Document QJkrMbQE59dxge7bJGJDV5erE

Reprinted from the A. M A. Archives of Industrie! Health June 1958, Vol. 17, pp. 634-453 Copyright 1958, l>y American Medical Associalioi FROM An Epidemiological Study of 4400 Mt!*1 Ave^0' Lung Cancer in Asbestos Miners DANIIL C. MAUN, M.D.. T. DAVID TXUAN, M-A^ PHtobwrffc PLAINTIFF'S EXHIBIT W- 1 73 Ever since the pronounced increase in the incidence of lung cancer among males became apparent, there have been attempts to associate it with one or another of the various elements in the environment of man. The approach used by some workers has been to suspect one or several sub stances and then set about in an intensive search for lung cancer among persons who have had any exposure to those materials. In this connection, Smith83 writes: "The tendency of authors reporting the coinci dental occurrence of primary lung cancer with silicosis or with any other theoretical etiologic conditions, has been to emphasize the percentage relationship in extremely small series of cases, with control cases which are not in any way comparable." It would seem inevitable that asbestos should come under scrutiny in this manner, because prolonged exposure to this material is known to cause a specific type of pneu moconiosis, and because persons who show this form of pneumoconiosis often come to autopsy and provide a ready source of materia! tor study. It was in this wav that reports of the simultaneous occurrence of lung cancer and asbestosis began to accu mulate after the re[>ort of a case by Lynch and Smith*8 in 1935. Within the next 10 years, about 15 additional cases were re ported. and in 1954 Merewether 76 reviewed all deaths from asbestosis recorded in Eng land since March, 1924. Lung cancer oc curred in 16% of these cases. Gloyne,*' Accepted for publication Jan. 20. 1958. This study wn made possible through a grant from the Qutlxx Asbestos Mining Association. Medical Director (Dr. Braun) and Statistical Consultant (Mr. Tritan), Industrial Hygiene Foundation. whose work is also frequently referred to as establishing a connection between asbes tosis and cancer of the lung, reported in 1951 that cancer of the lung was present in 14.1% of asbestosis cases examined by him. In 1941, Nordmann and Sorge7* claimed to have produced lung cancer in mice which they exposed to asbestos dust. Since 1951, additional cases of cancer of the lung coexisting with asbestosis have been reported, and, according to Hueper88 about 100 such cases had been reported up to 1955. As a result, an association between the two diseases appears to have been ac cepted by many authors, and several writers were using the term "asbestosis cancer" of the lung. Werber,** in 1952, stated cate gorically that in 7% to 17% of cases of asbestosis, after a latent period of about 1J^ to 20 years, carcinoma becomes estab lished in the lung. On the other hand, not all authors ac cepted this alleged association without reservation Saupe 80 m 1939 reported that he had discovered uo cases of lung cancer among 620 cases of asbestosis which he had examined; and in 1942, Holleb and Angnst<s expressed the opinion that the number of cases of asbestosis with lung cancer was loo small for statistical evalua tion. In 1947, Wegelius88 reported 126 radiologically diagnosed cases of asbestosis among 476 workers in Finland, and found no cases of lung cancer in this group. Goldblatt and Goldblatt in their section of Merewether's latest book,44 state: "But at no stage in all these impressive researches was any clue obtained which might have offered any support to the possibility that asbestos could act as a carcinogen. There 634 i "//j/fy / ( .so CAXCER IX ASRI.STOS MIXERS i> no reliable criterion by which one cais uii'cij<-Aic carcinogenicity anil, as is well known, relatively minute changes in the structure of a chemical carcinogen are suffi cient to diminish or eliminate carcinogenic action. If asbestos is indeed to be regarded as a carcinogen, the need is felt to demonstrate some property which can be regarded as something more than inertness." These authors advance the theory that, until some more experimental evidence of direct carcinogenesis by asbestos or a decomjiosiiion product of it can be obtained, asbestos might be considered as a "co-car cinogen" which only induces a' further de velopment of a preneoplastic condition brought about by something independent of the asbestos, such as an endogenous factor. Thus the literature, while tending to sup port the thesis that asbestosis is in some way related to the development of lung cancer, is by no means unanimous. Alto gether, it is perhaps more confusing than enlightening. A careful review shows that the majority of the reports are clinical and not epidemiological. They lack many ele ments necessary for the application of epidemiological techniques to their content, and most of the authors do not make claim to having done so. What has happened is that succeeding authors have drawn conclu sions and generalized bet-ond rhe scof/e erf the works which they quote. Nowhere, for example, have vve found references to a population o! asbestos workers, although several authors who have quoted the ob served incidence of lung cancer m autopsies of persons sssho also had asbestosis imply that this incidence applies to asbestos work ers, generally. We have likewise been unable to find any study which actually calculated the incidence of lung cancer among a population of persons who had asbestosis, and not just those who cum to autopsy. With the exception of a paper by Doll," none of those reviewed gave am data on cx[>osure anil dust concentrations, and even Doll's paper merely mentions "scheduled" areas, by which is meant, "those areas where processes are carried on which were scheduled under the Asbestos Industry Regulations of 1931 as being dusty." There is, furthermore, a complete lack of definition of terms as used in the pub lished literature. For example, the term "asbestosis," as used, may refer to changes observable only by microscopic examination of the lung tissue, or it may mean a radiologically detectable condition. Most of the published reports obviously included women among their cases, but some of them do not give the number or proportion of women involved-in the study. There is also a lack of uniformity as to what type of exposure most studies have dealt with. Of 99 cases enumerated by Huq>er 58 in 1955, only 10 ap[>ear tu have originated in the United States, and 7 in Canada. Sonic of the earlier reports ap parently included asbestos miners, but it can be assumed, since 82 of the 99 cases had originated in England, and since no asbestos mining operations are carried on in that country, that most of the reported cases have involved workers in the textile or fabricating industries. Such factors as smoking habits, family historv of cancer, length of time in the industry, and age o: the individual case are also- notably ab--mr in-the-majority of these reports. With this understanding of the limita tion; o; the existing literature with respect to epidemiological generalization, it may be ot value to consider in somewhat more de tail some representative earlier publications, a few of which were referred to briefly above. One of the most detailed studies and one which deserves the most serious considera tion is that reported by Doll18 in 1955. This study reviews causes of death among asbestos workers based on coroners' rec* nil >. It uUo attempt' ti> estimate the risk liv studying records of men who worked for at least 20 years in exposed situations. Broun--Truatt /V 635 .4 M ,4 AHUUt t.\ (il I \ I H'S THIA I. HI-.AI.TII Doll concluded cm! iut:g; cancer was a spe cific indusirui hazard of certain asbestos workers and that, after 20 years of expo sure, the risk 10 tunes as great as for the general population. This article is important for several rea sons, in addition to the definite conclusions at which it arrives. For example, it begins by stating that "in view of the infrequency of asbestosis, this large number of cases (61 cases of lung cancer) suggests--but does not prove--that lung cancer is an occupational hazard of asbestos workers." Neither this article nor any previous one which we have examined presents any fig ures... ta prove that asbestosis is an infre quent occurrence. Estimates of the number of |>ersons potentially exposed to asbestos dust in the United States alone vary from 10,000 to 35,000, and the incidence of as bestosis of any degree might be higher than Doll imagines. This study, like so many others, involves autopsy records. The number of persons involved in the statistical analysis is only 113, representing only 1,042.25 man-years of life. It is also true that in selecting men who had been employed for at least 2(1 years, the study automatically excluded those who died from other causes after shorter employment. Another reason why this publication is importance is a statement which it con tains to the effect that "the strongest evi dence that it flung cancer! may be a hazard i in asbestos workers! has been produced hv Merewether and bv Glovne In 19el Giovne presented a review of 1205 autopsies on persons who hail worked in various dusty occupations. This number included 132 asbestos workers, of whom 121 showed "pneumoconiosis"--pre sumably asbestosis. Primary cancer of the lung occurred 17 times in this group, an incidence rale of 14.1% for lung cancer among asbestosis cases coming to autopsy. There were in his series 7% cases with sili cosis, and 6.9% of these also showed pri mary cancer of the lung The incidence of lung cancer in other forms o( pneumoconio sis vjai 6.7%. and in 169 cases which proved not to have any type of pneumo coniosis it was 8.3%. Gloyne considered "the mortality of the asbestos workers" to be "disturbing." First of all, it is obvious that the paper does not deal with the "mor tality of asbestos workers," and secondly, it must be borne in mind that all of Dr. Gloyne's cases were submitted to him for study because the findings were unusual for uncomplicated pneumoconiosis. It can reasonably be assumed that cases, including those of asbestosis, in which the findings were not considered unusual were not sent to Dr. Gloyne for examination. As a mat ter of fact, in the same paragraph in which he expresses concern over the incidence rate in asbestosis, Dr. Glovne himself [K)ints out that the rate for lung cancer based on necropsies at the London Chest Hospital was 21.3% while the figures of the Registrar-General showed only 2.4%. He thus recognized that autopsies on a cer tain selected group of cases were not rqresematne of the general population. It would seem, then, that notwithstanding the value of Dr Gloyne's work, its imjiortance as an index of the prevalence of lung can cer in asbestotics has been misinterpreied by some who have quoted him All that it ready show s is the fact that in a group of 121 cti'-e-. selected for special studv pri marily brr.vj'-t- they seemed abnormal- bv prelmnnarv examination. 