This study analyzes the relationship between arsenic exposure through drinking water and bladder cancer mortality. The county-specific white male bladder cancer mortality data (1950–1979) and county-specific groundwater arsenic concentration data were obtained for 133 U.S. counties known to be exclusively dependent on groundwater for their public drinking water supply. No arsenic-related increase in bladder cancer mortality was found over the exposure range of 3 to 60 μg/L using stratified analysis and regression analyses (both unweighted and weighted by county population and using both mean and median arsenic concentrations). These results, which provide a direct estimate of arsenic-related cancer risk for U.S. residents, exclude the National Research Council’s 2001 risk estimate that was based on Southwest Taiwan data and required adjusting for differences between the body mass and water consumption rates of U.S. and Taiwanese residents.

Quantitative analysis for the risk of human cancer from the ingestion of inorganic arsenic has been based on the reported cancer mortality experience in the blackfoot disease (BFD)–endemic area of southwest Taiwan. Linear regression analysis shows that arsenic as the sole etiologic factor accounts for only 21% of the variance in the village standardized mortality ratios for bladder and lung cancer. A previous study had reported the influence of confounders (township, BFD prevalence, and artesian well dependency) qualitatively, but they have not been introduced into a quantitative assessment. In this six-township study, only three townships (2, 4, and 6) showed a significant positive dose–response relationship with arsenic exposure. The other three townships (0, 3, and 5) demonstrated significant bladder and lung cancer risks that were independent of arsenic exposure. The data for bladder and lung cancer mortality for townships 2, 4, and 6 fit an inverse linear regression model (p < 0.001) with an estimated threshold at 151 μg/L (95% confidence interval, 42 to 229 μg/L). Such a model is consistent with epidemiologic and toxicologic literature for bladder cancer. Exploration of the southwest Taiwan cancer mortality data set has clarified the dose–response relationship with arsenic exposure by separating out township as a confounding factor.

High levels (> 200 µg/L) of inorganic arsenic in drinking water are known to be a cause of human lung cancer, but the evidence at lower levels is uncertain. We have sought the epidemiological studies that have examined the dose-response relationship between arsenic levels in drinking water and the risk of lung cancer over a range that includes both high and low levels of arsenic. Regression analysis, based on six studies identified from an electronic search, examined the relationship between the log of the relative risk and the log of the arsenic exposure over a range of 1–1000 µg/L. The best-fitting continuous meta-regression model was sought and found to be a no-constant linear-quadratic analysis where both the risk and the exposure had been logarithmically transformed. This yielded both a statistically significant positive coefficient for the quadratic term and a statistically significant negative coefficient for the linear term. Sub-analyses by study design yielded results that were similar for both ecological studies and non-ecological studies. Statistically significant X-intercepts consistently found no increased level of risk at approximately 100–150 µg/L arsenic.