Document RakxgyvzGj62pG4jE9mKYxB1k

t 'k>vc then other ot. . basis Cities from .osis should e and other. sufficient to )rc a definite . not as -- 1; tal is greater tite, between less than or in 1967 and : sources, has eceased cases ` notifications 5 up to 1971, dng included MA RjECtSTEK 1970 1971 165 12* 11 " 3-- 3 184 138 tion not possible to rge number of suited from the ! the survey. If iications is con: to a change in :o a change in L l l Not Not British Journal of Industrial Sfsdicinc* 1974, 31, 105-112 Mortality and morbidity among the working population of anthophyllite asbestos miners in Finland IV L. O. MEURMAN, R. KIVILUOTO, and M. HAKAMA | Department of Pathology. University Central Hospital of Kuopio, Kuopio, and Finnish Cancer Registry. Helsinki, Finland Metinram, L. O., Kiviluoto, FL, and Hakama, M. (1974). British Journal ofIndustrial Medicine. 31, 105-112. Mortality and morbidity among the working population of anthophyllite asbestos miners in Finland. A study has been made in Finland of the effects of anthophyllite asbestos on mortality and morbidity of 1 092 asbestos workers first employed at two mines between 1936 and 1969; 95 % of workers were traced, 248 of whom had died. A similar number ofagesex-matched controls was selected from a township 60 km from the mines. -The causes of death included an excess due to lung cancer and asbestosis, but cancers of the digestive system occurred in equal frequency, and neither the cases nor controls had any confirmed mesotheliomas. Assuming a multiplicative effect of asbestos and smoking, the relative risk of lung cancer was 17 for an asbestos worker who smokes in terms of a non-exposed nonsmoker. The corresponding figures were 12 for a smoker without asbestos exposure and 1-4 for an asbestos worker who did not smoke. More heavy smokers were found among the asbestos workers than among the controls. A threefold excess of dyspnoea and a twofold excess of cough were recorded for the asbestos workers compared with the controls after adjustment for smoking. It has been demonstrated that asbestos dust results in harmful effects upon man's health in three different ways: lung cancer, asbestosis. and diffuse pleural or peritoneal mesothelioma (Wright, 1969). Some evidence also exists for increased mortality from other malignancies, particularly cancer of the digestive organs (Mancuso and Coulter, 1963; Selikoff, Chure. and Hammond, 1964; Enterline, 19651. Considerable interest has been focused upon the possible difference in health hazards resulting from various kinds of asbestos. It is known that asbestos minerals obtained from various sources in the world have a wide range of chemical and physical differences (Timbrell, 1970) but it is common to mix various types of asbestos for industrial purposes (Neuhouse. 1970). Studies of exposure to only one type ofasbestos can be made in populations working as near as possible to the source of production, i.e., the mines or mills. In North Savo, in Finland, asbestos mines have been worked since 1918. The Finnish type ofasbestos anthnnhvllite. which belongs to the amohibole group ot minerals, is relatively insoluble in human lungs compared to chrysonic asbestos, the cotnmonest type in the world, which slowly dissolves within the lungs. In animal experiments, it has been demonstrated that anmoohvllite induces lung horosis with a relatively short latent peno<l_Holt. Mills, and Young. I965i. Anthophyllite is rather brittle and cannot be woven as can the more flexible flfirysotile (Gaze, 1965). Chiysotile fibres are hollow tubes whereas anthophyllite fibres are solid tGaze, 1965). In rhe main, anthophyllite is utilized as a cheap filler or as an insulation material by virtue of its 105 V 106 L. O. Meurman, R. Kiviluoto, and M. Hakama excellent resistance to heat and chemicals, together with its "high electrical insulation. Since 1936; both mines in Finland have been owned by Suornen Mineraali Oy. One of the mines. Paakkila. is still in use, with an annual output of 10-15 000 tonne (Mg). The mine is combined with a dry hammer asbestos mill, which mithw th<- hmif>-n rock into asbestos powder for various industrial applications, tne other mine, Maljasalmi, has been used intermittently ana has not been in operation since 1963. Its production ot asbestos was small, and the main product was tremolitetalc. 'Tvorthiavo, in the heart~of Finland, is a lake- dotted area with large forests, mainly spruce and pine, and rather sparsely inhabited (11 pexsons/km*). The nearest urban community with any industry worth mentioning is 50 km from the mine to the west. The thinly scattered population around the mill, mainly farmers making their living from agricultural and forest work, was fairly stable until the 1960s when gradual migration began to the neighbouring urban areas and southwest Finland. There are three reasons for studying the effects of asbestos in Finland--the unusually high incidence of lung cancer (Doll. Muir, and Waterhouse, 1970); the high frequency of asbestos bodies in the lungs (Meurman. 