The Use of Biological Markers in Risk Assessment

Abstract

The use of biologic markers (such as DNA adducts) as more proximate measures of effective dose has many potential advantages for risk assessment. We can hope for: Better modeling of dose-response relationships, by avoiding the attribution of high dose pharmacokinetic nonlinearities to the fundamental multiple mutation process of carcinogenesis. Better interspecies projection of doses and risks. Improved evaluation of past doses in epidemiologic studies. Insights into the magnitude and significance of human interindividual variability. Possibly some identification of previously unrecognized genetic hazards. In the very long run, the quantification of rates of post-initiation stages in tumor development by comparative measurements of the prevalence of adducts, premalignant foci/clones and tumors as a function of age in different tissues. Realizing these advantages will require statistically oriented professionals in risk assessment to gain familiarity with more complex, simulation-type modeling approaches with multiple points of comparison between theory and experiment--rather than the straightforward curve-fitting that has built the field to this point. It will also require some precautions to avoid mistakes and misuse of these new kinds of data and related theory.