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The Impact of Mixture Composition, Mixing Ratio and Dose on the Interactions among the Four Trihalomethanes (THMs) Regulated in Drinking Water
Citation:
SIMMONS, J. E., C. A. Dingus, L. K. TEUSCHLER, G. E. RICE, Y. M. Sey, AND A. McDonald. The Impact of Mixture Composition, Mixing Ratio and Dose on the Interactions among the Four Trihalomethanes (THMs) Regulated in Drinking Water. Presented at Society of Toxicology (SOT) Annual Meeting, San Francisco, CA, March 11 - 15, 2012.
Impact/Purpose:
The U.S. EPA regulates 4 THM DBPs (chloroform, CHCI3; bromodichloromethane, BDCM; chlorodibromomethane, CDBM; bromoform, CHBr3) as a group. Our objective was assessment, under an assumption of dose addition, of hepatotoxicity (serum sorbitol dehydrogenase, alanine aminotransferase, aspartate aminotransferase) of the 6 binary combinations of the 4 THMs.
Description:
Oxidizing disinfectants reduce microbial contamination but react with inorganic and organic materials in water forming disinfection byproducts (DBPs). The U.S. EPA regulates 4 THM DBPs (chloroform, CHCI3; bromodichloromethane, BDCM; chlorodibromomethane, CDBM; bromoform, CHBr3) as a group. Our objective was assessment, under an assumption of dose addition, of hepatotoxicity (serum sorbitol dehydrogenase, alanine aminotransferase, aspartate aminotransferase) of the 6 binary combinations of the 4 THMs. Individual THMs and mixtures were tested in female CD-l mice (14 days of daily oral gavage) across a dose range that included no/low and overt response (0.1 -3.0 mmol/kg/day). DBPs were combined at equimolar ratios (EQ) and at ratios representing disinfection by chlorination (CI).. Dose additivity models consistent with Berenbaum's definition of additivity were developed with individual THM data. Toxicity increased significantly with dose for each individual THM and endpoint. The overall test for departure from dose additivity was significant (p<0.02 -p