Document mqXZJ6XzGNRmGyM4Z53BV94Rg

'7; 7'-.*! sm BRITISH JOURNAL OF INDUSTRIAL MEDICINE VOLUME TWELVE 1955 . EDITOR . RICHARD SCHILLING ASSISTANT EDITORS J. C. Gilson L. G. Norman LONDON BRITISH MEDICAL ASSOCIATION TAVISTOCK SQUARE, W.C.l SC-ALL-06246 SCF-FA-4500 PLAINTIFFS 1 EXHIBIT A /a-8~oo Sixty-one cases of lung cancer have been recorded Hueper, 1932) consider that a causal relationship in persons with asbestosis (Boemke. 1933 ; Hueper, between asbestosis and lung cancer is either proved 1932) since Lynch and Smith (1933) reported the or is highly probable and the reality of the relation first case. In view of the infrequency of asbestosis, ship was agreed at the recent International Sym this large number of cases suggests--hut does not posium on the Endemiology of Long Cancer prove--that lung cancer is an occupational hazard (Council of the International Organization* of of asbestos workers. The strongest evidence that it Medical Sciences, 1933). A minority, however, may be a hazard has been produced by Merewether remains sceptical (Cartier, 1932; Warren. 1948), and by Gloyne. Merewether (1949) found that lung and,according to Huepcr(1932), Lanza and Vorwald. - cancer was reported at necropsy in 13*2% of cases so that it was thought desirable to undertake a of asbestosis (31 out of 233) but in only 1;3% of fresh investigation. . cases of silicosis (91 out of 6,884) and Gloyne (1931), on personal examination, found lung cancer in Necropsy Data 14-1% of necropsies on subjects with asbestosis (17 Since 1933, records hare been collected of all the ,-ius :0n ng out of 121) against 6-9% in silicotics (33 out of 796). coroners' necropsies on persons known to have Neither author gave full details of the sex compo been employed at a large asbestos works.* Patho -al sition of the groups examined, but since women logical diagnoses in 103 consecutive cases are m form a higher proportion of asbestos workers than summarized in Table 1. Details of the cases in nd iie of persons employed in occupations liable to give rise to silicosis (coal-miners, stonemasons, pottery Tasu 1 . CAUSES OF DEATH DIAGNOSED AT NECROPSY AMONG workers, foundrymen, metal grinders) and since lung PERSONS EMPLOYED AT AN ASBESTOS WORKS (1>U-3Z> nnS 'ly canceris less common among women, the differences in the proportions of cancer cases .cannot be Caioa of Dnalb AstaMosie AtbauM All Pmnin Ahmt Cun accounted for by differences in sex distribution. In fact the proportions which are more properly com parable with the findings in silicotic subjection: the proportions of lung cancer found among men with ~ Han CaibMa " .. .. Ptiknonniy mbaimlwa .. 1 UfTf T* " * .. .. .. Other 4mm of the mpintory tymm ......................... Odnriiaaa......................... J4 12 15 10 4 II 9 3 4 3. 45 21 It 14 asbestosis, 17-2% in Metewether's series and 19-6% in Gloyne's. . Allcaainn .. ' .. .. 75 I 105 Animal experiments are inconclusive. A positive which lung cancer was found are shown-in Table 2. Jf result was reported by Nordmann and Sorge (1941) During the first half of the period eight deaths 'd d s who found that of 10 mice which had been exposed to asbestos dust and survived for 240 days, two developed lung carcinoma. Smith (1932), however, occurred in which lung cancer was found in asso ciation with asbestosis, while in the second half of the period there were seven such cases and a further considers that one of the " carcinomas " was, in three in which lung cancer was found without fact, an example of squamous metaplasia and that asbestosis. The number of asbestos workers the other, an adenocarcinoma, may have developed employed at the works increased steadily from 1914, spontaneously from the common mouse adenoma. A negative result has been reported by Vorwald and ntamwUnin ortmd by tb* < Karr (1938). The majority of workers (cited by in hi* spmioa, ibatn nay ba a eaauioa of aabawa busory cam* of ` ` "V cyjvwsfisg^iW. BRITISH JOURNAL OF INDUSTRIAL MEDICINE Taoix 2 OCCUPATIONAL. HISTORY and necropsy data of assestos workers with primary lung cancer Year. or | Death | m> -1 OOtl 1 Ast i M.62 OoCUpStioM Wotr Period of Exposure ` 1919-32 Years of i Years | , Year. Eowvfc ` from ! * or. ; before | . rl j ^ Exposure J laiu 1, 1 Esrotau 1 1 * 1933 to Death j Yean 5ES I >3 13 . 