1966); and the common occurrence of pleural fibrocalcific plaques, which are usually associated with asbestos exposure (Kiviluoto, I960; Meurman, 1966; Raunio, 1966). Moreover, cigarette smoking is and has for a long time been an unusually - common habit in Finland (Pedersen et al.. 1969). The aim of the present study is to estimate the ^health hazards of anthopnylhte asbestos and "To compare them with" Ihe elJcas ul Ollier' types of asoestos exposure investigated ClSeWliefi.-------- ; Materials and methods A personnel registry, in the form of salary lists of the two asbestos mines in Finland, had been maintained fairly completely by the mining company since 1936. The entire records were placed at our disposal for research purposes, and further information concerned with die workers in the mines and the mill was kindly given by the company. The lists contained the names of the workers and their length of employment, and as a rule the types of work they had done. In some cases, the files did not contain the date of birth or even the year of birth, but the identification data and place of residence were checked with the official Finnish national population registry. The Church in Finland, as a state church, has registered the population for several hundred years. Ifa person migrates from one municipality to another the change is registered by both local church registrars. From these sources and in the main from the salary' lists, personal data and postal addresses were collected for all the workers in both mines who had been at work between 1 January 1936 and I June 1967 for periods of three-months or more. Copies of the death certificates of those workers who had died were obtained from the Central Bureau of Statistics. The expected numbers of deaths for cases of lung cancer and gastrointestinal cancer were estimated, with allowance for age, using the observed proportions of deaths due to different causes ofdeath in Finland in I95. which was the median year of death of the asbestos workers. As do reliable comparative data were available for smoking habits and respiratory symptoms on a national basis, a special sample of controls was sejected within the rural neighbourhood of the mines. At the same time it was thought useful to have matched controls for the deaths, as it was felt that different types of bias might invalidate comparison of the national mortality data with the data on asbestos workers. However, no overt differences were observed between these two groups. A control group was obtained by selection from the local population registry of the township of Maaninka in North Savo, an agricultural area containing no mines nor other industrial plants. Maaninka has about 8 000 inhabitants and is about 60 km to the northwest of the asbestos mines, and the distance to the nearest urban area is about 40 km. The controls were matched with asbestos workers for date of birth, sex. and date of death or with asbestos workers alive on 1 June 1967. The addresses of the living control cases were taken from the electoral fists, and the death certificates for the deceased controls were recorded from the Central Bureau of Statistics. If the thing control case could not be contacted, someone corresponding most closely to the matching criteria for date of birth was chosen. If two or more control cases equally close to the date of birth of the case were found, the first to be noted was chosen. The matching was complete in all pairs, and the difference between the age of the case and the matched pair never exceeded one year. A quesu'onnaire was sent to each living asbestos worker and each control, together with a letter explaining the purposes of the study. This letter did not disclose that a survey of the effects of asbestos dust was in question but indicated only that it related to the problems arising from the possible effects of atmospheric pollution of any kind. The principal questions were in two pans--whether or not the interviewee felt well. had a cough, and had dyspnoea; and a more detailed inquiry into smoking habits, including information on the duration of smoking and the number of cigarettes smoked daily. The question naire further inquired into the duration, quality, and intensity of any dusty work, the age at the beginning of exposure, and thq-period-of such exposure. The risk of different respiratory symptoms and diseases was evaluated in terms of prevalence rates and the relative risks. The rates were adjusted in accordance with smoking habits, the distribution of different smoking categories in the total controls being taken as standard. Results The number of asbestos mining company employees known to have been at work for a period of at Least three-months between 1 January 1936 and-4 July 1967 was 1 092. The rnumber of employees^ with- 5- -- Mortality i complece follow on 20 May 1969 Number of Company kni Months or l and 1 JUL' Died before 1 July Died between 1 Ju Alive, questionnair No. followed up Follow-up impraci Tola! .. Analysis