Document wKrRqJm181RJNqq7XEyj9L6yJ

~T..>.fv--a * g**V ..:?.*'*'"< s u.` j iWH- leV '.fs!:a:::;c"^wjnt-:r,TeSS .The American Journal of Medicine VOLWI 'l-v -.v APRIL 1967 N -JM1ER 4 Editorial Asbestosis and Neoplasia I.v at least one fourth of the adults V ho die in urban areas in the United States and stiii an assumption, an extrapolation from the observed data since w>e do net know at this time other industrialised countries asbestos bodies whether or not the small amounts inhaled as the are found in the iungs (/--5). This observation result of asbestos air pollution have an effect has led to the recognition of ashesto-related comparable to the much larger amounts inhaled disease as a potential serious modern urban has- in industrial or intimate environmental cir itd [7-9). cumstances. The question will not be resolved for Indeed. Thomson [-} has predicted that some lime because of the lone lasent period aabvcios-induced neoplasms will rival cigarette- between initial contact and the appearance of induced lung cancer in the next several decades. clinical disease. Although there are variations This prediction is based upon five observations based upon individual idiosyncrasy, intimacy, and one assumption. The known data may be duration and continuity of exposure, and per rjmmarieed u follows: (1) Asbestos inhaied haps also upon sueh factors at the variety of under industrial conditions will produce a serious t'bettos ii-rd (cl'.ry<otiie, amosite, eroeidoiite, , neuntoeemesis (puimor.ary a*bestosii) [70) anthophylite, tremoiite) and the presence of m-en with relatiseiy light exposure (77). (25 other concomitant dusts, by and large it may be i-nder similar conditions of heavy [77] or light said thjt disease caused by .asbestos is rarely ,:JJ induttriai exposure, 'sorkmen die of neo- manifested in less than ten to twenty ; ears from riasini more frequently than expected. (3) onset of exposure. A'idespread contamination of the environment ,`JJS'l may occur both from industrial sources (such as asbestos-containing dusts from con- rcL'toxAay AsatsTotis ruction sites) and from disintegration or use of The ease report which gave the dilease its isoestos products (such as asbestoi-comainmg name {27) was of a woman asbestos textile 'uor tiles and brake linings [7dJ. () Such operator who had begun tlu'i work tw enty years mvironmental eantemination may result in before. Alerted by this and similar eases, a udespread inhalation and retention of small survey of British factories was undertaken; umbers of the mineral fibers f7--<7J. (5) Under evidence of asbestosis was found to be common, trtain conditions (for example, residence within hut only in these whose occupational exposure .talf.miie of an asbestos factor;' or in the house. to asbestos had begun many tears before (70). w'd of an asbestos worker) environmental Similar experiences were *oon recorrird in the ' posure has been shewn to produce serious United States (22). The counterpart of acute sili case [17-20]. The prediction that widespread cosis w as almost never observed, except perhaps westos rcutamtr.ation of eitv air will he associ- under the most unusual circumstances )2i). d with widespread neoplasia, however, is This situation still obtains. In a recent study 487 DUP 0930305 N \ Jr." i * t {;' tl .it r' ~)'r* 'u. j Wt :f wjrVr*) * irjsvs `.r: f ' * r,* *a r!c* f r/rf-t . 1-3 >V "V : * v> CvjVr*rsv?,v.:1i V^| ;p'S ' V***. ', .* -;r{5&fcy,,** ./rtSfc* -.^Tw.-X ACw.'i'i ?&* -5%i 5fi! ...n ,..'t ;?S7v:i ,vV.r^ 'iS'cW .aviii'* ?S3 wVdxyf A)r.-y `files -V s'fVf) Of I "ft** IlJi'.uM.ti r.tf. i* IfltmCL?.. VKCiC Cll.s'.Cl.l .V wSvtTf-S iv.i L suns Unasili Oflici trf r.