Human populations are exposed to multiple chemicals through all environmental media. Environmental policies are fragmented and were designed primarily to control exposures to single chemicals in a single medium. Information on low-level population exposure to multiple chemicals has been limited until recent years of the National Health and Nutrition Examination Survey. Epidemiological data on the health effects of chemical mixtures is urgently needed to interpret the health implications of actual environmental exposures. We propose to determine whether concurrent exposure to a mixture of nephrotoxic metals is associated with clinical measures of kidney disease. Our long-term goal is to advance our understanding of the health effects of mixtures and improve the scientific basis for environmental policy. We will examine metal mixture exposures in a representative sample of the US population. The metals are barium, cadmium, cobalt, lead, mercury, molybdenum, and uranium. These metals were selected on the basis of toxicological or epidemiological evidence of nephrotoxicity and known population exposure. Demographics and socio-economic characteristics of the exposed population will be described. We will test the hypothesis that multiple exposures are distributed differently across race/ethnicity or socio-economic status. A mixture exposure metric will be developed that accounts for differences in each metal's nephrotoxic potency. Nephrotoxic potency will be determined from research literature. We will examine 2 additional hypotheses: (1) the toxicity-weighted mixture exposure metric will reveal exposure disparities by race/ethnicity or socio- economic status;and (2) those with higher mixture exposure metrics will have reduced creatinine clearance and estimated glomerular filtration rates and increased urinary albumin-creatinine ratios. We will test our hypotheses using contingency table analysis, analysis of covariance, and multivariate regression. The significance of this project is three-fold. First, characterization of mixture exposure in the US population is a unique contribution of this project. Second, the burden of kidney disease falls disproportionately on minority and poor populations perhaps due to differential exposure to metal mixtures. Third, this research demonstrates the proposed exposure assessment design in individual-level epidemiological research. Environmental policies rest primarily on studies of single chemical exposure while actual exposures are to mixtures. This research addresses whether current environmental policies protect public health. The National Institute for Environmental Health Sciences stated in its 2006-2011 Strategic Plan that maximal public health impact depends on conducting research relevant to societal decision making.
