Document 1Q03r6qwe7qy1vxXYqrnEDRY5

/ INDUSTRIAL HYGIENE FOUNDATION OF AM ERICA. IN C. Mellon Institute. 4400 Fifth avenue Pittsburgh. Pa isaia PROGRESS REPORT NO. 2 on Fibrous Dust Studies /or' Johns*Manville Corporation PPG Industries Pittsburgh Corning Corporation Owens-Corning Fiberglas Corporation by Paul Gross, M.D. Director 0/ Research Laboratory Robert T. P. deTreviUe, M. D. Managing Director r,r\ June 1967 THIS DOCUMENT WAS NOT A RECORD OF PPG INDUSTRIES, INC. DID NOT COME FROM IT'S FILES. AND CANNOT BE AUTHENTICATED BY PPG INDUSTRIES, INC. |_BBJ)0235?2 1 am u*ocMrio or moustmcs roe tmc n~i---- or C*^T*fuw io cawemom ''SSSSS tV * r t- ti < "'*. * 7"* - *1 r~ J* ***-;--* .Ur.ii::\ p.snTU!! t-ur.i i:nu usuri i,rT7Hi:::iTi.*;i, su. 13213 O GO o ::'j PROGRESS REPORT NO. 2 On FIEROES DV3T S71'DIES tor pi iT5nt*o:r corning cor'.joig\T2ox Jl*\*K i "07 THIS DOCUMENT WAS NOT A RECORD OF PPG INDUSTRIES, INC. DID NOT COME FROM IT'S FILES. AND CANNOT BE AUTHENTICATED BY PPG INDUSTRIES, INC. 7"bB_0023593 T 4837 industrial ntoicnc rouNOATiCN or amcrica inc 1. Concerning the spucificity of ferruginous bodies, in the first'stage of this investigation, it has been found that ferruginous bodies, indistinguish able from asbestos bodies, are formed in the lungs of hamsters in response to respirable filamentous particles of such non-asbestos materials as ceramic aluminum silicate, silicon carbide, and glass. The importance of these findings may be judged from the attached correspondence with th editor of the AMA Archives of Pathology. Accordingly, Dr. Paul Cross has prepared a letter, transmitting a manuscript based on findings in the F undation's laboratory for consideration for publication in the same journal. The letter is dated July 19, and the manuscript will be forwarded that day if no objections are received. We believe that the best interests of the spon-^ t^ sers will be served by its publication in the most expeditious manner possible, but transmittal may easily be delayec temporarily if questions arise or if it seems desirable to do so. II. With regard to the pathogenicity of respirable fibrous dusts of dif ferent composition, results reported below are based only upon a study f S. . accrued mortality in ea'eh animal exposure group (either due to pneum nia * or repeated intratracheal injections of dust). As such, the findings are very preliminary and require substantiation based on observations of animals still % on test. 1. Class a. Class (uncoated). In hamsters, this dust evoked f cal macrophage reaction with associated ferruginous bodies. No fibrosis was Jj?002359r7 THIS DOCUMENT WAS NOT A RECORD OF PPG INDUSTRIES, INC. DID NOT COME FROM IT'S FILES AND CANNOT BE AUTHENTICATED BY PPG INDUSTRIES, INC. w 4888 INDUSTRIAL. HT6ICNC rOUNOATlON OT AMC*tCA *C 2. observed. In rats, no alveolar mural change* wen* noted. However, in several scattered bronchioles, there were obstructing polypoid structures ot inflammatory fibrous tissue that enclosed numerous glass particles. This bronehiolar inflammation is attributed to the entrapment (at the site) of large aggregates of interlaced glass fibers during the intratracheal injection. b. Class (coated with phenol-formaldehyde resin). As o co with the uncoated glass, this dust produced no discernible alveolar mural ^ UJ lesion; but, because of the impaction of aggregates in bronehiolar lumens, U.~ there were lesions in these regions of impaction comparable to those des-^`* cribed above. c. Class (coated with textile binder). Still in prepara* tion. No progress to report at this time. __ ~ J .