Document zoK3LGOZevY08oxME6NVaLjL0

VANDERBILT UNIVERSITY r\rkn/vn ^7 NASHVILLE, TENNESSEE 3 7 2 0 3 1 J! i. k mi n n h ? 3 4 - ` 4 I J Uu M Department of \\t;ht?n: cf MeJ; December 6, 1967 James J. La Penna 313 Stahlman Building Nashville, Tennessee 37201 PLAINTIFF'S EXHIBIT CT-16 Dear Mr, La Penna: You are correct in surmising that my statements are based on the medical literature. Enclosed arc two examples. If you care to read further, there are 27 references in the 1966 Cumulated Index Vcdicus which link asbestos with cancer, and an additional 14 such references in the 1965 Cumulated Index Mcdicus. They are listed under the heading "Asbestosis." The relationship of asbestos exposure to cancer of the lung has been well known for several years, being listed on page 708 of Rubin's Thoracic Diseases nublishcd in 1961. The original relationships were noted only in people working within industries using a lot of asbestos. About six months ago, however, in a pathology conference we discussed a patient who died of a mesothelioma (a malignant tumor) and was found to have asbestos fibers associated with the tumor despite never working in industries associated with asbestos exposure. Our pathologist stated he was seeing more of these tumors than over before, and in pconlc not working in areas of known exposure. We discussed the fact that asbestos was being put into many things these days, and that somehow it seemed to be involving more people than just miners or manufacturers. When I saw that water ripe was being made from asbestos, it really upset me. The Food and Drug Administration has taken drugs off the market for producing tumors only in experimental animals. Yet, somehow, an agent known to cause cancer in humans has been allowed to contaminate drinking water. Tne only possible defense is that the amount of asbestos each person gets from the water will be so small that only a very rare, susceptible, individual will develop cancer. Do you want to gamble on whether you or your family arc the susceptible ones -- just to save a little money? I do not. Respectfully JDS:jd Enclosures James D. Snell, Jr., M.D. :'D SrtciAL Report: Asbestos ant Tao mclhoiis of nie.iMiring the rai.-l.mcc or fcnsi: cmA. groceries to mercury dills lir.vc been LRllc d.iiYroicc 'VMS no!.*", hut the agar ' 1 lh 'd A prcfe::cd as it is tcchnirdlv tv,her to Jit -Mancc tn mercury appt .it . to ho .vsoci- t ,, u)i antibiotic tfsi'.l.iiif", li>il mi il ill r: cm r ill hclutiu the two penp-; v.eis ill ini.iiv.,.ii. it ri.i'.o.is *f ivitt.iccrchml injection nf mice. The ,.!Cti;v test roar have a place as a screening procedure : \ ;tA\ c; (he rc-iatjombip between the resistance to ir-ruirv-THid to antibiotics. We arc grateful to Miss Thiboamleju and Mi- J t-mp] h.-r ihur IciiuiKal assbi.mtc. r.ETEr.CNCrs ' Jin n:, r : l." t. ?: 4<3. l'-no. .* t >. jb ;ijfrJ ,sCj-r, ,,r rntifliifl, TO: 17". :3C< r',h\: vt-HhA'T 11. < f <ir ' l.n "* ti; ?' . ] : i *, A : /;t. * J. V.\y. 1`u`T. , 2I: `III. ? , iVr KMV-. r. .i\t- <\\nr:, U. V/. . 7 73 r : i ; i |;im/'|. .1. am, Mm 'i-n, )!.; .liter. J !'>), ?/t l'.u:s. ' 7 3; \( It. M , N V v IJ -1 , T* f-f. -I- x MI Win i I If *f J r X' l.tmrr2: i I 30. IV ILF 77:.a:.1. 77. ,\ut> M.: J. .1. M. A . ICC: ': v\ * t T.'. i S. T' ' ; jijj X.y. Arm! >rx., 6-5: *'7. 7 .*.`*7. I" T.in:. S. r ,i\i} Cu.xrsr, 1\ i:.; jint. J. 77 *>. .zz- 573. 7057. v 7'" m-1-m.!.. A., Fon'ia. S. axd I"\\X'f^sFT, M.: />: r<,*n.; 1-1; 7 32. U'.io. - i 5--n3*.il iz\ lu li '11 Ashcslos and Cancer The Rcjicrt anil Rccononcndnlions of a V.'orhiug Group Convened Under the Ai.