Reassessing the Link between Airborne Arsenic Exposure among Anaconda Copper Smelter Workers and Multiple Causes of Death Using the Parametric g-Formula

Abstract

Background: Prior studies have indicated associations between ingestion of inorganic arsenic and ischemic heart disease, nonmalignant respiratory disease, and lung, skin, bladder, and kidney cancers. In contrast, inhaled arsenic has been consistently associated only with lung cancer. Evidence for health effects of inhaled arsenic derives mainly from occupational studies that are subject to unique biases that may attenuate or obscure such associations.

Objectives: We estimated the excess mortality from respiratory cancers, heart disease, and other causes resulting from occupational arsenic exposure while controlling for confounding using the parametric g-formula.

Methods: Using a cohort of 8,014 male copper smelter workers who were hired between 1938 and 1955 and followed through 1990, we estimated the impacts of hypothetical workplace interventions on arsenic exposure on the risk of mortality from all causes, heart disease, and lung cancer using the parametric g-formula.

Results: We estimate that eliminating arsenic exposure at work would have prevented 22 deaths by age 70 per 1,000 workers [95% confidence interval (CI): 10, 35]. Of those 22 excess deaths, we estimate that 7.2 (95% CI: -1.2, 15) would be due to heart disease, 4.0 (95% CI: -0.8, 8.2) due to respiratory cancers, and 11 (95% CI: 0.0, 23) due to other causes.

Conclusions: Our analyses suggest that the excess deaths from causes other than respiratory cancers comprise the majority of the excess deaths caused by inhaled arsenic exposure. Healthy worker survivor bias may have masked such associations in previous analyses. These results emphasize the need for consideration of all exposure routes for upcoming risk assessment by the U.S. Environmental Protection Agency.

Figure 1

Age at death distribution for respiratory cancer (Resp. cancer), heart disease (Heart dis.), and other causes. The study population comprised 8,014 copper smelter workers, Anaconda, Montana, 1938–1990.

Figure 2

Cumulative incidence estimates for the observed data (dashed lines) and under the “natural course” intervention in the g-formula (solid lines) for all-cause and cause-specific mortality [respiratory (Resp.) cancer mortality (International Classification of Diseases, revision 8a codes 160–164); heart disease mortality (cardiovascular disease; International Classification of Diseases, revision 8a codes 410–414, 420–429)]. The study population comprised 8,014 copper smelter workers, Anaconda, Montana, 1938–1990.

Figure 3

Cumulative incidence curve under hypothetical interventions on arsenic exposure for respiratory cancer mortality (A), heart disease mortality (B) and all-cause mortality (C). The study population comprised 8,014 copper smelter workers, Anaconda, Montana, 1938–1990. Light/medium exposure interventions not included for clarity.