* JT` 2. Ceramic aluminum silicate. The pulmonary reaction;', r ' *^ to this dust in hamsters was similar to that observed with glass dust ex-C~ O eept that ferruginous bodies were more plentiful. No fibrosis was demon strable. In rats, there was an occasional bronehiolar polyp of inflammatory tissue enclosing refractile fibrous dust particles. Occasional small col- ,,lections of alveolar macrophages were also seen. There was no evidence of alveolar wall fibrosis. 3. Organic fibers. This material was either rapidly re* moved or underwent resorption because considerable difficulty was encountered % | BB 0023595 J THIS, DOCUMENT WAS NOT A RECORD OF 5583 INOUSTniAl HYQiCNC FOUNDATION T AMC*lGA INC 3 in recognizing evidence of dust injection. Few sniall collections of dust* containing alveolar macrophages were observed in hamsters and rats. There was no alveolar fibrosis. No ferruginous bodies were found in the lungs of hamsters. 4. Attapulgite. Aside from scattered small collections of alveolar macrophages, no other significant abnormality was observed in the lungs of hamsters or rats. No ferruginous bodies were found. 5. Natural chrysotile. In hamsters the pulmonary reaction^. %_ to this dust consisted of a diffuse proliferation of alveolar cells and macro*.'.;; phage reactions. Many asbestos bodies were present among these cells , ,, in the air spaces at nine months. In rats, the reaction was multifocal and ' consisted of mural fibrosis involving respiratory bronchioles, alveolar ducts, and their evaginating alveoli. 6. Synthetic chrysotile (Grandquist). In hamsters this ; dust provoked a moderate macrophage reaction. No ferruginous bodies were found. In rats, there were initially only slight focal alveolar cell proliferations associated with collections of macrophages. Nine months after the intratracheal injection of the synthetic chrysotile, there was 'questionable thickening of the wall of some respiratory bronchioles. Th re was no active inflammation and no evidence of fibrosis. 7. Synthetic chrysotile (Grandquist) plus adsorbed nickel phosphate. The pulmonary response to this dust in rats was characterized BB 0023596 J this document was not, a record of PPG INDUSTRIES, INC. DID NOT COME FROM .. IT'S FILES AND CANNOT BE AUTHENTICATED BY PPG INDUSTRIES, iNC. 4QSO IPtOUSTIVtAk WYOiCNC rOUMOATlOW AMERICA INC 4. by a moderately intense multifocal inflammatory reaction centered in the respiratory bronchioles. The inflammatory reaction at the nine-month period included the proliferation of fibrous tissue which obliterated the lumens of the air spaces. This reaction greatly resembled Lhat produced by natural chrysotile. No ferruginous bodies were found HI. A supplemental study was designed to explore the etiologic role of various components of chrysotile asbestos in the production of lung fibr sis and/or lung tumors. For this purpose, the following series of rats have; been injected intratraeheally with suspensions of the following materials, (all of them of respirable size); * 1. Chrysotile dust known to be carcinogenic 2. Synthetic chrysotile .' 3. Synthetic chrysotile plus nickel 4. Synthetic chrysotile plus chrome L;:, 5. Synthetic chrysotile plus nickel, chrome, and benzopyrene 6. Nickel with carbon as carrier 7. Chrome with carbon as carrier * 8. Benzopyrene with carbon as carrier 9. Filamentous glass with phenol*formaldehyde coating 10. Filamentous glass with textile binder coating 11. Filamentous glass, uneoated. 