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RENAL CANCER STUDIES OF DRINKING WATER MIXTURES
Impact/Purpose:
To study data that suggests that adding the individual risks for DBPs may over estimate cancer risk but not toxicity of the mixture.
Description:
Current default risk assessments for chemical mixtures assume additivity of carcinogenic effects but this may under or over represent the actual biological response. A rodent model of hereditary renal cancer (Eker rat) was used to evaluate the carcinogenicity of a mixture of DBPs. 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 treated with individual or a mixture of DBPs to 6 or 12 months of age. Potassium bromate, 3-chloro-4- (dichloromethyl)- 5-hydroxy-2(5H)-furanone (MX), chloroform, and bromodichloromethane (BDCM) were administered in drinking water 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 the low or high dose, respectively. A dose-response for total lesions was present with all treatments at 6 and 12 months of age. 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. The total number of renal tumors was less than additive in rats treated with the DBP mixture solutions. 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.