1992). A deeper understanding of susceptibility and the biomarkers that indicate heightened susceptibility would be a valuable tool in preventing avoidable adverse health effects due to environmental exposures to health hazards.
The 1989 NRC report defined a biomarker of effect as ''any change that is qualitatively or quantitatively predictive of health impairment or potential impairment resulting from exposures" (National Research Council, 1989b). Although these markers are more predictive of ultimate toxicity, they are less clearly associated with exposure to specific chemical agents (DeCaprio, 1997). That is, the presence of such a marker can be indicative of more than one exposure.
Some mutational events can be considered biomarkers of effect, especially if they have already been demonstrated to be the immediate precursors of clinical disease, for example, oncogene activation and tumor formation. In some cases, however, the distinction between a biomarker of exposure and one of effect is not clear. Thus, DNA adduct formation (biomarker of exposure) might or might not lead to subsequent mutations that are precursors of disease.
Biomarkers measure events along the continuum from exposure to effect. They are signal events but are not necessarily an explanation for an underlying pathophysiology. Nevertheless, they can be tremendously useful in environmental epidemiology. More work is needed to develop biomarkers of exposure and effect suitable for improving the power of epidemiologic studies, including molecular epidemiology. For example, biomarker screening studies could be conducted with residents living in close proximity to a site to provide information on the actual levels of uptake of the contaminant(s) of concern.
Large, collaborative research efforts that use batteries of biomarkers are needed. Markers selected for use in the screening of populations must be sensitive, specific, predictive, and selective (DeRosa et al., 1993). Selectivity refers to the ability to unequivocally identify a specific substance to which an individual is exposed. For example, urine phenol levels can be influenced by the ingestion of vegetables, exposures to several aromatic compounds, ingestion of ethanol, and inhalation of cigarette smoke; thus, their value as a selective marker is low (DeRosa et al., 1993).
Markers must also be sensitive to short- versus long-term exposure. For example, the presence of trichloroethanol (a short-half-life metabolite of trichloroethylene [TCE]) in urine is a good biomarker for use in the monitoring of populations after short-term exposure to TCE, whereas the presence of trichloroacetic acid (a long half-life metabolite) in urine would be a more appropriate