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Chad M. Thompson, Christopher R. Kirman, Deborah M. Proctor, Laurie C. Haws, Mina Suh, Sean M. Hays, J. Gregory Hixon and Mark A. Harris A chronic oral reference dose for hexavalent chromium-induced intestinal cancer Journal of Applied Toxicology 34

Article first published online: 14 AUG 2013 | DOI: 10.1002/jat.2907

Hexavalent chromium causes intestinal damage and intestinal tumors in mice; the mode of action for these tumors involves villous cytotoxicity and compensatory crypt hyperplasia. Physiologically based pharmacokinetic models were used to estimate chromium concentrations in the small intestine, so that the incidence for hyperplasia (an antecedent to tumor formation), could be modeled using benchmark dose and constrained nonlinear regression analyses. An RfD of 0.006 mg/kg/day was derived that is protective of both noncancer and cancer effects in the small intestine.

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