^ptmur Ur.) 10*V> 0*t No. 121 I'M 7T "i JJA 1.117 Per cent Nonn;J 53 i:.9 53 *> SV * Si j Tiff vrm Abnormal *34 2 t: i mi t 10 4 as 3 Asbo(0*i Curaue; 12 u w 25 UH j* 3<Xl 31 J*' IT 9 0 3 25 11 A 0 c iO Sciikotl rt xl. |Mj. of over l.ldO asltestos insulation workers. chest roentgenograms disclosed abnormalities in only 10 per cent of (hose whose exposure to asbestos began less than ten yean before and in nniv uu per cent of those who hud been first exposed to asbestos from ten to nineteen yean before. Moreover, these abnormalities (roenteenologically ^evident parenchymal fibrosis and/or pleural fibrosis and calcification) tended to lx minimal in extent. On the other hand, in those with onset ol exposure to asbestos from twenty to twenty-nine yean before, chest roentgeno grams showed abnormalities iit 72 per cent of the older workmen and in osrr 90 per cent of those with mine than thirty yean from onset of expovi ire (Table i) I / / ]. The explanation is twofold.' Tirst. nyhestus rarriv provokes an acute inflammatory react ton in the lung. Rather, the fibrosis which remits ii slow I v pi ottreuiv. The asbestos fiben rrmain in kiu where inhaled hut the tissue rr'ponsc to them is indolent, albeit progressive and appar ently irreversible. This coutse of events is seen both tn iuuiian and experimental asbesiuvis |2J-27). Second, asbestotic fibrosis is of tbe diffuw hiiervtiiiai variety, whieh mav not be readily app.trrm on roentgenograms iu its earlier stages [jJ| and sometimes not even when extensive" |J2|. There is a tendency, therefore, to underestimate the presence and extent of clinical cumuuc. ruimonary asbestosis has been aptly characterized as a tnonosymptoinatie disease, with dyspnea its cardinal clinical finding. Vet this feature, and the physiologic and morphologic changes responsible for it, are not early findings. In the asbestosis found among insulation workers in the United States, dyspnra was present in only 1 per cent of those with less than ten years of work "experience, and was minimal in each Case [//). Even in those with lea to niretue:: years from onset of exposute, esirpiaints ui dyspnea were recorded only in twenty-eight o.' 379 men examined anu tbrse were nmim-ji in ail hut one in,lance. In commit, of 121 men with inure than forty year, from utnet of exco sttre almost half had dyspnra. more often than net moderate or severe in decree. Finger duobine, cyanosis and extensive fine basal rales r.i: tend to develop only after a lung time fiom the Onset of industrial usbrstus exposure. Tile pulmonary pfivsioiotical defect tn asbestuais is associatrri with thr patient character iitic of the alveolar-capillary block s>ndroiit< J.Sf/1. with reduced vital c.tp.ictt'. fairiv uri prevurved uiaxiimiiit brrathmg capacity, Its per venitl.ttton at rest atict particularly on ewret.v tlccreastd diffusing capacity of the lung, tut paired oxygenation of the .ivierial b.'ood am reduced pulmonary compliance. None of t,n parameters show, significant change eativ m th cum .a: of the disease, not even vital capacity which has licrn cicmuusiratert to be perhap the most sensitive index of premcoion ol tif dtseaw* [o/,J3|. In ttto-i m.unces, therefore, the term `'carl asbestosis*' is of uncertain utejnme. If it iiuemted to dcsionuie clinical asucstem > ittiniiiul or limned extent and severity, cot sidcrahle tittle will have elapsed. perr.aps or or two decades before manifestations has Isecottte evident, in a lesser period from omof exposure it is likely that few or no chargindicative of clinical disease w ill be preset' even though histologic changes will be puiet underway {Jj|. L.UXC CA.XCCX In 1933 Lyneh U-'l reported a case of iu cancer tn a man with asbestosis. The asscctcti tsiucsa jou.ksc or utBiei 09303Q6 DUP 400 Editorial deaths from 1958 to 106-1 onh eieven were due to pulmonary insufficiency. Death from pul monary asbestosis occurred at an average o/ 25.7 years from onset of exposure whereas the latent period between onset of exposure and death from lung eaneer was 30.7 years. With improvement in industrial conditions, and less exposure to asbestos. Dresden asbestos workers survived long enough to reach the period in which'lungraneer