Daily Archives: November 13, 2011

Baja water deal for Southern California on hold

A key partner in the effort to bring desalinated water from Baja Mexico to Southern California is pulling out, putting the entire project on hold for now, and perhaps killing it.  Click here for more.

Thompson et al 2011: Comparison of the Effects of Hexavalent Chromium in the Alimentary Canal of F344 Rats and B6C3F1 Mice Following Exposure in Drinking Water: Implications for Carcinogenic Modes of Action.

This is one of several recent toxicological studies on chromium VI.  In this paper these authors conclude:

“In summary, the data herein together with that in Thompson et al. (2011b), support that oxidative stress may be a key event in the MOA for Cr(VI)-induced carcinogenesis. Additional analyses currently underway with tissues collected from the rat and mouse 90-day studies should further inform the key events in the MOAs. Moreover, the pharmacokinetic data collected in these studies will improve our understanding of the species difference in Cr(VI) disposition, and will be used to develop physiologically based pharmacokinetic models for extrapolation between species and from the very high concentrations of Cr(VI) that cause cancer in rodents to environmentally relevant human exposures.”

C.M. Thompson, D.M. Proctor, M. Suh, L.C. Haws, C.D. Hebert, J.F. Mann, H.G. Shertzer, J.G. Hixon, and M.A. Harris. Comparison of the Effects of Hexavalent Chromium in the Alimentary Canal of F344 Rats and B6C3F1 Mice Following Exposure in Drinking Water: Implications for Carcinogenic Modes of Action. Toxicol Sci. 2011 Oct. 19.

Abstract: Exposure to high concentrations of hexavalent chromium (Cr(VI)) in drinking water is reported to induce oral mucosa tumors in F344 rats and intestinal tumors in B6C3F1 mice. To investigate the modes of action (MOAs) underlying these tumors, 90-day drinking water studies (with interim necropsy at day 8) were conducted with concentrations of 0.1-182 mg/l Cr(VI), administered as 0.3-520 mg/l sodium dichromate dihydrate (SDD). Blood and tissue samples were analyzed for chromium content, oxidative stress, iron levels, and gross and microscopic lesions. Results for the F344 rats are described herein and compared with results from B6C3F1 mice published previously. After 90 days of exposure, total chromium concentrations in the rat and mouse oral mucosae were comparable, yet significant dose-dependent decreases in the reduced-to-oxidized glutathione ratio (GSH/GSSG) were observed only in rats. In the duodenum, changes in GSH/GSSG were only observed in mice. Levels of 8-hydroxydeoxyguanosine were not increased in the oral or duodenal mucosae of either species. Glutathione levels were increased in the duodenum but decreased in the jejunum of both species, indicating potential differential responses in the intestinal segments. Histiocytic infiltration was observed in the duodenum of both species, yet duodenal cytokines were repressed in mice, but increased in rats. Serum and bone marrow iron levels were more decreased in rats than mice. Collectively, these data suggest that Cr(VI)-induced carcinogenesis in the rodent alimentary canal involves oxidative stress; however, differences in histopathology, cytokines and iron status suggest potential contributions from other factors as well.

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