Human Exposure Biomarkers of Some Commonly Used Pesticides

Sammanfattning: The use of pesticides has caused pollution of surface and groundwater, soil and air across the world. Many pesticides cause health effects in humans. General populations are exposed to some degree and diet is reported to be a main source of exposure. It is important to study exposure and exposure-effect relationships in occupational groups and in general populations. For such studies, good methods to monitor exposure, such as human biomonitoring are needed. However, for many pesticides, there is a lack of knowledge on exposure biomarkers and analytical methods to measure exposure. Thus, there is a need for validated biomarkers of exposure and analytical methods.In this thesis, new methods were developed and validated to analyze the fungicides thiabendazole (TBZ), imazalil (IMZ) and pyrimethanil (PYM) and their exposure biomarkers in urine using LC-MS/MS. Further, an LC-MS/MS method for analysis of glyphosate (GLY) and one of its metabolite in urine was established. The analytical methods were sensitive enough to measure a wide range of concentrations of exposure biomarkers in populations and showed good precisions.Human experimental exposures (oral and/or dermal) with TBZ, IMZ, PYM and GLY were performed with 2-3 volunteers to investigate basic toxicokinetics. The excretion of biomarkers in urine was rapid with short half-lives for all the four pesticides. The biomarkers of IMZ, TBZ and PYM were found conjugated with glucuronides and sulfates. The concentrations of biomarkers varied quantitatively with the degree of exposure.The analytical methods were applied to biomonitor the exposure in occupationally exposed groups and in general populations. The measured biomarkers in population groups in Sweden reflect concentrations which seem to be far below the excreted concentrations after an intake of a dose equivalent to a dose half or equal to the ADIs. The diet of the general population could be a possible source of exposure. The measured exposure biomarkers of IMZ in greenhouse workers and of PYM in orchardists were higher than the general population and reflected concentrations that were sometimes close to those following an exposure at a dose half or equal to the ADIs. In conclusion, the analytical methods performed well and can be applied in biomonitoring studies. The identified biomarkers of all four pesticides were related to the exposures and the human experiments facilitated validation of the biomarkers. The short urinary excretion half-lives require a well-planned sampling strategy.