17. or 14 1 G . had lung cancer Mereu et!<-l47. n ;hc rr or: of the L' 't ; v.'.ccc o: I'acmnc-. reviewed alt ca-aw re;* tried between 1924 and 1946 in which .ssbeMcrMS was the cause of death or a coexisting condition. This work was later extended to include all such cases re ported up to December, 1954. by which time there were 344 deaths, including 205 males and 139 females. Among them were 55 cases (16%) of cancer of the lung, 41 in males and 14 in females. It is quite possible that a large number of asbestotics who did not die of their asbestosis. or in whose 636 I'ol IT, Juxr. ]W /.CSC CAS ( I R IS A SUESTOS MISERS death certificate it was not mentioned, may prior to that date and enumerated a total have been missed. The import of this 16% ' of 99. Eleven of these were those dis is enhanced by the simultaneous statement cussed by Doll ** and may have been cases that the incidence of lung cancer in autop covered by other authors. Eight were dis sies of the general |iopulation is only 1%. covered by Kenoaway and Kennaway in The danger of attempting to compare a an analysis of death certificates, and, unless rate found in 344 cases with the rate for Merewether's study was incomplete, these the general population without respect to cases should have been included in his re age, occupation, and many other variables, port. Of the remaining 80, it is quite pos such as smoking habits, is obvious. sible that the 31 contributed by Merewether Lynch,70 who with Smith *' had reported the first case in 1935, reported 4 cases of carcinoma of the lung in a series of 49 and the 17 by Gloyne contain some duplica tion with each other or with those of other English authors. autopsies on workers in an asbestos manu facturing plant who were shown to have "demonstrable deposits of asbestos in the Principles of the Epidemiological Method lungs." This, of course, is not necessarily identical with the disease asbestosis. Lynch, himself, points out that, although this is an Dorn 30 has pointed out that much of what is now thought to be pertinent concerning the comparative frequency of lung cancer incidence of 8.2%, "both figures are too in different population groups has been de small for very serious statistical types of veloped from the analysis of clinical ma calculation." Nevertheless, later writers terial, particularly surgical and autopsy have used this paper to strengthen the case records, supplemented to some extent by for an association of carcinoma of the lung the reported impressions of various clini with asbestosis. It is also of interest that cians based upon their personal observa Klotz 03 found only the same number of tions. More recently, however, attention cases of lung cancer in a series nearly 10 has turned to the systematic investiga times as large, i. e., 4 in 478 cases of tion of this problem bv the same methods asbestosis. that have proved so successful previously in Behrens, as cited by Merewether,7* esti the study of communicable diseases, that is mated that, of 309 cases of asbestosis in the to say, by epidemiological methods. literature, 44 showed associated cancer of In order to apply this method of investi the lung--giving an incidence of 14.2%. gation to the problem, under disenssjorr, we This, is- an illusrrarion of generalizing an were of the opinion that a study should be incidence obtained in a group of cases which were undoubtedly reported only because some of them showed lung cancer, to planned so as to provide (1) a well-defined population group: <2'. available data tor all members of this population, including the pos^bly hundreds of asbestotics whose healthy as well as the ill; (3) a sampie cases is ere never reported. The same ap which is truly representative of the popula plies to the conclusion of Teleky,8-' who tion; (4) reliable and valid observations appears to have reviewed reports of 39 relating to the problem of the study. autopsies on persons with asbestosis among which 6 cases of lung cancer occurred. In formation from sources such as these does not justify generalizations with regard to mortality rates. A serious defect, common to most of the studies which have been reported, is that little or no information concerning the healthy people in the group seems to have been available to the author. In order* to Perhaps no one has written so exten draw a generalization regarding all asbestos sively on the subject as has Hueper.67-5* workers, it is necessary for a study to in In 1955 he reviewed the cases ** reported clude living persons as well as the dead. Braun--Truan AV AV A M. A. ARCHIVES OR INDUSTRIAL Hi.A! TH Limiting the investigation to cases coining to autopsy, as has been frequently done in earlier studies, still further restricts its use in generalization. The problem with which we are concerned is whether asbestos miners experience more lung cancer than does the general population. The answer necessitates the collection of reliable infor mation on asbestos miners as a group, as well as on the general population. It seems advisable to discuss the differ ences between the epidemiological approach and that used in the studies which have been reported to date. A very important consideration is the fact that lung cancer, in spite of its increasing numbers, is still a disease of low incidence; that is, in a given population not many persons will contract this particular disease. This fact requires that large samples or groups must be stud ied to provide meaningful results. Recognizing the difficulty of obtaining such large samples, most earlier writers deviated from the epidemiological method and sought to circumvent the requirement of obsemng well persons by (1) compar ing the relative frequency of cancer in vari ous sites; (2) comparing the relative frequency of cancer in a group of hospital ized patients; f3) comparing the relative frequenev of cancc- in a group of cases coming to autopsy. Attempting to compare two [>opulation group*, looking onlv at the relative fre quency oi cancer m various body sites, may resuit in finding a higher percentage t'ro;uenev i ;r. one of the groups m the ''.'aiifs rate oi cancer of a particular organ is exactly the same m h-vh g'oups This is very clearly dem onstrated m the excellent article by Dorn.30 The mortality rate from a particular cause is the true measure of comparison. It is apparent that selected groups such as hospitalized patients or autopsy cases may not be in any way representative of a larger group, and that in dealing with such samples, the observer may easily find more cases of a given disease than would be found in another group of the same size, but representative of the general population. It is true that investigation of cases from such a sample can furnish information valuable for research, but the use of this information in drawing generalizations is necessarily restricted. It is the obligation of both the investigator and of those who read his report to make proper comparisons and to draw only those conclusions which are valid and justified. A good statistical study of cases of cancer of the lung occur ring in a group of autopsies can lead to a proper inference concerning the frequency of lung cancer among cases coming to autopsy, but only to such cases. For in formation. from, such study- to be pro jected to some larger group, it is necessary that the autopsies represent a good sample of that larger group. To assume that such is the case in any particular series is dan gerous and likely to be false. There is some danger that the figures rq>orted by some authors may be miscon strued as applying to asbestos workers or even asbestos miners, when, in fact, the authors in question do not make this gen eralization. nor can the generalization be made for the reasons staled. Close studv of the reports reveals that the percentages cited relate only to the group of autopsies covered by the particular investigation. The present study, in contrast to the earlier works, has been planned, to. utilize the epidemiological method A well-defined group of asl>estos miners has been estab lished m >uch a wax that it consti'ute? a g1 >od 'ample w! tile XX hole population of asbestos miners in Quebec. Data for ail members of this group have been collected and analyzed Those concerning lung can cer have received most careful considera tion. Details of the methods emploved will be set forth later, but the type of approach is considered to permit of fair comparison* and xalid generalizations. Collection and Analysis of Data A preliminary survey of potential sources of information in February, 1956, involved 638 Vo! 17. June 19 Vt /W S' erf'<2. O //'At, ( ./ \ ( / / V ,-t s HI. v 7m /'/A / . A' \ diseiLSiions with the physicians in charge of the asbcsio- companies' program' am! with clinician'. pathologists, representatives of City and Provincial health de|rtmciits and of the Canadian Cancer Society, anil other interested ]ktsoiis. It was found that morbidity data, although somewhat limited, were available from such sources as the hospitals in Montreal and Quebec City, and the 13 cancer detection centers in the Prov ince. However, because of the high mor tality in lung cancer, it seemed advisable to depend ujion data relating to death'. These we found to !