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V o 1. 2 /1L S - - i 5 , lb/6 A* INSTITUTE Or OCCUPATIONAL AND ENVIRONMENTAL HEALTH MONTREAL CANcna l37 g Code 17 36 38 63 70 80 LUNG CANCER AND MESOTHELIOMA DURING PROSPECTIVE SURVEILLANCE OF 1249 ASBESTOS INSULATION WORKERS, 1963 -1974 * Irving J. ScliLoff Environmental Sciences Lr.hcrr.tcry Mount Sinni School oj Medicine The City University oj New York New York, New York 10029 ii i I Introduction In 1963, it was found that a large group of asbestos insulation workers in the New York 'metropolitan area had experienced unusual mortality during 1943 -1962.1 Six hundred and thirty-two men had bean on the union's rolls on January 1, 1943. Ey December 31, 1962, 262 men had died, nine before teaching 20 years on'the job. Of those who died after 20 years from first employment, lung cancer was found in marked excess; 6.02 such deaths had been expected, and 42 occurred. In addition, there were several deaths due to pleural or peritoneal mesothelioma and a modest increase in deaths due to rastiointestinal cancer, where 9.71 were expected and 29 were observed. There were 12 deaths due to pulmonary asbestesis (Table 1). t l i Table 1 Expected and Observed Deaths among 632 Asbestos Insulation Workers, New York-New Jersey, 20 or More Years After Onset of Work, January 1, 1943 to December 31, 1962 Total deaths, all causes Tate! cancer, all sites burg cancer ?;u;2J fr.cvc*jhcr**ma reritcr.ea! mesothelioma Career of stomach, colon, rectum Afi other cancers Asbestosis All other causes Expected * 195.16 31.44 6.02 t t 9.71 15.71 t 16-4.72 - . Gbstr' 253 S5 -2 3 1 25 20 12 146 Nine men died before reaching 20 years horn first employment. Expected deaths are based upon white male nee-specific death rate data of the U S. National Office of Vital Statistics from 1949 to 1962. Rates were extrapolated for 1943-iy4S from rates for 1949-1955. ' t Rates arc not available, but these diseases are rare causes of death in the general population. . * Supported by the Health Research Council of the City of New York (U-1272). 44S (1239'.3 UCC 016003 SclikofT: Lung; Cancer L Asbestos 4.;9 II had previously been established that lung cancer ss-as a formidable ; n/.ird of asheMos f.iclory workers* and lliat leiminalion of employment did in-; abort Ihc risk; apparently. once Milhcicnl espu'urc had occurred wiih continued reten tion of asbestos within the lung, risk remained. This factor was of considerable concern, because a significant number of men were known to have wori cd as asbestos insulation workers in the New York metropolitan area, and mans were still in the trade. In addition to the 370 survivors of I lie original !9-3 c.'hort. S90 men had joined the insulation union t during the period 1943-1961, and S79 of them were alive on January 1. 1963. Together, the two groups icnstituted a total of 1249 men "ho were either working regularly as asbestos i isola tion workers in 1963 or svho had been recorded as having worked regularly at this trade for shorter or longer periods in previous y ears. Taule 2 Memnms of AsntsTOS Workers' Union on July 1, 1963. Admitted to the Union Before December 31, 1942. Classification nr Ace and Smoking Habits on or About January 1, 1963 Age (yr) 35-39 4 0--44 45-4 9 50-54 55-59 60-64 65-69 70-74 75-79 80-84 Total Total No. 2 13 32 109 60 42 49 38 21 .4 370 Never Smoked Regu larly '1 -> 2 12 6 7 6 7 3 2 48 Pipe, ExCigar cigarctle . Only Smokers* 1 --2 15 6 26 5 16 4 15 8 17 7 12 76 11 39 101 Current Cigarelte Smokers* 1-9/ 10-19/ 20-39/ 40 + / Day Day Day Day ____ __ - -- -- s 4 -- 12 12 3 5 33 24 -- 3 20 10 1 -- 11 4 --4 95 1 443 --13 l -------- 5 17 97 63 Includes cigarette smokers who also smoked pipes or cigars. __Bcferc_J ?63... there had_ hccn_no_r!:cuIar surveillance ,pf_.th;csc. asbestos workcrs._bccjusc ihcy-wcre not.awarc-of -their- special, risk.