Biokinetics and stability aspects of biomarkers: recommendations for application in population studies.

The knowledge of the toxicokinetics of chemicals is an important prerequisite of biological monitoring of exposure. Kinetic data allow to determine whether the test is likely to reflect the recent exposure or to integrate the exposure over a certain period of time. They are necessary to select the appropriate parameter, biological specimen and sampling time by taking into account the type of exposure and the sensitivity of the analytical method. Various mathematical models have been developed to provide a global and quantitative description of the behavior of the chemical in the organism. In practice, however, the parameter to which one usually refers is the elimination half-life of the biomarker which reflects both the affinity of the chemical for the biological matrix and the efficiency of excretory or metabolic processes. Since chemically-induced diseases usually develop following repeated exposures over many years, markers which are the most useful for population studies are those integrating the dose received by the organism or by the target organ(s) over a toxicologically relevant period of time exposure. For a reliable application of biological monitoring in population studies, information must be collected on the stability of the biomarker and the precautions to be taken during transportation and storage of samples. The factors most likely to affect the stability of the parameter are evaporation, chemical deterioration, precipitation, adsorption on vessel surfaces and contamination. This paper formulates a series of practical recommendations to prevent or minimize variations in the pre-analytical phase which might be caused by these factors.