>c obtainable at the ' mil statis*icj de[iarmiem of the Mmi'in of Health in Quebec City. From the pre liminary survey, it was apparent that exten sive and detailed information could be gathered with respect to both the persons employed in the asbestos mining industry and the mortality figures for the general Itfipulalion. Following this exploratory survey the initial effort was directed to the collection of data relating to all workers who had l>een proce-sed through the clinic at Thetford Mines since its inception in 1947. and similar information regarding all workers at Asbestos. Que. Data from the clinical records included the age family and per sona! medical histo-ovs smoking habit' "umber ot sears oi expu'tire. .in emmam "f weighted exoo'jrc. and the course of the individual's heailh Main' nr the cati'e of h:> death From t'rv' iiiionratn'iii it was possible to iormuiate a "cohrirt" which could !>e well defined, should be representative of the whole group, and could be followed for a definite period of time. All of the available experience indicates that the development of asbestosis in less than five years of ex posure must be somewhat rare. Accord ingly, the cohort was defined as including every miner who had a total exjvisure of five or inore years, and w'ho was on the employment rolls in 1950. Office and other nonexposed personnel, regardless of length of employment, were not included. This cohort was then followed by means of the annual physical examination records through a six-year interval, 1950 through 1955. All data regarding this group were then tabulated in order to determine the characteristics of the cohort. For those who survived the entire period, reference was made to the physical examination results and x-ray findings at the end of the j>eriod. Those who had died were tabulated sepa rately, and the cause of death was corroborated by examination of the death certificates A further search was made concerning those in the original cohort who remained unaccounted for when the living and the known dead had been tabulated. They represent men who had left employ ment through retirement or resignation. Fventuallv. all but a small number of these were accounted for as either living or dead, ;ui<I in the latter event, the cause of death was substantiated in a similar manner, and the result' added to the original list of deaths. Death certificates for the Province of Quebec for the years 1952 to 1955, inclu sive, were reviewed in the department of vital statistics of the Provincial Health Ministry, together with statistical sum maries of the causes of deaths in the Prov ince by counties- All cases m which death war certified a? Having been due to pri mary cance- of the lung were examined for -uch ir.to'irai'on a; [dace of residence, occur.cron da'- o: death ho<;v;a' which death occurred and whether or not an autopsy was i>eriormed. Cases in which lung cancer was given as a cause of death, but in which it was not specified as to whether the cancer originated in the lung, were also reviewed in an effort to include all instances of primary carcinoma of the lung in the study. The statistics for the Province of Quebec relate to population, total death? from all causes, total deaths from cancer of ail types, and deaths from lung cancer. These were collected and tabulated by counties and by sex for the years 1950 to 1955, inclusive. Braun~Tr\ta\n 63<> /*/ 6 f 11 A AHCHin-.S Ul IXDCSTR1AL Ht.Ai.TH lrom them, death rates tor the general population of Quebec and of individual counties were calculated for specific years and analyzed by cause Practically all employees of one company are covered by a group policy of life insur ance which, fortunately, nearly all of them continue to carry when they retire. A very few are not covered by this policy, and those who leave the industry for one reason or another except retirement usually are no longer covered, but this is likewise a small number. As an additional check upon the information obtained from the clinical records on this group, the records of the life insurance company were examined for alt death claims paid under the policy, and particular notice was taken of the claims in which the proof of death was based on cancer of the lung. Deaths from lung cancer among asbestos miners were thus determined from the clinical records in the medical service of the industry and checked by means of the death certificates and insurance company records. The deaths were then verified individually oy reviewing them with the physicians in charge of the medical services. In this man ner, there was established a list of cases in which primary cancer of the lung is con sidered to hare been proved as the cause of death A few cases in which lung cancer i< strongly suspected but not proved as the cause o; death were considered sepamtelv Mortality rates have been calculated, using both the "proved" and the total of "proved' and "su-pev.ed" cases during the veurs un der observation. Comparisons were then made between the death rates from the same cause among specific segments of unexposed persons. All lung cancer deaths, both suspected and proved, were carefullv ana lyzed to determine possible relationship or correlations between the development of lung cancer and any factor known from the clinical records, such as family history of cancer, personal history of heavy smoking, coexistence of asbestosis, or exposure to asbestos. In jddition to this analysis of deaths oc curring in the cohort and during the years under observation, every known death from cancer of the lung, as well as every case diagnosed but still living, has been tabulated and analyzed. They will be discussed separ ately from those included in the population and time-interval under study. A comparison of lung cancer mortality in the asbestos-producing counties has been made with that in counties which are far removed from the asbestos mines and in which, presumably, no asbestos miners live. Finally, in order to broaden the compari son of death rates in different population groups, the rates- have- been collected for C.mada generally, and for the United States, according to the most recent published and unpublished material. Results and Interpretation The cohort which was constructed accord ing to the criteria described in the preceding section has been considered individually and compared with the general population. Description of the cohort will be presented here as a preface to the results of the study: Original Cohort I^ost Persons DeJucted Final Cohort Living n 1955 /working jimI retired) Head by 1955 Cancer of lung Q>ue*ionjble cancer of lung' < nUer causes l nknown c-uSCS >no*.c'c NonNinokers l lUMOWtl 6.091 133 5.958 5,771 187 9 J :6* 6 4,673 1,265 :o Tables I. 2. .i and A present uuiiibcr of vears of emplovment. weighted average exposure, and smoking habits of 'he cohort. A comparison of the exposure to asbestos dust is presented in Table 3. All members of the cohort were placed in one of three categories, representing increasing degrees of exi>osure based on a weighted average of the years si>ent at various levels of dustiness. The degree of dustiness for each job category was determined after consulta- lion with persons familiar with the environ ment and conditions in the various work Vt. IT, Juji,\ 1V5X AV ? T-Z'0 LL.\C CANCER IS ASPhSTOb MISERS Table 1--Sumbtr and Percentage Dulnbution Table 2.--Sumber and Percentage Distribution by by Age i Length of Employment AC 30-44.................. <3-54................... 45-64......................................... ........... 64+................ ........... UoLbOvn__ . . ___ Touli._.................... ........... A**rc* A|c........ ................... ........... Number a.w 1.124 615 215 5,356 41 ' Lee ilieo 0.5%. Per Ceni IV 10 5 100 Length of Employment 5-9 .................................................... . 10-1...................... .............................. 30-29................ .................................... 30-39.................................................... 40-49..................................................... 50+...................................................... TeuU................................... Avertfe years of employment..... Number 1.795 2.JBb 933 603 165 65 5.956 16 Per Cent 10 40 16 10 6 1 100 areas. For the puqxoses of calculation, the assumption has been made that the relation ship between these categories is linear, and that Category II is twice as dusty, and Category III three times as dusty as Cate gory I. ually smoking more than five cigarettes per day. Persons who smoke pipes or cigars exclusively were not considered to be smok ers for the purpose of this study. Table 5 presents the year-by-year ex perience of the cohort and indicates the Table 3.--Number and Percentage Distribution by Exposure Category Table 4.--Number and Percentage Distribution by Smoking Habits EspMur. Citorjr I................. H11I.................................. UDkoow-n............... Touts....... A Tense Exposure Less than 0.5% Number 2,031 2,150 1,772 j ------- 5.058 2.0 Ter Cent 34 30 - 100 Smokin( Hebus Nombor Per Cent Smokers.................................................. Nonsmoken.......................................... Unknown............................................... TouJs.................................... 