What can we expect from epidemiologic studies of chemical mixtures?

Determining the health risks of complex mixtures is equally daunting to toxicologists using experimental approaches and to epidemiologists using observational approaches. Accurate exposure estimation is essential in investigating the health consequences of exposures to chemical mixtures; random and non-random errors in exposure estimation typically blunt the sensitivity of epidemiologic studies and constrain interpretation of findings. On the other hand, epidemiologic data have the implicit strength of directly addressing risks of exposures in human populations and, for this reason, the findings of epidemiologic research have received prominence in the development of regulations. Epidemiologic studies have proved informative about many complex mixtures including cigarette smoke, diesel exhaust, and even the human diet, perhaps one of the most complex mixtures to which we are exposed. The continued interest in studying complex chemical mixtures is emphasized by this and other recent meetings directed at the topic. The variety of approaches used by epidemiologists in approaching complex mixtures reflects the difficulty of exposure estimation. Five general strategies can be identified, each with differing underlying assumptions and yielding results with distinct implications from biological and public health perspectives. These include treating the mixture as though it were a single agent, using a single component as a surrogate for the mixture, creating a summary index involving multiple components, attempting to estimate independent effects of individual components, and characterizing the independent and joint effects of key components of the mixture. These approaches have proved successful in establishing the adverse effects of a number of complex chemical mixtures including mainstream and environmental tobacco smoke and outdoor air pollution. New approaches for exposure assessment, including personal monitoring and biomarkers, should strengthen future epidemiologic investigations of complex chemical mixtures.