of causr Of the I 092 en died by the tern employees and causes of death gives the numb asbestos emplc emphasis was lai cancer, cancer o liomas. No case tosis was the pri employees, wher this cause. The observed (ICD 162, 7th r digestive organ asbestos emplo listed in Table Observed and Age -- 1.5-24 25-34 35-44 45-54 55-64 65-74 75- " All ages i : Assuming SJETspc d from the st lung cn- .. with 'portions of and in 1958. :he asbestos lvailable for n a national ected within ic same time trois for the T bias might artality data er. no overt groups. ;on from the Maaninka in no mines nor about 8 000 hwest of the earst urban ; workers for ith asbestos . of the living lists, and the vere recorded .'inns control orresponding late of birth uallv dose to he first to be mplete in all 'the case and b worker xpiaming the lisdose that a i question but s arising from n ofany kind, s--whether or tgh. and had into smoking on ofsmoking The question. quality, and c beginning of is and diseases ,nd the relative tordance with :rem smoking a as standard. jiy employees iod of at least ;6 and 1 July aployccs with . Mortality and morbidity among: the working population of anthophylUtc asbesto miners f- Finland 107 complete follow-up at the termination of the study on 20 May 1969 was I 041 (95-3 %) (Table l). TABLE 2 Number of Deaths by Cause among Asbestos Employees and Controls TABLE l Number of Workers in Asbestos Mining Company known to have worked for Three Months or longer between I January 1936 and 1 July 1967, by Follow-up Status Died before 1 July 1967 .......................... Died between I July 1967 and 20 May 1969 Alive, questionnaire received.......................... No. followed up ...................................... Follow-up impracticable Total 24S 6 787 1 041 51 1 092 Cause of death Cancer of lung Pulmonary tuberculosis .. Cancer of digestive organs Other forms ofcancer Cardiovascular deaths Cerebrovascular deaths .. Trauma, poisoning or suicide......................... Asbestosis......................... Other causes AH causes......................... Employees Controls V F 21 32 7 --4 9I 71 12 16 < MF 13 _ IS 2 81 72 91 9 15 9 JO 10 4_1 -- 20 26 9 216 32 216 32 i Analysis of causes of death Of the 1 092 employees, 248 were known to have died by the termination of the study. In 35 asbestos employees and 25 controls information on the causes of death was based on necropsy. Table 2 gives the number of deaths by cause among the asbestos employees and the controls. Special emphasis was laid upon deaths from asbestosis, lung cancer, cancer of the digestive organs, and mesothe liomas. No case of mesothelioma was found. Asbestosis was the primary cause of death in 13 asbestos employees, whereas none of the controls died from this cause. The observed numbers of cases of lung cancer (ICD 162, 7th revision) and cases of cancer of the digestive organs (ICD 150-159, 7th revision) in asbestos employees, together with controls, are listed in Table 3. The differences in lung cancer between the asbestos and control groups were not sigrificant. Moreover, no excess risk of cancer was apparent in the digestive organs of asbestos employ ees, compared with either the controls or the expected figures derived from the national mortality data. However, the proportional mortality study showed a significant (r < 0-05) excess of deaths for lung cancer in asbestos employees compared to the national figures. The most marked differences between the observed and expected numbers were in the age group 45-54 (p < 0-01), and in cases with more than 10 years' exposure (p < 04)1. Table 4). It has been shown that smoking cigarettes is a strong and common aetiological factor in lung cancer (Smoking and Health, 1964). and that asbestos workers tend to consume more cigarettes than a normal population (Selikoff. Hammond, and Churg, 1968). The estimation of smoking habits was TABLE 3 Observed and Expected1 Numbers of Lung Cancer and Cancer of Digestive Organs in Deaths among Asbestos Employees and Controls,'by Age 15-24 25-34 35-44 45-54 55-64 65-74 75- All ages Asbestos -- -- I 10 7 3 -- 21 Lung cancer Controls __ -- -- 6 4 -- 13 Expected 0-0 0-1 0-7 3-4 5-6 2-6 0-2 12-6 Cancer ofdigestive organs Asbestos Controls Expected -* I 1 i 4 -- -- -- 4 i 4 -- 0-0 0-3 1-2 3-2 5-3 4*2 0-7 7 9 U-9 1Assuming age-specific rates for dea:hs from lung cancer and cancets of digestive organs in Finland 195$. 