4,873 1.365 JO ---------- 5.BS8 7 21 * -- 100 ------------------------------------------------------- * Less than 0-5%. The fourth variable, smoking habits, was similarly tabulated and is shown in Table 4. This was included because the informa tion was available and because smoking was regarded as one of the variables which, besides the environment, could conceivably influence the development of lung cancer. As used in this presentation, the term smoke- reters to a cigarette smoker, habit- number of deaths each year from specified causes. In general, a case was considered to be "proved" as one of primary cancer of the lung when the records showed that the diagnosis had been supported bv an autopsy or surgical resection of the lung with, microscopic examination of' the re moved tissue. In one case so considered, however, diagnosis was confirmed by bron- Table 5--> cz^-by - > car Experience c- Cohcrt erne Death Rates per }00 000 Man-Yesrs of Risk Cause of Death 'i ear No. Alive At Becmmoc of \ ear Pruned Primary Ca. of Lung Suspected Primary Ca. of Lung Other Causes 1950 .. 1051.... 1952........... 1953........................... 1954 . . . 1956................. 5.95* 5.942 5.665 5.646 1 2 0 2 1 3 2 12 0 i; 0 37 1 44 0 33 0 36 Totals.......... 9 0 `'Proved" rtc per 100,000 man-vear* of risk* - ----- 25.5 25,271.5 3 169 `Total'' rata per 100,000 man-years of risk * ---- J4.0 Unknown 1 1 0 0 4 0 6 Man-Yearj of Risk 5.950 5.932 5.903.5 5.666-5 5.829 5.790.5 45.771.5 Braun--"Truon /A > A M A ARCHII t '> Of IXDL'STRIAL Ht.AI.TH TABLE 6.--"Prozed" Cases of Prnnary Cancer of the Lung Cu< So. 1 2 3 4 4 6 7 8 0 Ajf 06 64 64 M 48 61 40 37 08 Smoker Ym Vu Yu Yu Yu Yu Yu Ym Ye* Exposure K jt. to Ci. tl 34 yr. id Cn. I )7 jt. in Ci. 1 J? yr. in Cl. 1 22 jt. Id Cat. II 33 yr. to Cel. Ill SO yr. in Ci. II 1G yr. is Cti. I a yr. In Ci. Ill Died 10-13-31 3- 3-34 7-20-45 8-20-40 -41 4-30-33 11-72-43 8- 4-44 4- -44 Autopsy Yes Yu No Yes Yu Yu Yes Yu Brooch. AstxSlOSiS Yes No No No Yes Yes Yu No No choscopv with visualization and biopsy. In another, although there was no autopsy, the diagnosis of primary cancer of the lung seems to have been beyond question. The term "suspected" primary cancer of the lung was applied to those cases in which- the diagnosis remains- rn doubt* but some of the evidence points to cancer of the lung. There were three such cases. The term "man-years of risk" has been used to mean the number of men at risk for the year under observation. A person who lived throughout the year was counted as a full man-year of risk, but one who died during the year was counted as one-half a man-year. Deaths occurring in the cohort, and in which lung cancer is considered to have been proved as a cause, are shown in Table 6 In Table 7 are shown three deaths which have been considered as "suspected" lung cancer cases An indication of the importance of these "suspected" cases in interpreting, the results, o! the calculations is desirable before fur ther discussion of the mortality rates which are der". ed -n !s`er tables For example, it happcr; that trie "ate found for the proved casec is close to the "expected" rate based on the general population figures for the Province, as will be shown later, and on this basis we should find eight deaths from lung cancer among the cohort. Actually, nine cases were observed. If, however, the 3 additional "suspected" cases were in cluded, increasing this figure to 12, the total would be very close to the 95% level of significance. However, having found just 12 cases, we are not above this level, and therefore the hypothesis that asbestos miners do not have a higher mortality from lung cancer than does the general population can not be rejected. Nevertheless, the occur rence of 12 cases in this sample would increase the rate to a point which approaches the significant level. Because of the tre mendous importance of the questionable cases in this respect, some detail regarding them will be given here. In one of these cases, the suspicion of cancer of the lung is based upon the x-ray interpretation, and, although no autopsy was performed, the death certificate indicates that death was due to lung cancer It is well known that the x-ray appearance of fibrosis, especially if a localized density or a superimposed tuberculous lesion is pres ent. can simulate that of a tumor, and bv itself, does n< it lustifv the inclusion of thri case av of - "proved" cancer of- the iung A -r-..ca<e was cert'tied a? having died h\ re.j'f-;; of hvdrothorax. possibly due to !u:ic but .igri-n i-ie-i. v.a- in- surgery .i'M m postmortem examination. In in-- thto! -a, although it was subjected to autonpv. two pathologists disagreed as to whether lung cancer was present. The death was certified as having been due to chronic myocarditis with nephritis and pulmonary- congestion. and possibly cancer of the lung On the basis of these facts, it seems unwar ranted to include these three cases among Table 7.--"Suspected" Primary Cancer of the Lung Cue No. l 2 3 Ate 49 46 64 Smoker Ye* Yes Yes Erposuro IS JT. In Cet. Ill 33 yr. In Cel. Ill 4J2 yr. io Cat. IT Died 10-24-40 7- -43 9-36-45 Autopsy No Yes No Asbestos** No Yes No Mi Vot 17. June. 195S /.( \(, C .IXl'I.R IX .ISHI V7YM MIKI.RS "proved" instances of lung Qiurr, On the other hand, they cannot, in fairness, be dis regarded completely. It is for (his reason that mortality rales have been calculated Isith ways. Table 8 gives the rates by age groups. The rates by length of employment are shown in Table 9. During the first 40 years of employment, the rate rises, an observa tion which seems plausible since the men were growing older. However, after 40 years of exposure there are no "proved" cases reported for a (Ota! of 240 men dur ing the six-yearsr or about 1440 man-years of exposure. When the "susi>ected'' cases are added, one case does show up in this Table 8.--Lung Cancer Deaths by Age Croups Table ').--Lung Cancer Deaths fry Length "l Employment Number of P<rw>rv *ih) Number of Luk Cancer Death* Etm^nplrotylimoel nt Persons No. ol Peolht Proved Toul 34310400-0--2-+41*99999.......................................................... ..... ....... 21..9637Ig2099525355* 300051 020711 TuUls . 5.U5& 9 12 Annual 1.unrMaCnanYceearr*DoefatEhxpRoastuerse per 100.000 ELmenpeloihymoef nt Procod Total 3241500000----+43219999............................................................... 153000487 0 15994030 Orer-tl) 26 34 Number of Person* and Number of !*uk Cancer Death* Age Group * No. of l'ervms ---- No. nf fMaths -- Prm+t Toial 20-44.............. . 4V54....................... >5-$4.......................... 5-*-......................... In known . .. 3.901 1.124 fil3 315 3 l l J 4 V 1 3 3 S 0 Totals.... 6.95b U 12 Annual I.unr Cancer Death Rate* p*r 100.000 Man Year 4 of Evosurr Age group Trovi-.l 1 Olfil 20-4................................ 45-54... . S5-+4.......... * sS--- ... 1" rik n< iv"it........................ 44 IS 44 %l >W Jfif 11 0 Overall... 23 34 i-cnod This wouul jr<kIucu ;t r;tic o! O'.-' per lUU.UIKJ. again demonstrating the im portance of these questionable. but un proved, cases to the finai conclusion. Isecause. if there were no cases in this number of men with long exposure, and if asbestos is a carcinogenic agent, it must be concluded that these 240 men have demon strated considerable resistance. This is a bio logical phenomenon which has been observed previously and is consistent with the theory of an intrinsic or endogenous factor in can cer. The only other explanation would be that the susceptible members of this age group had died earlier of lung cancer. Table 18. which appears later in this section, in- dicates that the members of the cohort did not die from lung cancer at a younger age than the general population. The rates by weighted exposure are shown in Table 10, and it will be noted that they present strong evidence against asbestos living a carcinogenic agent, for, if exposure to asbestos is in any way con nected to lung cancer, we would expect that the longer and heavier the exposure, the higher the rate that would be found. The only possible error in this interpretation couid occur if the weighted exposures were inverse!}' related to years of employment, It - 1 ancer Deaths b\ F.zp 'Su'r Number c* T-' ~ * a-it! Number c:' Lure Canrtr D?a:r* F.tnosun: Category i 11................................. M[............................ Unknown.................. No ol Persons 2.031 2.1:0 1.77? 5 No of Deaths -- --- . - --_ Proved Touil 44 34 24 00 Totals............. 3.95b 9 12 Annual Lung Cancer Death Rates per 100.000 Man Year* of Exposure F.ipnsuir Category Proved Tota I ......................................... . .......... U ......................................... II!......................................... ................ Uniuaown................................ ................ 23 19 0 33 31 37 0 Over-ail................. ................ 25 34 Hrnun -- Trusifi 643 A M A ARCHIVES OF INDUSTRIAL HEALTH TawlF 11 -- umber of Persons m I'Qriouj Weighted Exposure Categories by Length of Employment w etc hied Eip'Hurr Cjtecoriei Lfnfih of ____ _ Employment i 11 in - VnkDOtt-n 5-8 10-19 20-29 30*39 0-49 504* :or 509 400 0 6A3 883 ISI 1 JI4 363 243 2 747 319 137 1 67 41 \ X 71 10 0 Totals 1031 Atenjre vears of etpoture IT A 2,150 17.8 1.772 16.6 5 20.0 To 1*1 1.705 2.308 022 603 185 55 l.M 17.5 in which case the heaviest weighted ex posure (Category III) would show the shortest length of employment. Table 11, which lists the number of persons in various exposure categories by length of employ ment indicates that this error has not oc curred. In fact, the average number of years of employment for each exposure category is almost identical. Table 12, which develops the rates for smokers and nonsmokers, is most striking. It shows that not a single case of lung cancer developed among the 1265 nonsmokers and that all cases of lung cancer, both "proved" and "suspected," occurred in smokers. Table 12 was so striking that it was felt that funner verification was necessary. It was possible that some abnormal distribu tion ::-.a\ have occurred, e. g.. the non- * - ..c '--.Vumber jjta Percentage Distribution c; end .Wn smokers by Age Groups ` r* -r .