but not Cr(III), is a substrate of the sodium/sulfate cotransporter, providing a partial explanation for the greater absorption of Cr(VI).
Collins
Bradley J
BJ
National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Stout
Matthew D
MD
Levine
Keith E
KE
Kissling
Grace E
GE
Melnick
Ronald L
RL
Fennell
Timothy R
TR
Walden
Ramsey
R
Abdo
Kamal
K
Pritchard
John B
JB
Fernando
Reshan A
RA
Burka
Leo T
LT
Hooth
Michelle J
MJ
D000284:Administration, Oral; D000818:Animals; D001822:Body Burden; D002274:Carcinogens, Environmental / Q000493:pharmacokinetics*; D002840:Chromates / Q000493:pharmacokinetics*; D002857:Chromium / Q000032:analysis / Q000378:metabolism; D004326:Drinking; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010848:Picolinic Acids / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D013054:Spectrophotometry, Atomic; D013270:Stomach / Q000737:chemistry; D014018:Tissue Distribution
D002274:Carcinogens, Environmental; D002840:Chromates; D010848:Picolinic Acids; D002857:Chromium; C016104:sodium bichromate; C030614:picolinic acid