occurred! ULSOTHILIOUV Scattered reports of neoplasms of the mesotheiial surfaces of the pleural and peritoneal cavities in itiociation with asbestosis have been available for over thirty years. Weiss (42) suggested an etiologic relationship in 1953 but such proposals faced the difficulty of in frequency of reported eases and the absence of population and epidemiologic studies. The possibility of a causal relationship was greatly strengthened by the report of Wagner and associates in 1900 [43J of thirty-three eases of diffuse pleural mesothelioma in South Africa, thirty-two of the thirry.three patients having had at least suggestive evidence of potential exposure to asbestos. Other large collections of eases of mesothelioma of the pleura or peritorumm u<oc;tcd withxpo*ur to itbexoi have appeared, including these of MeCiuehey, Wade and Eltnes [J-fJ, Owen (<f5J, Hourihane [J6\, Churg, Rosen and Moolien [47], Webster [4S], Entiekr.ap and Smither [401. This tumor now follows lung cancer as an important cause uf death among asbestos workers. In fifty-six consecutive autopsies of workers in one asbestos factory, nineteen cases of peritonral meso thelioma were found [JPj. In a scries of 325 consecutive deaths (1943 to 1946) among as bestos insulation workers, seventeen were due to mesothelioma of the pleura or peritoneum (SO], an extraordinarily high incidence (ap proximately 5 per cent) for a tumor otherwise so rare; the prevalence in the general population at this -:me has been calculated to be approxi mately 1 in 10,000 deaths (Jf ]. The association of mesothelioma with exposure to asbestos is so striking as to suggest that a history of exposure to asbestos be sought whenever the histologic diajnosit of mesothelioma is made. Once again, there is a striking latency. As with lung cancer, it is unusual to find meso thelioma .iv>oc;ated with asbestos in lrs than twenty years from onset of exposure; generally, the latent period is over thirty years. Alto as vvith lune eaneer. there is no resular correlation between the severin' of asbestosis and the occur rence uf mesothelioma, ar.d many instances occur in subjeca in whom there it little or no roentgenologic evidence of asbestosis. The Dres den experience may be recalled in this connec tion, too. During the period when early deads from cor pulrribaale was common no meso theliomas were seen, but in the later period, when severe asbestosis was no longer as com mon, ;9.4 per cent of all thoracic turners were primary in the pleura. The latent pe.-ied from onset ct exposure in these eases averaged 31.3 years. . OTKtX XEOPLASUS The neoplastic potential of asbestos may not be limited to the lung and mesothelial surface. Other tumors may be related to asbestos ex posure. although the evidence for this is not as well defined at this time [jSJ1 ]. Cancers of the stomach and eolon seem to be significantly in creased among asbestos workers. In two studies in which the initial exposure to asbestos could be dated, the eancen of the stomach and colon occurred after the same long latent period char acteristic of lung cancer and mesothelioma \S1,S2\. rutususi. e.vLasiCATio.v . Scattered instances of calcification of the pleura, chiefly of the parietal pleura, were re ported in the 1930's but their frequency and importance as a roentgenologic sign of asbestos exposure were net appreciated until the report by Jacob and Bohiig [Jo] in 1955 who found such calcification in approximately 5 per cm of 343 Dresden asbestos workers. The signifi cance of this characteristic x-ray finding >a emphasiaed bv Kiviluoto's report in 1960 [//}. Recent studies have not only confirmed the frequency of pleural calcification among work men exposed to asbestos but have also demon strated that this finding too is strongly dependent upon a long latent period from onset of ex posure. As can be seen in Table It, roentgeno- logicaily apparent pleural calcification is rare within twenty years from onset of exposure, ocly five instances having been found among "25 asbestos insulation workers in this categoryOnce the twenty year point is passed, however, visible pleural calcification becomes much mere common and is found in more than half men in whom more than forty years have AMcaiCAN jovtsn or s .