Determinants of Whether or not Mixtures of Disinfection By-products are Similar


Through this summary the EPA announces the availability of 6 recent publications that offer approaches for using existing toxicity data on a known mixture to assess potential health risks from exposure to another related mixture (e.g., from a similar type of treatment process or emissions source) for which adequate toxicity data are unavailable and may be difficult or expensive to generate.


This project summary and its related publications provide information on the development of chemical, toxicological and statistical criteria for determining the sufficient similarity of complex chemical mixtures.

Humans are exposed daily to complex mixtures of environmental chemical contaminants, which can arise as releases from sources such as engineering procedures, degradation processes and emissions from mobile or stationary sources. The assessment of health risks associated with whole mixtures is challenging because typically these complex mixtures are comprised of many components that can vary depending on: how the mixture was produced; environmental factors that may act to alter differentially the mixture composition; and, where and how humans come into contact with the mixture. Because the chemical composition of such mixtures may vary over time or with different conditions under which the mixture is produced, understanding the likelihood and nature of potential health risks posed by exposure to such similar mixtures is critical. It is recognized that both the magnitudes and the types of the health risks associated with an environmental mixture could change with variations in exposure scenarios and with changes in the composition of the mixture.

The U.S. EPA has issued both guidelines (U.S. EPA, 1986) and general guidance (U.S. EPA, 2000) that discuss methods for assessing health risks associated with exposures to chemical mixtures. Two categories of methods are proposed based on data availability, those based on whole mixtures and those based on the mixtures’ components. If whole-mixture toxicity data are available, they are preferred in environmental risk assessments. When dose-response data are available for the actual environmental mixture to which people are exposed (i.e., the mixture of concern), these data provide the best information for dose-response assessment of the mixture. When suitable data on the mixture itself are not available, surrogate data might be used from a sufficiently similar mixture or a group of similar mixtures. Consequently, the determination of whether the mixture of concern is sufficiently similar to a tested mixture or a group of tested mixtures is central to the use of whole mixture methods.

Judgments of sufficient similarity can be extremely challenging for complex mixtures such as drinking water DBPs. The chemical disinfection of drinking water produces hundreds of DBPs through reaction of the disinfecting agent (e.g., chlorine, ozone) with the organic matter in the water, and health effects have been observed in both toxicological and epidemiological studies. Ultimately, the development of similarity approaches for DBP complex mixtures will allow a specified DBP mixture of concern to be characterized as sufficiently similar, or not, to a tested mixture based on comparisons of relatively inexpensive and quick measures between the mixture of concern and the tested mixture. The approaches should yield accurate and reproducible results that can be used to justify scientifically and objectively the use of toxicity information from a similar mixture. An example of this for DBPs is to produce toxicity and chemistry data on DBP mixtures formed using Reproducible Disinfection Scenarios that can then be used to evaluate environmental mixtures of DBPs formed from similar source waters and treatment processes (Teuschler and Simmons, 2003; Rice et al., 2008). The development of approaches for examining the similarity of such mixtures can help to identify the types of toxicity tests, the types of summary measures that need to be developed, and the types of DBP mixtures that should be examined.

This collection of six publications on sufficient similarity was developed collaboratively among scientists within the U.S. EPA’s Office of Research and Development and under contracts with Battelle and MoBull Consulting. The citations for these publications are listed under downloads.


Bull, R. J., G. E. RICE, AND L. K. TEUSCHLER. Determinants of Whether or not Mixtures of Disinfection By-products are Similar. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH - PART A: CURRENT ISSUES. Taylor & Francis, Inc., Philadelphia, PA, 72(7):437-460, (2009).

Additional Information

  • Teuschler, L. K., and Simmons, J. E. 2003. Approaching the toxicity of disinfection by-products in drinking water as a mixtures problem. J. Am. Water Works Assoc. 95(6):131 138.
  • Rice, G., Teuschler, L E., Speth, T. F., Richardson, S. D., Miltner, R. J., Schenck, K., Gennings, C., Hunter, E. S., III, Narotsky, M.G., and Simmons, J E. 2008. Assessing reproductive and developmental risks posed by complex disinfection by-product mixtures. J. Toxicol. Environ. Health. Part A, 71:17, 1222 — 1234
  • U.S. EPA (United States Environmental Protection Agency) 1986. Guidelines for the health risk assessment of chemical mixtures. Fed. Reg. 51(185):34014 34025.
  • U.S. EPA (United States Environmental Protection Agency) 2000. Supplementary Guidance for Conducting Health Risk Assessment of Chemical Mixtures. External Scientific Peer Review Draft. U.S. Environmental Protection Agency, Washington, DC.

This document has been reviewed in accordance with U.S. Environmental Protection Agency policy and approved for publication. Mention of trade names or commercial products does not constitute endorsement or recommendation for use.