^ It was considered that potential benefit might be obtained if a program of regular medical sur veillance could be initiated, with special focus on the principal risks that had been identified, namely, bronchogenic carcinoma, pleura! and peritoneal meso thelioma, gastrointestinal cancer, and asbcslosis. Of these risks, lung cancer took first place. In addition to the risk associated with asbestos exposure, a majority of the men had been regular cigarette smokers (Tables 2 & 3). Such history, even in the absence of asbestos exposure, carried a lung cancer risk of its own.' (It svas later to be learned that the combination of the tw-o factors, asbestos exposure and cigarette smoking, resulted in many more lung cancers than would be assumed from mere summation of the two clfccts. with asbestos exposure sharply increasing the lung cancer risk of cigarette smoking.*-) t International A'sociailon of Heat and Frost Insulators and Asbestos Workers, AFL-CIO, CLC, Locals 12 and 32. t * a: *^ V-. lb'" ,*v A r- * P* (^233 4 UCC 016004 450 \ Annals New York Academy of Sciences tc* r cos O n* ^. ! "I v> O ri n \ i -- -roooooo -- pj -- - n *r 7 r< OO o c jo I PJ V W> O c*v 'O -- m O O O O ^ r r* *3' t -- 5 i u DOh `' 3 no co 7-~C"ONn'" 1 o o o o o zo Of -- \0fNmo"c>QC:,c-?O P* c*I -'til < i: <o Vr~O' O'.< 2 <2/> *-- pj pj -- Z > -c _j o h* -- C"n r* - -- oooooo x 7O. 06 PO SS .So .53 C'ff'X'C'On'niN-iNOOOO -- V c > o -O O 2. vriis--es--,vrni m-- --o 7 nCSP-GOO < ti. O 5j* r- <w ps -r o -* _ in ri n n 7 T O ri CC >C0 p MO O H XX>P>rr.--,T.-y,...N; i.h, r > UCC 016005 :J._______________________________________ - v*. .-*vyf'. .V'*.*..*'*-. *-*. ^v.*_.-*v.y- . . '' y -' _-f ^23 9 ' ^ Tmili: 4 . X-Kav Ciiancis in Asm.sios Insulation Wohxlhs* Onset of Exposme (yr) 40+ 30-39 20-29 0-9 No. 121 194 77 346 1117 Normal (%> 5.8 12.9 27.2 55.9 51.5 Abnormal r/o) 94.2 87.1 72.8 44.1 48.5 Asbestosis (fr.n e) 1 23 35 51 2 si 102 49 18 35 17 ' 4 158 0 0 366 126 50 From Reference 7. Prospective Clinical Surveillance The program of clinical surveillance that was instituted was based on the realization that the chest x ray offered the best method for early dciccilon o' lung cancer then available.An initial pilot survey had demonstrated that the cooperation of the workers involved could be expected.7 Examination facilities, . including x-ray equipment, were set up in the union hails to facilitate attendance . of the men; it is not known whether equal cooperation would have as readily been achieved had it been necessary to site the survey in hospital-based facilities. The nature of the disease under surveillance required several modifications in usual chest x-ray survey design. First, it was considered that the standard "yearly" chest film would be inappropriate for many of the group (as it was later to be shown to be inadequate for many other individuals as wcil>). In the preliminary survey, chest x-ray examination had shown that many of the men, especially those with more than 20 years from onset of exposure, already had considerable asbestosis (Taulf. 4).7 If cancer were found, it would be best to discover it at a stage at which limited resection, as lobectomy or even segmental resection, w-as possible. Diminished respiratory reserve might make pneumo nectomy unavailable, even if the neoplasm was otherwise resectable. Therefore, serial chest x rays were advised at 6-month intervals for workers with more than 20 years from onset of exposure, yearly for those 15-19 years from onset, and every 1-2 years for those with shorter histories of duration from onset. Further, rather than the usual postcroantcrior film alone being taken, four films were made at each examination, two in the postcroantcrior projection (one with increased penetration) and one in each of the two oblique projections. With x-ray changes of asbestosis predominantly to be seen in the lower lung fields, and with a known predilection for asbestos lung cancer to be found in these areas, it was considered -advisable to visualize the lower lung fields as weii as possible. Other studies were simultaneously undertaken. Physical examination, with particular reference to the chest, abdomen, and oropharynx,'-1 was supplemented by careful occupational, clinical, and smoking histories; fingers w-ere examined for clubbing, although it w-as recognized that this finding would have far less diagnostic utility in the presence of asbestosis than it would for lung cancer in general; urine, hematocrit, and scrum for rheumatoid factor ,n were examined, and pulmonary function studies, including FVC and FEV, were performed. i - 'J fr*',i r1 , V-vNA-'. Ov. a.'