**** DUP 0930307 iK ./' " EciionaJ 491 \ T.sli a* PLtU*JU. CJkfcC'lCATlOW *mO*C AitfcITOI IMUXATtOH uoiuil Otwei d *ptmi* ' <vr.) a*;* ' 404- ' -f'shjo-jir '-v.jy 20-21 10-11 0-4 / * >' Na. 121 114 7? 379 J*4 1,117 Per cent Norma* 42.1 Si 4 914 91. 100.0 ' Per cent Calcification 57.9 34.J 10.4 i.i 0.0 txicnt of C*laft&iuon (grade) 123 17 20 13 44 IS 4 100 s 0d 0 0 0. H 3S Sae!. I.:. ll- ' tlpjed since she onset of exposure [5-]. Tliese d should be interpreted in the light of knowi ng* that pleura! ealeifieation of limited extent and radiooensitv is usually not visible in the i-ray film |5). It is likely that parietal pleural changes with hyaline and sumeiiiurs caleified plasties will occur m all asbestos workers, if they jive long enough. raoeacssiox or asbestos disease WITHOUT CONTINUED EXHOSUUE Knowledge concerning the latent period of axbesiot-reiated disease has been derived pri marily from observations of industrially exposed ^population groups, although epidemiologic ruches of random iufiances of such d >, specially mesotheliomas, have gixen similar results 125,4.;]. These and other epidemiologic studies have demonstrated that asIx-Mos-related disease may occur without continued exposure from industrial sources. The explanation for this prerumably is as follows: The asbestos fibers inhaled initially largely remain in place. al though some may be removed in the bronchial secretions for many decades after cessation of exposure and others may gradually be dissolved is body fluids [hJJ; this last possibility has not bees definitively established. As a result, tissue reaction 10 the retained fibers goes on, exen in the science of inhalation of additional amounts. Thus a workman who has been continually exposed to asbestos for, let us say, twenty-five >ears carries within him a composite biological effect. The initial burden of inhaled fillers is usoeiaied with a twenty-fiv- year effect, those inhaled rwenrv years before ore experiencing a twettry-year effect and <o on, the fibers but recently inhaied adding the effect associated with newly deposited material. The ellnieal reruitaat is the summation of all these effecu. vou. 42, if c 11 1947 This analvsis explains the reluctance of many physicians to advise asliestos workers xvith many years of experience but in food health to leave their employment, since their ultimate fate may be determined net by their esirrent exposure but by their exposure many years before. The same situation holds in many eases of minimal silicosis or respiratory disease associated with coal mining. EXPERIMENTAL. STUDIES Reference has already been made to the slowly progressive fibrosis in experimental asbestosil. counterpart of the latency in the human disease. Similar findings are observed in experimental srudies of neoplasia auoeiared with asbestos. Wagner [JdJ produced meso theliomas in rats by a single intrapleural in jection of several x'arieties of asbestos but these tumors did not appear for fifteen to twenty-three months, a considerable portion of the life span of the animal. Smith produced pleural meso theliomas xvith asbestos in the hamster but, again, these did not appear until 244 days after injection [57). Pleural disease has also been found in hamsters following the intratracheal instillation of asbestos but the same requirement of a long latent period has been observed (J5). OUCNOS1S OF ASBESTOS DISEASE It is clear that a painstaking occupational history is essential in those clinical circumstances in which the possibility of asbestos-related dis ease is being considered in differential diagnosia. This is particularly true in