Document 7RG6zzgrYYL8RJj417BrLVjzE

FILE NAME: CertainTeed (CERT) DATE: 1967 Dec 7 DOC#: CERT028 DOCUMENT DESCRIPTION: Letter from Vanderbilt University Dept of Medicine to James LaPenna with Medical Journal Articles Attached VANDERBILT UNIVERSITY NAS HVIL LE , TENNESSEE 37203 Decomber 6, 1967 James J. La Penna 515 Stahlman Building Nashville, Tennessee 37201 Dear Mr. La Penna: You are correct in surmising that my statements are based on the medical literature. Enclosed are two examples. If you care to read ^ further, there are 27 references in the 1966 Cumulated Index Medicus which link asbestos with cancer, and an additional 14 such references in the 1965 Cumulated Index Medicus. They are listed under the heading "Asbcstosis." 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 published 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 exnosure. Our pathologist stated he was seeing more of these tumors than ever before, and in people 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 pipe 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. The only possible defense is that the amount of asbestos each _ person gets from the water will be so small that only a ver-y 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, J D S :jd Enclosures James D. Snell, Jr., M.D. Castleman.CERT000186 Special Report: Asbestos and u-ancer SeMw-vnv.-- __ Tn o methods ~of~ measuring the resistance or scnsij)*;o"cncs to mercury sails 1in\e been ` 11 ittle diiiercncc was noted, l'it the agar . , '.'",,I, ;!, d is preferred ns it is tccl'.nirr.lly easier to r.i-sistnncc to mercury api'e.ii . to Re a^snci- , j wj|), ;nitiRiotic resist.nice. Rot no `RIR-icnee HI u c hctvci II the t<> ilieni'S as (lemniistl.ited n-er.is of ir.ti .(cerebral injection of mice, the ,cnIy tc<t max' have a place as a screening procedure ,' vieNV cf tire relationship between the resistance to i!vrcrvar;<fto antibiotics. - We arc "rateful to Miss Tliibcamleau and Mi'. J. Sun!! fur tlicir technical assistance. rj-rnreNC^s M'-f rr, V; M'R '<W, p t.tr>in* t. 2: \i 'in!. Aw>2. lf'OO. . ,bcrr. f. Cnv n . t n o: :oa. '. i:-n. 4. (V.liM.Act.';rvj-;Au\!T. J.K/.:<;f aV1t-i:'h,Cl: .::1i:. 11 <i , /.ti<?, 721 717, Wr -i; `1' -, !:. rj. .w:< t 11' 1* ' C. Lik 'i',. .1 . AM) Mri H : -1 /7 . ?h 4'-\ I'. i ! i:. M.. i f wti"i:. n (.i. -E AMI Will .1 m L u . i r ' 1 , 2 : 11 :ii. is uj. V TV lou.-nll..AoMa",. M.i t. a . ice, r ; . 65 : s;, 1. If. r 10. E: ,S.' T>! s. r. AND A"Hi Cu.vn.N-, 1'. [:. : jo J r *J.. p`!lh..22: 5T2. 1957, 11 . F: \ ul*11.!:. A gomw. S. AND Tanissst, Mo r.rv. C'lii.;, ;.Vn., 1-1: 132. l `j.33. S P E W ttA t L 3ISPO K ' .V shcsios a n d C a n c e r The Report and Recommendations of a Working Croup Convened Under the Auspices of the Geographical Tathnlngj Committee of the International Union Against Cancer Fenrm 's Note--In October 1961, the New 'loik .-rde-nv of Sciences sponsored an international meet- on 'the biological effects of ad.e-tos hollowing ,s come 40 delegates from Ami iaim, Canada, :.,i,``,d Franco Cenn.mv, Great lb dam and Ireland `..lv. South Africa and the United States were mvited 1 ciu.lv the. vast amount of information Inch had been re nted with a view to the organization of an mtcr- ationai study of asbestos and cancer. The terms of T.-enco of this Working Croup covered three major meeds of the problem-, epidemiology, pathology and xivrimental pathology, and phy-dcs and chemistry. The findings of the 'Working Group and tlu ir n enm- nrnditions arising from these studies aie naeii.eil, m ta-htlv abridged form, in the following u poit. Tin: Association' or Fxposnu; to Asbestos D ust and C ancer r~r''UE main tvpcs of asbestos of commercial 1 interest are amositc, anthophyllitc, clivysotde, 'dd.olitc and tvemolitc. There is evidence of an assi'eiation between exposure to asbestos and -i.dignant neoplasia. This has Reen established .e.dtily on information from Germany, Italy. South Afiie.t, the United Kingdom and the United States >[ \morica. T iv tvpcs nf tumours wbioli l'-ivo l'< <`it shown to be a.sMieiated with exposure to asbestos dust are: 1. Carcinoma of the lung. . 