- 41 4.-'M ` Pj. _''-4 f rt'C't. . Tcc&is .. . A re-izt 2Z:___ . . Number Nonsmoke' 3 >' 411 lf-4 2 6*9 224 20C ISO 0 4A73 39.3 1.265 44.2 Unknown 12 4 2 l 1 20 40.7 Table 12--Lung Cancer Death for Smokers ond Nonsmokers Number of Persons end Number of Lunf Cancer Deaths * by Smoking Hsbitt No. of Deaths l'tnoni Proved Toul Smokers...................... Nommokers............... Unknown.................... Touls............ 4,673 1J65 20 i. 5.058 0 0 0 -- 0 12 0 0 -- 12 Annual Lung Cancer Death Rates per 100.000 Man-Years of Exposure by Smoking Habits No. of Daaihs Prored Toul Smokers................................. ............. Noannoken......................... ............. Unknown.............................. 32 0 43 0 0 Os-*U................... ............. 54 smokers may have included a larger percentage of young men. Consequently, ad ditional Tables, 13, 14, and 15 were con structed to show the distribution of smokers and nonsmokers by age, length of employ ment, and degree of exposure. Although there are slight differences, they do not account for the fact that all observed cases of lung cancer were in smokers. In respect to age (Table 13) the combined average age of the smokers was 4 9 years less than that of the nonsmokers. Table 14 shows that as far as leng.h of employment is con- Tsbcf. 14--Xumber and Percentage Distribution of Smokers and Xcnsmokc'S by Length of Employment Lenetn of EmpkO'Tnent 5-9............................. 10-18................................. 20-29............................ 30-39................................. 0-49........................... 50+................................ Touls.......... A'trwt lenfth of employment.......... Sure ber Smoeen Vonsrjolers :.40 t>r: 722 433 no 33 1" o 10V* 1*0 22 4.673 1.265 K.O 19.3 Vnknou n )C 4 2 4 0 0 20 16.0 Perreouft Distribution Afe Group Smoker Nonsmoker 2t`>--M. . 4 5-54...................... 5>-64..................... 95- . . ................ Untnovn T o'wli........ 68.5 5.6 _3.5 100% 54.5 17.7 16.0 11.8 0.0 100% Unknown 60.0 20.0 10 0 5.0 5.0 100% Lrss than 0 05%. Perrentift Dis'ribuiion Lanctli ot Employment 5-0................. 10-19............................ 20-29............................ 30-39............................ 500-+49.............................................. Smoker 30.1 42.1 154 93 2.4 0.7 Nonsnioler 29 9 33.7 1ST 13.1 3.9 1.8 Touls........ 100% 100% Unknown 500 200 10.0 200..00 0.0 100% Vot. 17, /une, 1<?58 LL-SG CAXCER IS ASBESTOS MISERS Table 15--Sumbrr and Percentage Distribution of Smelters and Sonsmokers by Exposure Category Erpoiur** Cietry Number 6 mo ken Nonmoktn lioiiio'n 1.................................. II................................... III.................................. Unknown...................... l.JSJ t.Ml 1.4M 4 474 4 4M 7 UB # 10 ToUli............ AeerM* irpoeure etuiory.................... 4,673 3.0 1.3M 1.0 30 3J E ipomre Ceutory Pertcoute Dulrtbutlon Smokers Nooimokers 1.................................... II.................................... III.................................... Unknown.................... 33.3 36.3 30.5 0.1 37.5 15.7 36.7 0.1 Touls............ 100% 100% Unknown 30.0 35.0 45.0 0.0 100% cemed, the smokers had worked about 2.3 years less on the average than the nonsmokers. With longer exposure and greater age, one would expect the nonsmoking group to show a higher rate if lung cancer were due to asbestos. Table 15 shows that the average exposure category was almost the same for the two groups. Therefore, this variable seems to be of no importance in accounting for this difference. The result of this additional analysis is that none of these factors appears to lessen the effect of Table 12. Comparison of the Cohort Experience tenth that of the Province of Quebec, Do minion of Canada, and the United States.-- In order to matte a comparison of the experience among asbestos miners with that of the general population of the Province of Quebec. stat:st:cs were gathered, as stated earlier, m the office of the Division of Demography m the Provincial Ministry of Health. The data on total deaths, deaths from all forms of cancer, and deaths from cancer of the lung were obtained by sex and by county for the years 1950 through 1955. In addition, all death certificates which specified primary cancer of the lung, and all those which indicated lung cancer but did not specify the origin, were exam ined for the years 1952 through 1955. Table 16 gives a tabulation of the number of deaths from lung cancer in the Province and in the cohort for the years 1950 through 1955, and shows the annua! rate per 100,000 in these segments. It will be noted from the table that the mortality rate for the "proved" cases in the cohort is only slightly higher than the rate for the Province. When the "suspected" cases are included in the calculation, the rate for the cohort rises to 33.8 per 100,000, which is about 50% higher than the rate for the Province. This, it will be recalled from the previous dis cussion of the effect of the "suspected" cases on the results, approaches but does not exceed the significant level One further interesting observation from Table 16 is the rather marked increase in the total number of cases for the Province between 1950 and 1955. Tt is assumed that at least part of this increase is due to im proved recognition and reporting of lung cancer during the interval For this reason, the years 1934 and 1955 -a ere though; to be more nearly representative of actual condi tion; Ever, so ; o nuite iike'v that the genera1 ; " -i.v t. o w vut.nd lung cancer with the same diligence with which Table 16 --Comparison of Cohort with Province of Quebec Lang Cancer Deaths Annoel Number of Persoas 1950 1951 1952 1953 1954 1955 Total Rate per 100.000 Pro vine* 1,198.000 * 196 230 345 303 303 357 1.624 Cobon Total ProvPinroceved 6.923 f 3 2 0 3 1 3 12 1 2 02 1 3 9 1.192.000 193 218 245 300 302 354 1.612 *(reoirrtkodnt)nc asbestos r.6 33.8 2V3 22.5 lo the Prorince firures. It has been assumed el) mete lime cancer deaths ere for men of 204- years. * Approitcnau midpoint of tr* enumerated population for 1951, and tbe estimated population lor 1964 (Rapport, Dit. de 1 Democrephie). INumber thee to cohort at beginning of 1952. Broun-- Truoti 645 A(e Group 20-44 45-64 55-64 85+ Totals A M A ARCHIVES OF INDUSTRIAL HEALTH Tabu: 17.--Lung Cancer Deaths for the Provtntt of Quebec* Population rrr.ooo 202,1*0 ur.uuo 121.000 1.237,000 Number of Death* 1954 Total Certified Specified Primary Total Proved Tout Prosed 17 13 II 9 67 36 43 29 100 1* 66 32 111 63 66 29 -- ---- 195 120 m 99 1965 Tout Certified Specified Primary Total Proved Tout Proted 17 9 17 9 BO 66 K 22 117 57 ne $7 146 M 148 *4 --_ 642 155 in 153 A|e Group 20-44...................................................... 45-54...................................................... 55-64...................................................... 6M-. :........................................................ Ortr-all................................................. Death Rates per 100,000 1964 Total Certified Specified Primary Total Proed Total Proved 2.2 133 71.0#1.7 1.7 1.4 17J 21.3 27.7 SOX 17J 563 1.3 14.4 13.4 14.0 23.8 9.7 15.4 8.0 1966 Total Certified Specified Primary Total Prorad Total Prorad 2.2 28.1 154 122.3 i.l 17.1. 4L6 44.6 1.1 r.7 *4.7 122.3 1.1 153' 41.4 44.8 27.6 12.5 27.2 123 * Data Iron) death certificates t Estunaie lor population ooumed by applylnx 1951 percentages for aja (roups for males to tba total population tor 1954. u (Iran to Rapport, Dir. at ia DetDopaphte. this disease is looked for in the miners, and it seems probable that the mortality rates for the Province may be low. This would appear to be substantiated by the fact that the reporting of cases in the cohort showed no such increase over the same period. Table 17 was compiled to show the an nual age-specific lung cancer rate of cases in which the death certificate merely read "cancer of the lung." as distinguished from those In which the diagnosis was confirmed by autopst, surgery, or biopsy. The term specified 'primary" refers to those cases in these rwo categories in which the tumor was specified as haring originated in the lung. It wiii be noted that, of the total cases reported in 1955. a much higher percentage than in 1954 were specified as primary. The table also show's that a higher percentage of the total cases certified in 1955 were proved, again indicating increasing interest in this disease. A comparison has been made between the age-specific rates shown in Table 17, and those for the cohort, shown in Table 8. An average of the 1954 and 1955 rates for the Province has been used, since the 1955 figure was higher and may have been ex ceptional. This comparison, summarized in Table 18, shows that the observed number of deaths in our sample is not significantly greater than the expected number of deaths, based on the average of the 1954 and 1955 figures for the Province. It is true that, in the case of the age group of 65 and over, the five deaths provide a figure which is almost significant at the 95^c level. How ever, it should be noted that this number includes one of the suspected but unproved cases previously referred to Furthermore, it is rather likely that the rate for the general population is understated in this age group for the obvious reason that the exact cause of death ir. the very old is not Table IS--Comparison of the Actual end Expected Number of Lung Cancer Deaths by Age Among Asbestos Miners Ate Group Province Total Specified Primer* Raie per 100.000 20-44 45-64 65-64 85+ Uoknown 1.8 24.5 67.6 89.3 Obserred No. Erpected of Death* No. of No. of Miners Deaths Proved Total 3.901 1.124 615 316 3 0t 1 1 2 13 2 33 2 45 00 Ttw eipected number Is based on the a Terete of the 1954 tod 1955 ece-specific rtleJ for tbe Pronnee of Quebec, t Actually 0.4 646 Vol 17, June, 195S X>siy /j /4 *>v r r 4 j i | u i i J M n o m a r a M i i m uLjiu in - use CASCER IS ASBESTOS MISERS Tadul 19 --Age Distribution of Adult Moles for Tam.1 20--Annual Death Rotes per 1(>0,000 the Prenmee of Quebec, 1951 * Cancer of the Lung in Conada Age Group 20-44.................... 