Arsenic and respiratory cancer in humans: follow-up of copper smelter employees in Montana.

As a follow-up to an earlier study concerned with the role of arsenic in human carcinogenesis, the mortality experience during 1938-77 of 8,045 white male smelter employees in Montana exposed to arsenic trioxide was compared to that of the white male population of the same region. The excess mortality among smelter employees was due largely to respiratory cancer and diseases of the heart. Respiratory cancer mortality was analyzed with reference to period of first employment, length of employment, and degree of exposure to arsenic trioxide and sulfur dioxide. The excess in respiratory cancer was seven to eight times that expected among men first employed prior to 1925 who were heavily or moderately exposed to arsenic trioxide; it was more than four times that expected among men heavily exposed and first employed in 1925-47, and it decreased in direct proportion to degree of arsenic trioxide exposure. Inhaled arsenic trioxide was strongly implicated as the primary agent associated with the excess respiratory cancer, with sulfur dioxide perhaps enhancing the effect.