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RENAL CARCINOGENICITY OF INDIVIDUAL AND A MIXTURE OF DRINKING WATER DISINFECTION BY-PRODUCTS (DBP) IN EKER RATS
Citation:
McDorman, K, M J. Hooth, S D. Hester, AND D C. Wolf. RENAL CARCINOGENICITY OF INDIVIDUAL AND A MIXTURE OF DRINKING WATER DISINFECTION BY-PRODUCTS (DBP) IN EKER RATS. Presented at Society of Toxicology, San Francisco, CA, March 25-29, 2001.
Description:
RENAL CARCINOGENICITY OF INDIVIDUAL AND A MIXTURE OF DRINKING / WATER DISINFECTION BY -PRODUCTS (DBP) IN EKER RATS.
Eker rats develop hereditary renal cell carcinoma secondary to a germline mutation in the tuberous sclerosis 2 tumor suppressor gene, and are highly susceptible to the effects of renal carcinogens. The utility of this model is due to an ordered progression of proliferative lesions that are identified and counted microscopically. Renal lesions counted are atypical tubules, atypical hyperplasias, adenomas, and carcinomas. Male and female Eker rats were exposed via drinking water to individual or a mixture of DBPs until 6 or 12 months of age. Potassium bromate, 3-chloro-4-(dichloromethyl)-5-hydroxy- 2(5R)-furanone (MX), chloroform, and bromodichloromethane were administered at low doses of 0.02, 0.005, 0.4 and 0.07 g/L, respectively and high doses of 0.4, 0.07, 1.8 and 0.7 g/L, respectively. Low and high dose mixture solutions were comprised of all four chemicals at either low doses or high doses, respectively. Each kidney was examined microscopically for presence and number of renal lesions. A dose-response for total lesions was present with all treatments at 6 and 12 months of age. There was no difference in the severity of chronic progressive nephropathy between any groups. At 6 months of age, all treatment groups had increased numbers of preneoplastic lesions (atypical tubules and atypical hyperplasias) but no significant increases in adenomas or carcinomas compared to control. At 12 months of age, all treatment groups except low dose MX had increased numbers of total lesions compared to control. Treatment with the high dose mixture produced an additive increase in atypical tubules but not more neoplasms than the individual compounds, suggesting an additive response for toxicity but not for cancer. These data suggest that adding the individual risks for D BPs may over estimate cancer risk but not toxicity of the mixture.
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