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Reprinted from the Archives of Environmental Health 'i. Co C 186 August 1969, Volume 19 Copyright 1969, American Medical Association f r. r 63V j -j -J C/ Pulmonary Ferruginous Bodies in City Dwellers PLAINTIFF'S EXHIBIT c c o A Study of Their Central Fiber Paul Gross, MD; Robert T. P. deTreville, MD, D Sc; and Martin N. Haller, Pittsburgh ChrysofNe, which emprises more than Mtt of tho wtirtoa mod hi Wo country, hao chsmderMie glcclren dWhocMon poMorn tiewn of Ho scan undtr tho electron microscops. On the basis of Uw alacfron dWracflon psttsov chryaoIHe was decisively exduded as a conathuawf of tho cons of sil 2S farruginous bodtes Isolated TIMS CXCWHOn M GOlWQIfN because If the forrugbious bodlaa In Iho above- COy dWVMIV nN DM CHMQ By M MMDOII OT asbostoa duals, than aonw of tho corse should logically bo compsssd of chrysolite. It has recently been suggested that the prevalence of ferruginous ("asbestosjj bodies in the lungs of city dwellers not occupationally exposed to asbestos was largely dependent upon the method and diligence employed in searching for the ferruginous bodies.1 The reported prevalence of the positive cases was represented to range from 30% to 70% of the hospital deaths investigated; whereas, by digesting some of the lung tissue, a 97% prevalence of lungs positive for ferrugi nous bodies was found among randomly selected autopsied hospital patients in Pitts burgh.1 Ferruginous bodies, which are indistin guishable from those produced by asbestos dust, were recently demonstrated in lungs of hamsters injected intratracheally with Submitted for publication Feb 29, 1969; accepted March 17. From the Industrial Hygiene Foundation of Amer ica, Inc (Dra. Grose and deTreville), and the Mellon Institute (Mr. Haller), Pittsburgh. Reprint requests to Industrial Hygiene Foundation of America, Inc., 5231 Centre Ave, Pittsburgh 15232 (Dr. dSTtoville). Arch Environ Health--Vol 19, Aug 1969 187 S T00I1578 fibrous dusts other than those of asbestos.2 In view of this demonstration, it would seem proper to ask whether the "asbestos" bodies found in city dwellers have been evoked by the inhalation of asbestos dust or the inhalation of fibrous dust of other compositions.1 Based on the assumption that there is a substantial contamination of urban air by asbestos dust, it has been suggested that the source of such dust is from the brake lining of automobiles, the weathering of asbestos cement products (shingles and tiles), as well as from insulation used in the building construction industry.4 Inasmuch as 90% or more of the asbestos used in the United States is chrysotile,5 and since very little of other types of asbestos is used in the above-named products, the major compo nent of the asbestos dust that is assumed to contaminate urban air would logically be chrysotile. Since there are no grounds for believing that asbestos bodies develop with greater difficulty around chrysotile fibers than around the fibers of other types of asbestos that may be inhaled, it would be reasonable to expect the vast majority of ferruginous bodies in the lungs of nonoccupationally exposed city people to have a central core of chrysotile--if the ferrugi nous bodies are indeed asbestos bodies. Inasmuch as chrysotile fibers appear to be hollow in the electron microscope,* these may sometimes be identified by inspection. Furthermore, because of its hollow struc ture, chrysotile has a unique and readily identifiable diffraction pattern.7 Because chrysotile lends itself so readily to positive identification by electron microscopy, we undertook a study of the central cores of ferruginous bodies derived from lungs of people of Pittsburgh not occupationally ex posed to asbestos. We are here reporting the results of our study. Methods and Materials Ferruginous bodies isolated from the lungs of 