Document G5no0yx5ym69jGKbp9bRgYNMq

Pergamon 0003-4878(94) Anii. ortt/p. nyi/., 101. . n-. -------- .. Etsevwr Science Ltd British Occupational Hygiene Society Printed in Great Britain 0003-4878/94 S7.OO+0.0Q CANCER MORTALITY IN CHRYSOTILE MINING AND MILLING: EXPOSURE-RESPONSE Douglas Liddell (Received 9 December 1993 and in finalform 15 February 1994) Paper read at the Workshop on Health Risks Associated with Chrysotile Asbestos, . held in Jersey, Channel Islands, 14--17 November 1993. Abstract--see p. 412. THE QUEBEC COHORT ^OTiCE- T4.i COPYRIGHT UVV (HTLE17 U.S-CODE) Provenance The best information on exposure-response relationships in chrysotile mining comes from the Quebec cohort: this consists of all 10925 men bom 1891-1920 who had worked for 1 month or more in the mines and mills in the Eastern Townships of the Province of Quebec. They have been traced to the end of 1988, by which time 1105 had been lost to view; these included well over 800 never traced after very short service before 1930. Of those traced, there were 2508 survivors into 1989, and there had been 7312 deaths, 7% more than expected on the basis of the published vital statistics of Quebec. Reports on mortality to 1966, 1969 and 1973 were published in 1971,1973 and 1977. McDonald et al. (1980) reported on all 4463 deaths before 1976, and further analyses were described by Liddell et al. (1984) and by Vacek and McDonald (1990). A report on subject-years analyses of mortality 1976-1988 has been published (McDonald et al, 1993), and in this paper is referred to as BJIM '93; in a section ofthe current review there is a brief preliminary account of case-referent analyses of lung cancer, from the earliest recorded until 1988; mesothelioma in the corresponding period has been described briefly by McDonald et al. (1994). Mortality 1976-1988 Table 1 (adapted from BJIM '93) shows that there was an excess overall of 193 deaths. The most notable excesses were of lung cancer (91), mesothelioma (25) and pneumoconiosis (48); other differences from expectation were small either numerically or relatively. . In particular, there were 18 cases of laryngeal cancer where 13.8 were expected, but this excess was concentrated in smokers, and the associations with various measures of dust exposure were negative. There were also 56 stomach cancers (47.9 expected), but the excess was confined to Thetford Mines, and there were no associations with dust exposure. The excess of 13 deaths from respiratory diseases other than pneumoconiosis was only 5% of the expected number. 519 520 D- Liddell Table I. 2827 deaths, 1976-1988, by cause Cause of death (with ICD codes) Observed All causes Malignant neoplasms abdominal: stomach (151) other (150,152-9) respiratory: larynx (161) lung (162) genito-ufinary: prostate (185) bladder (188) kidney (189) lymphatic and haematopoietic tissue (200-208) other (rem 140-209) Mesothelioma Pneumoconiosis Other respiratory diseases (rem 460-519) Heart disease (391,392.0,402,404,410-429) Cerebrovascular disease (430-438) Chronic liver disease and cirrhosis, and alcoholism (571,291,303, 860) Injury and poisoning (800-999) All other causes (rem 001-999) [including respiratory tuberculosis (5)] 2827 56 146 18 321 81 20 13 56 76 25 48 256 1013 225 32 89 352 Excess J92.7 8.1 -16.9 4.2 91.3 4.3 ' -5.0 0.0 8.1 5.2 25 48 13.0 18.6 12.9 -7.5 12.8 -29.4 SMR 1.07 1.17 0.90 1.30 1.40 1.06 0.80 1.00 1.17 1.07 -- -- 1.05 1.02 ' 1.06 0.8.1 1.17 0.92 Table 2 (also adapted from BJIM '93) shows deaths from lung cancer, 1976-1988, in relation to exposure accumulated to age 55 years. There is no indication of a trend over the seven lowest categories of exposure in million particles per cubic foot (mpcf) x years. There is strong evidence that the lung cancer SMR of 1.27 for these 4145 men arose from comparatively heavy cigarette smoking. Table 2. Deaths from lung cancer, 1976-1988, in relation to EXPOSURE ACCUMULATED TO ACE 55 YEARS Exposure (mpcf-years) No. of men O Deaths E . O/E <3 3,<10 10, <30 30, <60 60, <100 100. <200 200, <300 708 36 31.4 1.14 582 40 25.3 1.58 712 33 31.3 1.05 569 39 24.4 1.60 525 30 22.8 1.32 663 32 28.3 1.13 386 20 17.3 1.15 <300 4145 230 180.8 1.27 300, <400 400, <1000 Sr 1000 253 16 10.7 1.50 621 42 25.4 1.65 138 22 7.2 3.04 Total 5207 310 224.1 1.38 i. ii t. Cancer mortality in chrysotile mining and