instances of (1) interstitial pulmonary fibrosis of undetermined origin. f2) pleural calcification (either unilateral or bilateral), (3) pleural or peritoneal meso thelioma. (4) alveolar-capillary block syndrom* (even in the absence of radtulogically evident DUP 0930308 ..a.. -d-r:?resiife- Ifl^a fger: jarnnam Italian r *92 Editorial weaver in a brake lining Eactury for only four months in 1 *)}$. with no mow-i^urm exposure to xiUimoi. Note that the fibrosis Aral became enurm on rctrmgfnooranw in 1051. interstitial fibrosis), (S) lung cancer and (6) fibrotic pieural plaques (unilaceral or bilateral). Id such cases the recent occupational history is of less interest than the work the patient did twenty, thirty or more years before (Fig. 2). The exposure may have been brief--a matter of a few months or leu--and the occupation not necessarily one ordinarily thought of as related to asbestos. Of the individuals industrially exposed only a minority arc asbestos textile and asbestos products workers. There are, for ex ample, more asbestos insulation workers than asbestos weavers. Over 3.000 uses for asbestos are currently known [J5J, ranging from Silers used in the manufacture of beer to repair Cements for heme furnace*. from re-entry rose cones for our space vehicles to certain valve packings and welding electrodes. The construc tion industry uses a great many materials con taining asbestos; for example, a carpenter may repeatedly saw asbestos building board, a plumber and steanifitter frequently uses asbestos rovings for joints, an electrician is no stranger to asoestos^overed wire and cable. In the ship building industry, asbestos finds many uses and. because of tight quarters and close working conditions, indirect occupational exposure (far example, a welder tr.r.aiing the asbestos d.s: derivrd from an insulator cinse hv) may oe usefully explored in the occupational .vs'.cry sullies* jotsssi or u * 1 e1*_s DUP 0930309 raSrjfrifc i i iim: jnuBzdL Editorial 493 Fic. 3. A projection of the potemiAl incidence of ncopUtin due to Athmet The curve ritmvn m Ktfurc 1 hai brtn u|Mrtmpiw4 i ml rM pMnnii mC A*bti n the rO* nair. Tlic t**o?U*U *Sth {traicr utilisation of abr*to W-ill not be in evidence until the IWi. The shaded areas indione the coo which have become ejmfcn, the umhadrd area* repre* atm potential ejHi Indirect occupational exposure may also be important in the building trades and in many other as vet incompletely investigated oecupat-ons. A complete list of potential direeT~ind indirect occupational exposures to asbestos is manifestly impossible iicrc, but perhaps enough has been said to indicate that a bit of detective work during the occupational history, especially w ith respect to work two, three or four decades before, may be diagnostically rewarding. Although many instances have been recorded, fata are tint available to characterise completely the effect of cessation of exposure from externa] 'eurees, since large groups of asbestos workers '-hose exposure hns been discontinued have not uren observed and compared with others with the same exposure who have continued at their -ork. Such data as are available [5J] would -ejest that both elapsed time since first exsuture and total years of exposure are of itn-srtanee. There are no epidemiologic data, 'i. <1, sstu I17 tueh ds ere available for cigarette smoking 150}, which indicate that cessation of exposure is associated with a subsequent decreased risk of lung cancer. Smoking data, moreover, should not necessarily be transposed to asbestos ex posure, in view of the retention of inhaled asbestos libers which has no clear counterpart in the cigarette problem. Definitive diagnosis of asbestos disease de pends upon the finding of asbestos, either in the form of asbestos fibers or asbestos bodies in effected tissues. However, their discovery in routine postmortem studies is simply evidence that ml jamr tsimr aibe-tos fibers