28 people1 were placed upon electron micro scope grids by means of a raicromanipulator. In the electron microscope, it became necessary to find a suitable fiber area on the ferruginous body that was free of electron-opaque encrusta tion (possibly ferritin) which would have inter fered with the study of the core. Work with "standard" samples of chrysotile, amoeite, and croddolite showed that useful diffraction pat terns could be obtained from fiber areas as small as 500 x 500 Angstrom, and as large as 5,000 X 5,000 A. All bodies examined had fiber areas suitable for such study. The bodies had to be manipulated in such a way as cn yield their characteristic electron diffraction patterns, so that measurements of interplanar crystal lattice spacings could be made. Typical "layer line" diffraction patterns are obtained if the fiber axis is perpendicular to the electron beam. Ferruginous bodies isolated from the lungs of hamsters killed 12 months after an intratra cheal injection of 25 mg of brake-drum dust (iron-free) were similarly placed upon electron microscope grids, and electron diffraction pat terns were obtained of the central filaments. Results None of the cores of the 28 ferruginous bodies showed the hollow, tubular structure characteristic of chrysotile. Measurements of the diffraction patterns obtained (to an accuracy of 1%) on each of the cores of these bodies from human lungs showed that none of the fibers examined were identifiable as one of the three forms of asbestos cited above. In particular, chrysotile could be excluded as being involved in the formation Arch Environ Health--Vol 19, Aug 1969 188 PULMONARY FERRUGINOUS BODIES--GROSS ET AL of the ferruginous bodies. On the other hand, the central filament of the ferruginous bodies isolated from hamster lungs injected with brake-drum dust yielded electron dif fraction patterns characteristic of chrysotile. Comment Although we have failed to identify the fibers that caused the population of ferrugi nous bodies in people not occupationally exposed to asbestos, we have decisively ex cluded chrysotile. This exclusion is highly significant in view of the fact that if asbes tos dust were the contaminant in urban air responsible for the formation of these bodies, chrysotile would be the mo6t promi nent constituent of the cores and should be identifiable in some of the ferruginous bodies recovered from the lungs of these people, particularly since we have demon strated that the cores of ferruginous bodies resulting from intratracheal injections of brake-drum dust were composed of chrysotile. From the fact that the central fibers of the ferruginous bodies examined demon strate an electron diffraction pattern, it must be concluded that the fiber is crystal line, but identification must await further electron diffraction information and possi bly electron microprobe measurements. Its crystalline diffraction pattern effectively rules out fibrous glass, glass wool, and other vitreous materials in this sample which have been shown experimentally to be capa ble of producing ferruginous bodies.* A recent analysis, utilizing an electron microscope, of Use central fiber of asbestos bodies removed from lungs of people who had worked in a Flushing (Netherlands) shipyard, led to the conclusion that these cores were composed of amphibole asbestos.* This might have been expected since crocidolite and amosite have long been the predominant types of asbestos used in the shipbuilding industry. However, the relevance, if any, of this finding to the ferruginous bodies found in the lungs of urban dwellers, not occupationally exposed to asbestos, would appear to be doubtful. This investigation was supported in put by Public Health Service research grant PH86-68-166, National Center far Urban and Industrial Health, and grant FR 05580 from the National Institute of Health. Michael D. Utidjian. MD. Department of Epide miology, University of Pittsburgh Graduate School of Public Health, isolated the ferruginous bodies and transferred them to electron microscope grids. References 1. Utidjian, M.D.; Gross, P.; and deTreville, R.T.P.: Ferruginous Bodies in Human Lungs: Prev alence at Random Autopsies, Arch Environ Health 17:327-333 (Sept) 1968. 