-rpirrt of the Geographical Tnlholo-pj Committee of the International Union \pmnst Cancer KriT'tn's Xoto--lr. October 19b', tlie New York v-.[ nv tif Sciences sponsored au jute: u-iiKin.d meet on tile 1a:01 -aeic:-! i lice's of a-hr-ins. I'dlrm ing - n;. 'tune, some -10 delegates ficm An-li.din. Canada, h.n'.c I'lance. Oepri.-.nv, C,rcat luitahi end, Ireland, h.,hc South ,\:iiia and the Uuired '-ecu - tic incited ' "i -In Sr the -cast aniniiut of inronn.rbca v. 1.ii li !ud l-ccn -.i - d. "nth i h",c to the o;`t.eu,-.,!i-"i of ,m inter ne .1 -piihr r \ a-'-epos and nno':. i'he 'eiuis of - ; no ot tin- A nihoip (Ctnnp n nil--! lb-,.-'- mainr . c; the p "'C ci; epidemi 'lenp, p.ilho' pp .mil p `cnH-ntal n.dh.'doev. aiu: php-:e> mi l < lu niistp.', S' fin.Jii.gs r-f titc S'-'''-hin-; Cu.-up md :1a t no cm- p :h 'in die--- -o S- - a.u d, m - -,c .cuid'tnd 1 '11n. in lie fel! m lie; n unit. Thl Association- nr l'\Tosrnr to ttSTOs Drst a\'Ti Cancer tiinin Apes of nsitestos of commeici.i] 'ii'-'rest nre imositc, anlliopliyllite. ehrysnlile, ' c .elite nnd. uernnlitte. Tlicic is oai-lence of air :,it;nn between exposure to .obedos mid ' rr-ant neonl.isia. Tins has been mi.iblMicd ' he on infrni.-ainn from Oornimiv, Tl.ilv. Sonih 9c: -i :)>e United Kitirclrm anil the X';ut-` 1 Slates f 'cunira. lypt'S nf tuivnv.iis wliieli have limn 'lmwii to -1 c-iul ,-d. v.-ph eipnsm'i' tn udustiJS ihivl nun h..i(1|num,s n: the lung. Diilnse ltm-otiieln'iiiia nf die phnua uni peri- l ni re is . in si h 'Veil eintcein. : 1 :n tuinonrs. Ec.-tinn of all ,l -anei.11 inn also r.ii'cnom.i. ,-ih1 pmlily witli Tiny latent, pterind betss'Cen first ('xpusuiv lo 'he du- t .and ilcteelhm of the related tuinniirs is in.urr 'ears. tiMiallv 20 nr mure. Instances itp In (it) t ears hive berm reported. For this reason, further r.c-iA nf these assneialotl tminuirs will be e'.jvele'l !a >reur for neinv sears to come, ev<-u if du-f - spnsnres an: now gvcuilv reduced. U11 -i11 u\ 'deuce iudieati's that the u-soeiate 1 i ,u t moiiias of liic lung arc not limivd to evpi-utc `o .uw one (\pr nf ashcslns tilirc. Ilnwveer. tiu :hi r uve tipalnuis are mgentlv needed tn nl.i1 I'-'i "diet 1 1 v the degree of risk is impel! anil', n labd tn 'i" I vpn of iihi iiihaha 1. In 'ur r.w of 1 iii-m it I j - linnias ovid-nti' fiml ' '.a 1.11 r mi n t; ms si i-e-p's | - that ryie.uir In 'in- a In kle iMuu filne) m.oe he nf ji.iilieiil.ir impm lam e, but ;t cannot lie uuuluiled (lint ic.K- this lepe i t I'hve is ( our or d-d with [hr-n tunin'us. and fu: the: iio'cs.'ig.: - mi of this problem is m/Tded. Certain Aprs nf asbestos fibres in the i.r:::n c!ale base lc m found to contain oils, ware- .m t nlln r or;:nnic >n Rer. In addition, asbes'ns fb'cs ieaddy ahsiu b hyi ha'carbons snbsr-qiii til b> imn;:"'- bin.el or Ir.iec amouuls nf s .irions , p-ni.-i its siu u .o nil ;.i 1 and (bruminin are also f.nuul a-sik i.i'' . \`,ilh si mu- ' i pos i if fibre, 'the j ins-ubh 11 ile n! 1''' ! .i""i'i lb 1 lu.niaials iu liu: ih-vi lupi.u lit of lum uis, follow me esjiosui e lo asbi 'tus du-l. is iml J '! i a .:. liu-'r' feuliiiE', wlinn ron.sidiiid in m 1 a 1.1:i - l die great iiurease in the u-e nf a-brsln- fm jiiiv]aisi-s ui all enunU'irs. suggest ilia! a ' -eiions and widespread lin/ard lliml npo::' 1 ' ash- -irs dim; may exist lban is widely appi<' 1 '1'' l i v.rrif'l,ASIA AMON'C IXSUI.ATJOX WOUKKUS IX Till: r\m:i> status with siticiat. liia'KiiKxri: 'i<> IX T! IA - A [ I>0 M1 N A1, X KO!' I, AS 1A IS O'. Hammond Altirriron Cnnccj1 S'lelchj, New York, N. 1'. I. .1. ScHkofT, J. Chnrg The Mount Soiai Hospital, New York, N. 5'. IVfore presenting the findings in our stud}- of insulation worker.