have been inhaled, without indicating when such inhalation oc curred. The connotation would be different in each cae since, at we have seen, disease could be anticipated only a< a result of inhala tion that had occurred a considerable lime before. Therefore, we should perhaps take little comfort from the circumstance that, in most DUP 0930310 iJ- T-V. . ... a.? * rT instances, neither pulmonary fibtuMi uur neo plasia it associated with trie a.Miotus currently being found postmortem. . It is likciv that most asbcstui hum being dis covered postmortem in persons hu have not been industrially exposed has been of recent deposition. The basu for this assertion lies in the economic data concerning asbestos. Until 1370 asbestos was an exotic raritv. The unusual qualities of these mineral fibers--fireproof, waterproof, wear- and cheniical-icsistant--were soon found to have important uses in our rapidly expanding industrial civilization, and almost each year saw a rapid iticiv.ue in the world production of this mineral. Frum 50 tons per year ninety years ago, wot Id production haa now reached almost *.000,000 tons per year. Aj Ciiion has pointed out [o'/j, asbtot can truly be called the twentieth century mineral, since its output has increased over a thousand fold in sixty years compared with a mere fifnfold for oil. ah industry often regarded as the symbol of industrial growth. The asbestos brought to the uuface of the earth increases year by sear, and the total is a cumulative one. As has been aptly taid [f J the fiber has -'a h-ilt life of infinity" so that each year's production adds to the cumulative total of all that has been produced before. The frequency, nature and otent of disease due to asbestos is a matter fut rutjiie ubservatiun. A graphic picture of this puicuti-il problem is given in Figure 3 in which the curve of the latent period of cancer of the lunar and pleura is superimpcscc upon the production ircurdi ofasbestos. The net'plasms now eneoumenxl associated both with industry and environment .ire consequent upon inhalation of asbestos .i.vswjira with the limited asbestos production of some- thirty vears ago. The neoplasms irsucutted with current utilisation and exposure to asbestos will not be evident until the 1990's. Vet to be resolved-aie such important questions as whether different kinds of fibers exert the same biological erfectv the namre of the dose-disease relationship, sources and extent of environmental eomaiuituviuit. the range of industrial exposure (iiudix]iiately docu mented at this time), the ranee of neoplastic effects of asbestos expourc. i:itulardization of roentgenologic and physiologic .-imiies, and even whether asbestos bodies uutv not ometimes be the resuit of inhalation of mineral fibers ocher than asbestos [62J. In our own laboratory, data are ieeiimuiatii.g to suegest an impnrr-r;; eo-earc.noccnie effect of cigarette smnvi.-.r asbestss workers (do) pouibiy.due to sesortsticr. ofcarcinogenic substances onto the asbestos fiber, but possibly siso due to hiitciogtc or other changes induced in the affected lung. CONCLCOLVC XZUAKKS Asbestos is a most valuable material, essential in our industrial sociery. We recognize and study its dangers so'that we may devise means of minimizing or avoiding them. Diligent, isgenious and often expensive improvements in industrial hygiene practice (fi-J j may help to eliminate heavy or unnecessary exposure. A wart ness of the potential risks of environmental contamination is also necessary at this time, at least until the future tells us whether Thom son's assumption is right or wrong. Ixvinc J. Szuuorr, u.o. Richaxo A. E*otx, u.o. Mo*TIMS* . Baoix, m.d. Jacos Ckuxc, u.o. end E- Cuvulx Hammond, tc.s. Dtpe'tnenu o/ Medicine end Cenmanil, Medicine The Meant Sinai Pleepitsi end tht Meant Sinai School ej Medicine iVstu i'erk, -Vrte lore xerexttsets ), 3- C-* KaaCMUUs, R. O- C. ino NUC> Oo**L0, R. R, fWxtiet ns a mouvrn weba* hazard. $0*iM .i/r/cea AS. J,, 37: 77, 1 '->63 2. C-acna, Om Tom*, R. S. and Gauss. I*. Ashrstfea bodies ift human lungs at .