2. Gross, P., et al: Pulmonary Ferruginous Bodies: Development in Response to Filamentous Dusts and a Method of Isolation and Concentration, Arch Path 85:539-546 (May) 1968. 3. Cralley, L.J., et al: Source and Identification of Respirable Fibers, AIHA J 29:129-135 (May-April) 1968. 4. Thomson, J.G., et al: Asbestos as Modem Urban Hazards, S Ajr Med J 37:77-81. 1963. 5. Rosato, D.V.: Asbestos: Itt Industrial Applica tions, New York: Reinhold Publishing Carp., 1959, P 4. 6. Rice, R.V.; Maser, M.; and Klug, H-P : Chryso tile Morphology, Amer Min 45:680-688, 1980. 7. Zuasman, J., and Brindley, G.W.: Electron Diffraction Studies of Serpentine Minerals, Amer Min 42:133-153, 1957. 8. Gaenaler, E.A^ and Addington, W.W.: Current Concepts: Asbestos or Ferruginous Bodies, New Eng J Med 287:488-492 (Feb 27) 1969. 9. Stumphius, J., and Mayer, P.B.: Asbestos Bodies and Mesothelioma, Ann Occup Hyg 11:283293 (Oct) 1968. STOOI I 579 Arch Environ Health--Vol 19, Aug 1969 Printed end Published in the United States ol Amencs - c\0 - < -xsri X.\* /' ^ C??A (as Stersulla fcetida oil) together vis- i pc's as'Iatoxin 3- is: 5 ucr.ths inn sr those sad s-uechyiccunsrin (50 pod), gossypoi (250 sc: sr pol;Tsrlzad vegetable oil (0.5.^) dr* addition so aflatoxir. moreover, cutouts isveloped earlier and liver carafe -as acre severe. --~--i -----------*,- value of processed sate 1" there is she problar os' the r. -trstioml value os' processed :ts. we have already reported (333d. vi. `365, 2j '23), tisare ' = r.o evsisr.se shat she partial hydrogenation os vegetable oils in the mnusuoture os' --------e and shortenings has ary harrs'ul nutritional es's'asss, although this leads to the ;ora:icr. os' srall anounxs of srar.s scorers os' polyunsaturated FA, ard decreases sonaveat the content of Fucrcgiycerides, produced by the xrarsesterificaxion os' triglycerides with mortis, are also innocuous except after prolonged ingestion os i.rge arourts .ibid `9c6, i52). Sven when sueroglycerides (lard-sucrose rucrorlyoersde assi pair oil-xylitol xyloglyceride) were s'ed to rats (for 200 ar.d '00 days, respectively) at dietary levels as high as 25Jj, liver ar.i oersr lipid concentrations were unaltered (luddsoo, Arzr.einuxxel- wtrsch. 're", ;50). Aid apart s'rcr slight unspecific changes in the iiver. attributable to the high fat content of the diet, r.o other organ Incerescerificacicr. of fats has also been introduced usthir the last few years so produce solid fats with a high lircieic acid content. In this process, ren-hydrogenated vegetable oils are razed with snail arour.ts of highly hydrogenated fats and then irteresterissed, in the presence os' a catalyst, to rearrange the FA radicals or. the triglycerido roleoule. Measurerents of digestibility, the biological activity of the contained liroleio acid, tissue cholesterol levels, growt.t, reproduction and longevity, together with histological exariration os' various tissues, show that these irteresterisied fats (S2.5b urrydrogerated ar.d :7.5b fully hydrogenated cottonseed oil) have no deleterious es's'ects when s'ed to rats at a dietary level of (Als'in-Slater et al. J. An. Oil Chen. Hoc. '?, Vj ''0; nutrition Reviews '556, 2i 20'). And their nutritive value is at least as good as that of unhydrogenated cottonseed oil and other edible fats with e-i--- contents of essential FA. O c c J UU id??::: a ?o a 2 : ? s v; i rAssisros ?hs widespread use of asbestos has ragnifiei its occupational and environner.tal hazard to health, the risk, formerly confined