108 L. O. Meurtnan, R. Kiviiuoto, and M. Hakama Mortality TABLE 4 Observed and Expected1 Numbers of Lung Cancer and of Cancer of Digestive Organs in Deaths among Asbestos Employees with .more than 10 Years of Exposure, by Age Ate 35-44 45-54 55-64 65-74 Total Long cancer Cancer ofdigestive organs Observed Expected Obserred Expected i 5 2- -- 0-0 t-0 1-0 0-4 0-0 I 0-8 0-8 t 0-5 S 2-4 2 2-1 'Assuming age-specific rates Tor deaths from lung cancer and cancer of digestive organs in Finland 1958 made with a view to avoiding confusion due to the effects of smoking upon lung cancer deaths. The smoking habits of persons already dead were not known. However, results were available, based upon the postal questionnaire, for the smoking habits of existing employees and controls (Table 5). On the assumption that similar differences existed among the dead employees and controls, and that there was a linear relationship between the number ofcigarettes smoked daily and the risk oflungcancer, the following are the relative risks (Kahn, 1968): Xumber ofcigarettes/day Risk None <15 >15 1 10 15 A relative risk of 7-3 of death from lung cancer will exist among the control population compared to a non-smoker, and a relative risk of 8-4 of death from lung cancer for asbestos workers. The expected figures for lung cancer should be adjusted for smoking if it is assumed that the excess smoking among asbestos workers is independent of TABLE 5 Smoking Habits of Employees and Controls (by postal questionnaire) Cigarettes smoked daily None <13 >15 Total Employees Suntber 262 33-3 300 38-1 zzs 23-6 737 100-0 Controls A'umber me 314 39-9 326 41-4 147 18-7 787 100*0 the asbestos environment. Given the smoking habits of asbestos workers, the expected numbers of lung cancer cases due to smoking would be 15 for the total group of asbestos workers, and 3 for the group with more than 10 years' exposure. The difference is significant (p < 0-05) only for the observed and expected numbers of employees with more than 10 years' expcfeure. With these assumptions taken as a basis, together with the multiplicativity of risk induced by cigarette smoking and asbestos exposure (Doll, 1971; Berry, Newhouse, and Turok, 1972), the relative risk, compared to a nonsmoker without exposure to asbestos, of lung cancer is: Non-smoking asbestos worker Smoker without asbestos exposure Asbestos worker and smoker 1-4 12 17 Analysts ofhealth condition and respiratory symptoms among employees of the asbestos company still living The employees of the asbestos mining company included a number of persons who cannot be regarded as true asbestos workers as they had never worked in the dusty environment of the open mines or the mill, or had worked for only a relatively short period in them. Consequently, a high-risk sub-group of living asbestos employees was selected. This sub group, which comprised only those who had worked for 10 years or more either in the mines or in the milL and had been heavily exposed to asbestos dust, was compared with controls matched by age and sex. Three variables, state of health, cough, and dyspnoea, were analysed from the answers given in the postal questionnaire. The different smoking habits of the asbestos employees and controls (Table 5) necessitated adjustment of the prevalence rates of respiratory symptoms and diseases according to the number of cigarettes smoked daily. The matched controls for both groups, the workers subjected to heavy exposure, and the Other-living employees displayed a systematic difference of prevalence rates. This is probably attributable to the higher mean age of the group with longer periods of exposure. The entire group of Jiving asbestos workers con sisted of787 cases; of these, 110 had been engaged in asbestos work, with heavy exposure, for 10 or more years. State of health Table 6 shows employees and controls, divided into sub-groups in accordance with their own evaluation of state of health. No effect of asbestos exposure upon the subjective state of health of either -the asbestos-workers as a whole or the sub-groupTfeaxily exposed uas apparent. = j Subjective Employees Employees w EmpU Healthy Not healthy Total 41 37 7S Occurrence of o A correlation exposure to asb all smoking cat method to the c controls. The prevalent to asbestos and But for the heanumber of cig' effect upon the group of asbes cough was twice controls. Furthe the occurrence (4-4) as commo prevalence of o statistically sigr the relative ris! to 3-6). Occurrence of c Dyspnoea at i considerable st for in the ques at rest were acc commoner amc Pre Cigarette smoked daitv None =15 <15 Total, adj 'SiHoking disrobt iking habits x T lung i, ior the ir the group difference is jserved and ;orc than 10 sis, together by cigarette 1971; Berry, elative risk, exposure to 1-4 12 17 >ry symptoms my still Bring ng company > cannot be icy had never e open mines datively short isk sub-group ;ed. This sub0 had worked ines or in the asbestos dust, 1 by age and .gh, and swers given in the asbestos ) necessitated of respiratory the number of ,-d controls for red to heavy ees displayed a rates. This is ican age of the -e. s workers con5cen engaged in for 10 or more jls, divided into own evaluation bestos exposure h of either the rb-group heavily Mortality and morbidity among the vorking population ofcuithophyllitr asbestos miners in Finland 109 TABLE 6 Subjective State of Health of Asbestos Employees and Controls, and Asbestos Employees with Heavy Exposure to Asbestos Healthy Not healthy Total All thing Employees Controls 412 445 375 342 in 7S7 Heavy exposure Employees Controls 45 47 65 63 110 110 TABLE 8 Relative Rates