Total imprecision of exposure biomarkers: implications for calculating exposure limits

Abstract

Exposure assessment is a key aspect of environmental epidemiology. In standard statistical analysis, the exposure variable is treated as an independent variable without error. However, commonly occurring non-differential errors tend to bias the dose-response relationship toward null [Fuller, 1987]. A measure of individual exposure is often obtained from exposure biomarkers, i.e., contaminant concentrations in samples of human tissue or body fluids [Grandjean, 1995]. The validity of these parameters is usually expressed in terms of laboratory uncertainty, where the imprecision is given as the coefficient of variation for repeated analyses of the sample [ISO, 1993]. However, the total imprecision includes both analytical and preanalytical sources of variation. The latter encompasses all types of variation associated with the specimen sampling, storage, transportation, toxicokinetic variability, and related factors. Thus, improvement of laboratory performance does not automatically lead to a reduction of the total error [Bonini et al., 2002], and the total imprecision may be underestimated.