to workers engaged in sts nsnufacrure, now extends to those involved in its nary ir.dustrsal applications and to a leoser extent to the public at large (232A cull. :566, 2., 26). Asbestcsis, the lung s'ibrcsss caused by inhalation os' asbestos particles, has been recognized s'or 10 yr. A nore sinister remit of asbestos exposure, waich has cone to Light in the last sew years, is the cevelotnent os' resotbeiial cutouts os' the pleura and tersttr.eun. ?his sudden discovery called for an irradiate assessnent of the zagruTude of the hazard and although several questions still renal.-, unanswered, neasura'sle progress has been achieved. :77 o t"' card chrysotile (white asbestos), crccidclize (blue asbestos;, nmcsiza, irtuczryllize, translate and aotinslite. Cirysotalo accounts for S2^S of zhs GZ market, arosize lyjj and crocidoliza 5;G. According zo a GZ ,:. ivi a a-- Pans! ("Problems Arising ircm zhs Gca of Asbestos: Zamcrardur a:' 'ha Senior Medical Inspector's Advisory Panel.'1 ZI Paczcry Imszectoraze. Z430, Ionian, '567), eoidamiclogical evidence zoimzs to crocidolize as The form mainly responsible bar the carcinegsnic hazard. ~rami experiments ircacsto trap other terms oi asbestos ara___ carcinogenic. Arosite and crocidolita buz not chrysotile v/era found zo produoa cancer in razs when injected subcuzaaaously (2oe at al. P.ap. 3r. Zap. Cancer Canpn `556, no.44, Part II, p.7), but a posiziva result with inhaled chrysotile was achieved in rats by Gross st al. (Archs envir. Zlth 1567, ^2, 345). Chase three donas and anzhophyilitc have each produced erperimerpal asbestosis in gudnaa-oir3 (Holt az nl. j, Pazh. 2acr. ijoo, 5?~ lop), but sdcce_zhe relevance of asbestosis in tie aetiology of duns tumours is still obscure, this experimemt throws no light cn the carcinogenic pctanzdal of tha four loans. As discussed by loaribame & McCaugbey (post-grad. ned. J. 1565, 42, cl 5), ns-chandcal as veil ss or.eau.cal factors contrdbuta to zhe production cf fibrosis and nay be involved in zhe carcinogenia process, and tha possible p-~--r.- r.azior. of contaminants, e.g. oils, iron, nickel and chromium, cannot be excluded. Cir.zrzi of use oa asoeszos Various authors have emphasized the aravitv nf the asbestos ha-a-d and the need for stringent controls (Gould, few Sciar.t. 1967. 35. 455; Gcnpar. Arsis sstts. 51taM96T,~.'2,~ 235; lancet ',957, i, 1511; Zritish ,'sdical Journal 1357, 62). Gould (loc.eiz.) puts the prehlea in perspective by pointing out that a total of only 530 cases of mesothelioma has so far been reported Throughout zhe world compared with 25, GOO oacas cf lung cancer diagnosed each year in zha GZ alone. Zhe lancaz (loc.clt.) welccnas zha 1967 draft UZ regulations, which will eventually supersede Those cf 193', out hopes that certain deficiencies will ba overcome before the draft beconas law. Tor example, zo e-rclrds ccmplezely zha amission cf asbeszos dust from tha workshop is mot a practical propcsizicn and instead a tvgi ~:r allowable concentration should be imposed. Gmless legislation us enforceable it tends to be neglected, arguas tha lancet ( loo. pit.). Aeanwaile, as has been mentioned earlier (31321 null. 1967, i7i/, zhe GZ Advisory Panel (icc.cit.) racomends the substitution of crociiclite by other foes of asbestos wherever possible. Czcuzazional ar.d environmental ertosura z has now bacoma establishsd that asbestc3 is am important atmesc corzssumart. Zore curious is the fact that asbestos firms its way beer ami other drinks as a result of its presence m pads'Usea for ozior. \iTZe'd A iuoersci, Zatura, Lend. `-563, 219. 