Opportunities for the development and use of biomarkers

Limitations in understanding the relationship between occupational and environmental exposures and disease present opportunities for using biological markers to fill gaps in knowledge. Three situations can be identified that could foster the development and use of biomarkers, where epidemiological evidence is (1) definitive, (2) equivocal, and (3) lacking. When there is clear epidemiological evidence of disease risk given an exposure, biomarkers could be used to identify high- and low-risk subsets of a cohort that might benefit from differential practices such as counseling about job risks, varying frequency and intensity of medical surveillance, and using protective equipment. Biomarkers could also be used to test the effectiveness of environmental controls. Assessment of blood lead in bridge workers and purified protein derivative (PPD) testing in health care workers illustrates biomarkers that have been used to evaluate control efforts. When epidemiological evidence is equivocal, a broad and consistent database on intermediate biomarkers in the path between exposure and disease could provide a compelling case as to whether a substance should be treated as hazardous. The case of ethylene oxide illustrates this situation: the epidemiological evidence of risk of lymphohematopoietic cancer is equivocal but there is an informative database on genetic and cytogenetic changes in various species consistent with carcinogenicity. Biomarker data also can be used to assist in the interpretation of inconclusive epidemiological information as is illustrated in the case of styrene where markers provide a mechanistic rationale for the epidemiologic findings. When there is little or no epidemiological evidence of risk in an exposure situation, such as around hazardous waste operations or with new technologies, biological markers can serve as early warning indicators of exposure or risk. In such cases it is important to have an underlying biological theory and an appropriate epidemiological study design if the principal results are to be of value in indicating risk and preventing disease.