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A NONADDITITIVE TUMOR RESPONSE TO A MIXTURE OF DISINFECTION BY-PRODUCTS
Citation:
McDorman, K. S., M. J. Hooth, S D. Hester, AND D C. Wolf. A NONADDITITIVE TUMOR RESPONSE TO A MIXTURE OF DISINFECTION BY-PRODUCTS. Presented at Application of Technology to Chemical Mixture Research Conf, Fort Collins, CO, January 8-11, 2001.
Description:
Current default risk assessments for chemical mixtures assume additivity of carcinogenic effects, but this may not be consistent with the actual biological response. We used a rodent model of hereditary renal cancer to investigate the carcinogenic response of a mixture of drinking water disinfection by-products (DBPs). Eker rats develop renal tumors secondary to a germline mutation in a tumor suppressor gene, and are highly susceptible to the effects of renal carcinogens. 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(5H)- furanone (MX), chloroform, and bromodichloromethane were administered at low concentrations of 0.02, 0.005, 0.4 and 0.07 g/L, respectively and high concentrations 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 concentrations or high concentrations, respectively. The kidneys of each animal were examined microscopically for tumors. At 6 months of age, treatment did not show significant increases in renal tumors compared to control. At 12 months of age, all treatment groups except low dose MX and the low dose mixture had increased numbers of renal tumors compared to control. Treatment with the high dose mixture produced no more neoplasms than any individual compound, indicating a nonadditive response for cancer in this study. These data suggest that the default assumption of additivity may overestimate the carcinogenic effect of chemical mixtures in drinking water.
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