Use of biomarkers in risk assessment

The systematic development and application of biomarkers in environmental h ealth risk assessment is a relatively new field. At first, the major intere st was in biomarkers of exposure, borrowing concepts from pharmacology, the n it moved from the external estimates of exposure to internal measures of dose, and ultimately, to markers of target dose. While these markers provid e evidence of exposures, they do not provide evidence of that toxicological damage has occurred. For this reason, measurements of DNA adducts and prot ein adducts are of interest, since they may provide bridges between exposur es and disease end-points. In parallel, more quantitative and more sensitiv e end-points for diseases have been sought. Again, with advancing technique s in cytogenetics, extensive studies were conducted on such markers as chro mosomal aberrations, micronuclei and other changes deemed to represent geno mic damage. However, these types of end-points are quite unspecific for app lication to new hazards of uncertain human toxic (carcinogenic) potential. Recent work focusing on more specific early-effect markers such as certain oncogenes and tumour-suppressor genes have substantial promise as shown by work with aflatoxins and vinyl chloride. Such studies have also enhanced me chanistic insight. The advances in molecular genetics have led to an upsurg e in interest in most susceptibility factors, and identification of polymor phisms of various enzymes has become possible. Ongoing search for "ultra-hi gh risk" individuals may be fruitful, but probably only relevant to a small segment of potentially exposed populations. Factors associated with a smal l differential risk, however theoretically or mechanistically important, of fer only little practical use.