2. Dilfuse mesothelioma of the pleura and peii- meuir,. There is . ... re sue gestion of an association also i`h gastrointestinal carcinoma, and possddy with a arian tumours. The latent period between first exposure to `lie dusVand detection of the n luted tumnnrs is many years, usnallv 20 or more. Instances up to GO sears Rave been reported. For this reason, further cases of these associated tumours ill be expected to occur for many years to come, own if met exposures are now greatly l educed. lVevut o\ donee indicates that the associ.w c a rc in o m a s of the lung arc not limited to expomre to any one type of asbestos fibre. However, f"Ue'tr investigations are urgently needl'd to obi whether the degree of risk is impoitantly relat'd to llm tvpo of fibre inhaled. In' the cum: of mesi>11a4ionee; evidence In-m a vi r.d roniiti iex suggests that eXpoMire to ` liu- (blue fibre) may be of pailieular impoi tame. Rut it cannot he concluded that only this 1>pc 1` fibre is conc erned iih them tumours, and In; the. investigAbon of this problem is needed. ^ Certain tvpes of asbestos fibres m toe wr .... stale have bean found to contain oils, axesw" t nilur organic maRcr. In addition, asbestos ...xw rcadilv absorb hydrocarbons subse-nunl to ciay. - Sm.21 or trace amounts of xarioiv- weiueuG s'uy)", nil 1,el and iliroininm are also found ""'a- ^ v, ill, some 'vpos of fibre. The possible Mile ' assoeiali d malelials in the del, loima "l ol l"|" following exposme to nsboAuS diet, is not vet ' ' Tlu'-'C findings, when luiisidind in '' r' ' 1 , the grout increase in the use of asl slo-, ,.a ^^ purposes ill all countries, suggest lien a ^ ' serious and widespread hazard iroin r ' l " '" " ) asberios dust may exist than is widely appo'' - ' Castleman.CERT000187 Nm i'LA S T A AMO.VC IN SU LA T IO N W OHKKRS IN Til'-- i m t i :). s t a t u s w i t h s p k o i a i , i w k i t n 'X' T m INTUA-AMMOMINAL NKOI'LA.SIA ' Ji. 0. 11;irnnii >nd American Cancer Society, N e w York, N. }'. I. J. SclikofT, J. Churg i The Mount Sinai Hospital, N e w York, N. }'. i Uefore presenting- the findings in our study of insulation workers, we uo;i!d like to discuss briefly some considerations which we believe to be noporlant. Malignant neoplasms produced by exposure to chemical arents or ionirinc radiation typically have a long latent period. That h to s a j. there is a long delay between first exposure and the appearance of the neoplasm. In the case of carcinogens which can be eliminated from the body, re peated contacts over a long period of time may be required. However, in tie case of agents which arc not eliminated, exposure of the tissues is continuous from time of first exposure. The probability that neoplasia will occur and how soon it appears generally depend upon the degree of exposure. Now let us consider the effects of exposure to an agent which can p ro duce neoplasia but which can also produce some other type of disease. Here we are dealing with the problem of competitive risks. If exposure results in death from some other disease within ten or fifteen years, then, because of the long latent period, it is very unlikely that neoplasia will result from such exposure. In 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 bo cured, or death delayed. An historical review of the literature from this point of view is most interesting. l All of the early reports apparently concerned workers who were very heavily exposed to asbestos dust. This was long before the development of the sulfa drugs and antibiotics. Pulmonary diseases including tuber culosis and pneumonia were among the leading causes of death. Life 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 100G, Auribault reported the results of what was probably the first study of mortality among asbestos workers.1 His account is interesting 519 ' Castleman.CERT000188 ,3:20 Annals New York Academy of Sciences In 1800 an asbestos spinning mill ami weaving factory was established in tl.e neighborhood of Condc-.sur-N'oircnti (Calvados). During 'he first five years of operation there was no artificial ventilation and the employees were heavily exposed to dust from the looms. According to Aunbanlt, fifty workers died during this five-year period. Furthermore, the dirmior, 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 some data from the industrial experience of the Prudential Life Insurance Company. From 189 i to 1911 there were 13 deaths of asbestos workers and three of these were at-tributod to pulmonary tuberculosis. It is of interest that nine of these 13 asbestos workers died under the aye of 14. This is in contrast with a much older average age at death reported for potters, molders, marble workers, and stone workers. Hoffmann notes that "in the practice of Ameiican 