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

Abstract

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).

Punica granatum L. protects mice against hexavalent chromium-induced genotoxicity

“…Because of that, attention has been focused on the toxic action of Cr(VI), since it is highly hepatotoxic (Rafael et al, 2007) and nephrotoxic (Khan et al, 2010;Molina-Jijón et al, 2011). Moreover, certain studies have indicated that this metal accumulates in the liver and kidneys (Sutherland et al, 2000;O'Brien et al, 2003;Collins et al, 2010;Chang et al, 2011), corroborating the results found here. However, the mice pretreated with the 25 and 50 mg/kg doses of PGE showed an interesting change in the bioavailability of FIGURE 3 -Survival analysis of animals prophylactically t r e a t e d w i t h d i f f e r e n t P G E d o s e s ( 2 5 , 5 0 a n d 75 mg/kg/day) for 10 days and exposed to a lethal dose of Cr(VI) (50 mg/kg) on the 11 th day.…”

An evaluation of in vivo models for toxicokinetics of hexavalent chromium in the stomach

“…This is consistent with data by Kirman et al (2012), which found concentrations of total chromium in the small intestine to be higher in mice than in rats when administered equivalent concentrations of Cr6 in drinking water for 90 days. The NTP studies found that stomach and liver tissue concentrations (when normalized by average dose) were higher in mice than in rats (Collins et al, 2010), which is also consistent with reduction in the mouse stomach being less efficient.…”

“…Following in vivo studies in rodents, mice were found to have accumulated more chromium than rats Collins et al, 2010). This may indicate more effective absorption and/or less effective Cr6 reduction in the mouse.…”

Oral Chromium Exposure and Toxicity

“…However, others argue that the reduction of Cr(VI) to Cr(III) outside of cells and absorption of Cr(VI) by cells via non-specific anion transporters occur almost simultaneously and both processes compete with each other for substrate [12,61]. This competition combined with other factors including gastric emptying time, food content, and interspecies difference in reduction, result in a portion of ingested Cr(VI) (10–20%) escaping gastric detoxification and being absorbed into cells of target tissues even at very low concentrations [12,61], This fact was well supported by the tissue distribution analysis of ingested Cr(VI) in both human and animal studies [32–34]. However, many questions still need to be addressed, including the reduction capacity of gastric fluid, the rates and capacities for Cr(VI) reduction along the GI tract, the rate of Cr(VI) absorption in the GI tract, and the factors that potentially affect Cr(VI) reduction or absorption.…”