43-M.................... 33-64.................... &+..................... Tout........ Pro.t-o..e..t.... ............- Number Temnuie 777.133 166.912 128.044 113.4*7 A3 16 U 10 1,138.498 1G0 rerrenuM in Cohort 66 19 10 3 100 * Rapport, IftM. a matter of the same intensity of interest as it is in younger persons. Table 18 also answers a question pre viously raised. It snows that the members of the cohort have not died from lung can cer at an age earlier than the general popu lation, and that such an explanation cannot be offered for the absence of lung" cancerin 240 men with more than 40 years of employment referred to on page 643. Before leaving this comparison of the Province with the miners, it should be shown that their age distributions are rea sonably the same. That this is the case can be observed from Table 19. It should be remembered that the miners retire and consequently, it can be expected that the oldest age group will be larger in the general population. The data presented in Table 20 indicate that the lung cancer rate generally decreases after age 70. There fore we could expect the rate for al! people over 65 to be smaller than the rate for the group between 65 and 75. which would apply to the oldest, group at. miners. It is felt that by using the whole adult male popula tion e ha\e de\eloped rates for the gen era: : ulntion u h:ch are somewhat lower than if wc had been able to exclude tnt people in the general population over 75 A comparison between the asbestos miners and the population of the Dominion as a whole was made, using statistical material from several sources. In one source. Phil lips T9 gave age- and sex-specific rates for Canada for three periods between 1931 and 1952. The rates for males are given in Table 20. These figures show strikingly the increase in rates between 1931 and 1952, and this Age Group Under 30 JO-W 33-39 40-44 43-49 30-34 3300-64 63-69 70*74 73-79 10-44 65+ All Agn 1931-1933 0.2 0.9 2.0 321 3.2 9.2 12.7 123 13.1 10 7 13.8 64 11.4 24 Group* of Y*n 1*41-1943 0-3 0.9 U 3.4 12 3 18.9 77.0 33.7 34.3 306 30.0 77 S H4 7.1 1930-1932 1.0 04 3U 64 16.7 374 69.7 77.8 102 9 8*4 83.9 49.7 714 13.8 "Morialiiy Irom Lunp Cancer In Cuna4u," IWI to 105?. increase is particularly marked after age 50, confirming an observation previouslymade, to the effect that until recently lung cancer has probably been underdiagnosed in the older age groups in the general popu lation. To use these figures for purposes of comparison, it is necessary to combine the rates for certain age groups in order to conform to the age distributions used in this study. Since the exact populations in each age group for the years indicated is not known, this must be an approximation. However, the rates would be somewhat as follows Ap? Croup 20-u 4- 54 55-64 65 + Rdie 5 69 90 9 These rates are, ir, general, lower than those- developed for the total f proved and suspected ) cases of lung cancer among the asbestos miners. The onlv large difference, howe-. er. -s in the age group of 6c vears and over, and it is quite possible that the rate for this group may ha\e increased for Canada between 1952 and 1954 as it did for the Province of Quebec (Table 17). A further comparison has been made with an over-all rate obtained from the American Cancer Society for respiratory cancer deaths in Canada in 1953. This rate, for males, is 20.8 per 100,000, or 5 more per 100,000 than Phillips' 1950-1952 rate, and compares with 25.3 per 100.000 for proved cases and 33.8 per 100.000 for total cases among the Braun--Truon 647 A hi. A ARCH 11 E S OF /XDUS TRIAL HT.ALTH Table 21 --S'umber of Deaths ond Death Rates pet 100,000 by Aqc Groups for the Adult Male PofuJatmn of the United States* An Oroup 30 <44 45-34 55-04 Tout Population 24.544 000 ft.0O5.lRti 6.34O.QU0 5.6*O.UOO 44,6)0.000 Cftses su t.VTV 6.254 6.463 16.599 1UI. per 1 S.S 36.9 96 6 1UJ J7.J D*u from "Viul Suusocs of ibt Vniiod Sui*i." Vol. 1 and 2. 1052. asbestos miners in this study. It is there fore obvious that there are no important differences between the rates for asbestos miners and those for the general [copulation of Quebec and the Dominion of Canada. Since it is probable that figures for the United States are more complete and, there fore, possibly more comparable to the data for the miners, age-specific rates were com puted from "Vital Statistics of the United States," Volumes I and II, for 1952. These rates have been tabulated in Table 21. It is apparent that these rates compare favorablv with those for the asbestos miners as shown in Table 8. Still other rates for the United States were obtained from the American Cancer Society, and for males, these were 25.3 per 100.000 in 1953, and 28.0 per 100,000 in 1955. They are not identical with the rate calculated from the figures of the office of Vita! Statistics, but this is possible because the American Can cer Society rates are for mnies of aifages Xe\ertheicss tne\. too. compare favorably with the rate- of 25 for for total C3ses) vottenmo am:.n~ me asbestos miners Turning for a moment to a comparison between the asbestos nrners and persons who are exposed to asbestos in one form or another fas distinguished from the gen eral population groups just discused. who have no exposure) an interesting observa tion can be developed by deduction. Hueper iS has stated that there are about 33,000 [>ersons exposed in the United States, and we ha\e found that the Canadian mines employ about 8000. Elsewhere, it has been estimated that the workers in England who have exposure total between 3000 and 5000. With workers in Africa, Denmark, Nor way, ajid other countries, at least 50,000 persofis must be exposed throughout the world, and it can be assumed that this number has been fairly constant in the 20 years since 1935 when the first case of asbestosis with lung cancer was reported. At least 1,000,000 man-years of exposure has thus been accumulated, and this figure can be divided by the approximately 150 cases of lung cancer with asbestosis re ported during the 20-year period. This gives a rate of 15 per 100,000, which is at least indicative that any lung cancer rate which can be calculated for workers ex posed. to asbestos dust- is- nor much- greater than that for the unexposed population. Comparison Between Eight Counties Ad jacent to the Asbestos-Producing Areas and Eight Selected Counties.--To compare lung cancer mortality rates in the counties sur rounding the asbestos-producing areas with another group of counties in which no as bestos miners are likely to reside, the rates were computed on the basis of figures for the years 1950 through 1955. The eight counties selected for comparison were Argenteuil, Chateaugav. Montmagny, Portneuf, Richlieu. Riviere-du-Loup, St. Hyacinthe. and Terrebonne, mainly because they represent a wide geographic distribu tion throughout the Province. The counties selected because of their proximiry to theasbestos mines include Art'nabaska. Beauce Drummond, Fronter.ac, Megantic. Richmo wd. ShcrbrO1''-^? _ _ j Wolfe Table 22 vho w* the nur~\;.vr c: : one cancer deaths for the ve':r~ 19SC t h T 0 ugh 1955 for each of these counties. and a mortality rate, based on the adult male population in 1952. To emphasize the comparison, Megantic County has been shown separately, as has the Province of Quebec and also the Prov ince with the eight "asbestos-producing" counties subtracted. Because of its unique lung cancer death rate, Montreal et Isle de Jesus has also been listed in order to provide further comparison. It is apparent from the table that the lung cancer death rate for the eight counties 648 Vol. 17, June, 195! /O LLXG CAXCER IX ASBESTOS MIXERS Table 22.--Xumber of Lung Cancer Deaths and Rale per 100,000 Man-Years Counun Mfnnc Count* Eljtu "A<liani' Countm Eltbt EalMwd Countki Protioo* o( Quebec froeiaet of Quebec W*s tl|hi "edleoeat" eouniiei MonireeJ tt Ilk de Jesui AduJt Mlr population 1932 13.100 9*.600 63.000 1,198.000 1.100.000 194.000 Mile Lent Cincer Dteihj ------------------------------------------------ ----------- ------------------ I960 1931 1932 1933 1934 1933 3 1% ) 3 l 4 6 3 9 U 4 16 2 10 3 11 3 9 196 so 34S SOI SOS 137 190 236 267 299 341 i 7 136 in 163 233 * It is usutned ibst li ault lun* cn<w deaths occurred slier e . ToUJ 13 34 49 1624 1370 no FUt per 100,000 (6 9 94 (J 22.6 236 S4 immediately surrounding the asbestos-pro ducing areas is practically identical with that of eight counties selected for comparison. While Megantic County has a rate nearly twice that of the combined eight selected counties, it is lower than the rate for the Province, and- considerably lower than the rate for Montreal. The figure for Montreal would certainly be higher except for the very low numbers of deaths reported for 1950 and 1951, and it would appear that in those years some error in reporting has undoubtedly been made. On the basis of the other years, 1950 and 1951 deaths would be expected to be about 200 greater. This would result in a rate of 40 per 100,000. The only possible conclusion from this comparison is that there is no evidence that the persons who live and work in the coun ties surrounding and adjacent to the as bestos-producing areas have ant' greater incidence of lung cancer than those who live elsewhere in the Province. Comment, on. AH Recorded Lung-CancerCases, Liz ing and Dead, amnno the Asbes tos Miners--Although a simple enumera tion of a!! the known or suspected ca^es of cancer of the lung in these areas has no particular value from a statistical point of view, it is of