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 E. L. Collins (Annual Report of the Chief In spector of Factories and Workshops for England and Wales for 1910' as having found five deaths in people having pulmonary tuberculosis in five years among a staff of under 40 workers in a factory weaving asbestos. Since Hoffmann's time, many authors have reported findings in series of eases of asbestosis. Until after 1940, emphasis was placed upon the role of secondary infections, particularly pulmonary tuberculosis and bronchopneumonia. For example, Mcrowcthor1, writing in 1933 commented. Usually, the fatal issue is determined by the onset of some acute in A ?tion with which the remaining undamaged tissue is quite un able to cope: this is commonly a low grade bronchopneumonia. The same year, Gloyne' stated that, "the writer has so far only seen one asbestos patient recover from bronchopneumonia. In two series of cases reported by Wood and Gloyne' in 1934 and Stone in I2M0, bronchitis, bronchopneumonia and pulmonary tuberculosis were the commonest terminal complications of asbestosis. However. Wood and Gloyne found two lung cancers and one cancer of the pleura in 2fi deaths of patients with asbestosis. With the passage of time, pulmonary infections were found less ire- quentlv and lung cancer was found more frequently in cases of asbestosis. We will not take the time to review the more v-eent literature, a 'Tge part of which was written by people present at the Conference and ade quately covered by other papers in this Annnl. It is sufficient to say that since the advent of the antibiotics, workers have generally been saved from death due to infectious pulmonary diseases resulting as a complica tion of asbestosis. Thus they began to live long enough for the neoplastic effects of exposure to asbestos to become manifest. Our study differs from the early studies in two important respects: Castleman.CERT000189 ) ) ) Hammond et al.: lntra-abdominal Neoplasia Castleman.CERTOOOl 90 , J , ZI. ff (3 ' U) -U O \ ............. o irt T.uu.t: ! OlISKUVIiD AND EXI'KCTKD N V M ll la t UF IlK A T IIS A MONO 3 2 ASHKSTOS W oiiK Eiis IS x ro sE D T i) A siu st o s D o s t 2 u Y ;ak s oit L onolii CAUSE OF DEATH Total, all causes Observed (asbestos workers) Expected (US white males) Total cancer, all sites Observed (asbestos workers) Expected (US white males) Cancer of luni; and pleura Observed (asbestos workers) Expected (US white males) C a n c e r of s t o m a c h , colon, and rectum Observed (asbestos workers) E x p ec te d ( US white m a l e s ) C ancer of all other site s combined Observed (asbestos workers) Expected (US white males) Asbestosis Observed (asbestos workers) 19431947 28 39.7 13 5.7 6 0.8 4 2.0 3 2.9 0 Years 19481952 19531957 54 85 50.8 5G.6 17 26 8.1 13.0 8 13 1.4 2.0 4 7 2.5 2.6 5 6 4.2 8.4 1 4 195819G2 88 54.4 39 9.7 18 2.4 14 2.3 7 5.0 7 " T'i'.j! 1v42 1.-02 4,_J 203.5 95 36.5 , _ 6.6 9 9.4 20.5 1 522 Annals New York Academy of Sciences (1 i The subjects had very light and intermittent exposure to asbestos dust as compared with the daily heavy exposure of subjects included in the obi studies; and f2) Wc a-c reporting deaths which occurred after 12-12; that is, after antibiotics became available for the treatment of pneumonia and after death rates from tuberculosis had been greatly reduced in this coun try. It also differs from most other studies in Unit we were able to 1rare an entire group of workers including those who had retired and .hu 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 here are confined to the experience of G32 men. They composed the total membership of New York Local 12 and Newark Local 32 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, 1052 and 253 of them died during that period of time. Most of them had been first exnos.-d to asbestos dust at least 20 years prior to 1913. The remainder passed the 20-ycar point between 19-13 and 19C2; and we counted their experience only after they reached this point. Table 1 shows the total number of deaths and the number of deaths from selected causes during each of four successive o-ycar periods. For comparison, wo show the number of deaths which would have been expected among these asbestos workers had their age specific death rates been 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 wore actively at work in 1913; and seriously ill men are unemployable. Thus their total death rates wore low. This selective effect gradually wore off. During the last 5-year p<-riod. S3 of the workers died compared with 51.