1 THIS DOCUMENT WAS NOT A RECORD OF PPG INDUSTRIES, INC. DID N.OTVSOME FROM IT'S FILES AND CANNOT BE AUTHENTICATED BY PPG INDUSTRIES, INC. ' i_f_002J597~7 INQUSTfllAk MY ICNC 'OUNOATION Or AMCMICA.IMC 5 As mentioned in II above, concerning results of the preceding phase, data are available only from a relatively few spontaneous deaths which have occurred and such tentative findings as have been observed, and their inter* pretafcion, are included in the above discussion. It appears at this point that the trace metals, injected as particulates into the lungs, will probably not be biologically active. It will probably be necessary or advisable to sup* plement these series by injecting rats intratradically with synthetic chryso- a tile to which the trace metals have been adsorbed in a manner similar to that used for adsorbed nickel phosphate. 7 pjQ A*- Comment on Findings to Date KviiV; PPG FILES 4* The appended manuscript furnishes irrefutable evidence that ferru- ginous bodies indistinguishable from asbestos bodies may be produced in lungs from certain non-asbestos filamentous particles of respirable size. Data so far collected shows that such dusts as aluminum silicate, silicon carbide, and glass, all previously shown to be "biologically inert, " will produce ferruginous bodies when injected into the lungs in filamentous form and also confirms their lack of fibrogenie potential. Therefore, there is no reason whatsoever to equilibrate production of ferruginous bodies and pathogenesis. Further data are needed to extend these observations to include lack of cancerogenic potential, however. THIS DOCUMENT WAS NOT A RECORD OF PPG INDUSTRIES, INC. DID NOT COME FROM IT'S FILES AND CANNOT BE AUTHENTICATED BY PPG INDUSTRIES, INC.' 4e&> 7"bb"oo7^b~~ THIS DOCUMENT WAS NOT A RECORD OF PPG INDUSTRIES, INC. DID NOT COME FROM IT'S FILES. AND CANNOT BE AUTHENTICATED BY PPG INDUSTRIES, INC. CcLLcri to the Editor APPENDIX A TOOArS PRESSING QUESTION-HOW SAP* IS UUAN AMIIENT Alt? To /*e Edi/ar--Professor J. G. Thnsnwn node notable mntribution to pMlwdogy when be * nounerd Umt discovery f "bshmtas" bodies in the juice of haigt taken from tmncrupetinnalljr ex- posrd urban population of Capcmwit, 5*uth Africa.1 Unfortunately, the tar-rcschinc rotsciusieni he has dtmti imk. ratine upon little or no evidence, tend to detract fran the value oi this finding. In the paper (,A*rk- Path *1:4SS, 1966). prakuar Thornton has shown an awareness of-- but dismissed too lightly--the obvious objection to his diesis, "the suspicion that asbestos fiber* are noar a hazard of urban lire* is evtfimttd more ampir than expected." This thesis appears to ba based on Dr. Thom* that ashestbs bodies art specific and to not form in rarest to other materials. As pointed out by. Thomson there arc. m addition to the "eurioos" bodies, also so called pseiadn asbestos bodies. The latter, ho rightly difieremiates from true ashestoa bodies by the opaque, irregvtar. central cares. . The pressing question today is the foOowing me: Are there muerials other than asbestos, that are of filamentous character and manufactured tm day. that are part of ambient urban air, and that will stimulate alveolar phagocytes to produce asbestoc bodies * * These materials could probably be classed mostly at plastics and would, most liksly, hare mm important feature in tuitunsn. namely, a biologic "ms mnii" As a possible example. one might ronaidcr that filamentous plastic dust has been psodmed in homes from carpets woven of synthetic yams. The am of eacmms sweepers equipped with bigh.ipeed beaters would tend to of the fibers to a respirable pertiele It is a carious fats that no