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FILE NAME State of the Art Literature SAL DATE 1964 Apr 6 DOC SAL072 DOCUMENT DESCRIPTION Journal Article - Asbestos Exposure and Neoplasia a4 pe yf 3 et. mE mere tee Ae ee rt ey Ade ere ts '23 Vol 188 22- JAMA April 6 1964 Asbestos Exposure Neoplasia and Irving J. Selikoff MD Jacob Churg MD and E. Cuyler Hammond DSc New York Building trades insulation workers have relatively light intermittent exposure to asbestos Of 632 insulation workers who entered the trade before 1943 and were traced through 1962 forty died of Cancer of the lung or pleura whereas only such deaths were expected Three of YW the pleural tumors were mesotheliomas 2 there was also one peritoneal mesothelio- deaths Four |deaths mesotheliomas in a total of 255 is an exceedingly high incidence for uch a rare tumor In addition an unex- pectedly large number of men died of can- og cer the stomach colon or rectum 29 compared with 9.4 expected Other can- $~x cers were not increased 20.5 were expected 21 occurred Twelve men died of asbestosis LTHOUGH PULMONARY CARCINOMA had been observed in the earliest studies of asbes- tosis association between the two conditions was first suggested by Lynch and Smith in 1935. Ad- ditional reports of such association followed Per- haps the most striking data was presented in the annual report of the Chief Inspector of Factories of Great Britain for 1955. Every death with asbestosis in the files of the Factory Department from the first recognition of asbestosis as a disease entity was studied Altogether 365 such deaths were recorded 1924-1955 Sixty or 17.8 were found to be accompanied by cancer of the lung or pleura Doll after reviewing the problem and adding data of his own concluded that lung cancer was a specific industrial hazard of heavily exposed asbestos workers Nevertheless some investigators have held that while these observations might be suggestive they did not establish an increased incidence of carci noma of the lung in pulmonary asbestosis and further that the association was unproved The factor of selection was considered a poten- tial weakness in evaluating reports of autopsy series It was noted that complicated and unusual cases would be more likely to come to autopsy thus raising the apparent frequency of associated lung neoplasms Further it was argued that autopsy statistics which dealt with particular groups of those who died do not reflect total populations of asbestos workers Additional reservations were based on the frequent absence of data regarding From the Division of Thoracic Disease Department of Medicine and the Department of Pathology Mount Sinai Hospital Read before a joint meeting of the sections on radiology and diseases diseases of the chest and the American College of Chest Physicians at the 112th Annual Meeting of the Amencan Medical Association Atlantie City NJ June 17 1963 exposure smoking habits and personal history on the size of series and on inadequate histological verification in some cases Within the last few years a number of additional problems connected with asbestos exposure have appeared making clarification and resolution of the foregoing statistical uncertainty a matter of considerable concern First there has been greatly increased use of the various types of asbestos a fold increase in world utilization of this group of minerals from 500,000 tons to 2,500,000 tons per year in the last 30 years as well as a greatly in- creased number and variety of industrial applica- tions of asbestos over 3,000 such uses now re- corded Second suspicion has been growing that malignancy associated with asbestos exposure may include neoplasms other than carcinoma of the lung Thus a significant relationship has been claimed between diffuse mesothelioma of the pleura and peritoneum and asbestos exposure This communication is concerned with investi- gations undertaken to study the following factors 1 the incidence of deaths due to pulmonary car- cinoma among a group of workers exposed to as- bestos under United States industrial conditions in the past several decades 2 whether or not such individuals would also found to have an increased risk of other neoplasms and 3 whether such risks would be present in an industry other than the producing or products industries with which most reports in the past have been concerned but