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Environmentally Realistic Mixtures of the Five Regulated Haloacetic Acids Exhibit Concentration-Dependent Departures from Dose Additivity (Presentation)
Citation:
SIMMONS, J. E., C. DINGUS, E. D. WAGNER, L. K. TEUSCHLER, G. E. RICE, AND M. J. PLEWA. Environmentally Realistic Mixtures of the Five Regulated Haloacetic Acids Exhibit Concentration-Dependent Departures from Dose Additivity (Presentation). Presented at 2009 Annual Society of Toxicology meeting, Baltimore, MD, March 15 - 19, 2009.
Impact/Purpose:
The objective of the present study was to evaluate environmentally relevant mixtures of HAAs under an assumption of dose addition. Mixtures were tested at an equimolar mixing ratio (EQ) and at ratios representing disinfection by postchlorination (CL) or preoxonation/postchlorination (OZ/CL).
Description:
Disinfection of water decreases waterborne disease. Disinfection byproducts (DBPs) are formed by the reaction of oxidizing disinfectants with inorganic and organic materials in the source water. The U.S. EPA regulates five haloacetic acid (HAA) DBPs as a mixture. The objective of the present study was to evaluate environmentally relevant mixtures of these HAAs under an assumption of dose addition. Mixtures were tested at an equimolar mixing ratio (EQ) and at ratios representing disinfection by postchlorination (CL) or preozonation/postchlorination (OZ/CL). The 5 individual HAAs (chloroacetic, dichloroacetic, trichloroacetic, bromoacetic (BA), and dibromoacetic acid) and the HAA mixtures were evaluated in a Chinese Hamster Ovary cell chronic cytotoxicity assay. Each chemical and mixture was evaluated at a minimum of 10 concentrations. The individual HAA data were used to develop a smooth additivity model consistent with Berenbaum’s definition of additivity. The fitted model provided reasonable fits to the experimental data. The slope of each individual HAA was negative and statistically significant, indicating that cell density decreased significantly with increasing HAA concentration. BA was markedly more toxic than the other regulated HAAs. The overall test for departure from dose additivity was significant (p<0.001) for each mixture. Individual dose levels (with Hochberg’s correction applied), demonstrated less-than-additive (antagonistic) departure from additivity in the higher portion of each mixture dose-response curve (EQ, CL, OZ/CL). In addition, the lowest two concentrations of the EQ mixture exhibited statistically significant greater-than additive departure from additivity. In summary, all 3 HAA mixtures exhibited less-than-additive toxicity in the higher dose region but only the EQ mixture, the least environmentally realistic, exhibited detectable greater-than-additive toxicity. (This abstract may not reflect EPA policy)