Arsenic ingestion and bladder cancer mortality - What do the dose-response relationships suggest about mechanism?

The Black-Foot Disease (BFD) endemic area of SW Taiwan has historically been the principal data source for assessing cancer risks from arsenic in drinking water in the United States, most recently in a 42-village ecological study. The data showed a discontinuity for bladder cancer risk at about 400 μg/L. A proposed explanation was that the arsenic-dependent bladder cancer risk was found only for those villages that were dependent on water from the artesian well aquifer (As > 350 μg/L and co-contamination with humic acids) and not for those villages receiving water from the shallow aquifer (As <350 μg/L without humic acids). The humic acids were present from the algae that grew in the uncovered tanks holding the artesian water. The risk factors (slopes) developed from these subpopulations of the SW Taiwan study were applied to the data from an ecological study of median groundwater arsenic concentration and bladder cancer mortality in 133 U.S. counties dependent on groundwater to determine the slope most predictive of U.S. experience for bladder cancer mortality and arsenic ingestion (Lamm et al. 2004) .The U.S. data excluded the SW Taiwan slope estimate derived from the artesian well-dependent subpopulation but were consistent with the slope estimate derived from the subpopulation using shallow aquifer water. Both the SW Taiwan data in the absence of high arsenic levels (<350 μg/L) and humic acids and the U.S. 133-county data with As <60 μg/L are consistent with no increased bladder cancer mortality risk from drinking water arsenic concentrations in the exposure range of observation. These analytic results are consistent with both co-carcinogenesis and high-exposure (hundreds of μg/L As) dependence models of toxicological mode-of-action. These dose-response relationships should influence prioritization in the remediation of arsenic-contaminated drinking water supplies.