publication hat he pulmonary leictina to There is. of coarse, no answer to tW at the present time. Yet. far from accepting Dr. Thnmwm's mumps ion that athestos bodies are specific for uhestos fibers, tfar US ruhlic Ifmlth Service has reemtly authorized sad funded work in several laboratories in the United Siam to investigate this question tas well as others) to the tunc of over SGUOjQOO. A nmnlsrr of other statement* in Dr. Thomson's paper dsssrie omuutiil. His declaration. "Dwrt are statements in the literature ms asbestos. mainly by people other than pathologist*, that* (he asbestos fasly is nmwpceific. These opuwnws are not held * by hiMnraludietists Why . ..." is lU necessarily true. I. far cam Dr. Arthur J. Vurwahl.' Dr. John 11. fi. Daria,* of Cambridge. England. and Dr. A. Cdlet * in Dr. Tolward's bfamatory near lfari* hare Anotlwr natcnwnt requiring cusnaim. apparently ms hmdequair mfswwation. is that. "Han and the guinea pig teem to he the mdy missals in which ashrsn- libers are rceoiariy and rapidly emrserted into asbestos bmiies." Winer* leas I ashevto* bndir* in the Isms* of lahhitt and uwwskeyt caposed tn ahe*tus dust. We hare fosnei aleualam tshcMo* bedim in the liases of hamsters exjwwcd tn chrysolite ashesmt dust/ Bemuse of the prevail aseertsimr irjardiug the specificity of the asbestos body, the term "ferritin" " was soerested. This term was criticized ` the tumposition of ferritin hat nm been ? _ adequatefy characterized. Periapt the use of the term "ferruginous* body will stria the purpose ' until it can be shown that them structural arv specific fur asbestos fibers. Dr. Thomson declared that, "Many of tho eery L than aid sharp athestos fibers toward the bmp bases owing to hssg mrdiac action, and grarity." In the prasencr.of "dry" Imgs such transport of athestos fibers and famtgiuous biriies wooid uemtarily fat least in the lower lobes) hire to go comwer to the mueo> alia>7 escalator s feat which is difficult to marine. A mnre reasonable explanation of the ob servation that fcrmainnui bodies are more abundant tn the basal porti>ww of the longs is that in many people dying f natural causes, tint is where fluid tmds to accumulate terminally. Under the latter conditions, the opposing action of the escalator is overewwt by the sheer volume os' railing over the mucous blanket like tidal with every inspiration. According to this concept, the rancenuatinu of the basal frwtkwis of the clerical bnpiicatmn utip that M a terminal event, similar tn, if not identical with, terminal hypostatic congestion and edema of the lawn. Part Gaos*. MO 4400 Fifth Are Pittsburgh 1S211 RETTJIENCES * t. Thmmou. JIjG, at ala AOvont a* Moslem Urban tUrmL S At* I/rd J J7.T741. IPO], 2. Dsvia, Ut G.: Ebctrou>Micioscufw Stsdin %t Adminii in Man sad Annuals. Amn NT 4ssl St i U1.SMII. I9*S, 1. VarwaU. AJ.: Ptnnual tnnwausiintiea so Hw aauwr. May 70. !*. A Davis. J.X1 G.: Personal eemnuaiitjiiru in the ausbar. May. 19M. S. Collet. A; fsrinnal rnsnimaurst' ia w riw author. May. )**. A Warner. J.Ct Admjuis in Itspcsuucmal Animals. hit 1 ImUmrn* Mrs/ 5rl*I2. IW. T. Crra. I*- *od deTreville. ILTJj Ptsistm' iim td ha T# ike FJitm* --Tin critieisms in the letter of Dr. Cm* which cull W a rvjWjr am nmrerm il -T . 