-, w. )11!i 1 like to discuss briefly some considerations which eve believe to be important. Mali,'-riant neoplasms produced by exposure to chemical agents nr ionis ing radiation typically have a long latent period. Tli.it is to say, tireio is a long delay between first cxposuie and the appearance of 111C neoplasm. In the ease of carcinogens which can be eliminated from the body, re pented contacts over a long period of time may be required. However, in trie case of agents which arc not eliminated, exposure of the tissues is continuous from time of first exposure. The probability that neophron will occur and how soon it appears generally depend upon the degree of exposure. Nun- let us consider the effects of exposure to an agent which can pro duce neoplasia but which can also produce some other type of <!.- a Here eve are dealing with the problem of competitive risks. If exposure results in death from some other di.acnsc within ten or fifteen years, then, because of the long latent period, it is very unlikely that neoplasia will result from such exposure. Tn these situations, the outcome depends in part upon the time required to produce the other disease in relation to the time required for the de velopment of neoplasia; and this in turn depends upon the degree of ex posure. Of equal importance is whether or not the other disease can be cured, or death delayed. An historical review of the literature from this point of view is most intere. ting. All of the early reports apparently concerned workers whu were very heavily exposed to asbestos dust. This was long before the devebippi.'nt of tire sulfa drugs and antibiotics, rnlmunary diseases including tuber culosis and pneumonia were among the leading causes of death. Info ex pectancy in the general population was far shorter than it is today, and a relatively small percentage of people lived to an age where the incidence of cancer becomes high. In mnq, AuribnuU reported the results of what was probably the first study of mnrtn'itv among asbestos workers.1 His account is-interesting. 519 V20 Annuls New York Academy of Sciences Tn ISHfl .in acbnsfos spinning mill and weaving factory was established in the neighborhood of Comle-sur-Noirenu (Calvados). During the first five roars of operation there was no artificial ventilation and the employees v. ere heavily exposed tn dust from the looms. According to Anrihault. fifty workers died during this five-year period. Furthermore, the director, previously owner of a cotton mill, had recruited seventeen of his former employees and "sixteen of them were wiped out by the Chalicosis." In 1918, Hoffmann was able to present suiue data from the industrial experience of the Prudential Life Insurance Company.' From 1897 to 1015 there were 13 deaths of asbestos workers and three of these were at - triboted tn pulmonary tuberculosis. It is of interest that nine of these 1.3 asbestos workers died under the aye of 44. This is in contrast with a much elder average aye at death reported for potters, moldcrs, marble workers, and stone workers. Hoffmann notes that "in the practice of American and Canadian life insurance companies, asbestos workers are generally de clined on account of the assumed health-injurious conditions of the in dustry.'' He also quotes R. L. Collins fAnnual Report of the Chief Insi'eclnj- uf Factories and Workshops for F.nglnnd and Wales for P'lfli ns having found five deaths in people having pulmonary tuberculosis in five