Combining occurrence and toxicity information to identify priorities for drinking-water mixture research

Characterizing all possible chemical mixtures in drinking water is a potentially overwhelming project, and the task of assessing each mixture's net toxicity even more daunting. We propose that analyzing occurrence information on mixtures in drinking water may help to narrow the priorities and inform the approaches taken by researchers in mixture toxicology. To illustrate the utility of environmental data for refining the mixtures problem, we use a recent compilation of national ground-water-quality data to examine proposed U.S. Environmental Protection Agency (EPA) and Agency for Toxic Substances and Disease Registry (ATSDR) models of noncancer mixture toxicity. We use data on the occurrence of binary and ternary mixtures of arsenic, cadmium, and manganese to parameterize an additive model and compute hazard index scores for each drinking-water source in the data set. We also use partially parameterized interaction models to perform a bounding analysis estimating the interaction potential of several binary and ternary mixtures for which the toxicological literature is limited. From these results, we estimate a relative value of additional toxicological information for each mixture. For example, we find that according to the U.S. EPA's interaction model, the levels of arsenic and cadmium found in U.S. drinking water are unlikely to have synergistic cardiovascular effects, but the same mixture's potential for synergistic neurological effects merits further study. Similar analysis could in future be used to prioritize toxicological studies based on their potential to reduce scientific and regulatory uncertainty. Environmental data may also provide a means to explore the implications of alternative risk models for the toxicity and interaction of complex mixtures.