-1 expected. During the entire 20year period, 255 asbestos workers died compared with 203.5 expected. Now observe the number <>QleatJis_fr(>m_caiicer of the lung and pleura. During every 5-year period., far more than the expected number of as bestos 'worker sH icd""ofThi s cause. AUopetjiejJherejvere .13 deaths from cancer'oT Theliing'a'nd plcura compared with, fi.fi expected; a mortality ratio of nearly 7 to 1.. To our surprise, these asbestos workers.also had extremely high death rates attributed to cancer of the stomach, colon and rectum. T1.5 observed number of deaths"from thesc'canccrs was 29 compared with an expected 9.1; a mortality ratio of 3 to 1. Castleman.CERT000191 Hammond cl nl.: lntra-nlxlumimil Neoplasia It is of interest that out of a total of 2.V> deaths only 12 were attributed ashcstosis. As previously mentioned, our first report was based upon the records of G'2 men v.dio were members of the two locals on December 21, Id 1'2. An additional S0 men joined between January 1, 1943 and December 21, 1922. Tims a total of 1,522 were in the two locals at some time between 12 12 and 1022. Wc have traced all of them through August 19G-1 and Dr. SelikoiT had medically examined most of those who were living as of the end of 1922, Of the 1,522 men, 2C4 were dead as of January 1, IOC.", and an additional 43 died between January 1, 19C3 and August 31, 19G1. The !mding. shown in ta.mi.i-: 2 are based upon these 207 deaths. T aiii.k 2 N. Y. C. A siu stos I n s u i .atiox W oiikwis 307 Oonswttivi: Pi.writs J am'auv 1, 19-13 - Aucust 31, 1901 Total deaths AU neoplasia Bronchogenic carcinoma Mesothelioma G.I. carcinoma Upper respiratory Bladder Generalized carcinomatosis All other Asbestosis All other causes 307 _ 124 c 'J 53 17.3% 10 3.3" 34 11.1% 6 1.9% 4 1.3% 7 2.3% 10 . 2.2% 17 ' 1G6 5.5% 54.1% Of the 207 deaths, 124 (40.4 per cent) were attributed to cancer, 17 (5.5 per centl were attributed to asbestosis and ICG (54.1 per cent) were attributed to various other causes. The Table shows the 124 neoplastic deaths classified by type of neoplasm. Fifty-three (or 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 53 deaths attributed to bronchogenic carcinoma, 34 occurred in Castleman.CERT000192 524 Annals New York Academy of Sciences hospitals. In 13 the diagnosis was based upon post-mortem examination and in 13 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 personally examined sections on all of the 10 deaths attributed to mesothelioma. Four of the 10 were pleural mesotheliomas and six were peritoneal m e.. .lieliomas. Of the 3-4 deaths attributed to gastrointestinal cancer (cancer 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, 19 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 other cancer deaths, 1G occurred in hospitals. Fifteen of the diagnoses were based upon autopsy or operative specimens, and 12 were based upon less reliable evidence. ^ Of the 17 asbestosis deaths, G diagnoses were based upon post-mortem evidence and 11 upon clinical evidence only. Tn most prospective epidemiological studies, the investigators are forced to be content with information from death certificates plus a little addi tional information. We 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 does not imply that all of the cases were correctly diagnosed. For example, the diagnosis is certainly open to question in those cases where it was based upon clinical evidence or death certificate information only. This is particularly true in the case of deaths attributed to generalized carcinomatosis (with primary site unknown 1, 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, hut the diagnosis is not certain. Taken at face value, it would appear that asbestos workers have an abnormally high risk of dying of gastrointestinal cancer. However, wc will refrain from drawing conclusions on this matter at the present time. Returning to the subject of pulmonary neoplasms, taulf. 3 shows the lapsed time from onset of exposure to time of death of 57 of our subjects who died of cancer of the lung and pleura. (A few recent cases are m>t 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 30 years and many did not occur until after d0 years. Obviously, light exposure to asbestos dust docs not lead rapidly to pulmonary neoplasia. Equally obviously, this disease is unlikely to appeal Castleman.CERT000193