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THE CARCINOGENIC RESPONSE TO A MIXTURE OF DRINKING WATER DISINFECTION BY-PRODUCTS (DBP) WAS LESS THAN ADDITIVE
Citation:
Hooth, M., K McDorman, S D. Hester, M H. George, L R. Brooks, A E. Swank, AND D C. Wolf. THE CARCINOGENIC RESPONSE TO A MIXTURE OF DRINKING WATER DISINFECTION BY-PRODUCTS (DBP) WAS LESS THAN ADDITIVE. Presented at Society of Toxicology, San Francisco, CA, March 25-29, 2001.
Description:
THE CARCINOGENIC RESPONSE TO A MIXTURE OF DRINKING WATER DISINFECTION BY -PRODUCTS (DBP) W AS LESS THAN ADDITIVE.
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 DBP. Male and female Eker rats were treated with individual or a mixture of DBP for 6 or 12 months. 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. All tissues were examined macroscopically for masses and all masses were diagnosed microscopically. The large intestine was examined for aberrant crypt foci (ACF). There was no increase in renal tumors (adenomas and carcinomas) in male or female rats after 6 months of treatment in any test group. A dose response for renal tumors was present in most treatment groups after 12 months. The total number of renal tumors was less than additive in rats treated with the DBP mixture solutions. The number of uterine smooth muscle tumors was also less than additive in female rats treated with the DBP mixture solutions. ACF were increased in high dose BDCM, low dose mixture, and high dose mixture treated groups after 12 months compared to control. This study suggests that the default assumption of additivity may overestimate the carcinogenic effect of chemical mixtures in drinking water.
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