Effects of arsenic ingestion from drinking water on human health: Ecologic and biomarker studies in Argentina and Chile

Studies in Taiwan show a dose-response relationship between inorganic arsenic (In-As) ingestion from drinking water and internal cancers, with highest risks found for bladder cancer. The generalizability of the findings and their applicability for extrapolation at lower doses have been questioned based on specific issues: the possibility of a biological threshold for detoxification via methylation at high exposures; genetic factors or nutritional deficiencies may make Taiwanese more susceptible to arsenic effects; other water contaminants may account for the high risks. This dissertation addresses these points combining a bladder cancer ecological study in a region of Argentina with past exposures, and a methylation study of a currently exposed Chilean population.; The ecological study in Cordoba, Argentina analyzed five-year bladder cancer mortality rates in 26 counties, grouping them into three exposure categories based on historical exposure evidence. The resulting dose-response relationship, with a two-fold relative risk in the highest exposure group, is consistent with the Taiwanese results, in another population with different ethnic background and diet and no reported associations between arsenic and humic substances in water.; The methylation study in Chile compared the distribution of urinary In-As and its metabolites, monomethylarsonate (MMA) and dimethylarsinate (DMA), as a measure of methylation capacity in two phases: comparison of residents of two towns with contrasting arsenic water concentrations (600 ug/L versus 15 ug/L), and comparison of highly exposed individuals before and after changing water supply (600 ug/L to 40 ug/L). The findings of the two investigations were consistent. There was no evidence of a saturation of methylation even under very high exposures. Lower exposures and longer residence were associated with small decreases in %In-As and MMA/DMA, and other factors such as gender, smoking and ethnicity had similar effects on MMA/DMA only. Overall the effects of exposure and other variables on metabolite distribution were small, with no substantial contribution to explain the wide interindividual variability observed across the entire study population.; In conclusion, there is growing evidence that arsenic ingestion causes bladder cancer and that there is no support for a threshold in cancer risk based on the methylation patterns observed in chronically exposed populations.