5S3C- Ank Par*--r* . Aw? m* l -SB 00235<Jo"'*~ C THIS DOCUMENT WAS NOT A RECORD OF PPG INDUSTRIES, INC. DID NOT COME FROM IT'S FILES AND CANNOT BE AUTHENTICATED BY PPG INDUSTRIES, INC. LLTTIMS TO THL U'tTUR till tlir -tfreilHTiy uf lulolm htlitl ml with M. Hr. Intwvsrr, c tin: imtnnLilwl.l. tiw movement. ><i a-le-t* birr. in tin human. t the <lmasu>l ibw-st ui atlrwm birr* ...! |r. I^m ]<rn> with nr tint tin* |>wiiilunlarMm a>lw-tw- Iswlir* , an et*ul Iw4\ twi. >1 . nn l ilitirmnntni irum ilw* (mnint idea fit thr indy |aMilile mreluni-nt *d tin*. - ! a-la-sb- lir by the nature nf thrtr central thrnk. eery l*lk **f hi- wn Mainiwt On thi- > cur\ Inn n4rad .at ondwiinb a I do, that true arc m complete agnumiU. but hr fi*> me ctnww it a4n-4n- lhr are arrrtwaiilc marker* of a-iw-im on the nhcuus- mcehannot to the article. iwyhtHi. hr (MuUta* that lymiwtr fiber* art The cridenee tliat ashestin Den hrfiare tisry lw - premtt in nrtun air ami nhaht kail to the fmiac- uuw ashestn* Uulie- move downwards ami Utnajly turn of a*hrrti hmhew. I b m* knmr 4 my eridrwre u> that lAttt He ( <wi to diacm* m intrttrnlar fibunewtiiu* dost from tiriiu woven (nail *ymbefie yams, ml expreww -urprts* that wi publication lia appeared <at the pwhtnmary (rum lime murewncuu ami *rarity i- auvrentiid. Ion bet explain wane nf tin: mwrund feature- i ItlnUiMi, which are utlnerwhe awxplwaldr. Tlw main obreethm to h a> far an I can wr i- that it hurtdoers a mude of tramf-m nu prr-ent iu >e!w-r rvanwm to orh lu-l. 1 ant me aurpruwd, a* thne trarictic* of pnnamteuniesis, but mher punnmi- syutlwtk filer* arc elastic and me of the type eouiosi are not due tn thin sharp film. Tlnr luuw that pniiurc* fine duel. but it *ueh a publication eontaining tlw uecdWHibe sharp fiber- of a*i*-<- &r* aptrar I tlull be mere surprised than Dr. * could be regarded as a thakimt machine, ami OfiM i( it mdntle* a deteriptiun of adewa Witt, which is always in action as thr lung is neecr at re-t a* the man-made Abert in nrfwrt* art much thicker The fiben we are ditcuuing are often too lous t iw than the fiiwf in the center of an atheitm body. phagecywsed by dust cells, and would tend iu w-r Farther. ert fragments u than asbestos bidiet. averaging dike to 50w from lyiwhctic Abort would imply brittle characteristics which thrtr downwards sa the erect posture occupied by m -t human beings far two thirds of the day and Uu-rally (nr the remaining third during steep. This explam- flattie fibere do am possess, and would feature ' srhy asheetsnis is more marked aa the haar unlike --mthinf mare than a vacuum sweeper few their ocher ptwimwcreiioiri aueh as tdicoeis. wldeli ptiWtctiow. if they emdd be produced at all with is more msrked in the apical portsms of thr upm-r out the ete ot a mtenwome or other cuttmg Utah lofam; why pleural piuturs. oloheri or am. tn-w Vnteu one can suggest an mhaM mattriai with accepted by most as malting from inhalutitm *' the feature* of an asbestos Aher mide an aahtatot asbestos, are present posterioriy and laterally m the body with a length of St to lJOw and a thickness parietal and nut the visceral pleura; why ibcy'are of In or 1m. a* Dr. Croat ha* (ailed to do, if sort tominon uifcriorly than superiorly and are t>4 would teem c-.r logical and practical to regard sited anteriorly, as adults rarely sleep in the poise asbestos bodio* a* marker! of aaheatot mhalxtitm. pontiam The nmri uuut of these snhesto* filer- bmeeir nwdtmt or inomtemuent to tome that outwards ftam the lungs explains why such pkurvl cunchuien may be. Dr. Grots suggests that my statement that man and the guinea pig appear to be the only anhnaJ* in which asbestos fibers are regularly and mpidly omratod into asbestos holies is incorrect, and as plagues ore mitially men over the wryirhUiat rdtsad not over the soft easily penetrated inmwcil regions, end for the same reasun are found ni thr diaphragm over the tradinuar ^irtnm, and me tlw owscitlir portions It is prabsidy the reawm wh- miens that asbsitus bodies hoto been them pieunl plaques see sen awwe freuorncly in I in the hntgt of rabbits. monkey*. and hamsters caws erith little or no pulmonary ashretnua. a* time exposed to asbestos dost. Ho emdd also have Wdrd that m author on owe occasion saw one asbestos body sa the Umg of s rat exposed to dost: k is ruusHy irreleram. I was dbthe animal rpscisr' that rrynfurfy and mpidly itemed asbestos bodies, not them in which is no pulmonary fibrosis Os block their mnwani passage, and this may well be the expianatum an the apparent paradnr that malignant mesmhslinuu- < pleura are teen more often with a mild or tritlme ssbestinie than with a severe eiauiral ashestmi*. It ie a ratkmal oxplanatnai why them mibl case* < they would he found. asbennsii may he asseetated with a maligiom sv-- This matter is ust an aiimportent oc, and it thrlauma of the inlineworn. It is surely sigmnrane would teem desirable hi experimental vbttotii that bare asbestos fibers, bat not inumihilc aslwsn- me not rats or rabbits, but to use the guinea pig. bualies. hare been demonstrated m all time extrathe animal that crmistently shuwa a pulmonary pulmonary lesions. tesponss to asbestos Man smalar to that in nan, with the pnnltKthm of pulmmmry fifarosis as writ aa of BabesttM bwlirv Hast hnpnnam jwrhaps is his last paragraph eatmine the mormwiii of sshestos fibers. Dr. Grass owns the first pan of the named icstcnee and that which Meet if. in gbieh t stmt that .while the needle-like ashrstus fiber* can move To cenrimte. perhaps it would be easier tw am preetate the bask differences between other (wiewn-- cowioses sad asbrttosis and its complicatitnt- u we mopped talking of a-bestos dost, amt owst inwrd.1 the tarm employed m the German literature--aA nrrdks. J. G. Tuowsnw. Mil downwards, the asbestos huiy with its sharp innwts Medical Schoul bloused by the pratma and Iran mruttauop can Capa Town. South .Vinca * Artk fuk-Vtl a. At mt o1 Jt 7~BB~q523600~7 APPENDIX B r cjCelLerl to ihc ldilor unr TO OB. THOMSON Tm the Edtt~rr--\n rim ttl bi> JwviinM. Am Mtviui nr l'.\TiNUr I.Wl IlMi. cmcrmom I Jr. < ln~' mtiii' 'l> that iwnwil. fiJamrm>Mi* ihM panick' way hr iresent in the eminent air, cianttaralalr in *iar ! that i esin-tti*. filT tint liiitr raunii li* ilnHfmiM 4 al"4i haht-., I Jr. Tltttt--tt nil fimi ilr aitarhnl waifntdH httmM iFig t ami Ji, N'imen> ach Clan ant huwl in imlinary hnaw ilat ami tlvir ditanmnw mi lint thee arr im He. Tkmn'* ^mi that mawnmrrai hls-i. at amim'nt air air nt tariWimll? line Urtn the iwb nf (emieii* Wntic^ i* ihm tWfnuti-ly *en tn ipt nimu At |evnn. Ilr. (ihm is umrum tn ii. nlmi hmal aiHanulWai nm-miie innteiiia *a" icr- nomax, luiiri in*TM a eanetr at fihim ihMv l>r. TIidihii it m in a pailtii tv afnii it*r X 1 '2T *.#* . 3; 5* * 4* 0 '.4 o 'J _i A tf* . H 1,-/_-fr, Fihrnut tfoat panicfe m Jk diameter ami atumaitmtrly Mi in length before icrimicinrraitm. Same alter tmcrmnciiaTaix*. The panicle hat dittppeared. Ft* i--fo-ff. Fthmae dn*t fnicir Xtm m diameter ami mar* than tMI* tow atmn. A'foAf. It. tan. hat tfo--npeaml hi the pn mtnvnwinmtiim. A A *a y X, .