95). Ore pint of yields about 5300 asbestos fibres but their size is sruch that all laid end zo end are estimated to measure lass than. 0.1 in. Zo court environmental sources have yet to be discovered, but the important ion to be answered is what level of erzosura constitutes a hmmasd. asaoumy has i-.n cade an resolving this problem. Asbestos particles capo, it themselves in the lungs and after a process of phagocytosis are near Glasgow, 2J r.or.e were found i 1567, 2C_, 57C). was observed it a women (54p) showi J. 1956, ii, 1 `75 occurrence of asb asbestos bodies i Zha forma zhe davelopsez asbestosis or hazard in its Lf -- t-- asseszosas, ,4 . 619). Sorcv e c-- increase in ti --1 of zhe daversi -- -- a<?r.T)* tn 1 a lisben a Piste q of nescthelion __ and heme ccrza. exposure was quest exposura could he claims that in its contrary, there he in the absence of needed to ensure z removed by recent 2ased on a sz ever 21,COO asbesz Znzerline a Zer.dri increased mortaliz wa.3 due partly to workers shoved a 3 nznn csscn rs.es zr (irzr. 5'^tt zr.cziar.C3 ci Izn^ -iizheu^h bote. this che nasxrc-inzesci Par, el (lee.cIt. ) i (Invir. has. :5c7, izccor in ovarian early scales oi hr: however, only the . Isbestos verb exsniracions. Icy or. ics early oro&ressicn ci che a-cions in verhers t aSbSS vOS ~ - ^1 *. transferred into asbestos bodies. Tasso ssis.es are to is feurd sots -a vomers occupationally exposed to asiostos sr.s _a ptopic laving da -noun rsjscas. la ".CO consecutive hospital autopsies os' .stools 1-vanj asar Glasgow, 2; os' tic cases cxiubitoi asiostcs bodies sat, surprisingly, asaa ware found da assy si sis carts, , G___T.. he dtlssttds da ".o: . differ'cn: zir.'zzzzzcn aatctsy, 52 sen \ j worer (34;'} shoving asbestos bodies (irgilvel - Tat rileck, ZZZL. -nd. 13S 'iso, 22., '.'79). Neither study pointed to ssioa iesveea t.te oi asbestos bodies sad sal: -nancy bat a airier prevalence os asbestos bodies is usually icuni ir. cases oi nesosielucra. S IU U I Ib b d Hie forsssion oi asbestos bodies is part si the process leading to tha develcprent oi asbestosis. '..hasher lung caacer is a coatlicatisa ci asbestosis or is produced ia the absence oi this condition, thus being a as sard ia its cvn right, has still to be decided. In 63 venders vush asbestosis, *5 presented lusts cancer (Theban, irons ecvir. Zita '.566, ~ 5. 6:5). Isrcv et al. (j. .In. nad. ios. -557, IT'., 53?) consider taat the increase an the iasidence oi aesotaeiiona and. asbestosi3 is a reilectiGH ci the iiversss'ication in asbestos usage and report that si 'T7 cases oi nesstaslisra e~.atr.ei, tvo had as lists--ci sssutatesaal ettsccure. tvir. ~sh `567, ^ 555; doc- 12 cas=s Oocupaticaal exposure ac .j oi these. er.sa_ exposure an tae vacana ty os an assestss p^astt tor asti hone contact vith asbestos '-.-criers ior three. Oi the rest, exposure '..-as cucstiorabla but probable ir. ton oases, but ao history os eats rare could be o'staaaed in oases. The TZ diva scry Pastel (itc. cit.) clalns that in its experience and despite tsrtativs evidostsa to tha contrary, there has bean no excess oi lung cancer axeng asbestos workers in the abseres oi densnstrasle asbestosis. Prospective studies are needed to ensure that the hazard oi excess sre renoved by recent dnprovereats in factory conditicns. cased cn a study oi nsrtaldty data covering a "o.p-ytr period cn ever 2*. ,CCC asbestos workers and over 6CC0 workers act exposed to asbestos, Thtterliae U lendriok (ircks er.vir. Zita "967, 'o':) found that the increased nortality rate (2~.fj above renal) in heavily e:.-posed '..-erhers was due partly to cancer of the respiratory syszen. less aeavily exposed vs--:ers shoved a slightly raised daath rate iron r:-_parasory earner and a high death rate iron asbestosis. In another nortality study by ZTi.efrfeld_ et al. (ibid '567, 15. '77) on da asbestos-snrulator ..orxors, she aaoacer.se of long earner -.as rara tines that auor.g average CI catizeno. ^Ithougn both these studies showed an increased incidence of cancer of the gastro-intestinal tract arong asbastos workers, the CX iivisory Panel (isc.cut.) is sceptical about such claim. Trahan h Grain (Znvir. P.es. '.567, '.'