Document zzjVBRxvNN48EvxRXXzk3nmV6

SYMPOSIUM MONOIAL SUR L'AMIANTE 2*. 25, 28, 27 Mai 1982 MONTREAL Out., Canada WORLD SYMPOSIUM ON ASBESTOS May 24, 2S, 25, 27, 1982 MONTREAL Out., Canada Stance I - 25 sal I'Mijntc Its donntes ntdicales Session I . May 25 Asaestos: The Medical Oata AS3EST0S-4ELATE0 DISEASE - An "VERY IS*, 1332 I r-/i no J. Se1 *koY-* iUN.--ED STA'ES; A-774 1 1/ 112007. PLAINTIFF'S EXHIBIT Asbestos-related dmm - o owmt. 1982 Irving J. Selikoff, S.D. Environ--ntal Sciences Laboratory Souat Sinai School, of hedicine of the City University of Sew 7ork Introduction This Sysposiun s>7 prove to be a landmark to the history of asbestos use sod asbestos diseise- In thus respect, it resembles the confer ence held by The Me* York Acadeay of Sciences in 1964. Cnlilce that meeting, however, the outco-- is not secesaanly sanguine cor broadly optiaistic. e have cone to a decision point, with several directions passible. which are taken will, in considerable measure, be influ enced by this aeeting. The Hew York Conference Altecugh the fibrogenic capacity of asbestos--potentially fatal-- had been increasingly studied since the 1910s and 1920s, it was not `until the following two decades that the significance of cancer actracted broad mention. This, coupled with the exponential growth of the use of asbestos, spurred scientific inquiry. By '.?64, accumulating data warrseted critical review and m October of caat year The :(ew Tors Acaoeay of Sciences convened an Internaltonal lonfcrence to consioer what was known. The prospective! at that meeting were defines by its title "Biological effects of asbestos". The presentations largely focused on observations recently made in defined areas where aediliooal scientific data could assist in clarifying scientific ques tions. Many had confidence that, with what was 'mown and wnat wouio be studied, tie disease hazard would be controlled. Scientific infomation would allow us to avoid barard associateo w-.th tnis vsluaci; material. A :?75C '/ A 2 Tilt Montreal Swoosiua la lit years since 1964, this optimsa has ba tespered. Asbestos disease has continued, and chart is so unaniaity chtc Lit conditions foe its central, have been achieved. The fact that this Symposia* will sddrtss tit question ''Should the use of tsbtstos bt continued?" is i stature of our past inadequacies, and current uncertainties. This Meting will i|aia be sdeact*basad. But it will, unlike 1964, have the additional responsibility of considtrial the econoaic, poli tical, social, adainiitritive, ethical problcas associated with tit continued and projected uses of aabestoa. Perhaps we were reaiss in Mew Tork in not addressing these probities earn vigorously. Science was aecesaary, but not sufficient. This Syaposiua, then, baa a double responsibility: careful renew of the scientific prospective* that have developed since 1964 and their translation into the use of asbestos without significant risk to auaen health. Scientific perspectives, 1964-1982 Buildiat upon and extending the scientific LniocBation that had becoae available by 1964, we have now achieved a useful overview of the scientific background against which ihe asbestos disease problea nay be viewed. At the 1964 aeeting, a nuaocr of questions were unre solved. Additions! data were needed to fully characterize me nature and extent of the cancer risk, the influence o: fiber dose and fiber type on such disease aa would occur, the significance of noo-occupalional exposures, and how standards and controls could best be de veloped. duel indorsation has been obtained, to help ucoerstand these critical issues. In addition, prooleas not predicted in :?6 have also been identified, and useful data obtained. A : 775 3 Soectrua of asbestos-ssiociaced jmm W bov have a fairly good undarstaading of the spectra* of asbestosassociated disease, at least chat whicb obtains with heavier exposure. Two cohort studies illustrate the extent of this knowledge. In the first, 17,300 asbestos insulation workers were registered on January 1, 19-67 and followed to December 31, 1976, and included 166,353 aanycars of obsecration. Table 1 suMerlxes their aortalicy experience during that decade. There was significant increased aortalicy of cancer of the lung, pleural and peritoneal aesotheliona, cancer of the esophagus, steeach, colon-rectua, cancer of the oro-pharynx and larynx, cancer of the kidney, and aibestosis. These data were based upon 1,271 deaths. The experiences of a second cohort confira this outlook, providing support froa another epidcaiolological direction. On January 1, 1943, there were 632 asbestos insulation workers in the Jew Tork-Jev Jersey locals of this Union. This group was followed to Oecenber 31, 1931, covering 14,547 nan-years of observation. In the 39 years, 532 sen died; this aortalicy experience thus covers alaost the entire experi ence of this group. Table 1 demonstrates that 46 of the sen died of asbestoses (approximately 8"). Tar greater risks were deaths of cancer. Age, year and sex-specific data indicate that 63.9 deatrs of cancer were to have been expected. Two nunared ana thirty-eignt oc curred (45"). The aajoc neoplastic risk was lung cancer. 