Problems in Dose Response and Risk Assessment : The Example of Asbestos

Abstract

The selection of an inappropriate model of carcinogenesis can lead to gross errors in the predicted effects of exposure to a carcinogen. For example, the increase in lung cancer incidence caused by cigarette smoking is approximately proportional to the product of the dose (number of cigarettes smoked per day) and the fourth or fifth power of duration of smoking (Doll, 1978; Doll and Peto, 1978; in fact, the dose-dependence may include linear and quadratic terms). It is therefore impossible to base useful predictions on the cumulative dose (total number of cigarettes smoked), as the eventual risk caused by smoking 10 cigarettes/day for 40 years may be 50 times greater than that caused by smoking 40 cigarettes/day for 10 years. The term “dose” should therefore be used only to describe the dose-rate of exposure to a carcinogen (cigarettes per day, or fibres/ml of asbestos), and the effects of temporal variables (age, time since first exposure, duration of exposure) should be examined separately. There is no useful general formula that describes the effects of all carcinogens. Asbestos appears to act as an initiator (early stage carcinogen) in mesothelioma induction but as a promoter (late stage carcinogen) for lung cancer (Peto et al., 1982); cigarette smoking seems to both initiate and promote lung cancer induction: and ionising radiation probably acts primarily at one or more intermediate or late stages in the induction of most or all carcinomas (Doll, 1978).

Originally presented at a meeting at the Banbury Center, Cold Spring Harbor Laboratory, New York, 11714, 13–16 May 1984.