Modeling exposure-biomarker relationships: Applications of linear and nonlinear toxicokinetics

Establishing and characterizing exposure-biomarker relationships represent important steps to understanding how exposure to a harmful environmental toxin ultimately leads to disease in human populations. Here, we present a statistical model to characterize a nonlinear exposure-biomarker relationship and use occupational benzene exposures to illustrate the application. We also attempt to estimate the range of linear metabolism of benzene by fitting our model to data from a recent study of biomarkers (benzene-oxide-albumin adducts) measured in a population of Chinese workers exposed to benzene. Estimating the parameters of interest is difficult due to within and between subject variability in exposure and biomarker levels and because of exposure measurement error.