Evaluating the Similarity of Complex Drinking-Water Disinfection By-Product Mixtures: Overview of the Issues

Abstract

Humans are exposed daily to complex mixtures of environmental chemical contaminants, which arise as releases from sources such as engineering procedures, degradation processes, and emissions from mobile or stationary sources. When dose-response data are available for the actual environmental mixture to which individuals 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. This article provides an overview for a series of companion articles whose purpose is to develop a set of biostatistical, chemical, and toxicological criteria and approaches for evaluating the similarity of drinking-water disinfection by-product (DBPs) complex mixtures. Together, the five articles in this series serve as a case study whose techniques will be relevant to assessing similarity for other classes of complex mixtures of environmental chemicals. Schenck et al. (2009) describe the chemistry and mutagenicity of a set of DBP mixtures concentrated from five different drinking-water treatment plants. Bull et al. (2009a, 2009b) describe how the variables that impact the formation of DBP affect the chemical composition and, subsequently, the expected toxicity of the mixture. Feder et al. (2009a, 2009b) evaluate the similarity of DBP mixture concentrates by applying two biostatistical approaches, principal components analysis, and a nonparametric “bootstrap” analysis. Important factors for determining sufficient similarity of DBP mixtures found in this research include disinfectant used; source water characteristics, including the concentrations of bromide and total organic carbon; concentrations and proportions of individual DBPs with known toxicity data on the same endpoint; magnitude of the unidentified fraction of total organic halides; similar toxicity outcomes for whole mixture testing (e.g., mutagenicity); and summary chemical measures such as total trihalomethanes, total haloacetic acids, total haloacetonitriles, and the levels of bromide incorporation in the DBP classes.

The authors acknowledge and appreciate the many helpful comments of Drs. Richard C. Hertzberg (Emory University) and Belinda Hawkins (U.S. EPA). These comments greatly improved this article.

The views expressed in this article are those of the individual authors and do not necessarily reflect the views and policies of the U.S. EPA. Those sections prepared by U.S. EPA scientists have been reviewed in accordance with the U.S. EPA peer and administrative review policies and approved for presentation and publication. Mention of trade names or commercial products does not constitute endorsement or recommendations for use.

Notes

¹ U.S. EPA (2000) presents detailed descriptions of available mixture risk assessment methods, as well as user fact-sheets which provide concise overviews. These method-specific fact-sheets provide information relative to the mixture risk assessment approaches including: the type of assessment (e.g., dose-response assessment, risk characterization), data requirements, references, strategy of the method with calculations, ease of use, assumptions, limitations, and uncertainties.

²Reference dose (RfD): an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. Reference concentration (RfC): an estimate (with uncertainty spanning perhaps an order of magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. Slope factor: an upper bound, approximating a 95% confidence limit, on the increased cancer risk from a lifetime exposure to an agent.