15.7 were expected, 1C5 occurred (20" of all deitns). There were 50 deaths of aasothelioaa (9") and a oodest but statestically significant increased risk of death of gastrointestinal cancer. Both Table l and Table 2 indicate that the aajoc concerns are lung caacer, nesothelioaa, aibestosis and gastrointestinal cancer. Populations it nsk By 196A, it waa already clear diet early tspbasis oa 'asbestos wore* trs" (asbestos Biaers, sillers, asbestos products sanufscture) wax insufficient. Raider, hazards aaaociaced with product use vastly increased Lb* amber of people at risk of esbescos-isaociiced disease. The insulation worker experience pointed to Lb* construction iaduatry-, the reporta by Barries and Scuapoiua in 1968 added shipyard work aa a sajor concern. Against Lbis background, atadies in a variety of trades expanded bocb the potential for dixease and the necessity for controls--cbeedcal plants, refineries, power production and utilities, transportation, ship repair and shipboard exposure, etc. Further, utilizini sesotheliona as a Barker and "signal" (the work of Cochran and Webster has been particularly telling m this regard), there was further esphasis on the likely ioportance of disease among faaily contacts and aaong those exposed m a nuaber of environmental circumstances. Dr. tf.J. Nicholson vill discuss in this Symposium the results of his analyses concerning occupational populations exposed 19M-198C in the Qmted States; the nuaber of people involved can only be described as buge. It will be valuable to have analyses aace of exposed populations m other countries, to provide a global perspec tive in this regard. Latency Perhaps at the heart of our difficulties concerning asbestos-associ ated disease has been the long incubation period before iaportant clinical evidence of such disease is noted. The "20 yeir rule* had been propounded for radiological asbestosis in 196a. Ic is clear that the same bolds true for cancer, as wcLl. Table 3 shows that little lung cancer or aesachelioaa occurs m less than 20 years from onset of exposure. This is depicted in Figures 1-3. A corollary of this is that we learned the semantic oifference between "curstiaa of exposure" and "duration froa onset of exposure'. The two are by no scans synonymous. 1'ith ascestos exposure of sufficient intensity, only short-term exposure is needed to yield long-tern risk. X420078 5 W'e !u< aoc yec Learned how to Looks cilia iron grip of Latency. la practical cam* it swans that the disease we are aeeing now is the reault of paat exposure. By the aaae token, however, and important for this conference, La the fact that prtient exposure will reault la future disease. Low-level exnosura I'e aot sura that this commonly used phrase is entirely appropriate; perhaps we should employ the sore uavneldly "lower level exposure", since there is sou contradiction in speaking of exposure as "low" when it produces disease and death. Further, we are not very confi dent about quantitation of "lower level exposure" since it was pre cisely us such circumstances that, in the past, few aeasuresents were aade. This has been the case for family contact disease. When this phenom enon, heralded by Wagner'1 description of environmental aesatheliooa in 1960. was documented by Mevtouse in 1965, we had in information on vast level of exposures aight have been responsible for vast was seen. Nicholson sad 3ohl in our Laboratory have aade some measurements in recent years, but I believe that t valuable opportunity was Lost after the New Torx meeting wnen extensive household asbestos exposure studies were not done. We would now know something at least about the lower limits of exposures associated with aabescos-associsied disease. Low-level exposure is sometimes used to characterize what baa happened m occupational situations where exposure has been intermittent and indirect. These nay not be the sama as exposures m family contact circumstances, since the intensity of exposure oa occasion can be sore or less severe, albeit for short periods. It signt well be that three hours in che hold of a snip where asbestos was being extracted coulc proriae a nuen heavier lung burden than iO years or residencs m an asbestos warier's name! Too, the general uae of the phrase "law-l-vei exposure' say not oe at all pertinent to me levels of exposure that