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ADDITIVITY ASSESSMENT OF TRIHALOMETHANE MIXTURES BY PROPORTIONAL RESPONSE ADDITION
Citation:
SIMMONS, J. E., W. STITELER, R. C. HERTZBERG, T. A. MCDONALD, Y. M. SEY, L. K. TEUSCHLER, G. E. RICE, J. COLMAN, AND P. DURKIN. ADDITIVITY ASSESSMENT OF TRIHALOMETHANE MIXTURES BY PROPORTIONAL RESPONSE ADDITION . Presented at Society of Toxicology Annual Meeting, Charlotte, NC, March 25 - 29, 2007.
Description:
If additivity is known or assumed, the toxicity of a chemical mixture may be predicted from the dose response curves of the individual chemicals comprising the mixture. As single chemical data are abundant and mixture data sparse, mixture risk methods that utilize single chemical data are useful risk assessment tools. The present study examined, by proportional response addition, the assumption of additivity for mixtures of the four regulated trihalomethanes (THMs) that are formed during chemical disinfection of water. Under proportional response addition, the expected (predicted) effect of the mixture is a proportionally weighted sum of the responses that result from exposure to the individual components at the concentrations at which they are present in the mixture. A series of 16 experiments were conducted, including evaluation of: dose response curves for the individual THMs (chloroform, chlorodibromomethane, dibromochloromethane, bromoform); the six binary combinations of the four THMs; and, mixtures containing all 4 THMs. Female CD-1 mice were exposed by daily aqueous gavage for 14 days. Hepatotoxicity was assessed by relative liver weight and serum levels of enzymes indicative of hepatic damage (SDH, ALT, AST). A statistical approach based on comparison of expected and experimentally observed means was developed and applied to the data. Generally, the experimentally observed and the predicted mixture responses were not statistically different. As the variance in the responses increased, the ability (power) to detect departures from additivity decreased. In summary, novel proportional response addition methodology was developed and applied to evaluate the assumption of additivity for mixtures of the regulated THMs. The mixture data were supportive of a conclusion of additive joint toxicity as few statistically significant deviations from additivity were detected. (This abstract may not reflect EPA policy.)