16 . 3 , Pathological Beport ;**--* Htttolosfcal Tne of Primary Lon; Cancer <'.present ^Cudawia*1 ' ' 1935 M. 34 Weaker 1909-12 21 23 26 * | Epithelial carcinoma 1936 M.CJ JTberuer 1913-34 23 19 23 Leathan 1 j * EodothcKoma ofpteura 19J4 M.47 Weaver ri9t<M2 11929-37 19 14 28 *I M Carcinoma** 1929 M4 Duiatecraicr /1919-14 11919-39 24 17 29 Lctttiual ! T1911-1* r Less than 1 | Carcinoma** >940 M. 32 Disintegrator ( 19(9-21 32 13 29 *4 ** Carcinoma H ' ( 1923-39 1941 9132 . .Waver j 1913-19 \192403 20 >4 7$ 3 - ' OaUctUad cardooou 1942 M-59 Baf earner >913-41 28 19 29 *' OsteelW csieaaou IMS M.39 Weaver /1912-14 \ 19)8-43 32 16 36 . Lruiluo | `Anaplastic Carcinoma ' 1943 . M. 5) Weaver 1922-33 13 10 76 !- ** Carcinoma " IMS M.43, Spncef 1922--44 3& 10 26 Leas than I ** Carcinoma ** -Jr >940 M.63 hlalnleosnc* man >919-44 29 13 29 LosUoaI OaKcScd carcinoma ' 1930 f. 31 Spinner . 19X3-0 27 17 33 S ** Carcinoma ** 1931 M.74 Ftberoer 1917-43 26 13 34 1 * Adenocarcinoma . 19*1 M.60 Weaver _ /1919-3S \ 1929-30 27 9 32 1 " Carcinoma ** * 1944 M.IS 1951 . M. 41 1952 SCSI Weaver Kberiier Weav 1942-44 . 1959-45 rt94io.'t J\1943-J2 i 2 9 7 0 2' Lcsithaal Absent Oatedled carcinoma 0 12 3 | - Anapliuic cuemooio l\ Lcsatiunl i ** Carcinoma ** "Abo pulmonary lubocutoA. and a great increase In the number of lung cancer Method of Estimation of Risk deaths was also recorded among the whole popu Although the necropsy data shownin Tables I lation of England and Wales over the same period. and 2 suggest (1) that some groups'of;asbestos It might, therefore, have been anticipated that a tworkers ' have sufFeredlan increased, risk of lung larger number of cases in which the two conditions cancer, and (2) that the riskmay now have decreased. were associated would have been found in the last' It is not possible to be certain of either or these 10 years. National regulations for the control of ' propositions without a more detailed knowledge of asbestos dust were, however, introduced in 1931 the whole mortality experience of the workers. The (Asbestos Industry Regulations, 1931) and the first proposition has, therefore, been tested by precautions taken to prevent dust dissemination in comparing the mortality experienced by that section the works had become effective by the end of the of the male employees of the works referred to following year. All the subjects in whom the two above, who had worked for at least 20 years in diseases were found -together had been employed " scheduled areas *'*, with the mortality recorded for for at least nine years under the old conditions, and all men in England and Wales; and the second although 11 of the IS rewn and women died within proposition by comparing the incidence of Jung 30 years of their firsCexposurey the association of cancer among men employed for- different periods the two conditions has-'hbfyet 'been found in any under the prc-1933 conditions. The investigation person taken invo: employment rduring the last 31 was limited to the small group of men who had been years (1923-53). It is, therefore, possible that the employed for at least 20 years, since the labour reason more cases were not found in the second half involved in searching out the individual records of of the period is that reduced exposure to dust has already begun to lessen the incidence and severity of asbestosis. ' . * B>' ."icMuM Aheai k meant' those >t<A)>hcra processes . svu yarned oa ^hicb *ere*chIuk^.vfld*r the Asbestos ladunrr RctatttioweTvl^l ' '' . ' "" 'CER Trm of >ofpiun 4" ^ "ables | `Sbcstos f lung teased, 31 these edge of s. The ted by section ;|Ted to ears in -ded for second J| lung Periods t'gation Jd been labour :rds of ''/HMlimnrny T* >1 * LUNG CANCER IN ASBESTOS WORKERS 83 men employed for shorter periods would be dis proportionately great and, so far as was known from Table 2, would be comparatively unrewarding. The date