.5) suggest that asbestos nay be an aazioIogicaJ. factor in ovarian cancer, isbestos-irduced change0 in the guinsa-pig and rabbit ovary were histologically sir, liar to those occurring in tha early stages of '.turar. ovarian cancer. Cn the avariable evidonse, however, cri.7 tae lungs can be caned as a confined site of nalignacoy. isbestes vorhers are obviously advised to undergo routine neiical er.-.ratloaa. icy inprovenent in the prognosis cf -cbc-szcsis rust depend :r ats early odagnosis so that no further exposure contributes to the progression of the disease. Zernedy i Zoutlecge (or. J. ird. Zed. 1957, II. 2;2) carried cut clinical, radiological and lung-function onvestigataans _n vorhers exposed to different atncspheric concentrations of asbestos. Zigh-level exposure in tvo vomers produced ninor radiological choreas ar.d a's-.-it--1 pulconary function. Only two cf ton lass eccposed a ra auction ir. ir.opiiuaory capacity vaas fount as be the n-ca oono.aive -r-ioaaor of early aobosaosis. Apart fron alia ncoi for an early ware_crg cystor for asbesaosis, ia is essential that universal agrc-erena 13 reached an aba clinical, physiological ana -- nlolcyiaai criteria asa a. a'ar oaagrosir.g abas disease. Ca.aerwiss, aha full value oa' aha ep-ieracicgioai saudics currently being -deraahen will r.ca be realized. .'.abaaaas badass In cases of resoaheliora and asbesaosds, asbesaos bodies are ao be found ir. abundance in lung tissue. Other a'ibroas aaterials when inhaled ac-- ainilar bodies in aha lungs and ia is irportant that in'*rspcraing ana presence of asbestos bodies, positive identification of asbesaos should be race (Lewinsohr., 3r. ned. I. '-S63, 2_, "20; Gross ea al. ia. ini. Zyg. Ass. S. '967, 1Z, 54'; ievrevalla, J. la. cad. iss. 'JoS, '".12). Investigators should r.oa rely cr. ccrpholcgical diagnosis ale..a ar.i unless asbesaos fibres car, be deccnsaraaed ahe bodies snculd re called "farruginous bodies". Asbesaos can be detecaed in biological notarial by a neared involving ularcsonas aroints--aaior. followed by enannuaian of heaa resisaanca, wader iasoluiiliay ar.d optical pro perties (reacscic, Lar.cea 1568, i_, V.55). aha forraalor. of asbesaos :: a_cc an guinea-tigs' lungs has been saudiei by Zola A Young (Z. ?aah. a_oa. '957, 21, 9) and *7 Eavis (3r. J. exp. Path. iSS7, 8, 579). It appears a:aa ahe asbesaos fibres are swallowed up by ahe caorcpiaages ao farr. shagesores. Cytoplasmic proaeins are adsorbed inao ahe asbosaos fibre resulaing in a oonaraoaion of ahe phagosoce ao fore residual asbestos bodies having a beaded or corrugated sarucaure. Once ahe asbesaos fibres ream aha pleural cavity, they are unlihely to be transported to other sites cf the body as any significant extent. Osing radioiabellea asbestos, Zolres A Yorgan (ZZAZA research C-roup Hepora AZ2S-3. 9289, 130, London, 357) found that less than '0-;3 of an intrapleural dosa had vacated ahe crest ragacn even after 50 days. --- - Zear.e A Zavon (Archs envir. ZZth '565, ` a. "7") have concluded that :f '.he raaerdals encountered by pipe insulators, asbestos alone presents -a serious health hazard, and it is icicely that in other iniusaries, tco, aecesaco provides the caagcr hazash.. Zhe asbesaos trebles: presents a form-able challenge which is being net conscientiously by aha respons-ble parties. Vnile there is little rocn for oocplacency, there is even less for ahe exaggerated chains of danger cade by ahe Zachel Carsons of cur society. 21V Zardbcah of P wo., Cnio, ;5 Chic volsocavhaa expensive for uses and legs collected, an wonhers in in. Zhe open discusoicn on plained defer* deportarea to cn the -s aoidclants arc end starches c free salad drs servatdve ccac technology cf alcohols, the namitol ends bar fudge and synthetic flat charasaerisaao flavouring (is so on) and the potentiators a one cn non-nut -is seeon a cc one C C c c c