Interindividual Variability in Modeling Exposure and Toxicokinetics: A Case Study on Cadmium.

This case study on cadmium illustrates a methodological framework for modeling the relation between external and internal dose in which interindividual variability is an integral component. The interindividual variability in intake of cadmium together with the variability in organ weights cannot explain the interindividual variability in internal doses. Therefore, variation in physiology was taken into account as well by assuming that some of the parameters of the toxicokinetic model are stochastic. This "second-order" modeling approach enables the prediction of internal dose distributions relating to the population, as opposed to "first-order" modeling, in which only the internal dose of the average individual is predicted. In the case of cadmium, where the critical internal concentration (in the kidney) is relatively well known, the fraction of the population at risk can be derived immediately. The use of this modeling framework to estimate risks for specific risk groups, defined by (combinations of) specific risk factors, is illustrated.