which would not necessarily represent the most important areas of as- bestos exposure at this time Further it was hoped that study of an industry with asbestos exposure of limited extent and intensity would throw some light on the potential problems associated with minimal exposure to asbestos Materials and Methods Our investigations have been concerned with 1.522 members of the Asbestos Workers Union in the New York metropolitan area members of New York Local 12 and Newark NJ Loca 32 of the International Association of Heat and Frost Insu lators and Asbestos Workers As the full title im- plies these men are insulation workers Although the union is considered one of the building unions its members do insulation work in a vas riety of industries including shipbuilding Called Laggers in Great Britain they are often desig- nated pipe coverers insulators or asbestos workers in this country The union is one of the oldest in the country A ald, Auch i 4 We fone dee dda aha ce aide ded ie! be EN ena can Vol 158 No 1 ASBESTOS EXPOSURE ET AL 23 The New York local as the Salamander Associa tion of Boiler and Pipe Felters was the first union of insulation workers in the United States It amal- gamated with other locals as the current Asbestos Workers Union in 1912. The stability of this union has been reflected in the stability of its membership rolls Once a pipecoverer always a pipecoverer has been of epidemiological importance to us and has made this group of men particularly suitable for the study of term effects of asbes tos inhalation Unlike unskilled workers exposed to asbestos inhalation in poorly paid industries there is little labor turnover among insulation workers Accurate employment records are maintained by the union which has also been concerned with health problems in the industry The trade was badly hit during the depression some men had to drop out and very few were added during the 1930's By the end of 1942 the union rolls consisted mainly of men with consid- erable experience plus a few who joined in 1940 1941. and 1942. Between 1946 and 1962 union membership increased substantially Source of From union records a list was prepared of every individual who was a member of either of the metropolitan locals on Dec 31 1942. or who joined between that date and Dec 31 1962. No one was omitted whatever his subse- quent work history The 1942 list included 632 men 890 men joined after 1942 Personal data were obtained from union records and the work history of each man was detailed including withdrawal from employment war service other employment retirement illness These data gave the baseline for calculation of the onset and duration of exposure For members who had died records of the Health and Welfare Fund provided date and place of death Copies of death certificates were obtained on all but one of them Autopsy protocols histological specimens and hospital records were obtained and reviewed in those deaths approximately one half in which the ter- minal illness had occurred in a hospital Statistical Analysis Previous studies have sug gested that neoplasia associated with asbestosis sel- dom occurs until 20 years after first exposure to asbestos dust Therefore we decided to limit the present analysis to men with such an exposure history Our complete records cover all members of the union including active and retired members both dead and alive during the year period from Jan 1 1943 through Dec 31 1962 However with few exceptions the only men with a history of 20 years or longer since first exposure to asbestos were the 632 men on the union rolls as of Jan 1 1943. The exceptions were a few men who joined the union after Jan 1 1943 but who had been employed previously as asbestos workers elsewhere 1.1963 1.1963 Of these 632 men 255 died before Jan Table Years of Experience of 632 Asbestos Workers Exposed to Asbestus Dust 20 Years or Longer Years 1943 1943 1947 1953- 1948- 1953- 1952 1957 19583962 85.0 185.0 7.0 11.0 230.5 486.5 291.5 70.0 339.5 324.0 530.0 314.5 391.5 364.0 308 0 502.5 382.0 390.0 316.0 268.5 221.0 139.0 341.5 181.0 344.0 ' 286.0 255.0 280.0 83.0 115.5 137.0 197.5 31.5 70.0 70.5 75.0 5.5 18.5 38.5 23.5 3.5 2.0 8.0 13.5 : Totals 2.0... 