of birth, date of completing 20 years' work in the " scheduled areas ", and, where applic able. date of ceasing employment and date and cause England and Wales aged 53 to 59 in 1951 was 2*778 per 1,000. The numbers of years lived in this age group in the five yean 1949-53 were respectively 15 years, 15 years, 17$ yean, 19 yean, and 19 years. The number of deaths expected in the period was, therefore, estimated to be (15 4-15-1- 17$ ~ 19 4* of death were obtained, for each man, from the 19) x 2-778/1,000 = 0*238. The total number of records of the firm's Personnel Officer. Full details deaths expected from each category of diseases was were, in most instances, already available for the men obtained by adding the numbers thus calculated for who had ceased employment as well as for the greater each age group for each of the five periods. number who continued to be employed, since some The great majority of the men lived and, when they of those who had left were registered as having died, died in the town in which the works was asbestosis and the attention of the firm had been situated, so that it would have been preferable to drawn to the death of others, in view of the have based the calculation of the expected deaths on possibility of the cause of death being industrial in the death rates observed in that town rather than on origin. All the remaining men were successfully the rates for all England and Wales. These, however, traced and the relevant details obtained. This was were not known in sufficient detail. Little error in not difficult since, by limiting the study to men who the expected number of deaths from lung cancer is had.been employed in one place for 20 years,' few likely to have been introduced on this account since, were found to have changed their job or to have according to Stocks (1932), the age-adjusted death moved out of the region. rate for lung cancer among men in the town con From the data the numbers of men alive in each cerned was 96% of the rate for England and Wales. five-year age group were counted separately for each Stocks's figure was calculated only for the period of the yean from 1922 (the first in which a man was 1946-49, but.the proportion is unlikely to have recorded as having had 20 yean' service) to 1933. A varied greatly over the longer period of the inveeti- . man who hadcompleted the 20 years before the begin gallon. The expected number of deaths from all ning of a year and who was alive at the end of it was causes is, however, likely to be somewhat under counted, for that year, as one unit; a man who estimated since the age-adjusted death rare from all completed the period before the beginning of a year causes for the town is about 23% higher than the but who died during it, and a man who completed the England and Wales rate (f.r. the excess was 22% in period during a year and who survived to the end of 1950, 28% in 1951. and 22% in 1952). it, were each counted, for that year, as halfa unit; the one man who died the same year as he completed his 20-year period was counted as a quarter of a unit. The causes of death were recorded as they were given on the death certificate or. when available, as Results . The number of men studied was 113; the numbers of man-years lived in each of the five periods in each age group are shown in Table 3. The total number they were finally determined by necropsy. The causes were classified in five categories (see Table 4), and the numbers in each category were then compared with Table 3 NUMBER OF MAN-YEARS LIVED BY MEN WITH 20 OR MORE YEARS OF WORK IN A " SCHEDULED AREA " those which might have been expected to occur by multiplying the numbers of men alive in each fiveyear age group by the corresponding mortality rates for men in England and Wales over the same period. Because of the small numbers, however, the popula tions were not considered separately for each year, but were added together to form five groups living in the periods 1922-33, 1934-38, 1939-43, 1944-48, and 1949-53, and the mortality rates used for each Af* Piriotf (yin) 1922-})! I9J4-J* 