**,, X- f UCC 016006 After evaluation of the findings, each inn was informed of the resui s of the examination. and, when requested. a detailed review of the data was sc to the individual's personal physician. Confidentiality of examination results v.is care \ fully guarded, with none of the individual findings nude known either to the employer or to the union, although statistical summaries of resuits were made available to both. In some instances, in which it was difficult for the worker to attend for the examination (some retired and were living in California, Florida, or either distant states, and others were residing up to 150 miles from the unions' headquarters), the worker was encouraged to regularly visit his personal physician fer similar examination and to send the films obtained for review. Also, a union health plan included opportunity for regular examination of the worker and his family in a program of general medical surveillance, and the advantages of participation in such surveillance were stressed. When an abnormality was suspected or found, immediate review with the worker's personal physician was sought, and details were provided. Ciose co operation during the ensuing special studies was offered, and. in many instances, the diagnostic and treatment facilities of the Mount Sinai Hospital were re quested and utilized. ,v'*.*> .*/S . V' Lung Cancer and Mesothelioma, 1963-1974 From January 1. 1963 to December 31, 1974. 19S of the 370 survivors of the original 19*12 cohort died. The distribution of causes of death was very much the same as that in the previous 20 years, but the percentages within each category* and the ratios between observed and expected deaths were appreciably altered (Table 5). Three factors influenced this change. First, as the indi- # '. . v t* r /V\ , .-V, ' Table 5 Expected and Observed Deaths among 370 New Voric-New Jersey Asbestos Insulation Workers, January 1. 1963 to December 31, 1974 Trial deaths Total cancer, all sites Lung cancer Pleural mesothelioma Peritoneal mesothelioma Cancer of stomach Cancer of colon, rectum All other cancers Asbestosis Ail other causes Number of men Person-years of observation Expected * Observed . 109.04 20.58 6.18 - t t 1.17 2.75 10A1.48 88.46 370 3075 198 105 47 7 21 7 7 16 25 68 * Expected deaths are based upon age-specific white male death rate data of the U.S. National Olliec of Vital Statistics from 1963 to 1973. Rales were extrapolated for 1973-1974 from rates for 1968-1972. t U.S. dealh rates not available, but these diseases are rare causes of death in the general population. UCC 016007 i\2 3 9 i ? * OCIIMUl : I .UIIj, Tahi.f. 6 Deaths among X79 Amusios Insui atiiin V/mhxi ks. First Rt cisti m:n in Tin: Insulation Worki us' Umon January l. 1743 in Dicimiilr 31, 1962. Duhing January 1, 1963 io Diclmiu r 31, 1974 Number of Deaths Total deaths 54 Total cancer, all sites 18 . l.ung cancer 9 Pleural mesothelioma 2 Peritoneal mesothelioma 1 Casiroinicstinal cancer 3 All other cancers 3 Asbestosis 5 iii All other causes * 31 j viduals in ihc cohort aged, the distribution of death by cause would also be j expected to charge, even in the absence of an occupational disease influence, j Second, many of the individuals were still at work in 1963 and continued their j employment. The influence of total exposure on mortality would therefore be ! evident; this factor might be of