1,912.0 2,478.0 2,336.5 2,011.0 Of these 632 men 339 had been exposed to asbestos dust prior to 1924. In other words as of Jan 1 1943 20 years or longer had elapsed since these 339 men were first exposed The remaining 293 men reached the exposure point at some time after Jan 1 1943 and before the end of 1962. The 339 men who were first exposed prior to 1924 were counted in each of the 20 years or up to the time of death of those who died The 293 who were first exposed in 1924 or later were counted only after they reached the sinceexposure point those who died being dropped at the time of death When the statistics were completed we found that we had records covering a total of 8,737.5 years of experience of men with a history of 20 years or longer since first exposure to asbestos dust Of the 8,737.5 years 1912.0 were in the five- year period 1943-1947 2,478.0 were in the period 1948-1952 2,336.5 were in the period 1953-1957 and 2,011.0 were in the period 1958-1962 Table 1 shows the age distribution of the years in each of these year periods Table 2 shows 1 the average specific death rates of all US white males during each of these periods and 2 the average specific death rates from cancer of the lung pleura mediastinum and trachea among US white males during each period as reported by the US National Office of Vital Statistics The years were then multiplied by the cor responding reported US death rates to ascertain the expected number of deaths under the null hypothesis that the death rates of asbestos workers do not differ from death rates of all US white males both age and date being taken into consid- eration The results are summarized in Table 3 Results Total During the first five years 19431947 only 2S deaths occurred among the asbestos workers whereas 39.7 deaths would have occurred had their specific death rates been the same as for all US white males during those years Table 3 In other words at the start of the study the asbestos workers had below average death rates This is by no means surprising Indeed such ayy ay Be Cte MAG 24 ASBESTOS EXPOSURE ET AL JAMA April 6 190 Table Total Deaths and Deaths From Cancer of the Lung Lung Bronchus Pleura Mediastinum and Trachea per 10,000 White Males per Year B5 . cecsssunee 1943-1947 Total 36 Lung Cancert aon 55 : 1245726 85 12457266 133 12457266 196 12457266 295 12457266 435 1245726 634 12457266 977 12457266 453 in 2,422 m 1948-1952 Total 30 48 78 124 189 281 417 605 915 1,353 2.162 Lung Cancer ~~ t , 5 8 10 11 11 10 8 7 1953-1957 Total 26 43 72 115 178 276 416 586 878 Lung Cancert ten I 3 5 10 14 17 16 14 1.346 12 2017 g 1958-1962 Total 25 42 70 116 173 272 415 607 866 1.363 2,148 Lung Cancer i 1 3 7 11 17 21 21 17 15 11 Office Death rates as reported annually by the US National Statistics Statistics for 1958-1962 is a of 1958-1960 since 1961-1962 of Vital A yeya ear r average is vehnere projection Death rates include include include cancer of the lung bronchus rates pleura are not yet available to 1949 and to No. 160-164 thereafter mediastinum mediastinum and trachea assigned to international for each period Averag list code No. 47b pric is almost always found in the first few years of a prospective epidemiological study of this type The explanation is almost certainly as follows The 632 men in this analysis were actively employed as asbestos workers in 1942. Since disability from illness or other causes precludes employment in a trade of this type these men were presumably well or at least not disabled at the start of the study pe riod Almost any group so selected as to exclude the ill and disabled has a lower death rate during the ensuing few years than does the general population since ill and disabled persons have extreme- ly high death rates A selective effect of this type gradually wears off with time and largely disap- pears within five to ten years from the time of initial selection During the second year period 1948-1952 the death rate of the asbestos workers was slightly higher than the death rate of all US white males ie 54 observed deaths compared with 50.8 ex- pected deaths In later periods the death rate of the asbestos workers was proportionately higher For the period 1953-1957 there were 85 observed deaths compared with 56.6 expected deaths and for the period 1958-1962 there were 88 observed deaths compared with only 54.4 expected deaths Table Observed and Expected Number of Deaths Among 632 Asbestos Workers Exposed to Asbestos Dust 20 Years or Longer Years Cause of Death 1943- 19513.953. 