years among a staff of under 40 workers in a factory weaving asbestos. Cilice Hoffmann's time, many authors have reported findings in series of rases of asbestosis. Until after 1940, emphasis was placed upon the nee of secondary infections, particularly pulmonary tuberculosis and bronchopneumonia. For example, Mcrcwether1, writing in 1933 commented: Usually, the fatal issue is determined by the onset of some acute inf :t:on with which the remaining undamaged tissue is quite un able to cope: this is commonly a low grade bronchopneumonia. The crime year, Clloyne4 stated that, "the writer has sn far only seen one asbestos patient recover from bronchopneumonia.'' In two series of cases reported by Wood and Oloyne' in 1934 and Stone' in 1 940. bronchitis, bronchopneumonia and pulmonary tuberculosis were the commonest terminal complications of asbestosis. However. Wood and Cliiync found two lung cancers and. one cancer of the pleura in `hi deaths of patients with asbestosis. V. itli the passage of time, pulmonary infections were found less fre quently .ami lung cancer v ns found more frequently in cases of asbestosis. We will nut take the time to review the more recent literature, a i-mgc pare of whieh was written by poopl" present at the Conference ami ade quately covered by other papers in this Annal. It is sufficient to say that since the advent of the antibiotics, workers have generally been saved from dcatli due to infectious pulmonary diseases resulting as a complica tion of asbc tosis. Thus they lieuan to live long enough for the neoplastic effects of exposure to a-hestos to become manifest. Our study differs from the early studies in two important respects: Hammond ct (il.; Intra-abdominal Neoplasia 322 Annals New York Academy of Sciences f] ' The subjects bad verv light and intermittent exposure tn aifl i ^tos di;r.t ns cnrr't'.i i (] xvith the dmlv heavy f,xrv'fMi <_ *'f subjects infhvlnf! in inn t.'r! studies; and (2) We arc report in" deaths which occurred after 1112; that is, after antibiotics became available for the treatment of pneumonia arid after death rates from tuberculosis had been greatly nalured in this ("entrv. It also differs from most oilier studies in that we wer" able to trace an entire group of workers including those who had retired and ttm-e who had left the trade. The data we are presenting here is an extension of data we published last year.' Therefore, we will start by briefly reviewing our first report, the results of which are Summarized in TABLE 1. The data shown Imre are confined to the experience of G32 men. They composed the total ni'-mbcrship of New York Local 12 and Newark Local 22 of the International Associa tion of Heat and Frost Insulators and Asbestos Workers as of January 1, 10-13. All of them were traced through December 31, 1062 and 2.13 of them died during that period of time. Most of them bad been first exons, -d to asbestos dust at least 20 years prior to 19-13. The remainder passed the 20-ycar point between 1913 and 1962; and we counted their oxporieme only after they reached this point. Table 1 shows the total number of deaths and the number of deaths front selected causes during each of four successive 5-vear periods. For cnmpnrirwn, wc ohow the number of deaths which would have been p\pect>-d among these asbestos workers had their age specific death rates Iwen exactly the same as those reported for all white males in the Fnitcd States during the same intervals of time. First note the total number of deaths. During the first five-year period, fewer deaths occurred among the