for Couch by Exposure to Asbestos and Smoking Habits, compared to Rate for Non-exposed Controls with Same Smoking Habits as Exposed Employees Cigarettes smoked daily None <15 >15 Moderate 1-91 l-SI 1-46 Exposure Heavy 5-88 4-24 2-97 Total 2-51 2-42 1-75 Total, adj. 1-73 4-38 2-25 Occurrence of cough A correlation was observed between cough and' exposure to asbestos (Tables 7 and 8). The rates for all smoking categories were adjusted by the direct method to the distribution of smoking habits for all controls. The prevalence of cough increased with exposure to asbestos and number of cigarettes smoked daily. But for the heavy exposure group an increase in the umber of cigarettes smoked did not exert any effect upon the prevalence of cough. In the whole group of asbestos employees, the prevalence of a cough was twice (2-2) as common compared with the controls. Furthermore, in the heavy exposure group, the occurrence of cough was more than four times (4-4) as common as in their controls. The increased prevalence of cough among the exposed group was statistically significant (99% confidence interval of the relative risk for the total group was from 1-7 to 3-6). Occurrence of dyspnoea Dyspnoea at rest, under light strain, and under considerable strain such as running was enquired for in the questionnaire. Only cases with dyspnoea at rest were accepted for the analysis. Dyspnoea was commoner among the asbestos workers than among the controls, but no trend in the prevalence of dyspnoea with increased exposure to asbestos was apparent. The relative risk of dyspnoea slightly exceeded 3 both in the heavily exposed group and in the moderately exposed group (99% confidence limits being 2-2 and 4-9 for the total group). The prevalence rates of dyspnoea in relation to smoking habits displayed- a somewhat inconsistent pattern (Table 9). The prevalence was higher for asbestos workers than for the controls in every TABLE 9 Prevalence (per cent) and Relative Risks of Dyspnoea, by Smoking Habits, for Asbestos Employees and Controls Cigarettes smoked daily Prevalence rate Employees Controls None <15 >15 " 19-8 23-0 13-3 3-8 7-7 7-5 Total, adjusted1 19-9 6-1 `Adjusted for smoking distribution ofcontrols Ratio 5-6 3-0 1-8 3*5 TABLE 7 Prevalence (per cent) of Cough by Exposure to Asbestos, and Smoking Habits Cigarettes smoked daily None 15 <15 Tout, adj.1 Moderate Employees Controls 13-9 7-3 27-3 15-1 30-2 20-6 22-5 13-0 Exposure Heavy Employee* Controls 58-8 57-4 i '56-S 10-0 13-6 1943 57-8 13-2 Total Employees Controls 16-8 6-7 32-0 13-2 35-6 19-7 26-6 II-S `Smoking distribution of controls as standard -TV 110 L. O. Meurman. R. Kivituoto, anti St. Hakama Mortality at smoking category, even if the risk of dyspnoea did at necropsy but with no evidence of asbestosis. not continuously increase with an increasing number Of the 12 remaining cases of death from lung cancer, of cigarettes smoked. only four had been employed by the asbestos mining company for five years or more and of these three Discussion might have had some degree of asbestosis at death. From these figures the entire group of 21_lung Of the 51 cases who could not be traced because of cancer cases included a maximum of l l_cas_with unknown address or non-response, despite the asocstosis and Iung_canccr.cqnjbined. questionnaire being posted to them several times, In ttie whole scries of 248 deaths of former only seven had been employed by the asbestos employees of the asbestos mining company, 35 mining company for two years or more. Four of cases had asbestosis either as a primary cause of them had worked in either the mine or the mill. This death or as a co-factor. It is possible that gap in the material is small and does not materially anthophylIite-asbesto5 and lung cancer am only affect the results, which are naturally much more weakly associated in Finland, since only eight dependent upon the reliability of the information (possibly 11) of the 35 asbestosis cases had lung compiled. cancer at the time of death. By comparison. Buchan No mesotheliomas were found in this series, and an (1965) stated that in England half of those with the possibility that they are hidden among the cancer asbestosis at death also suffered from lung cancer. cases is small. Ten cases of malignancy other than This study indicates an excess of lung cancer lung cancer or cancer of the digestive organs were cases, probably attributable to asbestos exposure, found: three of these were of prostatic cancer, one but this excess is less than that reported in most cancer of the bp. one of the bladder, one of the other mortality studies of asbestos workers (Konig, breast, one Hodgkin's disease, one laryngeal cancer, 1960; Mancuso and Coulter, 1963; Selikoff et ai., and one cancer of the thyroid gland. In one case the 1964; Buchanan, 1965; Doll, 1965; Enterline, primary site was uncertain, but there were generalized 1965; Smither, 1965; Enterline and Kendrick, 1967; metastases including bones; this is not typical of Elmes and Simpson, 1971). However, these