1947 1952 1957 Total all causes ....... . Observed asbestos workers Expected US white males 28 39.7 54 50.8 85 56.6 Total cancer all sites oo 13 17 26 Observed asbestos workers Expected US white males 5.7 8.1 13.0 Cancer or lung and pleura Observed asbestos workweorrkesrs Expected US white males - 0.8 8 1.4 13 2.0 Cancer of stomach colon and 1958- Total Total 1958- 19431962 1962 88 255 54.4 39 203.S 95 9.7 IB 36.5 45 2.4 66 Observed Observed asbestos workers Expected US white males 2.0 2.5 2.6 2.3 9.5 of all other sites com- Observed asbestos workers ) Expected US white males Asbestosis ....L . il becanteseetcueeeecee Observed asbestos workers 2.9 [] 4.2 i 8.4 4 5.0 7 20.5 202 . Cancer of the Lung Pleura and Trachea each of the four year periods far more death from cancer of the lung and pleura occurred among the asbestos workers than would have oc curred had their death rates from these diseases been the same as for all US white males Table 3 Altogether 45 of the 632 asbestos workers died o cancer of these sites whereas only 6.6 such death would be expected from general US experience Of these 45 deaths 42 were recorded as due to br^...nchogeniccarcinoma and 3 to neoplasms of the pleura The pleural neoplasms were all recorded as mesotheliomas Thus it was found that the death rate from can- cer of the bronchus and pleura was 6.8 times as high among these asbestos workers as in the gen- eral US white male population both age and date being taken into consideration It may be asked whether the high rate of lung cancer among these asbestos workers could pos sibly be attributed to an unusually large proportic of cigarette smokers among them We cannot an swer this question directly since we have not yet been able to ascertain the smoking habits of the men who died However the following pieces of evidence indicate that unusual smoking habits cannot account for the high death rate from lung can- cer among these workers We have interviewed 320 of the 377 surviving members of the 1942 group Table 4 gives a sum mary of the smoking habits in this group comparec with a sample of men drawn from the genera population of 1,121 counties in 25 states The un- ion sample is somewhat inadequate since it does not include the men who died and does not in- clude all of the present living members of the union Nevertheless it shows that a substantia proportion of asbestos workers never smoked ciga- rettes regularly Certainly the 632 men in our analy sis of death rates were not all heavy cigarette smokers cancer In the general male population death rates are about ten times as high among cigarette smokers as among nonsmokers and the tte ao ms * Vol 195 No 1 ASBESTOS EXPOSURE ET AL Table Table Smoking Habits of 320 320 Abestos Workers Exposed to : Compared With Sample of Men From Ascestos Dust 20 Years or Longer * the General Population Never Smoked Smoked ** 404 5059 re te Asbestos Workers % 9.3 14.3 20.3 25.5 Regularly General Population % 18.8 19.9 23.6 37.1 Pipe Cigar Never Cigarettes Asbestos Workers % 4.6 6.1 10.1 11.8 General Population % 7.5 9.9 16.2 23.9 Sample of men from general population as reported by Hammond and Garfinkel History of Cigarette Smoking Asbestos Workers % 86.1 79.6 69.7 62.7 General Population % 73.7 70.2 60.2 39.0 death rate from lung cancer increases greatly with the amount of cigarette smoking However a large proportion of all men in the United States have posure to asbestos by insulation workers as studied here results in a marked increase in the inci- a history of regular cigarette smoking From data in dence of cancer of the lung approximately six to a prospective study on smoking it be esti seven times the expected incidence Altogether 45 may mated that if all men smoked a pack of 17.6 of 255 men with more than 20 years cigarettes a day ie if all the or more elapsed since the onset of exposure died of cancer nonsmokers cigar smokers pipe smokers and light cigarette smok- of the lung or pleura These data do not give the incidence of ers had instead been heavy cigarette smokers the cancer death rate would be approximately cancer of the lung in asbestosis They relate to the cific conditions of spe- 3-4 3-4 times as high as it is at this time our investigation to a group of From this we may conclude that even if all our men with only intermittent exposure to materials asbestos workers had