1939-43 1944-tf 19*9-53 JO- 4043JO3V 60657075-79 0 43 9*3 9-3 63 12 li -1 0 0 05 2 IS 19*2 25 5 6 j 13 5 2 0 13 It 33-3 30 39-3 30 3 25 3 9 I 0 17 3 46 71-3 u 32 23-5 10 3 ^ 13 0 9 33 14 9SI (3*1 3S 21-3 J-J 0*3 AU fnlMI 2 44 162 2*1-3 23) IS3-3 S4-73 49 17>5 J group were those for the years 1931, 1936, 1941, 1946, and 1931. The rates for 1931 were used for the period 1922-33, rather than those for the mid-years, since disproportionately few men were under observation during the early part of the period. As an example of the method, the morality rate for all neoplasms other than lung cancer among men in All ** 1 SS 113 73 321 - j 391-3 10*2-23 of deaths from all causes and the number of deaths observed in each of the five disease categories, together with the expected number of deaths, are shown in Table 4. From Table 4 it appears that the men who had been exposed to asbestos dust suffered S4 BRITISH JOURNAL OF INDUSTRIAL MEDICINE Table 4 ' the increase in mortality attributed to lung canocr CAUSES OF DEATH AMONG MALE ASBESTOS WORKERS COMPARED WITH MORTALITY' EXPERIENCE OF ALL MEN IN ENGLAND AND WALES over the past 30 years is certainly due to improve ments in diagnosis and in therapy (Doll, 1953). Even, however, if it were postulated that the whole Cause of Death No. of Deaths j Tt of Siemfcanoc Expected] fDifference No. j on 1 Holland between Observed Observed, oJ and Wales Expected Raus. (Value of P) of the recorded increase between 1931 and 1951 was spurious and that the real mortality from the disease throughout was that ascribed to it in 1951, the expected number or deaths is increased to only 1-1 and the observed excess is still grossly significant.' Ltugcaac<r*: with mention of asbestow.. without taeatioo or osbesteib Other respiratory (todud* inf pulasooofy tuberculosis} sod cardiovascular diseases: wstb mention of asbestosis without mcsiSofi of asbestos** Neoplasms other than funs cancer All other diseasrif.. ,, .. n 0 14 4 4 } ooooooi W 7-6 y <>ooi 2-3 4*7 } For the actual number of lung cancer cases to be so little in excess of the expected as to be reasonably attributable to chance, it would be necessary for the expected cases to be 6-2, that is 5-6 times the number estimated on 1951 rates. In other words, it would be necessary to postulate that in 1951 (and throughout the previous 20 years) there was 5.6 times as much cancer of the lung as was recognized in 1931, AH causes M . - 1H - <0000001 which would mean that the condition would have * lodudfaf ooe ob with pulcwnao' lubcrcul^vii. Tlndudtns two oto (bcaign itridarc of ooopfaitu Bad septi caemia) la which nkuofii vs present but m not (houikt to ban bcco a cMUnbtUeqr cause ofdeath. to have been present and capable of detection in over 20% of all men at death. Moreover, even if this were so, it would still not account for the fact that all the- cases of lung cancer were found in an increased {moi^Iity ^roni lung cancer, other association with asbestosis., , ^respiratoryidiseases~and cardicrvascular diseases, in It is, therefore.-'.c&hclude&That the fourth explan assodatidri Wth asbestosis, but that their mortality ation is the most reasonableone and that the asb&tos from other discasejlwas dose to that expected. workers who had worked for 20 or more yeats m the Four .explanations-of the findings are possible t scheduled areas " .suffered a notably. JtigherJrak (1) that all the men who had died oflung cancer were from lung cancer.than'thc rest or the populationl- recorded because of interest in the condition, but To test if the risk' Iras altered since the 1931 that some of the records or other men dying of other regulations were introduced, it is not only necessary diseases or stilt alive were omitted, with consequent to make allowance for duration of employment underestimation of the expected number of deaths; before the end of 1932, but also to allow for the men's (2) that lung cancer was incorrectly and excessively ages and for the total durations or their employment diagnosed among the asbestos workers; (3) that in the " scheduled areas ", since the men employed