milling 521 Case-referent analyses of lung cancer This section is a brief preliminary statement concerning the analyses presaged in BJIM '93; they will be fully reported after completion. Case-referent comparisons have been made, using conditional logistic regression, on the 548 deaths from lung cancer up to 1988 (245 before 1976 and 321 since, with certain exclusions). For each case one ' referent was chosen at random from among survivors to a greater age, after matching on place of employment, age of starting work, smoking habit and date of birth. For each man, and for each year of employment, we obtained the fraction of the year worked at each of six levels of intensity, assessed in mpcf, as follows: <5; 5, < 15; 15, <30; 30, <40; 40, <50; and 50-140. We then calculated how many years each man spent at these various levels; the years, adj usted for the length ofthe working week (66 h until 1937; 48 h 1938-1949; 40 h 1950-1985), were accumulated up to 10 years before the age of death of the case. The risk of excess lung cancer after exposure to concentrations of less than 15 mpcf was estimated as nil (i.e. the calculated Odds Ratio was less than 1), The risks of lung cancer after exposure at the four higher levels, i.e.. to dust concentrations of 15-140 mpcf, appeared substantial, but exposure-response relationships were irregular, and quantification is not yet possible. Mesothelioma The proportional mortality from mesothelioma'in the Quebec cohort, even including the factory workers many of whom are known to have been exposed to crocidolite, had reached only 0.45% (33 deaths among 7312, almost three-quarters of the cohort) by the end of 1988. This is much lower than has already been observed in cohorts exposed to commercial amphiboles at a much earlier stage of their mortality, and after markedly less severe exposure; in South African crocidolite miners, for example, the corresponding figure had reached 4.7%, when the overall mortality was still, much less than one-fifth of the cohort (McDonald et of., 1994). Discussion . No apology is made that intensity of exposure is expressed in terms of million particles per cubic foot, if only because these were the terms in which the original measurements had been made (Gibbs and Lachance, 1972). A further reason is explained below. . The complex relationships between dust counts and fibre counts in the Quebec mines and mills have been studied by Gibbs and Lachance (1974) and by Dagbert (1976). Liddell et al. (1984) explained how a fibre/dust ratio was assessed for each job in which any of 2217 subjects had worked: these ratios ranged from 0.3 to 30 (fibres ml"J )/(mpcf). Nevertheless, the relationships between mortality from various causes and accumulated exposure were closely similar whether adjustment from dust terms to fibre .terms was made job by job and subject by subject (involving about 10000 adjustments) or by use of a single `average' ratio close to 3.5 (fibres ml~!)/(mpcf). The risk of lung cancer as a result of exposure at intensities of less than 15 mpcf was minimal; higher intensities, i.e. above about 50 fibres ml-1, are well outside today's experience, even in the worst conditions in developing countries. Thus, risks associated with such severe exposures have become irrelevant, and it is of no practical importance that these risks cannot be quantified reliably. 522 D. Liddell It must be emphasized that all the `new' findings are confirmation and strong reinforcement of earlier findings from the same cohort; in other words, the differences between present findings and those previously reported are of degree rather than of kind. THE BALANGERO EXPERIENCE Provenance the mortality of workers at the Balangero chrysotile mine and mill in northern Italy was first reported in 1972 on men employed between 1932 and 1970. Rubino et ai (1979) examined mortality from 1946 to 1975 of 952 men first employed between 1930 and 1965. An `update' on mortality from 1946 to 1987 of 1058 men who had worked for at least 1 year between 1946 and 1987 was published by Piolatto et al. (1990). A summary of the relevant material follows. The 427 deaths were almost 50% more than expected on the basis of national rates, an excess of 141 deaths. Most of this excess arose from causes not related to asbestos exposure, namely `other causes' (71), hepatic