smoked a pack or more of containing limited amounts often % to 20 of cigarettes a day and indeed from our asbestos under working conditions varying from know they did not and if exposure tsoamapsbleestwoe s very dusty as in extracting old insulation in closed were of no significance then their lung cancer quarters to those with little dust exposure as in death rate would have been about 3.4 times as building construction in open air Moreover they high as the rate in the general US male relate to the relatively recent past in a trade with popula- building tion Clearly the smoking habits of the asbestos the shorter work week of the strong trades workers cannot account for the fact that their lung- unions in an era when industry has been aware of cancer death rate was 6.8 times as high as that of potential asbestos hazard and the working popu- white males in the general population lation has had some consciousness of potential Gastrointestinal Rather to risk associated with dust exposure These data the death rate from cancer of the stomoaucrh surprise would not necessarily apply to asbestos and the death rate from cancer of the colon and in other industries such as the factory proedxupcotsiuorne rectum were higher among the asbestos workers than of asbestos products the asbestos textile industry would be expected from the rates reported for the etc where conditions of employment might be : US white male population calculated in the same quite different Our results do not contradict the * way as for lung cancer Twelve deaths from gastric even higher incidence of lung cancer suggested in other studies gig cancer occurred among the asbestos workers as they are merely a shade less strik- = 0 3% compared with only 4.3 expected Seventeen deaths ing = sm from cancer of the colon and rectum occurred Diffuse Pleural and Peritoneal Malignancy- Mesothelioma BP among the asbestos workers as compared with 5.2 the incidence of dif- i 5 expected fuse pleural mesothelioma is complicated by the Cancer of All Other Sites combined death insecurity of its histological verification While oe rate from cancer of all sites other than lung and some pathologists will so categorize a high propor- SY en pleura and stomach colon and rectum was not tion of diffuse pleural tumors in the experience of hoot increased Twenty such deaths occurred others it is a very rare tumor and be mim- asbestos workers as compared with 20.5 expaemcotnegd may icked by anaplastic peripheral carcinoma of the Asbestosis the 255 deaths 12 were due to lung and diffuse fibrosarcoma of the pleura It is asbestosis pulmonary male The insufficiency cor pulmo- lapsed time from first asbestos exposure difficult to evaluate completely the published re- ports of diffuse pleural mesothelioma to death from asbestosis averaged 45.8 with in the absence of in asbestosis range of 32 to 59 years complete details of each case years To the present time there has been no informa- Comment tion concerning the incidence of diffuse pleural 4 Carcinoma of the Lung results with mesothelioma in asbestosis since the published to carcinoma of the regard cases are reported without reference to a total lung are clear Industrial ex- ulation in which they occur Nevertheless potph-e ~~ 26 ASBESTOS SELIKOFF ET AL JAMA April 6 1964 growing number of reports of individual cases becoming suggests that these tumors are becombeiconmigng relatively frequent complications of asbestos ex- posure Our observations in this series are similarly sug- gestive In three of the 255 deaths among the men who had worked for 20 years or more the exam- ining pathologist considered the death due to diffuse pleural mesothelioma and in the two cases in which we have been able to review the histological material the histological appearance was that of- ten so categorized and asbestos bodies were present This incidence of more than % of deaths from pleural mesothelioma is strikingly high for a tumor which is generally considered to be extreme- ly rare In one case in our series pathological examination suggested diffuse peritoneal mesotheli- oma This single experience is too fragmentary for evaluation instances Gastrointestinal Carcinoma instances of gastrointestinal carcinoma in the presence of asbestosis have been known but there have been no data to indicate that these were more than coinci- dental findings Among