Cr(VI) MOA Study Manuscripts

In 2008, NTP completed a Cr(VI) drinking water study in which mice and rats consumed 5,000 – 180,000 μg/L (ppb) Cr(VI) as sodium dichromate dihydrate for 2-years.  At the higher Cr(VI) drinking water concentrations, dose-dependent increases in tumors of the mouse small intestine and rat oral cavity was observed.  Initiated in 2009, the Cr(VI) Mode of Action (MOA) study was developed using EPA Cancer Risk Assessment guidance (2005) and was designed to provide information as to how these tumors occurred.   This study also provided information on the differences between rodents and humans with regard to the pharmacokinetics of Cr(VI), and developed the models and data needed to do a state-of-the-art human health risk assessment.  The results of these studies have been published in the peer-reviewed scientific literature, and several publications have received awards from the Risk Assessment Specialty Section of the Society of Toxicology.



Suh M, Thompson C, Kirman C, Carakostas M, Haws LC, Harris M, Proctor. 2014. High concentrations of hexavalent chromium in drinking water alter iron homeostasis in F344 rats and B6C3F1 mice. Food and Chemical Toxicology. 65:381-388.



Thompson CM, Kirman CR, Proctor DMHaws LCSuh M, Hays S, Hixon JGHarris MA. 2013. A chronic oral reference dose for hexavalent chromium-induced intestinal cancer. Journal of Applied Toxicology. DOI: 10.1002/jat.2907

Kirman CR, Aylward LL, Suh MHarris MAThompson CMHaws LCProctor DM, Lin SS, Parker W, Hays SM. 2013. Physiologically based pharmacokinetic model for humans orally exposed to chromium. Chem Biol Interact. Apr 17. doi:pii: S0009-2797(13)00082-3. 10.1016/j.cbi.2013.04.003.

O’Brien T, Ding H, Suh MThompson C, Parsons BL, Harris MA, Winkelman WA, Wolf JC, Hixon JG, Schwartz AM, Myers MB, Haws LC, Proctor DM. 2013. Assessment of K-Ras mutant frequency and micronucleus incidence in the mouse duodenum following 90-days of exposure to Cr(VI) in drinking water. Mutat Res. Apr 9. pii: S1383-5718(13)00075-2. doi: 10.1016/j.mrgentox.2013.03.008

Thompson CMProctor DMSuh MHaws LC, Kirman CR, Harris MA. 2013. Assessment of the mode of action underlying development of rodent small intestinal tumors following oral exposure to hexavalent chromium and relevance to humans. Critical Reviews in Toxicology. 43(3): 244-274.


Kirman, CR, Hays, SM, Aylward, LL, Suh, M, Harris, MA, Thompson, CM, Haws, LC, Proctor, DM. Physiologically based pharmacokinetic model for rats and mice orally exposed to chromium. Chem Biol Interact. 200(1): 45-64.

Kopec, A.K., C.M. Thompson, S. Kim, A.L. Forgacs, T.R. Zacharewski. 2012. Comparative Toxicogenomic Analysis of Oral Cr(VI) Exposure Effects in Rat and Mouse Small Intestinal Epithelium. Toxicol Appl Pharmacol. 262(2): 124-38.

Kopec, A.K., Kim, S., Forgacs, A.L., Zacharewski, T.R., Proctor, D.M., Harris, M.A.Haws, L.CThompson, C.M.2012. Genome-wide gene expression effects in B6C3F1 mouse intestinal epithelia following 7 and 90 days of exposure to hexavalent chromium in drinking water. Toxicology and Applied Pharmacology. 259(1):13-26.

Proctor, D.M.Suh, M., Aylward, L.L., Kirman, C.R., Harris, M.A.Thompson, C.M., Gürleyük, H., Gerads, R., Haws, L.C., Hays, S.M. 2012. Hexavalent chromium reduction kinetics in rodent stomach contents. Chemosphere. 89(5): 487-93.

Thompson, C.M., Y. Fedorov, D.D. Brown, M. SuhD.M. Proctor, L. Kuriakose, L.C. Haws, M.A. Harris. 2012. Assessment of Cr(VI)-Induced Cytotoxicity and Genotoxicity Using High Content Analysis. PLoS ONE. 7(8): e42720.

Thompson, C.M., J.G. Hixon, D.M. Proctor, L.C. Haws, M. Suh, J.D. Urban, M.A. Harris. 2012. Assessment of Genotoxic Potential of Cr(VI) in the Mouse Duodenum: An In Silico Comparison with Mutagenic and Nonmutagenic Carcinogens Across Tissues. Regul Toxicol Pharmacol. 64(1): 68-76.

Thompson, C.M.D.M. ProctorM. SuhL.C. Haws, C.D. Hebert, J.F. Mann, H.G. Shertzer, J.G. Hixon and M.A. Harris. 2012. 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. 125(1):79-90.

Thompson, C.M.D.M. Proctor,and M.A. Harris. 2012. Duodenal GSH/GSSG Ratios in Mice Following Oral Exposure to Cr(VI). Toxicol Sci. 126(1): 287-288.


Thompson, C.M., D.M. Proctor, L.C. Haws, C.D. Hebert, S.D. Grimes, H.G. Shertzer, A.K. Kopec, J.G. Hixon, T.R. Zacharewski and M.A. Harris. 2011. Investigation of the Mode of Action Underlying the Tumorigenic Response Induced in B6C3F1 Mice Exposed Orally to Hexavalent Chromium. Toxicol Sci. 123(1): 58-70.

Thompson, C.M., L.C. Haws, M.A. Harris, N.M. Gatto and D.M. Proctor. 2011. Application of the U.S. EPA Mode of Action Framework for Purposes of Guiding Future Research: A Case Study Involving the Oral Carcinogenicity of Hexavalent Chromium. Toxicol Sci. 119(1): 20-40.