Implications of the multistage theory of carcinogenesis applied to occupational arsenic exposure.

The multistage theory of carcinogenesis and its implications for evaluating the effect of exposure to carcinogens in the workplace are described. This theory predicts different relationships between excess carcinogenic risk and duration of exposure, age at initial exposure, and follow-up time since exposure stopped. These relationships are shown to depend on the stage of the carcinogenic process affected by the carcinogen, i.e., action at an early stage or a later stage. The patterns of excess lung cancer mortality were examined for a cohort of copper smelter workers exposed to atmospheric arsenic and other contaminants. Under this multistage hypothesis, the results indicate that arsenic appears to exert a definite effect on a late stage of the carcinogenic process, although an additional effect at the initial stage cannot be conclusively ruled out. Other factors, such as exposure to sulfur dioxide in the environment, calendar year at start of employment, and the potential bias resulting from incomplete exposure histories are also discussed as well as the implications of these results to experimental animal studies.