the asbestos workers studied here cancer of the stomach colon and rectum was three times as frequent as expected These data suggest that there may perhaps be an etiological relationship between industrial asbestos exposure and carcinoma of the gastrointestinal tract Environmental Asbestos Exposure recent demonstration by South African * and British investigators of pleural and peritoneal neoplasms among individuals who had chance environmental exposure to asbestos many years before raises the very important question of possible widespread carcinogenic air pollution The possibility of environmental exposure has long been known Soon after the initial clarification of asbestosis as a clinic 10 entity Haddow demonstrated asbestos bodies in a man not employed in the industry but living next door to an asbestos factory This finding was later mirrored in the finding of chronic beryllium disease among residents of a community near a beryllium factory What is new however is an appre- ciation of the potential extent of the problem 12 Thomson and associates have reported the fre- quent findings of asbestos bodies in the lungs of urban dwellers Among 6.312 individuals rayed in an area about an asbestos mine in Finland 13 Kiviluoto found 499 cases of pleural calcification of the type characteristically seen among asbestos workers without obvious cause In a comparable area without any asbestos mine no cases were found among 7,101 persons rayed It should be noted that these were not people who worked in the none but rather were farmers housewives and others who lived in the general location In one subject who came to autopsy polarized microscopy demonstrated asbestos fibers in the lung Similarly the lung of a cow graz- ing near the mine also showed the presence of asbestos A particular variety of environmental exposure may be of even greater concern Asbestos exposure in industry will not be limited to the particular craft that utilizes the material The floating fibers do not respect job classifications Thus for example insulation workers undoubtedly share their exposure with their workmates in other trades intimate contact with asbestos is possible for electricians plumbers metal workers steamfitters laborers carpenters boiler makers and foremen perhaps even the supervising architect should be included 1 E 100th St New York 10029 Dr. Selikoff ) This study was supported by the Health Research Council of the City of New York Cooperating in this investigation were the executive of- ficers of the International Association of Heat and Frost Insulators and Asbestos Workers Washington DC and the officers and membership of the New York and Newark NJ locals of this Union References 1. Lynch K.M. and Smith W.A Pulmonary Asbestosis Carcinoma of Lung in Silicosis Amer J Cancer 56-64 May 1935 2. Annual Report of Chief Inspector of Factories for Year 1955 London Her Majesty's Stationery Office 1956 cind p 206 3. Doll R Mortality From Lung Cancer in Asbestos Workers Brit J Industr Med 81-86 1955 4. Bohlig H. and Jacob G Neue Cesichtspunkte ^...ber den Lungenkrebs der Asbestarbeiter Deutsch Med Wschr 231-233 Feb 17 1956 . 5. Braun D.C. and Truan T.D Epidemiological Study of Lung Cancer in Asbestos Miners AMA Arch Industr Health 631-653 June 1958 6. Wagner J.C Sleggs C.A and Marchand .: Diffuse Pleural Mesothelioma and Asbestos Exposure in North Western Cape Province Brit | Industr Med 260-271 1960 7. Hammond E.C. and Carfinkel L Smoking Habits of Men and Women J Nat Cancer Inst 419-442 Aug 1961 8. Hammond E.C. and Horn D Smoking and Death Rates Report on Forty Months of Follow Follow of 187 783 Men I. Total Mortality II Death Rates by Cause JAMA 1159-1172 March 8 1294-1308 March 15 1958 9. McCaughey W.T.E Wade O.L and Elmes P.C Exposure to Asbestos Dust and Diffuse Pleural Mesotheliomas Brit Med J 1397 Nov 24 1962 10. Haddow A.C. in Report of Annual Meeting of British Medical Association Manchester 1929 Lancet 230-231 Aug 3 1929 . 11. Chesner C Chronic Pulmonary Granulomatosis in Residents of Community Near Beryllium Plant Three Autopsied Cases Ann Intern Med 1025-1048 June 1951 12. Thomson J.C. Kaschula R.O.C and MacDonald R.R Asbestos as Modern Urban Hazard S Afr Med j 77-81 Jan 19 1963 13. Kiviluoto R Pleural Calcification as Roentgenologic Sign of Occupational Endemic Anthophyllite tosis Acta Radiol Suppl 194 pp 1-67 1960