interest to summarize such cases for the record. There were nine deaths prior to the beginning of the time period covered by the study, including one in which the diagnosis was mediastinal lymphosar coma. During the period covered by this inve'*igat'on, there were nine proved cases and three suspected cases in the cohort. Through 1956 and to date in 1957, there were eight deaths, six of which were merely suggestive of cancer of the lung and in cluded such diagnoses as mediastinal lymphosarcoma, mesothelioma, cancer of the leg with metastases to lung, abscess of lung, and cancer of the pancreas. One other was diagnosed on the basis of x-ray only. Inaddition, there are now living four cases in which the diagnostic evidence is strongly suggestive of lung cancer. This is a total of 33 cases of all types, including 10 "sus pected" but unproved cases, and 4 that are still living. The remaining 19 constitute the total of proved cases of cancer of the lung among the asbestos miners since 1940. The proved cases averaged 59 years of age at death, and varied between 37 years and 68 years. Their working span covered periods varying from a minimum of 14 years to a maximum of 37 years. Onlv three men had less than 25 years of em ployment in the industry. Seven among those on whom such information is avail able had a weighted exposure, placing them in Category III, and six worked in an exposure represented by Category I. There were only 17 among these pro-, -d ung cancer cases in which we have in formation regarding the presence of asbestosis. Asbestosis was present in nine, although it was minimal in two. Two path ologists disagreed regarding its presence in another. At least seven of the 19 proved lung cancers, therefore, were not accom panied by asbestosis. Summary and Conclusions Interest in the question of whether there may be an association between lung cancer Brotm--Truan /6 649 V A M. A ARCHIVES OF INDUSTRIAL HEALTH and exposure to asbestos has been evident since the report in 1935 by Lynch and Smith of a case in which lung cancer and asbestosis were both present. As additional cases in which the two diseases coexisted were reported, a causal association appears to have been gradually accepted by many authors, although some workers considered the correlation to be inconclusive. The pres ent study was undertaken in an effort to de termine whether a causal relationship did, in fact, exist between exposure to asbestos and cancer of the lung. Since most earlier studies had been limited to enumerating the lung cancers found in certain selected samples, such as cases coming to autopsy or death certificates in which asbestosis was mentioned, it was apparent that they could not fulfill the re quirements of an epidemiological and sta tistical approach to the problem. The present study was, therefore, designed to meet the requirements of this method. After a preliminary survey to explore the availability of reliable information, data were gathered on workers in the asbestos mines in Quebec, based on their medical records A cohort was defined as a group of asbestos miners having at least five years of exposure and who were in the industry in 1950. Data relative to their characteristics were collected and their status at the end of a six year period of observation was de termined In the case of those who had died an exhaustive search of death certific.ves and insurance records was carried out in order to determine as nearly as possible the exact cause of death. Mortality rates from lung, cancer for the general population of the Province of Quebec and its various counties and for the Dominion of Canada, as well as the United States were calculated from statistics collected in the appropriate places. Comparisons of the rates obtained for asbestos workers and for the other popu lation groups were made according to ac cepted statistical methods. Records were obtained on 6091 persons who fulfilled the criteria of the cohort. It was not possible to trace 133 of these for the whole period, but 5771 of the remaining 5958 were found to be still living in 1955 or later. Of the 187 known dead, cancer of the lung was considered to have been reasonably proved in 9 and to be strongly suggested in 3. The members of the cohort were studied with respect to age, length of employment, a weighted average of their exposure, and their smoking habits. It was found that 4673 were smokers within the definition of that term as used in this study. Thirty-four per cent of the cohort were more than 45 years of age, and thirty per cent had been employed for longer than 20 years. Thirty per cent had a weighted exposure which placed them in the category of highest ex posure. The mortality rate for lung cancer, as computed on the basis of nine "proved'' deaths among the cohort was 25.3 per 100,000. When the three "suspected" cases were added, the "total" rate for the cohort rose to 33.8. The importance of the suspected but unproved cases in determining these rates has been reiterated because it is likely that such cases would not be included in the statistics for the general population and because they influence the results so mark edly. According to the findings in this study, the mortality rate from lung cancer does not appear to increase with length of ex posure or with degree of exposure, a fact which presents strong evidence against the carcinogenicity of asbestos Comparison of the experience among the asbestos miners with that of various seg ments of the unexposed, comparable popu lation shows that the observed number of deaths among the miners is not significantly greater than the expected number. The rate for proved cases among the asbestos miners (25.3 per 100,000) compares well with the rate of 22.5 per 100.000 for the rest of the Province, and 20.8 per 100,000 for adult males throughout the Dominion of Canada. It also compares satisfactorily with rate* 650 Vol. 17, Jure I9SJT /7 LL'XC CAXCER IX ASBESTOS MIXERS of 37.2, 25 3 and 28.0 obtained from various sources for adult males in the United States Finally, in this matter of comparison, it would appear that the world-wide experience of persons exposed to asbestos dust is not 6 Behrens. W.. Experimental Asbestosis, Schweiz Ztsclir allg Path 14 275-297, 1951. 7,i Behrens, \V., Jr.: The Clinical Picture and Pathology of Asbestosis, Ztsclir Unfallmed u. Berufskrankh 45:129-140 (June 15) 1952. 8. Berblmger, W.: Increase of Lung Cancer worse with respect to lung cancer than that and Diseases Due to Dust Inhalation, Med. Klin. of the unexposed population. The counties surrounding the asbestos- producing areas, in which it is presumed most of the asbestos miners live, have al 27:1337-1342 (Sept. 11) 1931. 9. Berenblum, J.: Irritation and Carcinogenesis, Arch. Path 38:233-244 (Oct.) 1944. 10. Bohne: Asbestosis, Deutsche med Wchnschr 62:928-930 (June 5) 1936. most identical mortality rates with those of 11. Bohme, A.: Results of Periodical Examina eight counties w idely scattered through the tions of Workers in an Asbestos Factory, Beitr. Province, and are lower than those for the Stlikose Forsch. 11 :34, 1951. remainder oi the Province, and much lower than the rate for Montreal. Since 1940 there have been 19 cases in which the diagnosis of primary cancer ofthe lung mav be considered to have been proved. Approximately half of these cases 12 Bowles, O.: Asbestos-Milling, Marketing and Fabrication, Information Circular No. 6869, U. S Department of the Interior, Bureau of Mines, 1935, pp. 1-26 13. Breslow. L ; Hoaglin, L.; Rasmussen, G., and Abrams. H K.: Occupations and Cigarette Smoking as Factors in Lung Cancer, Am. J. were associated with asbestosis. All but one Pub. Health. 44:171-181 (Feb.) 1954. died in the recognized "cancer-age" and at 14. Bristol, L. J.: Roentgenologic Aspects of least one-third had only the lightest ex Silicosis and Asbestosis, A.M.A, Arch. Irrdust. posure (Category If to asbestos dust. Health 11:189-195 (March) 1955. i On the basis of what are believed to be 15. Cancer of the Lung: An Evaluation of (lie Problem, Proceedings of the Scientific Section, complete and reliable data, it seems fair to Annual Meeting, American Cancer Society, lr.c., conclude that the asbestos miners in the Nov. 3-4, 1953, New York. American Cancer Province of Quebec do not have a signif Society, Inc., 1956 icantly higher death rate from lung cancer than do comparable segments of the general population Furthermore. the death rate from lung cancer in the areas contiguous to the asbes tos operations comparable to that in areas 16 Cartier. P Asbestosis Cancer of the Lung, in discussion on Smith, \V. E . Survey of Some Current British and European Studies of Occupa tional Tumor Problems. A M A Arch Indust. Hyg 5 262-263, 1952 17 Cartier, P.: Some Clinical Observations of Asbestosis in Mine and Mil! Workers, A. M A widely scattered throughout, the. Province of. Arch. Indust. Health 11:204-207 (March) 1955. Quebec and lower than in some urban ized area- within the Province. 18 Clerens. J. Research mu Pulmonary Asbes tosis in Belgium, Arch beige* med Sociaie 557565 (Nov ' 1951 REFERENCES 1. Alasci" Escotar. R Bronchial Carcinoma Review oi XX) Cases, I Internal Coll Surgeons 26 375-379 (Sept ) 1956. 2. Allen, M L.: Bronchiogenic Carcinoma As sociated with Pneumonoconiosis: Report of 2 Cases. T Indust Hyg 16:346-347 (Nov ) 1934. 3. Cartier. P. : A Contribution to the Stud> of Asbestosis. Arch mal. profess. 10:589-595, 1949. 4. Anderson. C S, and Dible, J. H.: Silicosis and Carcinoma of the Lung, J Hvg. 38:185-204 (March) 1938. 5 Baader, E \V Asbestosis. Deutsche med. Wchnschr. 65 407-408 (March 17) 1939. 19 Llvntr- \eel - ' ar.d y .,-iX" M J 1 .379, 1931 20 Coffin. G J ; Dury et, H C.; Maicr, H C ; Pardee. H. E B., and Wynter, E. L. The Effects of Tobacco Smoking. Panel Meeting, Bull. New York Acad. Med. 32:133-156 (Feb) 1956 21 Cohart, E. M.: Lung Cancer and Economic Status, Cancer 8.1126-1129 (Nov-Dec.) 1955. 