reports mesothelioma. Among cancers of the digestive on the carcinogenic effect of asbestos have been organs, one was oesophageal, one colonic, one derived mainly from mortality data on employees pancreatic, and the remainder were stomach can in the asbestos textile trade, or insulation workers cers. It seems unlikely that any of these cases of and pipe coverers in urban areas, with higher malignancy could have been a mesothelioma. exposure to other carcinogenic factors (Wright, Of the 36 cases of tuberculosis, 10 had been at 1969). work during the war years, 1940-44. All of them Only three reports have been published on were young men who had worked for only a relatively mortality amorig~ast>cstor miners and millers. All short period and who died soon after leaving .the oT~thn afe based on chtysotilfc as&tStos (Braun and work. In all probability they had been employed Truan, t958; Kogan, Troitsky, and Gulevskaya, without any medical examination because of the 1966; McDonald er al.. 1971). McDonald has shortage of manpower during the war. reported from Canada that among the 5% in.the The excess of tuberculosis among the asbestos highest dust category, the age-standardized mortality group resulted in an excess of traumatic deaths in rate was 20 % higher than in the other groups with the control group. The matched controls for the lower exposure. This excess was accounted for in seven young cases of tuberculosis who died during equal proportions by respiratory, cardiovascular, the war years 1939-45 included three young men and malignant diseases. The authors conclude that killed in the war. the true difference between maximally and minimally The 36 deaths from tuberculosis included 11 exposed mortality in fung cancer is about threefold. which took place during the war and six cases under However, the overall risk of lung cancer among 40 years of age; two cases confirmed at necropsy, asbestos workers was not higher than that in the seven cases confirmed radiologically and/or general population. The whole group ofemployees bacieriologicaliy at a sanatorium, and 10 cases with- who had died included 100 cases of respiratory incomplete evidence of the cause of death. Some of malignancy, with only three mesotheliomas. these 10 cases might possibly have been pleural In the present material for the heavily exposed mesothelioma or lung cancer. group a similar difference is seen between the In 13 cases, asbestosis was riven as the primary observed and expected numbers of cases of lung . J cause of death on-thc death certifiratc, and it was cancer (8 against 2*4). The present series included no - mentioned as a_corIacj_qr._ia. _J2_cases. Of the 21 mesotheliomas (or possibly one) as compared'with cases who had- died of lung cancer, eight also had thrcejruihe Canadian ^eries-'-However, the-number asbestos!*; five were found at necropsy. Of the of deaths, 24J5, isj>ntyr I 0 % of those in-theCanadian "remaining 13 lung cancer cases, only one was fougfc; study. - _ ~ - `r "* -a ; - ,- A Soviet invi (Kogan et al., IS lung cancer by . millers, and 2-3 with the general parable with the present study. The combinec upon lungcance al. (1968) among i-i al. (1970) amc authors reported worker who smo exposed non-sme great as the estir. The present foundation for c smoking and ast multiplicative or asbestosis for the from 1-4 to 4-4 exposed non-str additive rather ever, an increas eta/.. 1968; Doll multiplicative h two carcinogens. The number results obtained been at work foi cases had been , heavy exposure cases had been < of them had asb died from lung c the workers witl died from lung far-reaching co malignancy and Finland. The results g living employee: indicate that th health of the cative to permit > siderable numfcx taneously admi dyspnoea. Lang, have concluded abnormality of from 13% in mi 10 years to 85% Of 252 former a have pleural an radiographs (Ki A higher nun- found amofig a popuiatiori^sch f ' tstosis. 1. aacer, estos mining f these three >sis at death, of 21 lung 1 cases with > of former ompany, 35 ary cause of ossibie that rr are only only eight had lung son. Buchanaf those with ung cancer, lung cancer :os exposure, rted in most rkers (Kanig, cltkoff et al., i; Enterline, ndrick, 1967; these reports is have been an employees tdon workers with higher :ors (Wright, at .led on d millers. All os (Braun and Gulevskaya, icDonald has he 5% in the 'ized mortality _t groups with ounted for in ardiovascular, conclude that and minimally out threefold, stneer among in that in the i of employees of respiratory oroas. .javily exposed between the cases of lung ies included no uampared with a-, the number a the Canadian Mortality and morbidity among the working population ofanthophyllite asbestos miners in Finland 111 A Soviet investigation into asbestos mortality' 1971). In this study also asbestos workers smoked (Kogan et a!.. 1966) has shown an increased risk of more commonly than did their controls living in the lung cancer by a factor of 1-9 for miners. 