exist m amoient nr aaa X420079 6 experience of brake repair and brake nameearner workers. at sheet aetal workers u> the construction industry provide no accessary guide to evaluation of risk of tbc general population. Selection wjtbin bleb risk trouns When it is said that one in five aabeatoa insulation workers dies of lung cancer, it ts also isplied that four In five don't. Similarly if one in IS dies of nesothelioaa, 14 do not. Tbc reasons for such selection within groups at high risk have begun to be explored. One factor thac has beea Identified has been the ixportanee a: tobacco sinking, primarily cigsrettes. Asbestos exposure by itself increases the risk of lung cancer, by about five tines. However, since the risk of aon-saokers is low, even such increase does not produce a very large auaber of cases of lung cancer. Cn the other band, the sane five tines increase anoag cigarette saokers results in sharp aultiplication oi an already very iign m>, resulting in a devastating lung eincer incidence. In one study 'the 17,300 asbestos insulation -on ers aentioned above) in which the experience of nor: than 73,300 like aea were used as a control, the rate fot sen vao neither saoked cigar ettes nor worked with asbestos was 11 per 100,000 sec y-ar. for nan-saokers who varied with asbestos, it was 53. Anoag those wao sooted, but wet: not asbestos-exposed, the risk was 1U per 100,000 per year and far those who bad both exposures, asbestos and cigarette saoaing, it was 301. The multiple factor interaction oi asoestos ana cigarette looking pertains as well is cancer of the esopaagus, cancer of the otopahryna and buccal cavity, cancer sf the larynx sue sot is nesothelioaa, cancer of the stouach or colon-rectum or cancer of the kidney. There stay well be auitipie factor interaction wna other in fluences for a variety sf asbestos cancers, hut tms has seen little studied. Cue set of circuastaaces that can turn out to he s: con siderable importance is mmunamodification: this is a subject jf li cense reseircn at this time ih our Laboratory. A : 75"7 L /O 8rtnl of risk During the cigarette smoking-asbestos exposure investigations, as im portant observation vaj made. Those aabestot workers with a history of cigarette smoking who (tapped smoking, within 5-10 peats had only ooe-half Ca two-thirda the lug caecar risk of those who continumd to saoka. Data art sot pat available concerning whether risk of oro pharyngeal and buccal cavity cancer, laryngeal caacer, aod esophageal cancer will show the seat happy effect, but I aaticipate that it will be so. Cigarette seeking was also found to increase the risk of death of asbestosis, presumably bp adding the esrphpseaa-bronchitis burden of seehint to the paeuaecouiotic effect of the dust. Sera, agtia, it is likely that cessacioa of seeking will have an ieportant beneficial affect. This raises soee very practical--and ethical--questions. It has bees deeoastrsted that we can, at least m part, reverse the risk of lung caacer aeoag individuals ;rtviousl7 exposed to asbestos by cessation of ranting. Is it meusbent upon us to aoctcy all those who we know have been exposed to asbestos to tell then of the added risk they have of death of lung caacer, caapared to smokers in general, sad of the potential of reversing that risk by smoking cessacioa' Jose-response ample evidence has now been accumulated to indicate that an important dose-disease response gradient exists for asbestos, as for many other carcinogens. We will hear about this, I sm sure, in some detail at ihia symposium. While the exact projections may be deoacad, it is clear that the less asbestos inhaled, the less the disease risk and, conversely, the aore asbestos inhaled, the greater tne risk. A cor ollary will be mat avoidable exposure translates into avoicable disease. >'420081 a An addendum to this suoject lus bees added in recent jeara. We knew in 1964, and this baa been confined aince. Out different exposed populations bad variable disease outcoae, as aeasured by mortality experience. One possible explanation was chat different fiber types bad different pathogenicity and after tbe Sew York Conference, tbe experience of populations exposed uniquely to one or another fiber type was sought. This was not easily cone by in industrial circuastances, due to raised exposures. In our Laboratory, we have been able to obtain inforaatian oa two fiber varieties. First, we have been investigating the experience of 1,663 sen who were employed in an aabestoa producca factory in Pater* son, Sev Jersey 1941-1964. A great deal of indorsation demonstrated that aaosite was the sole fiber used in this plant, apart from some minor aaounts of chrysotile. Table 4 summarizes tie experience of 532 sen who began work 1941-1943 and were