*utOps*. 105; 371, VM. 3. ClmMo t. C, McCavchov, W. T. . and Wage* O. L. DtiTna* mnuheiiufTM of (he p.cura and aihmot. $fit. At, J.% i'. 35C. 1763. 4. Tuum>om, 3. C. and \V. M. Asoetco* as zo urban air cnituvimnant. A*tA. PmA., l: 454, 1944. 5. MtwauA.N. L. Asbntoi bodies an* picural plaques in a FinnUh win wf autopsy easev .4,t* p*t*. u mHtmAiai. lit (ittpp.): 1, 1764. 4. Houhjkasi. D. O. B,, Lessor, L. an* RitHAaosox, B. C Hyalin an* catafied pleural plaques u an index of capture to astmioe. A study rad^ logical and pacholcfteal features oC 100 e:ia uh a consideration of epidemiology. Brit. At. J...U 1069. 1966. 7. Editorial, Asbrstosit and maltfnant disease. t*ihW J, A/^ 272: 590. 1965. I. Editorial. Health hazards of ubnios. U*, 1: 530, 1966. 9. Editorial. .Ubeumis in urban populadons. 196: 732. 1964. 10. MeatwiTWx*. E. R. A. A memorandum on abo tcs.w TwirtU, IS; 49, 109, 152. 1933-1934. It. Scuacrr, t. 3., Ckvxs, J. -isd Haiio.,*o, E. C. *V AStCttCAX jOUISil Of MiSIClf' DUP 0930311 - Editorial 4"S \ t otrurrenet o( uboioui insuuwon *orki * ia the Ctuted Suio. j*. Va 1V gfcak. &,, 122: 129, 1914. . * Dou* ft- Morufiiy lung canetr m ubwoi fitrt. Jo/, y. ltduK. 12: ll 1944* U. Sckaorr, I. J- Otvie. J. tad Hamuono, . C Asbstos mpoum od scepJaMft* til: 22,1944. 1C Kivskuer, ft. Hcvrai ftilfiifiefttiea at t roerugwio- Jape sign of non <gcup*uocnl endemic *mh phvUitc--udviMb An* tsdimL, 194 (tupp,): 1, 1940. IS. L*am*k(k. A.. Noao, X. and Raukiq, V. Obi-v*- uot op simospheeio air pollution uumO by uootQL Wa- AVu* I'mi MU. St-. 122: 2<0, 194$. 14. HvtrtK W. C Occupational and nonoceupational esoesura to atbetoa. Am. An* Ymk Ami. J*, 122: 144, 1944. 17, H*ooowt a. C In: Report of annuo! meeting of British Medical Aifooauoo. Mcndic*\ 1929. Umti. 2: 220,1929. 15. \V*cub F., M0kv*m H. cud Anipacu, M. Cibt m cine cndemitcho Atbaietc? Zitt4r. gtt. htg.. 4:244. 1962. 19. tcs. ft C and W**ecf Q. L. RcJctkimliip between c\pour to itMtot end pleural nviltjAsney in Atm. AVif Yik AtU. St.. 132: $49, 1964. 20. KruHOUtl. M. L. Ifd ?MOMPtcx. 1<1. Mcvoiftcftoraa * of pJeurc and peritoneum folios ing tVpetur* to otbeftet in the London area. Mrtt. J. iMwtt. Altd,, 22: 261. 1964. 21. Cooks. W, . Pulmonary o'bcstoww **t. .If. 2: 1024, 1927. \22. Datutcx. IV. C. Dau^vauJL. J. XI.. du`**m, T. X., 2. IV., . H. F. **vA Ties, XL T. A Study of A*bo* m ti>e Atbruoe Tex- tile Industry* Public Health Bulletin No. 241. Washington. D. C. 1921. U. S. Government * Prinuof OlReo. 22. Aukto*ukT, Xf. Note >ur 1'hvftcne tt la feunt4 dm ouvnen dans la AUrura mu;n d*amiama. Sid/, Ctmptt. 7Vr., 126. 1904. 74. Caovxc. S. ft. The morbid anatomy and hittology of Ai0aie*h. Tomtit, 14: 4*4, 493, 540, 1933. 25. Govcm, i. Differential dlagnmi* in die pathology of i^otoiia Am. .Viu }'< AtU. Si.. 122: 364, ' 1964. 74. CaabvtK. i_ V. and Cummings. V. , Studios on experimental pneumaermimm. vi, Inhalation of bc*;o dun: effects upon primary tub^cuious infection. J. Musi. Hyg.. 13; 97, 1931. Z7. Wc.vca, J. & A<bUKU in expert mental animak. Bn:. J. JUusi. AW., 20: 1. 1943. 21. ftowue. H,, Jacoi, C. and MCilxk. H. Die AsImm tote dr Lungen. C<nme. Kiintk. ftCmgcnolOf. Stuttgart, 1940. Crorg Thitme. 21. hfCn.Lt&, H. Cber tehwert Pormen der Asboooac la; Die Staublungcnerkrankunecn, ol. 3, p. 441. Edited bv JOttcn, K. W. and Klnuribte, W. Dvinuabt, 19SS. SieankopC 20. Ba:<ca, M. ,, DaOCB, ft. A. and ScLiaorr, 1. J. Pulmcnars- function in a^botmii of thc lung; an aitecMAr^pilUf^ block svndrofne. Am. 20: 235. 1961. Baoca. M. ., Baocx, ft. A., TLiatixtN, a. S. and Saukorr, 1. J. Pulmonary function in atboteon; (*U. <2, apiu 1147 icrtal mu in a long*crm ptotpectite udy .Ina. A*o Vma .stad. Si., 132: 391, 294i. 32. Hunt, ft. Routine lung funeuoa studies on 130 employees ia aa asbauos proesung factory. Am, A'no )V/. AtU. St.. 132: 06. 