3-1 for agricultural area. However, the prevalence of cough millers, and 2-3 for factory' workers, as compared or dyspnoea among the asbestos workers is not with the general population. This is roughly com completely attributable to the more prevalent smok parable with the twofold risk (21/13) observed in the ing of cigarettes. Cough was more than twice as present study. common among asbestos employees than among The combined effect of asbestos and smoking their controls, after adjustment for the effect of upon lung cancer has been estimated by Selikoff et smoking. The increase in the prevalence of a cough al. (1968) among insulation workers and by Mcurman in relation to the number of cigarettes smoked daily et al. (1970) among lung cancer patients. The former is steeper among controls than among asbestos authors reported a relative risk of 92 for an asbestos workers. In employees with heavy asbestos exposure worker who smokes cigarettes compared with a non- there was no trend of cough with number of cigar exposed non-smoker. This is more than five times as ettes smoked. The results indicate that mild exposure great as the estimate of 17 from this study. to asbestos exerts an additive effect upon cough in The present material docs not provide any different smoking categories, whereas the effect of foundation for distinguishing whether the effect of ' heavy exposure to asbestos outweighs the effect of smoking and asbestosis oh the risk of lung cancer is other factors (smoking). Dyspnoea is more than multiplicative or additive. The estimate of risk due to three times as common among asbestos workers as asbestosis for the Finnish asbestos workers increased among their controls, after adjustment for smoking from 1*4- to 4-4 in terms of the unit risk for non- habits. It can be assumed that the excess ofdyspnoea exposed non-smokers' on the assumption of an among asbestos workers is attributable to asbestos, additive rather than a multiplicative model. How and might indicate more or less advanced asbestosis. ever, an increasing amount of evidence (Selikoff The somewhat inconsistent pattern of dyspnoea in etal., I968;Doll, 1971; Berry era/., 1972) favours the relation to the smoking ofcigarettes may be attribut multiplicative hypothesis for the action of these able to some of the interviewees having stopped two carcinogens. smoking as a consequence of dyspnoea. The number of deaths taken as a basis for the As the exposure is of relatively short duration, it results obtained is rather small; only 43 cases had is possible that the results obtained here under been at work for 10 years or more and, of these, 34 estimate the long-term effects of asbestos upon the cases had been actual miners or mill workers with morbidity of the population exposed. heavy exposure to asbestos. Furthermore, only nine cases had been employed for 20 years or more. Six The authors are indebted to Mrs. Tuuia Tuunainen, who of them had asbestosis at death, and five of the nine died from lung cancer. Thus, even though one half of the workers with exposure lasting 20 years or more died from lung cancer, it is too, early to draw any far-reaching conclusions on the association of has collected the personal data and controls for the present study, and to Mr. Urpo Joutsenlahti, M.A.. for assistance in data-processing the material. The study was supported by a gram from the International Agency for Research on Cancer. malignancy and anthophyllite asbestos exposure in Finland. References The results given in the section concerned with living employees of the asbestos mining company indicate that the estimate of the general state of health of the cases and their controls is too subjec tive to permit of any reliable evaluation. A con siderable number of cases who felt healthy simul taneously admitted a chronic cough or severe dyspnoea. Langlands, Wallace, and Simpson (1971) have concluded that the prevalence of radiographic abnormality of the lung fields or pleura increases from 13% in men exposed to asbestos for less than 10 years to 85 % in men exposed for 30 years or more. Of 252 former asbestos workers, 140 were found to have pleural and/or pulmonary pathology in chest radiographs (Kiviluoto and Meurman, 1970). A higher number of heavy smokers is likely to be found among asbestos workers than in a general population (Selikoff et al., 1968; Elmes and Simpson, Betty, G-, Newhouse. M. L.. and Turok. M. (1972). Combined effect of asbestos exposure and smoking on mortality from lung cancer in factory workers. Lancet, Z. 476-479. Braun, D. C. and Truan, T. D. (1958). An epidemiological study of lung cancer in asbestos miners. Archives of Industrial Health. 17. 634-653. Buchanan. W. D. <1965). Asbestosis and primary intrathoracic neoplasms. Annals of the AVw York Academy of Sciences. 132, 507-518. Doll. R. t!965). Mortality from lung cancer in asbestos workers. British Journal of Industrial Medicine, 12. 