cirrhosis (30), and accidents and violence (23). There were five more laryngeal cancer deaths than the 3.0 expected. There was also an excess oflung cancer, but it was tiny and not related to exposure, and there were no excesses of gastric or intestinal cancer. There were two mesotheliomas (PMR=2/427--0.47%), both pleural, and both after exposure for more than 20 years. Discussion It is apparent that the findings in relation to lung cancer, gastrointestinal cancer and mesothelioma are strongly supportive of those from the Quebec cohort. As for laryngeal cancer, the interpretation of the associations with asbestos exposure is difficult (Liddell, 1990), especially in a region where there is particularly heavy alcohol consumption, as at Balangero. But whatever the interpretation, the risk of laryngeal cancer as a result ofchrysotile exposure ofless than 100 (fibres ml~1) x years must be considered minimal. CONCLUSIONS The following conclusions are drawn from all the evidence about cancer mortality among chrysotile miners and millers. There is strong evidence that the risk of lung cancer as a result of exposure to chrysotile at concentrations of less than 15 mpcf is vanishingly small. At higher concentrations, the relative risk of lung cancer is elevated, probably less so in smokers of 20 or more cigarettes a day than in others, but the magnitude of the elevated risks cannot be evaluated with any certainty; this is of no importance, because such higher concentrations--i.e. of the orders of 50-500 fibres ml"1--are well outside the range of any experience nowadays. There is no evidence that the risk of laryngeal cancer is increased as a result of exposures up to at least 100 (fibres ml - *) x years. There is no evidence that the risk ofstomach cancer is adversely affected by exposure to chrysotile; and there is no evidence of increased risk of other abdominal malignancies or of kidney cancer among chrysotile miners and millers. Cancer mortality in chrysotiie mining and milling 523 The risk ofmesothelioma in chrysotiie miners and millers is very low compared with the risks in other asbestos-exposed populations, except those exposed only to chrysotiie. [For the discussion of the issues raised in this and the other allied papers see pp. 413--415 ] REFERENCES DaGBErt, (1976) Etude de correlation des roesures d'empoussierage dans I'industrie d'aroiante. Document 5. Quebec: Comite d'etude sur la salubrite dans I'industrie de I'amiante (President: Rene Beaudry, jcp). Gib&s, G. W. and Lachance, M. (1972) Dust exposure in the chrysotiie asbestos mines and mills of Quebec. Archs Environ. Hlth 24, 189-197. Gibbs. G. W. and Lachance, M. (1974) Dust-fibre relationships in the Quebec chrysotiie industry. Archs Environ. Bith 26, 69-71. Liddell, F. D. K. (1990) Laryngeal cancer and asbestos. Br. J. ind. Med. 47,289-291. Liddell, F. D. K., Thomas, D. C-, Gibbs, G. W. and McDonald, J. C. (1984) Fibre exposure and mortality from pneumoconiosis, respiratory and abdominal malignancies in chrysotiie production, 1926-75. Ann. Acad. Med. Singapore 13, No. 2 Suppl., 340-344. . McDonald, A. D., Liddell, F. D. K. and McDonald, J. C. (1994) Malignant mesothelioma in Quebec chrysotiie miners and millets: a preliminary report. In Proceedings ofthe 9th International Symposium on Epidemiology (n Occupational Health, Cincinnati, Ohio, September 1992 (in press). McDonald, J. C., Liddell, F, D. K,, Dufresne, A. and McDonald, A. D. (1993) The 1891-1920 birth cohort of Quebec chrysotiie miners and millers; mortality 1976-1988. Br. J. ind. Med. SO, 1073-1081. McDonald, J. C,, Liddell, F. D. K.t Gibbs, G. W., Eyssen, G. E. and McDonald, A. D. (1980) Dust exposure and mortality in chrysotiie mining, 1910-75. Br. J. ind. Med. 37, 11-24. Piollato, G., Negri, E., La Vecchia, C-, Pira, E,, Decaru, A. and Peto, J. (1990) An update of cancer mortality among chrysotiie asbestos miners in Balangero, Northern Italy. Br. J. ind. Med. 47,810-814. Rubino, G. F,, Piolatto, G.,Newhouse, M. L., Scansetti, G., Aresisni, G. A. and Murray, R. (1979) Mortality of chrysotiie asbestos workers at the Balangero Mine, Northern Italy. Br. J. ind. Med. 36, 187-194. . Vacek, P. M. and McDonald, J. C. (1990) Effect of intensity in asbestos cohort exposure-response analyses. In Occupational Epidemiology (Edited by Sakurai, H. et ai). Elsevier, Amsterdam.