asbestos workers than would have been expected on the basis of general U. S. death rates. This is accounted for by the fact that all of the workers were actively at work in 10 13; and seriously ill men are unemployable. Thus their total death rales were low-. This selective effect gradually wore off. During the last 5-year period, S3 of (lie wrrkors died compared with 51.4 expected. During the entire 211year period, 255 asbestos workers died compared with 203.5 expected. New olen-ryn the number of deat_lis_from cancer of the lung and pleura. During every 5-year pemd, far mere than the expected number of as bestos workers Tiled of this cause. A1toget 1 icr_there_wore 1f> deaths from cancer ofTheTung and pleura compared with 6.6 expected; a mortality ratio of nearly 7 co 1.. To our surprise, these asbestos workers also had extremely high death rates attributed to cancer of the stomach, colon and rectum. Ti.5 observed number of deaths from these cancers was 29 compared with an expected 9.-1; a mortality ratio of 3 to 1. ilaiimimHl r! nl.: lnti':i-nli<I<imiiinl Neoplasia It is ,.r mt'.'U'.st that out of a total of 2,>5 deaths only 12 wore attributed is. \s nrpvinusly mentioned, our first report was based upon the rtv((!' rwr: who were members of the t'.vo locals on December 31. lb-12. An i Mitione.! SfiO non joined between January 1. 10-12 and December 21. 1002. Tims a total of J ,.'>22 were in the two locals at some time between 10 at .vul 1002. We have traced all of them through August 1061 and Dr. feliko.T had medically examined most of those who were living as of the end of ]t>C2. Of the ],722 men, 2Ci were dmrl as of January 1. 19G2 am! an additional -1C died between January 1, 10C3 and August 21. lt'Cl. The findings shown in taiu.k 2 are based upon tlie.se 307 deaths. Tnur.c. 2 A'. 1'. C. Asro's'Tos Jn.sti.-itiox tVocKiats 3i*7 CoNsim m: 1 )r eras J.i m: \ ky 1, 1013 - At:(;rsT 31, 1001 Total deaths All neoplasia Droncho^cnic carcinoma Mesothcliomn C.I. carcinoma Upper respiratory BlnriHo- Generalized carcinomatosis All other Asbestosis All cither causes 307 124 53 10 34 6 4 7 10 17 1G6 ,-'77' ,, <f______ ) 17.37 3.37c 11.17 1.97 1.37 2.37 . 2.27 ' 5.5/0 5-1.17 Of the 307 deaths. 12-1 f40.-1 per cent) were attributed to cancer, 17 15.5 per cent' were attributed to asbestosis and ICG f 5-1.1 per cent! were attributed to various other entires. The Table snows the 121 neoplastic deaths classified by type of neoplasm. Fifty-three tor 43 per cent of the cancer deaths'; were attributed to bronchogenic carcinoma. Ten were at tributed to mesothelioma, 3-1 to gastrointestinal carcinoma, 6 to upper respiratory cancer, 4 to cancer of the bladder, 7 to generalized carcinoma tosis and 10 to various other cancers. In studies of this type, accuracy of diagnosis is of prime importance. Of the o3 deaths attributed to bronchogenic carcinoma, 34 occurred in 1)2-1 Annals New York Academy of Sciences hospitals. In IS the diagnosis was based upon post-mortem elimination am! in 15 the diagnosis was based upon histologic examination of opera tive specimens. The remaining 20 were based upon clinical evidence or information reported on death certificates. J. Churg has personally ex amined specimens from 15 of these 53 cases. J. Churg has also personal!}' examined sections on all of the IP deaths; attributed to mesothelioma. Four of the 10 were pleural mesotheliomas and six were peritoneal mesotheliomas. Of the 31 deaths attributed to gastrointestinal cancer fcancer of the stomach, colon and rectum plus one cancer of the esophagus;, 20 occurred in hospitals. Six of the diagnoses were based upon post-mortem examina tion, ID were based upon operative specimens and nine were based upon less reliable evidence. J. Churg personally reviewed sections from 12 of these cases. Of the 27 othm cancer deaths. 