22. Cooke, W. E.: Pulmonary Asbestosis, Brit. M. J. 2:1024-1025 (Dec. 3) 1927. 23. Cureton, R. J. R.: Squamous Cell Carcinoma Occurring in Asbestosis of the Lung, Brit. J. Cancer 2:249-253 (Sept.) 1948 24 Culler, S. J : Schneiderman, M. A., and Greenhouse, S. \V.: Some Statistical Considera- Brmm--Trua A. M. A. ARCHIVES OF INDUSTRIAL HEALTH linns m the Study of Cancer in Industry, Am. J Hub Health 44 1159-1166 (Sept.) 1954. 25. Davies, D. F.: Current Status of Lung Cancer Research: Some Pathogenetic Aspects, CA 6:169-174 (Sept.) 1956. 26. Desmeules. R.; Rousseau, L.; Giroux, M., and Sirois, A.: Asbestosis and Pulmonary Cancer, Semaine de. hop. Paris 23:1820-1823 (Aug. 7) 1947. 27. Doll, R.: Bronchial Carcinoma: Incidence and Aetiology (Milroy Lectures, abridged), Brit. M. J. 2:521-527 (SepL 5); 585-590 (Sept. 12) 1953. 28. Doll, R.: Mortality from Lung Cancer Among Asbestos Workers, Bril. J. Indust Med. 12:81-86, 1955. 29. Donnelly, J.: Pulmonary Asbestosis, Am. J. Pub. Health 23:1275-1281 (Dec.) 1933. 30. Dom, H. F,, and Cutler, S. J.: Morbidity Irom Cancer in the United Slates, Pub. Health Monograph No. 29, P. H. S Publication No. 418, U. S. Public Health Service, 1955, 121 pp. 31. Dom, H. F.: Cancer Morbidity Surveys: A Tool for Testing Theories of Cancer Etiology. Am. .1. Pub. Health 45:615-621 (May) 1955. 32. Egbert D. S., and Geiger, A. J.: Pulmonary Asbestosis and Carcinoma: Report of a Case with Necropsy Findings, Am. Rev. Tuberc. 34:143-150 (July) 1936. 33. Ellman, P.: Pulmonary Asbestosis: Its Clinical, Radiological, and Pathological Features and Associated Risk of Tuberculosis Infection, J Indust. Hyg. 15:165-183 (July) 1933. 34 Ellman, P . Pulmonary Asbestosis. Proc. Roy Soc Med. 34:557 (July) 1941. 35 Feil. A. Pneumoconiosis in Asbestos Workers. Presse med. 39:1872-1874 (Dec 19) 1931. 36 Fulton. W B.; Dooley, A.; Matthews, J L . and Hourr. R. L : Asbestosis: Pare-HI The Efiects of Exposure to Dust Encountered in Asbestos Fabricating Plants on the Health of a Group of Workers, Special Bulletin No. 42, Pennsylvania Department of Labor and IndustryBureau oi Indus-. Standards, Sept. 20, 1935. 37 Gardner, L U, and Cummings, D. E. : Studies on Experimental Pneumoconiosis. Inhala tion of Asbestos Dust; Its Effect upon PrimaryTuberculous Infection, J. Indust. Hyg. 13:65-81 (Feb ) . 97 (March) 1931. 38. Gilliam. A G : Mortality Trends in Lung Cancer, Cancer 8:1130-1136 (Nov.-Dee.) 1955 39. Gilliam, A. G.: Mortality Attributed to Lung Cancer in the Large Cities of the United States in 1948 and 1949, J. Nat. Cancer Inst. 15:1307-1312, 1955. 40. Gioyne, S. R.: Two Cases of Squamous Carcinoma of the Lung Occurring in Asbestosis, Tubercle 17:5-10 (Oct ) 1935. 6S2 4{. Gioyne, S R. : Pneumoconiosis: A Histo logical Survey of Necropsy Material in 1205 Cases. Lancet 1:810-814 (April 14) 1951. 42 Gioyne, S. R.: A Case of Oat-Cell Car cinoma of the Lung Occurring in Asbestosis, Tubercle 18:100-101 (Dec.) 1936. 43. Gioyne, S. R., and Merewether, E. R. A.: Asbestos, Occupation and Health, Supplement to Encyclopedia on Occupation and Health, Geneva, International Labor Office, 1938. 44. Goldblatt, M. W., and Goldblatt, J.: In dustrial Carcinogenesis and Toxicology, in In dustrial Medicine and Hygiene, edited by E. R. A. Merewether, London, Loodon, Butterworth & Co.. Ltd, 1956, Vol. 3, pp. 185-188. 45. Hacnsrel, W. M.: Epidemiological Tests of Theories on Lung Cancer Etiology, Pub. Health Rep. 71:163-172 (Feb.) 1956. 46. Hammond E C. Lung Cancer and Com mon Inhalants, Cancer 7:110(31108 (Nov.) 1954. 47. Hammond E C. Etiology of Bronchiogenic Carcinoma, CA 6:156-168 (Sept) 1956. 48- Holleb, H. B., and Angrist, A.: Bronchieu genic Carcinoma in Association with Pulmonary Asbestosis: Report of 2 Cases, Am. J. Path. 18: 123-135 (Jan.) 1942 49. Homburger, F.: The Co-Incidence of Primary Carcinoma of Lungs and Pulmonary Asbestosis: Analysis of Literature and Report of 2 Casts, Am. J. Path. 19:797-807 (Sept.) 1943. 50. Horn, D. Is Lung Cancer on the Increase? Evaluation of Present Day Evidence: Cancer of the Lung, Proceedings of the Scientific Section, Annual Meeting, American Cancer Society, Inc., Nov. 3-4, 1953. 51. Homig, F. Clinical Considerations on the Question of Industrial Cancer of Asbestos Work ers, Zlschr Krebstorsch 47.281-287, 1938 52. Hueper, W. C. Cancer in Its Relation to Occupation and Environment, Sui! Am Soc Control Cancer 25 63-69 (June) 1945. 53. Hueper, W. C : Significance of Industrial Cancer in the Problem of Cancer. Group. Med 2 190-200 (Sept ) !<-U6 54. Hueper W. C - Environmental and Occupa tional Cancer. Public Health Service, Supp 209, U S. Public Health Service, 1949 55. Hueper, W. C.: A Methodology for Environ mental and Occupational Cancer Surveys, Public Healtli Monograph No. 1, P. H S Publication No. 12, U. S. Public Health Service, 1950. 56. Hueper, W. C.: Environmental Lung Cancer, Indust. Med. 20:49-62 (Feb.) 1951. 57. HuepeT, W. C.: Occupational and Environ mental Pulmonary1 Cancers with Special Reference to Pneumoconiosis, Proceedings, 7th Saranac Symposium on Pneumoconiosis, 1952 58 Hueper, W. C.: A Quest into the Environ mental Causes of Cancer of the Lung, Pub. Vol. 17, hi*.t, J9SS ^ o lung cancer in asbestos miners Health Monograph N'o 36, P H S Publication 75 Merewether, E R. A.: Annual Reports of No. 452. U S Public Health Service, 1955. 'the Chief Inspector of Factories, London, His 59 Hueper. W. C : Environmental Causes of Majesty's Stationery Office, 1947. Cancer of the Lung other than Tobacco Smoke, 76. Merewether, E. R. A., editor: industrial Dis. Chest 30:141-158 (Aug) 1956. Medicine and Hygiene. London, Buite'worth & 60 Isselbacher, K. J.; Klaus, H., aid Htrdy, Co., Ltd., 1956, Vol. 3. H. L.. Asbestosis and Bronchogenic Carcinoma: 77. Nordznann, M.: The Industrial Cancer of Report of One Autopsied Case and Review of Workers in Asbestos, Ztschr. Krebsforch. 47:288- Available Literature, Am. J. Med. 15:721-732 302, 1938. (Nov) 1953. 78. Nordmann, M., aid Sorge, A.: Pulmonary 61. Kehnaway, E. L., and Kervnaway, N. M.: A Cancer Produced by Asbestos Dust in Experi Stud)- of the Incidence of Cancer of the Lung mental Animals, Ztschr. Krebsforch. 51:168-182, and Larynx, J. Hyg. 36:236-267 (June) 1936. 1941. 62. Kennaway, E. L, and Kennaway, N. M.: 79. Phillips, A. J.: Mortality from Cancer of Studies of Incidence of Cancer of the Lung and the Lung in Canada (1931-1952), Carud. M. A. J. Larynx, Brit. J. Cancer 5:153-158 (June) 1951. 71:242-244 (Sept.) 1954. 63 Klotz, M. O.: Association of Silicosis and 80. Saupe, E.: Further Contributions to the Carcinoma of the Lung. Am. J. Cancer 35:38-49 Roentgenological Diagnosis of Asbestosis, Arch. (Jan.) 1939. 64. Lanza. A. J ; McCotmclL- W, ).r and Fehneb- J. W.: The Effects of the Inhalation of Asbestos Gewerbepalh. u. Gewerbehyg. 9:391-406. 1939. 8L Smith, K. \V, r Pah-nonary Disability in Asbestos Workers, A M. A. Arch. Indusl. Health i Dust on the Lungs of Asbestos Workers: Pre 12:198-203 (Aug.) 1955. liminary' Study, Pub Health Rep 50:1-12 (Jan. 4) 1935 63 Lanza, A. J., editor: Silicosis and Asbestosis, New York and London, Oxford University Press, 1938. 66. Lew, E. A.: Use of Life Insurance Com pany Records for Cancer Studies, A. M. A. Arch. 82. Smith, I- W.: Pneumoconiosis and Lung Cancer with Special Reference to Silicosis and Asbestosis, Compens. Med. 2:3-10 (Nov.) 1949. 83. Smith, W. E.: Survey of Some Current British and European Studies of Occupational Tumor Problems: Part III. Asbestos, A. M. A. Arch. Indust Hyg. 5:242-263 (March) 1952. Indust. Hyg 5.198-203 (March) 1952 84 Stoll, R.; Bass, R-, and Angrist, A.: 67 Linzbach, A. J., and Wedler, H W.: Occu Asbestosis Associated with Bronchogenic Car pational Cancer among Asbestos Workers, Arch, cinoma. A. M. A Arch Int. Med. 88 831-834 I path. Anat. 307 :3S7-409, 1942. (Dec) 1951. I 68. Lynch, K. M., and Smith, W A.: Pul monary Asbestosis. Carcinoma of Lung in Asbesto-Silicosis, Am. J. Cancer 24 56-64 (May) 1955 6pj Lynch. K M., and Smith, W, A.: Pul monary Asbestos's A Report o: Bronchial Car 85. Teleky, L. . Occupational Lung Cancer, Acta Union internat. centre Cancer 3.253-273, 1938; also, Zentralbl. Gewerbehyg 27 :33, 1940 86 Vorwald, A J.; Durkan. T. M., and Pratt, P. C.: Experimental Studies of Asbestosis, A, M. A Arch. Indust Hyg. 3:1-43 (Jan 1 1951. cinoma and Epitheha! Metaplasia. Am. J Cancer 87 Wedler. H W : Asbestosis. and. Lung. 36 567-575 i Aug > 1939 Cancer, Deutsche med Wchnschr 69.575-576 70 Lynch. K M.. and Cannon, W. M.. Asbes- (Aug. 6) 1943 tosis Anai.. s-j o: 40 Necropsied Cases, Dis. Chest 88. Wegelius. C- Changes in the Lungs in 126 i- .-74-y-"- . No-. -Dec } 194-5. Cases oi Asbestos.-! Observed in Finland Acta 7! McPhtv.ers. 5 B. A Survey oi a Group radio! 28 139-132, 1947. oc Employees Exposed to Asbestos Dust, J 8 Werber, M. Pulmonary Asbestosis Asso Indus'. Hyg 18-229-239 (April) 1936. 72 iferewether. E. R. A : The Occurrence ol ciated with Carcinoma ZenrraJbi. Arbeitsmed. u. Arbeitsschutz 2:179-180 (Nov.) 1952. l .1 Pulmonary Fibrosis and Other Pulmonary Affec 90. Wood, W. B , and Gloyne, S. R.: Pulmonary tions in Asbestos Workers, J. Indust. Hyg 12. 198 (May) ; 239 (June) 1930. 73. Merewether, E. R. A., and Price, C. W.: .Asbestosis Complicated fcy Pulmonary Tubercu losis, Lancet 2:954-956 {Oct. 31) 1931. 91. Wyers, H.: Asbestosis, Postgrad. Med 25: 3 i Report on Effects of Asbestos Dust on the Lungs 631-638 (Dec) 1949. and Dust Suppression in the Asbestos Industry', 92. Wynder, E. L., and Graham, E. A.: London, His Majesty's Stationery Office, 1930. Etiologic Factors in Brondiiogeiuc Carcinoma 74. Merewether, E. R A : A Memorandum on nith Special Reference to Industrial Exposures; Asbestosis, Tubercle 15:109, (Dec.) 1933; 15: Report of 857 Proved Cases, A. M. A. Arclc 152 (Jan.) 1934. Indust. Hyg. 4:221-235 (Sept.) 1951. itewartLQ, .-!. tAaaw Mvk.. Braun--Truan Prinltd 4 Pniliiktd in IJo Vnittd SuitJ W A nmfl 53 i