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Summary.-Mesothelioma death rates in asbestos workers appear to be proportional to the 3rd or 4th power of time from first exposure under a wide range of conditions of exposure for both pleural and peritoneal tumours, though the peritoneal: pleural ratio depends on fibre dimension and type. Age at first exposure has little or no influence, however, which supports the "multi-stage" model of carcinogenesis under which the increase in most cancer incidence rates with age is due to a constant incidence of genetic or epigenetic accidents, rather than to progressive generalized changes in regulatory or immune function. These relationships provide a simple basis for risk assessment, and support the suggestion that mesotheliomas may constitute a high proportion of cancer deaths resulting from early exposure to asbestos. THERE IS persuasive if inconclusiveevidence that the extraordinarily sharp increase with age of many human cancer rates is due to the uniform occurrence of pre-neoplastic changes in individual cells and the subsequent proliferation of partially transformed cells, rather than to agerelated somatic changes such as the progressive breakdown of immunosurveillance hypothesized by Burnet (1965). Changes in national lung-cancer incidence patterns in successive birth cohorts can be explained on the assumption that the risk to smokers is a function of duration of smoking, independent of age, and the incidence of lung cancer in continuing smokers appears to rise as the 4th or 5th power of duration of smoking, whereas in non-smokers incidence rises as the 4th or 5th power of age. These observations were reviewed by Doll (1971Doll ( , 1978 who suggested that the disease process may be identical in smokers and non-smokers, the "natural" occurrence of certain cellular accidents that happen at a fairly constant rate throughout a non-smoker's life being increased substantially in smokers from the time the habit is adopted. He postulated that excess lung-cancer incidence among continuing smokers should therefore be determined by duration of smoking, irrespective of age at starting to smoke. The importance of duration of smoking is qualitatively confirmed by the marked difference in age-specific lungcancer incidence between those who started to smoke before age 16 and those who started after age 25 (Kahn, 1966) but the effect is confounded by differences in consumption, inhalation, and perhaps the length of butt and type of cigarette smoked, and it is not possible to demonstrate directly that incidence is entirely independent of age. Age-independence has thus not yet been demonstrated for any human cancer, though Peto, R. et al. (1975)

Two thousand two hundred seventy-one deaths were recorded among 17,800 asbestos insulation workers observed from January 1, 1967-December 31, 1976. There was little increase in cancer deaths or of asbestosis in less than 15-19 years from onset of employment. In general, though, the period of clinical latency was 2-4 decades or more and there were important differences among the several asbestos-associated diseases. Lung cancer peaked at about 30-35 years from onset and asbestosis at 40-45 years. Each tended to decline in incidence afterwards. Pleural and peritoneal mesothelioma reached their highest incidence later than lung cancer, but the incidence did not decline. In studies of effects of asbestos exposure, it appears advantageous to observe for at least 35-40 years or more from onset of exposure and to analyze the experience in duration-from-onset categories. If this is not possible, only the very limited early effects will be identified and the full import of the exposure may not be appreciated.

Estimates have been made of the numbers of cancers that are projected to result from past exposures to asbestos in a number of occupations and industries. From 1940 through 1979, 27,500,000 individuals had potential asbestos exposure at work. Of these, 18,800,000 had exposure in excess of that equivalent to two months employment in primary manufacturing or as an insulator (greater than 2-3 f-yr/ml). 21,000,000 of the 27,500,000 and 14,100,000 of the 18,800,000 are estimated to have been alive on January 1, 1980. It is further estimated that approximately 8,200 asbestos-related cancer deaths are now occurring annually. This will rise to about 9,700 annually by the year 2000. Thereafter, the mortality rate from past exposure will decrease, but still remain substantial for another three decades.

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