Region II in northern Chile (population 442 570) experienced a sudden major increase in arsenic water concentrations in 1958 in the main city of Antofagasta, followed by a major reduction in exposure when an arsenic removal plant was installed in 1970. It provides a unique opportunity to study latency effects of exposure to arsenic, and this is the first study with mortality data up to 40 years after exposure reduction. Methods: We previously identified high mortality rates in Region II up to

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... e year 2000. Here we present rate ratios (RRs) for Region II compared with all the rest of Chile from 2001 to 2010, and with unexposed Region V (population 1 539 852) for all years from 1950 to 2010. All statistical tests were one-sided. Results: From 2001 to 2010, comparing Region II with the rest of Chile, lung and bladder mortality were still greatly elevated (RR ¼ 3.38, 95% confidence interval [CI] ¼ 3.19 to 3.58, P < .001 for lung cancer in men; RR ¼ 2.41, 95% CI ¼ 2.20 to 2.64, P < .001 for lung cancer in women; RR ¼ 4.79, 95% CI ¼ 4.20 to 5.46, P < .001 for bladder cancer in men; RR ¼ 6.43, 95% CI ¼ 5.49 to 7.54, P < .001 for bladder cancer in women). Kidney cancer mortality was also elevated (RR ¼ 1.75, 95% CI ¼ 1.49 to 2.05, P < .001 for men; RR ¼ 2.09, 95% CI ¼ 1.69 to 2.57, P < .001 for women). Earlier short latency acute myocardial infarction mortality increases had subsided. Conclusions: Lung, bladder, and kidney cancer mortality due to arsenic exposure have very long latencies, with increased risks manifesting 40 years after exposure reduction. Our findings suggest that arsenic in drinking water may involve one of the longest cancer latencies for a human carcinogen. ARTICLE