lung cancer was insufficiently diagnosed among the in the earlier periods can also have been employed general population or England and Wales; or (4) longer and lived to be older. On the other hand, that the asbestos workers studied suffered an excess there is no need to consider the changing incidence mortality from lung cancer. of lung cancer in the total population of England and It certainly cannot be claimed that the records of Wales since the nori-industrial risk has been shown the Personnel Office were necessarily complete, but to be small in comparison with the industrial one. they we're believed to be complete and no deficiency The data required for comparing the risks among men on this score would account for.the total excess of employed for under 10 years, for 10 to 14 years, and deaths unless it were so gross that more than half the for IS years and over in the prc-1933 conditions arc defined population had been omitted. Moreover, the shown in Table 5. The ages shown' are the ages at number of deaths due to conditions unrelated to death of the men who have died and the ages in mid- asbestosis was close to the estimated number and this 1953 for the men who arc still alive. The expected is unlikely to have happened unless the population numbers or men in each pre-1933 employment group had been estimated approximately correctly and the found to have asbestosis or asbestosis and lung deaths from all causes fully reported. cancer are estimated by multiplying the numbers in All the It. deaths attributed to Jung cancer were each age, total employment, and prc-1933 employ confirmed by necropsy-andTustological examination ment subgroup by the proportions of men with so that the excess number cannot be attributed to asbestosis or with asbestosis and lung cancer in the incorrect diagnosis among the group of asbestos same age and total employment group for all lengths workers. Some of the excess may welt be due to an of prc-1933 employment combined. For example, underestimation of the expected deaths since part of three out of the nine men aged 50 to 54 years who had LUNG CANCER. IN ASBESTOS WORKERS Table S VIFFEREHT PERIODS BEFORE 1*11 AND NUMBERS KNOWN TO HAVE AS8ESTOSI3 a>d llng cancer in association with asbestosis divided by total duration of employment in a SCHEDULED AREA AND BY AGE been employed for 20 to 24 years in the areas in which they might be exposed to asbestos dust were found to have asbestosis and lung cancer.. SjiKvi three men had worked for under 10 years in the pre 1933 conditions, three had worked for 10 to 14 years, and three had worked for 13 or more years, the expected number of cases in each of the pre-1933 employment groups would have been the same, i.t^ 3 x 3/9, or 1. In fact, the numbers of found were 0,1, and 2. The total numbers expected in each pre-1933 employment group are obtained by adding the numbers calculated for each of the age and total employment groups within it. The results are as follows: The differences between the numbers of men observed and the numbers expected in each employ ment group, had the incidence of the conditions remained steady throughout, are statistically signi ficant (total asbestosis, x* =* 7-52, n = 2, P -- 0-025; asbestosis and lung cancer, x* =" 8-74, n 2, P TM 0-01*). They are highly so if the trend, that is. Total number of man!Lebaamd *iih aabanaaia , expttttd Numbtr at man uuh\,obatrrtd ubmoMiadluflij 'tapraad ccmbt Laapih of Emptoynwaa baton ____ Jaouwr I. ISM Under 10 Yaan 10-M Yaan IS Yaan and Om 11 14 14 iit JO-A IM t 3 .T Ji ji * T*-- t-irtnrl nnmtun ofhmi r.ni in mull mil lira pmhpMIjiy that iha diirarancn cauid am, bjr ebanea baa raniaqiHy baa lonnkai, but not Mriouaiy, unOamstimatau. If ail man wnb man tbaa 10 >aan ptt-lU) ampiarmam ara troupad lopaihar and Yaiaa' canaauon mada for unatl ownban, x* I U, 0 -- I, P -- ML  A, S6 BRITISH JOURNAL OF INDUSTRIAL MEDICINE ihc biologically important reduction in the propor One hundred and thirteen men who had worked tion between observed and expected numbers as the for at least 20 years in places where they were liable length of prc-1933 employment is reduced, is also to be exposed to asbestos dust were followed up and taken into consideration, it U dear, therefore, that the mortality among them compared with that which the incidences both of asbestosis and or lung cancer would hare been expected on the .basis of the associated.with asbestosis have become progressively ' mortality experience of the whole male population. less as the number of years during which men were Thirty-nine deaths occurred in the group whereas exposed to the pre-1933 conditions has decreased. 