still alive ZO years later, and were followed prospectively from Chat point to 1973. It will be seen that their mortality experience was very much like that of asbestos insulation workers. Aaosite, apparently, did not have a unique poten tial to result in ocher than the anticipated isbestoa-issociaced diseases. We have bad the opportunity of investigating the experience of asbes tos insulation workers in the Mew Tark-Sew Jersey area for two periods of tiae; one, in whitb employment began and continued when only carvsotile was uaed (before World War III and a second group a: men in the same union locals. In the same cities, doing the same work, employing the same work practices but exposed not only to chrysotile but poten tially to amosita aa well, which had by then been added to asbestos insulation materials. Tables 3-3 show that, for equivalent times from onset of exposure, no difference could be seen m the mortality exper ience of those exposed only to rnrysotile or to chrysotile and amosite, Unfortunately, we have so experience with crocidolne exposed popula tions m our Lascrator7. *420092 9 It ny well b that the question posed in 1964 wu much coo restric ted. The assumption was made chit fiber type would be the major dif ference in explaining observed variations in eke disease risk of various groups. It is now realized that exposure intensity certainly plays a very important role, perhaps a critical one. However, ocher factors aay be of equal or even greater importance. I would go even further than 3r. HcDoaald (this Symposium) when he staces that '"while it is clear that, in experimental animals, fibres of different type but similar dimensions hsvc much the same pathogenicity, various in dustrial processes could have a major effect on fibre size...." focus ing, ss be did, on the size of the inhaled fibers as a determinant of pathogenicity. Other changes besides those m size esn occur m the fiber during its journey from the time it is extracted in the mine to its use m a variety of industrial processes. Dr. Danger will address this question here later. Cose response, then, may reflect not only the number of fibers inhaled, but various attributes sucb as fiber type, dimension, surface, structural alteration, etc. Conclusion Vnen a death of as'aestoais was observed in 1900 and recorded in 1906, it could not nave been widely known. But t: would have been difficult to overloot the serious potential of the dust vnen the careful clini cal atudies and surveys in the decade after 191- found that aacestosis waa ccsaon among exposed workers, and that deaths could occur. De spite this understanding, the 1930s. 1940s, 1950s went by with iev precautions in trsdes in vnich there was asbestos exposure. Kor die accumulating scientific knowledge concerning the cancer potential of aabeatoa increase protective measures 'until the 1960s and l?!Cs. This Symposium again, as tie meeting m S'ev Tcrx m '.So*-, will sull be science-baaed, aowevec, it will also have cne case of identifica tion and resolution of industrial, economic, social, political and ethical ouesiiona. Thus, there will be debate concerning tee dimen sions of tie disease legacy we now fact as tie result of our years 10 of failure-exactly how such Lua| cancer or nesotnelioma or gsstrointestinal cancer or cancer of the Larynx or other cancers or asbestoj11 -- lo shipyards, the construction industry, transport, nines, fac tories, chemical facilities and refineries, power plants, insulaeion work or ocher trades. We will he asked whether levels of 10,000 or 1 aillion f/a^ of air (0.01-2.0 f/al) will protect people in the future and we will not be able to answer confidently because few measurements were aabc years ago to correlate with subsequent cancer experience. Still, we'll be able to five the key answer--that thera ia a "doaeresponsc" for all asbestoa disease-- tha note asbestos, the sore risk, the less asbestos, the less risk. But this discussion will not be able to answer the critical ques tion-should the use of asbestos be continued-- if evidence will ioc be available thee it can be safety used, that there will be vigorous insistence on all fassible safety neasurss; not aininal controls but uxinua capabilities. Would this prevent all asbestos disease? Ho--but it vouid avoid all that can be avoided, at leaat with wnat is presently known. It asy well be that to do less than we can will prove unacceptable. Therefore, one perspective by which to judge this Symposium is that it has as its task the unique opportunity ct seeli ng who 'will Live, and who will die. It is this decision wnicn will inswer me question o: waether or aot asbestos should continue to oe used. A ; 775J D*chs at 5othlIom U <HM d*l li (iMim 0ACh of lung exactr A ; 776C >'420085