81-86. ------ (1971). The age distribution of cancer: Implications for models jf carcinogenesis (with Discussion). Journal of the Ttoyat Statistical Society. Scries A. 134, 133-166. ------ . Muir, C_ and Waterhouse. J. eds. (1970). Cancer Incidener in Five Continents, vol. 2. International Union against Cancer. Springer-Verlag. Heidelberg, Berlin, New York. Elmes, P. C and Simpson. M. J. C. (1971). Insulation workers in Belfast 3. Mortality 1940-1966. British Journal of Industrial Medicine. 28, 226*236. Enterline. P. E. (1965). Mortality among asbestos products 112 L. O. Sfcurman, R. Kiviluoto, and M. Hakama workers in the United States. Annals of the New York Academy of Sciences. 132. 156-165. ------ and Kendrick. M. A- 0967). Asbestos-dust exposures at various levels and mortality. Archives ofEnvironmental Health, '15. ISI-I86. Gaze, R. <19651. The physical and molecular structure of asbestos. Annais of the Sew York Academy of Sciences, 132. 23-30. Holt, P. F-. Mills, J-, and Yount, D. K_ (1965). Experimental asbestosis with Tour types of fibers. Importance of small particles. Annals of the Sew York Academy of Sciences, 132, *7-97. Kahn, H- A. (1966). The Dora study of smoking and mortality among U-S. Veterans: Report on eight and one-half sears of observation. National Cancer Institute, Monograph So. 19, 1-126. Kiviluoto, R. (I960). Pleural calcification as a roentgenologic signofnon-occupaU'oual endemic ambophyllitc-asbcstosis. Acta Radialofica, Suppl. 194. 1-67. ------ , and Meatman. L. (1970). Result* ofasbestos exposure in Finland. In: Pneumoconiosis: Proceedings of the International Conference, Johannesburg 1969, pp. 190-191, edited by H. A. Shapiro. Oxford University Press, Cape Town. Kogan, F. M-, Troitsky, S. Y,, and Gulevskaya, M. R. (1966). ,On the carcinogenic effect of asbestos dust. Gigiena l Saniiariya, 31. No. 8 28-33. KSnig. 3. (I960). Ober die Asbcstose. Arckiv fur Gewerbe- pathologic uni Gewerbehygiene, 18, 159-204. Langlands, J. H. M,, Wallace. W. F. M. and Simpson, M. J. C. (1971). Insulation workers in Belfast 2. Mor bidity in men still at work. British Journal of Industrial Medicine. 28, 217-225. Mancuso, T. F. and Coulter. E- J. (1963V. Methodology in industrial health studies. The cohort approach, with special reference to an asbestos company. Archives of Environmental Health, 6, 210-226. McDonald, J. C. McDonald. A. D- Gibbs; G. W., Siemiatycfci, J.. and Rossiter. C E. (1971). Mortality in the ehrysotile asbestos mines and mills of Quebec. Archives ofEnvironmental Health, 22, 677-686. Meurman, L. (1966). Asbestos bodies and pleural plaques in a Finnish series of autopsy cases. Acta Pathologica et Microbiolagica Scandinavica, Suppl. 181, 1-107. ------ , Hormia, M., Isomiki. M. and Susinen, S. (1970). Asbestos bodies in the lungs of a series of Finnish lung cancer patients. In Pneumoconiosis: Proceedings of the International Conference, Johannesburg 1969, pp. 404-407, edited by H. A. Shapiro. Oxford University Press. Cape Town. Newhouse. M. 1- (1970). The mortality of asbestos factory workers. In Pneumoconiosis: Proceedings of the Inter national Conference, Johannesburg 1969, pp. 158-164. edited by H. A. Shapiro. Oxford University Press. Cape Town, Pedersen. IL, Magnus, K-, Mork. T., Haugen. A- Bjeike. E, Hakama, M.. and. Saxen. E- (1969). Lung cancer in Finland and Norway--an epidemiological study. Acta Pathologica et Microbiolagica Scandinavia, SuppL 199, 1-74. Raunio, V. (1966). Occurrence of unusual pleural calcifica tion in Finland. Studies on atmospheric pollution caused by asbestos. Annates Medicinae Internae Fenniae, 55, SuppL 47.1-61. Selikoff, L J- Churg. J-, and Hammond, E. C. (1964). Asbestos exposure and neoplasia. Journal ofthe American Medical Association, 188,22-26. -------, Hammond, _ C. and Churg, J. (1968). Asbestos exposure, smoking, and neoplasia.Journal oftheAmerican Medical Association, 204,106-112. Smithes, W. J. (1965). Secular changes in asbestosis in an asbestos factory. Annals of the New York Academy of Sciences. 132,166-181. Smoking and Health (1964). Report of the Advisory Com mittee to the Surgeon General of the Public Health Service. Public Health Service Publication No. 1103, pp. 17-387. U.S. Department of Health, Education and Welfare. Washington DC U.S.A. Timbrell. V. (1970). Characteristics of the International Union against Cancer standard reference samples of asbestos. In: Pneumoconiosis: Proceedings of the Inter national Conference. Johannesburg 1969. pp. 28-36, edited by H. A. Shapiro. Oxford University Press, Cape Town. Wright, G. W. (1969). Asbestos and health in 1969. American Review ofRespiratory Disease, 100,467-479. Received for publication 21 May 1973 Accepted for publication 17 August 1973 British Journal o. Renal i parame with di*. kim craw MARION H Department of Chemistry, Un Pathology, Un Carolina, USA Cramer, of Indus lead tox from fiv renal fu year wh renal fu obtains plasma tyrosine tests we Plasma found t urinary in thostubules found i nephroconseqi The potential reversible pro? structural chai renal failure poisoning ther bodies which ! complex (Goy Other ulrrastn mitochondria men? of mspi'