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COMPONENT-BASED AND WHOLE-MIXTURE ASSESSMENTS IN ADDRESSING THE UNIDENTIFIED FRACTION OF COMPLEX MIXTURES: DRINKING WATER AS AN EXAMPLE
Citation:
Simmons, J E., L K. Teuschler, C. Gennings, T F. Speth, S. D. Richardson, R J. Miltner, AND M G. Narotsky. COMPONENT-BASED AND WHOLE-MIXTURE ASSESSMENTS IN ADDRESSING THE UNIDENTIFIED FRACTION OF COMPLEX MIXTURES: DRINKING WATER AS AN EXAMPLE. Presented at Intern. Conf. on Chemical Mixtures, Atlanta, GA, Sept. 10-12, 2002.
Description:
Component-Based and Whole-Mixtures Assessments in Addressing the Unidentified Fraction of Complex Mixtures: Drinking Water as an Example
J. E. Simmons; L. K. Teuschler; C. Gennings; T. F. Speth; S. D. Richardson; R. J. Miltner; M. G. Narotsky; K. D. Schenck; G. Rice
NHEERL, ORD, U.S. EPA, Research Triangle Park, NC, USA; NCEA and NRMRL, ORD, U.S. EPA, Cincinnati, OH, USA; Virginia Commonwealth University, Richmond, VA, USA; NERL, ORD, U.S. EPA, Athens, GA, USA
Humans are often exposed to very complex environmental mixtures. In contrast, most laboratory investigations of mixtures, with the exception of mutagenicity assays, have focused on mixtures comprised of a few chemicals. Over the past decade, great advances have been made in component-based assessment of simple mixtures with development of appropriate, efficient and novel experimental designs, statistical methods and risk assessment techniques. Similar gains need to be made for complex mixtures. Component-based approaches that use information on the individual chemicals contained in the mixture are not by themselves sufficient for complex, environmental mixtures as significant portions of the mixture mass are unidentified. A highly complex mixture with broad, chronic, low-level exposure in developed countries is water disinfection byproducts (DBPs). Chemical disinfection of drinking water, while a major public health advance that dramatically decreased water-borne diseases, results in the formation of a wide variety and number of DBPs. The oxidants react with naturally occurring organic and inorganic matter in the water with the number, chemical type and concentration of DBPs dependent on source-water characteristics such as concentration and type of organic matter, bromide concentration, temperature and pH; and on treatment characteristics such as type of treatment employed, disinfectant, its concentration and where in the process it is used. More than 500 DBPs have been identified; yet, many remain unidentified as the known DBPs might account for less than 50% of total organic halide (TOX) mass. Use of drinking water concentrates allows evaluation of the ?mixture as a whole' in combination with component-based approaches. Methods were developed based on reverse-osmosis techniques for preparation of drinking water concentrates in a water matrix. Because volatiles were lost during concentration, a limited number, including the trihalomethanes (THMs) chloroform, bromoform, bromodichloromethane and chlorodibromomethane, were ?spiked-back' into the concentrate reflective of their initial concentrations and the concentration factor. After spike back, ~80% of TOX was accounted for, resulting in concentrates in a water matrix palatable to rats. Joint chemical and toxicological evaluation of these concentrates allows, with appropriate methodology, for health risk estimation based on the concentrations of the chemicals in the mixture. This methodology has been developed for simple mixtures and is illustrated by binary combinations of the four THMs. In low-dose regions, dose-additive hepatotoxicity was observed in mice; in high-dose regions, the mixtures were additive or antagonistic, but not synergistic. Joint theoretical and experimental work to extend these methods to more complex mixtures is in progress, including power and sample-size estimates, and methods to determine the portion of any observed toxicity attributable to the unidentified DBPs. (This abstract does not reflect EPA policy.)