| Exposure to arsenic (As)-contaminated drinking water affects tens of millions people worldwide. The health effects of As are well established yet the mechanisms and dose-response relationships of As toxicity are not fully understood. Inaccurate exposure assessment, limited sensitivity of analytical techniques and metabolic variations across human populations are key factors that have complicated risk assessment efforts. This dissertation aimed to identify populations with greater susceptibility to As-induced heath effects, in three ongoing investigations of As-exposed individuals, by utilizing ICP-MS methods developed for measuring trace elements in blood.;In a case-cohort analysis of 303 newly diagnosed cases of skin lesions, and 849 subcohort members randomly selected from 8092 participants in the Health Effects of Arsenic Longitudinal Study (HEALS) blood, urine and water As concentrations, and their associations with each and with skin lesions were measured. Blood As concentrations were highly correlated with urinary As concentrations (r = 0.85) and with water As (r = 0.75). Dose-response relationships between the risk of skin lesions and all of the As exposure measures were observed.;In a similar case-cohort analysis the association between prediagnostic selenium (Se) concentrations in blood and skin lesion risk was evaluated. Higher baseline blood Se was related to as much as a 50% reduction in risk of As-induced premalignant skin lesions.;The extent to which As is transported to the fetus during pregnancy was characterized in a study of 101 pregnant women who gave birth in Matlab, Bangladesh. Maternal and cord blood pairs were collected and concentrations of total As were analyzed for 101 pairs, and As metabolites for 30 pairs. Strong associations between maternal and cord blood concentrations of total As (r = 0.93, p < 0.0001) were observed. Maternal and cord blood arsenic metabolites (N = 30) were also strongly correlated: in DMA (r = 0.94, p < 0.0001), MMA (r = 0.80, p < 0.0001), AS+3 (r = 0.80, p < 0.0001), and As +5 (r = 0.89, p < 0.0001). |
