AMERICAN JOURNAL OF INDUSTRIAL MEDICINE 52:633–644 (2009) Mortality Patterns Among Workers Exposed to Arsenic, Cadmium, and Other Substances in a Copper Smelter Gary M. Marsh, PhD, 1 Nurtan A. Esmen, PhD, 2 Jeanine M. Buchanich, PhD, 1 and Ada O. Youk, PhD 1 Objective To evaluate the long-term mortality experience of workers exposed to arsenic, cadmium, and other substances at a copper mine and smelter in Copperhill, Tennessee studied earlier as part of an industry-wide study. Methods Subjects were 2,422 male workers employed three or more years in the smelter or mill between 1/1/46 until the plant strike and scale-down of operations in April 1996. Vital status was determined through 2000 for 99.4% of subjects and cause of death for 91.3% of 878 deaths. Historical exposures were estimated for lead, SO 2 , arsenic, cadmium, dust, and cobalt. We computed standardized mortality ratios (SMRs) based on U.S. and local county rates and modeled internal relative risks (RRs). Results We observed overall deficits in deaths based on national and local county comparisons from all causes, all cancers and most of the cause of death categories examined. We found limited evidence of increasing mortality risks from cerebrovascular disease with increasing duration and cumulative arsenic exposure, but no evidence of an exposure–response relationship for cadmium exposure and bronchitis. Conclusions Our limited evidence of an association between inhaled arsenic exposure and CVD is an exploratory finding not observed in other epidemiology studies of more highly exposed occupational populations. Possible alternative explanations include chance alone and uncontrolled confounding oreffect modification by co-exposures or other factors correlated with arsenic exposure and unique to the Copperhill facility. Am. J. Ind. Med. 52:633 – 644, 2009. ß 2009 Wiley-Liss, Inc. KEY WORDS: cohort study; mortality; copper smelting; arsenic; cadmium; cerebrovascular disease; bronchitis; copper; lead; SO 2 ; dust; cobalt BACKGROUND The Copper Basin area of southeastern Tennessee is the site of a copper mining, milling, and smelter facility in the town of Copperhill, TN. Copper smelting began in the Copper Basin in the mid-19th century and was conducted at the Copperhill site from 1901 to 1986. Due to the high sulfur content of the local ore, the facility also produced a variety of sulfur products during its history. These activities continued until April 1996 when a strike occurred and production activities were scaled down considerably. The Copperhill facility was one of the eight smelters included in an ß 2009 Wiley-Liss, Inc. 1 Department of Biostatistics, Center for Occupational Biostatistics and Epidemiology, Graduate School of Public Health, University of Pittsburgh,Pittsburgh,Pennsylvania 2 Division of Environmental and Occupational Health Sciences, School of Public Health, University of Illinois at Chicago,Chicago,Illinois Contract grant sponsor:National Institutefor Occupational Safety and Health (NIOSH). *Correspondence to: Dr. Gary M. Marsh, Department of Biostatistics, Center for Occupa- tional Biostatistics and Epidemiology,Graduate School of Public Health,University of Pitts- burgh,Pittsburgh,PA15261.E-mail: gmarsh@cobe.pitt.edu Accepted 23 April 2009 DOI10.1002/ajim.20714.PublishedonlineinWileyInterScience (www.interscience.wiley.com)