Biomonitoring of industrial chemicals in human tissues and fluids has shown that all people carry a "body burden" of synthetic chemicals. Although measurement of an environmental chemical in a person's tissues/fluids is an indication of exposure, it does not necessarily mean the exposure concentration is sufficient to cause an adverse effect. Since humans are exposed to multiple chemicals, there may be a combination effect (e.g., additive, synergistic) associated with low-level exposures to multiple classes of contaminants, which may impact a variety of organ systems. The objective of this research is to link measures of body burden of environmental chemicals and a "holistic" measure of wellness. The approach is demonstrated using biomonitoring data from the National Health and Nutrition Examination Surveys (NHANES). Forty-two chemicals were selected for analysis based on their detection levels. Six biological pathway-specific indices were evaluated using groups of chemicals associated with each pathway. Five of the six pathways were negatively associated with wellness. Three non-zero interaction terms were detected which may provide empirical evidence of crosstalk across pathways. The approach identified five of the 42 chemicals from a variety of classes (metals, pesticides, furans, polycyclic aromatic hydrocarbons) as accounting for 71% of the weight linking body burden to wellness. Significant interactions were detected indicating the effect of smoking is exacerbated by body burden of environmental chemicals. Use of a holistic index on both sides of the exposure-health equation is a novel and promising empirical "systems biology" approach to risk evaluation of complex environmental exposures.
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