15-4 were expected. The excess was entirely due The extent of the risk or lung cancer over the to excess deaths from lung cancer (11 against whole period among the men studied appears to have 0-8 expected) and from other respiratory and been of the order of JO times that experienced by Cardiovascular diseases (22 against 7-6 expected). other men. This agrees well with the data reported All the cases or lung cancer were confirmed histo by Merewether (1949), but it is somewhat greater logically and ell were associated with the presence than that suggested by Gloyne's data (1931). The of asbestosis. .- great reduction in the amount of dust produced in From the data itcanbe concluded thatlung cancery asbestos works during the period has been accom wns u specific industrial hazard of certain asbestos! panied by a-reduction in the incidence of lung cancer workers and that the average risk among menf among the workmen so that the'risk before 1933 is - employed for 20 or snore years has teen of the order likely to have been considerably greater--perhaps 20 of lO times that experienced by the general popula times the general risk- Whether the specific industrial risk oflung cancerhas yet been completely eliminated cannot be determined with certainty; tin number or men at risk, who have been exposed to the new tion. The risk has become progressively less as the duration of employment under the old dusty con ditions has decreased. . jr conditions only and who have been employed for a I would like to offer ray thanks to the management of sufficient length of time, is at present too small for confidence to be' placed in their experience. It is clear, however, that the risk has for some time been greatly reduced. The extent of the reduction is particularly striking when it is recalled that between the firm concerned for permission to carry out this w-ork and to the Medical Officer and members or the staff of the works where the men were employed, who carried . out the greater part of the work on which this report is based. . * 1933 and 1933 the incidence ,of the disease among men in the country at large has increased sixfold. . " REFERENCES : AlbeUOl Industry Refutation* (1931)- Statutory Rule* and Olden. . Summary 1931, No. 11-10. H.MS.O, London. Boerak*, F.<19JH. Mrd. hhckr^l, II. . ' . Cartier, P. (1953). Arch. InJtacr. S. 3G (contribuiion to The cause of death, as determined at necropsy, is discussion}. Council or the International Or*anuatlons of Medical $dene reported for 105 persons who had been employed at (t95J). Acta Vtt. InI. Ce*C'.. 9, 443. . one asbestos works. Lung cancer was found-in 18 Dolt, R.U933). BHt.med.J* 25 521. Ctoyae`S.H(t9M). Lancet, 1.810. * . ** ' . instances, 13 times in association with asbestosis. Horpcf, W. C. (IV52). stum. To be published. cf the Srrreth Saranac Sfnpa* All the subjects in whom both conditions were found Lrrtch.'K. M.. sad Smith, W. A. fl. Awrr. /. Cower. 24.36. had started employment in the industry before 1923. MercWcitier, E. R A. (1949). Amatol Report tf tkr Chief Inspector cffactories for the 1W7.U\ ' H.M-S.O.. London, and had \vorke4 in the industry at least nine years Hordtmnn, NL. bod Sorpe. A. (1941). Z. Krebsforttk^, jj I6S. Smith. \V,, E. (1952^. Arek. fadastr. lire* 5, 209. before the regulations for the control of dust had Stocks, f. (I9S3J. firlt. A Cancer. $.97. . , become effective. `. . VonrmM,' A J-, nd Karr. J. W. <1936}. Amtr. J.faih.. 14, 49. Warren, S. (I943>. Oceup. $. ?49. ^ssstsssassmgss^ssssssx&ssssm^ssssxs^^