1G occurred in hospitals. Fifteen of the dl.ignores were bnacd upon autopry or operative specimens, amt 1 were based upon less reliable evidence. Of the 17 a.sbostosis deaths, G diagnoses were based upon post-mortem evidence and II upon clinical evidence only. Tn most prospective epidemiological studies, the investigators arc forced to be content with information from death certificates plus a little addi tional information. IVc think it fair to say that in this study we were able to obtain a reliable diagnosis on cause of death In the majority of cases. This docs not imply that all of the cases were correctly di.v.moscd. For example, the diagnosis is certainly open to question in those cases where it was bared upon clinical evidence or death eortifirato information only. This is particularly true in the case of deaths attributed to generalized carcinomatosis fwith primary site unknownl, and deaths attributed to stomach cancer or liver cancer. Furthermore, it is not unlikely that a few mesotheliomas were missed. Indeed, in addition to the 10 deaths attributed to mesothelioma there is one lesion which looks suspiciously like this dis ease, hot the diagnosis is not certain. Taken at face value, if would appear that asbestos workers have an abnormally high risk of dying of gastrointestinal cancer. However, we will refrain from drawing conclusions on this matter at the present time. Upturning tn the subject of pulmonary neoplasms, taiu.F. 3 shows the lapsed time from onset of exposure to time of death of 57 of our subjects who died of cancer of the itttig and pleura. (A few recent cases arc nt included here.' Not a single one of these deaths occurred in less 'ban 20 years after first exposure. The majority did not occur until after .".0 years and many did not occui until after -10 years. Obviously, light exposure to asbestos dust docs not lead rapidly to t ";] j 11111 j, ij, m'.-m] 'l,t a In. F'jnnlly obviously, thin clincnr-o io uriHbolv to upprar Hammond r.t nl.: Intra-abdominal Neoplasia Taiu.f. .*1 CAC'-IVOMA It!' l.IF.Nt: AM* V IN r>7 ASI'.ESTOS WORKF'lta Lapsed time fror.i onset of exposure to death Years Less than 20 20 - 24 - 25 - 29 30 - 34 35 - 39 40* Number 0 3 7 16 n 20 57 if workers die at a young age due to some other effect of asbestos ex posure. However, with light exposure and the availability of antibiotics for the treatment of infectious disease, neoplasia is a major cause of d".\th of such workers. References 1 Arson\n.T, hi 1906. Observation regarding the hygiene and safety of workers in asbestos spinning and weaving mills. Hull. Insp. Travail ; 190. 2. Hokkmann', i\. <fr L. FitunnacK. 10IS. Mortality from respiratory dis. in dusty trades. Innrrnnic dusts. Lull, U.S. Bureau of Labor Statistics No. 231 (Industrial Accidents and Hygiene Series: N'o. 17). Washington, RC. 3. MKni.wimrtit, E. F.. A. 1933. A memorandum on nsbestosis. Tiib*rr!e 1.7: inu-ns. 4. Glovnu, S. It. 1933. The morbid anatomy and histology of asbestosis. Tn- b. . 14. 5.sn_r,.-,s 5. tVoon. V,'. B. & S. E. Gloyne. 1934. Pulmonary Asbestosis, a review of one hundred cases. Lancet 2 : 13S3-1335. (5. Stone, J. J. 1940. Clinical studies in asbestosis. Am. Rev. Tuber. 41 : 13-21. 7. S:-LlKiiFF, I. J., J. Churc E. C. H \mmo.\d. 1964. Asbestos exposure and neoplasia. J. Am. Med. Assoc. 1SS: 22-26.