particular importance among individuals with j clinical asbestosis,11 for whom additional dust exposure would be particularly ; disadvantageous. Third, and perhaps most important, the lapsed period from onset of clfectivc exposure progressively lengthened, with increasing likelihood of clinical onset of malignant disease. Because the periods of clinical latency between onset of exposure and evidence of disease vary among the several neoplastic risks of occupational asbestos exposure, it wouic be expected that there would be differences in incidence of these neoplasms during the decade of observation. In the event, 47 deaths of lung cancer occurred, while 6.IS had been expected; there were seven instances of pleura! mesothelioma and 21 0* peritoneal mesothelioma, in addition to 25 deaths due to asbestosis. Also, more deaths due to cancer of the esophagus, stomach, colon, and rectum occurred than were anticipated. We have not yet analyzed the mortality experience of the S79 workers w-ho first joined the union between 1943 and 1962 and were still alive on January 1, 1963.* These men were young, most with considerably less than 20 years from onset of exposure, and their risk of death during 1963-1974 was likely to be limited. Observation showed that 54 deaths occurred, and Taiilf. 6 provides categorization by cause. Observation of these men continues, and it is antici pated that analysis of their mortality experience by caiwc. contrasting expected and observed deaths, will be able to be usefully undertaken within the next ` several years. Occurrence of Lung Cancer and Mesothelioma * Altogether. 59 instances of bronchogenic carcinoma occurred among the 1249 asbestos insulation workers under uur observation in the New York metropolitan area from January 1, 1963 to December 31, 1974. Forty-nine eases occurred among the 370 individuals who had already been members of r-V ' X-'-'' ** - w. '* x V v,. . ... VS -VAX' F--------------------- UCC 016008 ?39 1 POi TVr- ' -o4 Annais New York Academy of Sciences \ Table 7 t.uso Cancer in New York-New Jersey Asbestos Insulation Workers ' January 1, 1963 to Decemhcr 31, 1974 Number as of January I, 1963 Lung cancers to January 31, 1974 Deaths cue to lung cancer Admitted to Union Before 1943 1943-i762 370 ` 49 48 7' I- o the Insulation Workers' Union in 1942, and 10 cases occurred among the S79 younger men who first became members of the union at some time from January 1, 1943 to December 31, 1962 (Tahee 7). Review of the clinical status of these 59 men on January 1. 1975 showed that 57 were dead; two were alive. One. a member of the 1942 cohort, had been found to have a bronchogenic carcinoma during the clinical survey under taken in 1963. Lobectomy was performed, and observation since has yielded no evidence of recurrence. He stii! works activciy at his trade. The second man joined the union in 1946. In 1972, he suffered hemoptysis, underwent lobec tomy, and has remained weii. Doth, men had been regular cigarette smokers; no instance of lung cancer was seen among workers without history of regular smoking. Analysis is now underway to study the causes of this dismal record. It is already evident that the usual causes for failure in the management of bronchogenic carcinoma were also present here; in addition, there were other factors, such as peripheral location of the neoplasm and early pleural invoivement, important respiratory insufficiency, and occasional difficulty in radiologic diagnosis due to concomitant pleural and parenchymal asbestosis. Twenty-eight instances of pleural and peritoneal mesothelioma occurred in the 1942 cohort, and three eases of these diseases occurred in the men who joined the trade more recently. Ail arc dead (TaplE S). There was no effective therapy available. Table 8 ` Mesothelioma among New York-New Jersey Asbestos Insulation Workers, January I, 1963 to December 31, 1974 Number of men Pleural mesothelioma Deaths Peritoneal mesothelioma Deaths