Genotoxic effects among Bolivian farmers exposed to mixtures of pesticides : population and in vitro based studies

Abstract: Human exposure to pesticides has increased exponentially in recent decades, especially in low- and middle-income countries where regulations on the use of pesticides and personal protective equipment (PPE) are not fully controlled. Studies have shown that compared to the general population, people occupationally exposed to pesticides have a higher risk of developing acute and chronic adverse health effects, and increased risk of genotoxic damage and cancer. The general objective of this thesis was to evaluate the correlation between exposure to mixtures of pesticides and genotoxicity in the agricultural Bolivian population. For this, a cross-sectional study was used in three agricultural communities, whose production represents almost the entire diversity of the country. The use and exposure to pesticides were determined by applying a survey on lifestyle factors, behaviors, and pesticide management, and by analyzing 10 urine pesticide metabolites (UPM). Our results demonstrated that the Bolivian agricultural population is highly exposed to mixtures of pesticides. High exposure levels of chlorpyrifos, 2,4-D, and some pyrethroids were found, and especially among men. Furthermore, we found that farmers who were better at following directions for using pesticides and PPE, in general, were less exposed to pesticides (Paper I). We also investigated the correlation between pesticide exposure and genotoxic effects. We found that high exposure levels of certain pesticides, e.g. tebuconazole, 2,4-D, and cyfluthrin, was associated with high levels and increased risks of genotoxic damage (Paper II). To gain a better understanding of possible cellular effects of pesticide mixtures, we studied cytotoxicity and genotoxicity in human liver carcinoma cells (HepG2 cells) exposed to mixtures of pesticides, which were based on UPM and survey profiles. Our results showed that while neither of the mixtures nor their constituent pesticides induced formation of reactive oxygen species, increased levels of genotoxic damage were observed. Mixtures that were primarily composed of paraquat and cypermethrin demonstrated the highest genotoxic potency, as did paraquat and cypermethrin as single compounds. (Paper III). In conclusion, the results from our population and in vitro studies suggest that specific pesticides may act as drivers of toxic effects observed from exposure to mixtures. More studies are however necessary to get a clearer understanding of these effects. Finally, we want to emphasize the need to train farmers in pesticide management and personal protection to reduce exposure levels and thereby decrease the risk of health adverse effects.