Validation of Biological Markers for Quantitative Risk Assessment

Abstract

The evaluation of iolgia markers is recoied as necsry to the future oftokcOy , epideniology, and q Iive risk assment.For bio cl nmrkes to becm widely accepted, their validity must be ascertained.This paper explores the range ofconsiderations that compose the concept of validiBt as it applies to the evaluation of bioogical markers.Three broad categories of validity (meaem ent, internal study, and external) are discussed in the context of evWaluating data for use inquantitative risk at.Frticular attention is given to the importnce ofmeuement validity in the con- sideration ofwhether to use biological markers in epidemiologic studies.The concepts developed in this presentation are applied to examples derived from the occupational environment.In the first example, measurement of bromine release as a marker ofethylene dibromide toxicity is shown to be of limited use in constructng an accurate quantitative assess- ment ofthe risk ofdeveloping cancer as a reslt of long-term, low-level exposure.This example is compared to data ob- tained from studies ofethylene ade, in which hemoglobin alkylation is shown to be a valid marker ofboth exposure and effect.