Admitted to Union Before 1943 1943-1962 370 7 7 ' 21 21 879 *7 2 1 1 _________ :t .v - > w- V v ' c_< :***? if * s-- x '* -V ^r-V- V UCC 016009 SciikoiT: Lung Cancer & Asbestos 455 SUMMARY AND CONCLUSIONS Fifty-nine cases of bronchogenic carcinoma were observed among 1249 asbestos insulation workers followed prospectively from January 1, 963 to December 31, 1974 in the New York metropolitan area. Despite the fact hat these men, and their medical attendants, were well aware of their risk of such disease, and despite the availability of a standard program of radiologic and clinical surveillance, 57 of the 59 men died. Il is clear that survc.ii.incc to* grams as utilized were insuflicient to appreciably improve the prognosis among such individuals. At best, carly diagnosis of laic disease can be said to have '.con achieved during; the surveillance. Far more effective measures of prcclinical diagnosis arc needed if anticipated disease in this group at high risk of cancer is to be effectively treated. The important influence of the lapsed period from onset of exposure was evident. Forty-nine lung cancers occurred among the 37U workers who were in the union in 1942, and 10 lung cancers occurred among the S79 men who first joined the Insulation Workers' Union :n the New York metropolitan area during 1943-1562. Nine eases of pleural mesothelioma and 22 of peritoneal mesothelioma were seen. Effective treatment was absent, and all 31 were dead at the end of the study period. Prospective surveillance with the likelihood of earlier diag nosis failed to appreciably improve prognosis in this disease. Acknowledgments . Janet S. KalTenhurgh and Frances Pcrc7 made many important contributions to the clinical examinations and surveillance. The fact that the entire group of 1249 men has been successfully followed is in large part the result of their skill, competence, and dedication, which arc gratefully acknowledged. References 1. Seukoff, I. J., J. Cnur.c A E. C. FUmmond. 1564. Asbestos exposure and neoplasia, J. Amer. Med. Ass. 1SS: 22-26. 2. Doll, R. 1555. Mortality from lung cancer in asbestos workers. Brit. J. Ind. Med. 12: S1-R6. ' _ 3. Hammond, E. C. t966. Smoking in relation to the death rates of 1.0C0.000 men and women. In Epidemiological Study of Cancer and Other Chronic Diseases. Monogr. 19: 127-2U4. National Cancer institute. Uclhesda. Md. .4. Selikoff, 1. J., E. C. Hsmmono & J. Ciil'RG. 1908. Asbestos exposure, smoking and neoplasia. J. Amer. Med. Ass. 2U4: 106-- I 12. 5. Hammonu, E. C. A 1. J. Ski.ikoi f. 1973. Relation of cigarette smoking to risk of death of ashe'tos-assoeiaicu disease among insulation workers in the United Slates. In Biological Ejects of Asbestos. E. P. Uogovski, et ah, Eds. IARC Sc. Hub. N'o. 8: 209-216. Lyon, France. 6. Boucot, K. R., D. A. Cooi'Kk A W. Weiss. 1970. The Philadelphia pulmonary neoplasm research project. Med. Clin. N. Ampr. 4: 549-553. 7. SttLUun-, 1. J., J. Cmukg A E. C. Hammond. 1965. The occurrence of asbesiosis - among insulation workers in the United States. Ann. N.Y. Acad. Sei. 132: 139-155. \ 456 Annuls New York Academy of Sciences 8. V.'nss, W.. H. ScmM\N & K. R. RoiTor. 1975. The Philadelphia pulmonary neoplasm rcscaich project. Thwarting factors in periodic screening for long cancer. Amcr. Rev. Resp. Dis. Ill: 2S9-297. 9. Ski.uoi r. 1. J-. E. C. IUmmonh & i. Comic. 1970. Mortality experiences of asbestos insolation workers, /n Pneumoconiosis. Proceedings of the Interna tional Conference, Johannesburg, 19fi9. H. A. Shapiro, Ed. : 57-69. Oxford University Tress. Capetown, South Africa. 10. PI.H.NIS, B-. E. C. Vict.iAM ft I. J. St i.HsOKK. 1965. Rheumatoid factor in serum of individuals exposed to asbestos. Ann. N.Y. Acad. Sci. 132: 112-120. If. Baum, M. E., R. A. H.u:h. A. S. Ti.mxu in. A. Mi; UR & I. J. Srlkiiit. 