1945. 33. Hoaxs. Tivpmoto* T-, Uumima. M.. Hica- smuoam'a, M- 5ano, >L Ucda, J.. NAiUTAMi, H. ane tq. H. 5tudii oo nbc^wu. v. Applica tion of needle biopey of the lunge fnr the dtagnosu of aibcuruL J. A'ar# if. Am 11: 719. I960. 34. Lyncm. K.. M. and Sum, W. A. Pulmonary asbo^ tests, in. Carcinoma of the King in aabmtpMilkocifc Am. J. Ctmtr, 24: 44, 1934. 34. Annual Report of she Chief Inspector of Tactoris tor the ytir !9<7, p. 79. Lond.fc J9*9. M.jaty't Smuocmtt Office it. Annu.l R.rvart ( in. Qutf lnptttor at Fwiii. tar Ult Vur IJ5S. p. 206. Umdo., 19S*. Her M.jmr'l Snu.nenr O/Rec. J7. 2ikha*.*, W. O. AsbiMeuc and primary intra. tharacic nc.pl.tmi Am. .Vi* ) .i Aiit. St.. 1A2: 507, 1945, St. Stuaorr, I. 3* Cnu.o, J. and H.unovo, . C Relation hetwRit npotnrt to ailiaio. and mow ihclioma. AVni Exi.t.md J. Mti.. 272: SO0, 1945. 19. McYrmi, }. C Di^ua'i.n. A... .Vr IM At.4. St^ 122: 112. 1945. 40. Iomuo, H. and 3teat, C. Nruc CoichupunLie uber den Lun{enLrcbt do Aibcuarbeitcr. JitutitAi Mti. KVtauhr^ (1: 251, 1954. 41. J.coa, C. and Animat, hf. Pulmonary neoplasia anionf Ornden aabena .ori.cn. Arat. A*nv 1V4 At.*. St., 132: 5 3d. 1945. 42. Went, A. Plrurakrcbt bet Lun,enabeMOR. in vivo imyhui^neh ttwhrrt. AWiawnti, p. 93. 19S3. aj. W.OKca. J. C~ Six.nt, C. A. and M..O..VO, P. Dtffuw pleural iimnihrlioma and atbertot expw Hire in N'nrth Weuern Cape Province. Aril. J. Wui. Afrg.. 17: 260. 1940. 44. McCausmcv. W. T. E-, iv.ot, O. I_ and Elhci. T. c Cxpmure to atbeatet dust and diffuve pleural me*mheliomaa. Correspondence. Am. M. -C, 2: 1937. 1962. 45. Oms, W. C. Diffuse mnothelioma and exposure to sabaatM duu in the crvcvlide area. Bnt. At. J., 2: 214. 1964. 46. t?otniKxe. D. O. B. The pathology of mp> thcliomata and an analysts of t!ie a'toeiauon mth nbwot espaure. 7haeax, 19: 261, 1964. 47. Chukc, J., Rotes. S. H. and Mooltt*. S. Histw lofical eharactcriniei of mesothelioma aitneialed with aUtotoL Am. A'nn IVI At--t. St., 132: 614, - mj' e a 45. Wtaina, J. Mootheiwmatoui tumors in south Africa. Pathology' "d esperimtntal pathology. 4aa. .Yeui J are Atai. St., 132: 623, 1965. 49. Esnca.var, 3. S. and Emitwcs. \v. J. Peritoneal tumors In atbestotia. Snt. J. Itdutt. 13ft^ 21: 20, 1944. 50. Caivee. 3. and Rcuaorr, 1. J. Ceoeraphie patholo^ of me'OlhcLii.m* of the lung. In prcM. 51. Hawuovo. E. C. Seuaorr. 1. J. and Cxime, J. Veoplatia amonj imulaiion workers in the United States with tpceial reference t. tmra.aho'ominal r.eoplatma. .tan. Art. lari At.t St., 132: 319 1963. DUP 0930312 496 Eduorial 52. Nl vNCwft. T. F. Oiacu^MOA* .4*e. ,\Viv )Vi .Usd. St- 132. 5'JO. 1904. 53. Jacob. G. and Bonus. frL KocMtftr*uloh;al com* piirniont in pulmonary auntwt. Fsnieir. 0*i. /liMtnutmki**. 53: 515, 1935. 54. StUfcOrr, 1. J. The occurrence of pleural cnktfca* non amtmf asbcMM imvauon kcrs. Asa. .Vt 132: 351. 1704. 55. Nccucmuipt. G Some observations of the dust content And composition in tunes *tth ,'ubewOMft. Asm. Xtw >V< .Usd. St., 132: 04. 1944. 54. Was***. J. C. Experimental production of mco> thefui rumour* uf the pieura by wnpiaatauon of dusta in laboratory aninwU. Xstart, 190; 150. 1902. 5?. Shit*. W. E.. Miiu. U* Cutrnc. J. and Stunorr, I. J. Mesotheliomas itt hauwen following intro* pleural ia}*>ctteft uf aibestoi. J. Alt. Situt H*tp 12: U 1963. 51. Suit*. \V. .`Unpublished data. 59. Retsro. V. Juhesti*. Its Industrial AppiieanufU. p! 4?S. Now York. IVS9. Knnnohd Publisftm* Co. 00. Hauusso. E. C. Evidence on the effects of ctvirtf tip etr.vettc smoking. Am. J. A*. 53: 312, IHS/ 01. CtLso*. X. C Mas and asbestos. As*. AW JW Atud.*, 132; 9. 1905. 42. Report and Mooimntadatsons of the worLinf f*og- on asbestos and cancer. In; biological E5rca ef Ashestok da*. AW J>* Attd. St- 132; 700.1903. 43. Stukorr, X. Sn Ha*so*, E. C and Cuvoe, J. L*npublkW_daca. 04. Hflia. O. W. Economics of dust control. dm. .Vex Vsti .Usd. Su, 132: 3r, 1905. ; amuiui ;oui.iu or itaoict* DUP 0930313