Biomarkers and mechanistic approaches in environmental epidemiology.

Environmental epidemiological research involves the identification of relationships between previous exposures to putative causative agents and subsequent biological effects with study populations. Such relationships are often hard to fully characterize because of difficulties in accurately quantifying exposure, dose, and effect. Biomarkers are indicators, residing in biological systems or samples, of exposure, dose, effect, or susceptibility. Biomarkers of exposure indicate the presence of previous exposure to an environmental agent; a biomarker of dose bears a quantitative relationship to previous exposure or dose; these include exogenous substances, interactive products, or interactions that change the status of the target molecule. Biomarkers of effect indicate the presence and magnitude of a biological response to exposure to an environmental agent; these include endogenous components, or measures of the functional capacity or state of the system. Biomarkers of susceptibility indicate an elevated sensitivity to the effects of an environmental agent; these include the presence or absence of an endogenous component, or abnormal functional responses to an administered challenge. The development of molecular biomarkers for environmental agents is based upon specific knowledge of metabolism, interactive product formation, and general mechanisms of action. The validation of any biomarker-effect link requires parallel experimental animal and human epidemiological studies.