1970. pulmonary function and radiographic chances in 59S workers with varying duration of exposure to asbestos J. Mount Sinai Hosp. XXXVII: -192-500. UCC 016011 A23921 < \ Nicholson: Asbestos---The TLV Approach 163 In the research that led to these data, it was reported that peak exposures could be extremely high. It was not uncommon, for example. Tor two-to-fivc- ininulc conccntintionx of asbestos to ranee between 50 f/nil and 100 f/ml haring the mixing of cement. This mixing, however, would consume only a few minutes' lime and he done pcihaps once an hour. Thus, exposures mccsutcd during that hour, including the mixing, would seldom average more than 5 f/mh Similar experiences were subsequently reported by Cooper.3" at I.yon. who staled, "Peak concentrations may be high for brief periods, while time-weighted averages arc often deceptively low." We have direct information on nsbesics-fiber concentrations, measured by the currently prescribed analysis procedures during recent years only. Insulation materials have changed from earlier years. Fibrous glass has found extensive use, but w'ork with cork is scidom seen today. Moreover, changes in the asbestos composition of insulation products ha-c taken place. Pipe covering and insula tion block may have had twice the asbestos content in past years as they have today. During this period, however, work practices were virtually identical to these of past years, and during the period of these measurements. few controls of significance were in use. Thus, dust concentrations measured under these conditions have relevance for the estimate of levels of past years. Considering the possible doubling of asbestos content of insulation materials, and considering that workers may have used asbestos materials more often in the past than now, the data from these three studies would suggest that the insulators" average exposures in the United States during past years could have rar.ced from 10 to 15*f7ml. '~ The only early research of note on asbestos-dust concentrations in past insulation work is '.he 19-15 study of Fleischer and his colleagues.'" who reported asbestos dust levels during insulation application in four United States shipyards. In this study, dust concentrations were assessed with use of a konimeter (an ipstrument widely used at that time, but no longer employed), and both total 'oust and fiber levels were recorded. The study is difficult to evaluate, since the I average dust levels reported in different shipyards varied by nearly 100 times, un two yards, average dust concentrations of about 1 f/ml were found; in a "bird yard, 90 f/ml; and in the fourth, 35 f/ml. During 1965 and 1966, the fourth yard was re-surveyed by person: 'l cf the Department of Industrial Hy giene, Harvard School cf Public Health.** In the resurvey, a time-weighted average c.x; sure f/.v.: Vip.s ^dlcrfr^r.'^d. These fiber counts represent all fibers visible in the field of view of a kc- nimeter. Fibers per heps as short as 1.5 ^ w ould be enumerated. Supplementary I data" on the sire distribution of amesite aerosols in shipyards suggest that this overestimates the number of fibers longer than 5 ^ by a factor of two. If we take this factor into account, and simply average the data from the four ship yards studied by Fleischer in 19-t5. an estimate of from 15 to 20 f/ml is obtained for average asbestos concentrations in insulation work during this period. Similar considerations would yield a value of 4 f/ml for the shipyard survey by Murphy in 1965. It must be emphasised, however, that averages arc highly subjective and depend strongly on the vagaries of the particular work practices selected for sampling and the conditions present at that time. These summaries of asbestos concentrations frcmi 1945 through 1971 by five different research groups in two countries arc summarized in Taiile 7. The I estimate of from 10 to 15 f/ml for past insulators' average asbestos exposures 1 p--* - -- " . # I ------- ...................................- ------------------ - UCC 016012 --...... --........ - XV . v- v. ~V :-4 . c * .-rv y-.v -v , * w '-V-> A23922