Susceptibility Based Upon Chemical Interaction with Disease Processes: Potential Implications for Risk Assessment

Abstract

Numerous host and environmental factors may modulate vulnerability and risk. An area of increasing interest is the potential for chemicals to interact with background aging and disease processes, an interaction that may yield cumulative damage, altered chemical potency, and increased disease incidence. We evaluate the interactions possible between chemicals and background disease and identify the type of information needed to evaluate such interactions. Key among these is the existence of a clinically relevant and easy to measure biomarker of disease risk which is also modulated by a particular chemical of interest. This biomarker may be a physiological, biochemical, or genetic indicator that corresponds to a phase of the disease process and indicates where an individual is on the continuum between health and disease. The impact of toxic chemicals on this biomarker can then be used to predict how the chemical modifies disease risk, with this evidence strengthened by additional toxicology and epidemiology data showing toxicant effect on the disease process. Several case studies are presented which describe the toxic chemical, the clinical biomarker, the impacted disease and the evidence that the chemical enhances disease risk: fine particulate matter/decreased heart rate variability/increased cardiopulmonary events; cadmium/decreased glomerular filtration rate/increased chronic kidney disease; methyl mercury/decreased paraoxonase-1/increased cardiovascular risk; trichloroethylene/increased anti-nuclear antibody/autoimmunity; dioxin/increased CYP1A1/hypertension. These case studies point out that consideration of how a chemical interacts with background aging and disease processes may increase the public health relevance of risk assessment, identify important vulnerabilities, and provide new ways to calculate risk from exposure to environmental toxicants.