# `4635 I BB~002360'l**7 TO1S DOCUMENT WAS NOT A RECORD OF PPG' INDUSTRIES, INC. DID NOT COME FROM IT'S FILES AND CANNOT AUTHENTICATED BY PPG INDUSTRIES, INC. IMTTliKX Tt> Tim uunut U bspaltnAeiikt--wrrtuinly 4 Dr,, (iiim Is* hr tlw ikIkt m*n. Inm ihe I'aanl Suh>. tkwi Itritam. ami Prunes lt-ii-1 in 1H. IrUrr i--m the mutter u| ^seHmt) ni irrn<smrt> Iwlif' as'benq; easxil smijr It) nleUix. In hs* Ittattil tit IJr. t inM* kttve. I >r. TWanvm attain wen lu attt-mm .tu tynlt U<t thr ieirii when Its -ay* tiiat pleural |da>tm nsm are ""srTrptrd hy must* a rwsdtmc Intm ushalulk-u iu eiwwUw. In a twin wMnwtal imly bividvhw dJIt esNmlkt iwr>) om> Motrncui1 cmwludc* Ip Ml; "Thr frequrnry of nr* with plaqwre ns aiaait the *amr m two of the three hoiked district- wreMtcatsil in different pert* ni Fbsland. whilst in the third it wa Imrt. I'hitm wintil u> be an equally (ommai Undine in a district in South- we*t Kokand with no a*i*tiw deiswt* and tin parisrutar akhe*m* Mwrits. a as a district in Kart Finland -ith an a*hr*h mine and mill end extensive inthnphyllhe aaiastm drpswit* near ii mtsm hnrdcr. Plaques were cucnuiuered in $2% pi the urban pnpulatsun and JIJI of the ratal population." The purpmeiuJ puhJiraikn of crnweiwis arwmp- tinm. which have aw apparent haw* in {act and lave prmurr (iwusaul apt-al a> errisrind In the lute Ih. Prank lYusri* u> Id* tlusiman- \ddesk* t Unlied IVrqes-iire nt AunqJktv lly* a*sr*r i Wee tltv AM A Sewuttiie Snsinss Prcvcntne AJln-twr in I'W a hws iut v-- coermsun. lie cwilvsl hut aDatene in ilsr annittiic meiinal the part pi wientnte, indiraluqc these rrsfkei-dalitio m the ptddir a* wrll'a* t wimre in mrh analten. Thu-e wl> Wtv w* Aw w tfowid ft siew l>r. Priuef* anwie hi Italst in' thr p*ttent dhtcrraaml ami tar (Wsl arcswdiugly In the prrseTst state in Imm lnlty. I h. Tikes*-ei` htittoec un the wctlicie imwam Uslip* anti tdcoral plaque* h* xlsum tibcT- * u jmtifsed krieutiikajly. Rohm T. P. deTrerilW. MU . WOO Filth Are Pittsburgh I3JU RtImMM I. Mntrman. L.: Aitnin Min and Dearat Plaque* in a Fcwist Sets** of Anww Cam*. Actm Patk .WimM Scand (tuppll 1(1:1904. i .Prase*. F.: Medical hrsrwin in Atmmrherti.Hnwac. JAAJA )3:0Jfr4 (No* Ml l9Wi RAPID MISTOLOftlCAL DIAGNOSIS Tm tit Editor.^-The *oprsvital trrhtiique for arnicine tan tissue dtaftwHe* at thr time of sutcttt waa simplified twenty year* aeo.' * Since then, the method baa conriimed tn yield ha reward* in a <ew place* but it ha* tan rained ub> new adherent*. Tin* ntuttirei wimld appear to haw been tamed Hr the incrcasim; popularity id the more cumbersome "ffnenttetnas* technique which pravulrk mnee faitniiar pollens* pi auwr embalmed perjuratisask. 0 ewperiraet with these two <snstra*imc prtuntypes srf taammaucm i brine recorded in an effort t> verify qwmuatrrcly sue the many wtnu may haw fraud Jims** mdy * thr few. The data (the Table) those a eery email mspmwwwuc hai &JQ- nseralt error a thr period when smiy the mpravital rapid-tretiun (R*S> tedmique ww* rmptowd tl9M-W2) tn t.^i *m the later period when crysntat miertmnne in^rntaction method* were added. Thi* may lie at tributable to an increased hrmdtit of neperimrr and inumnrcd jadttetnem *r the year*, ratiwr than in Rirtisndnlucical differs****. Either liiciirs osmparr* favtmhly with the i*"r nrerall iuarrnras-y chctl by other nttstiptwi.** In tt*r later periml ilW-WL where the dOMCwinlity of employina an arirird t fmaen-srctuai lechniqim sra* dewirmoad by the dwGeahse* uf aaeh case, it pwradntticwl that the mdy fal* pmctisre errs** weearted m arttmo* wherr thr aUri effort tea* ant trade, and oaty fat an e*prsrr > f mi imdarihle mhnatum of Usiure f perfunnan>T. More aaponant thm numerical data are thr Ucm SAocrmy Comroif Srftm* Amaru..Tnrfisw end H`S TiT*** Mk IMS MM- law MW R-Smir hsMi AM Tamn uw na m a P*hr ham* Mm % a u a u a AT* U Pah* M--tm Mw. A aa La u u a li * 14 PMm htr e Ih aa u 14 14 a L> A 14 |^H Mw A M U rt u .a M ta 44 Arrk PutA--IV X2. .Y-r 19M Cmi4 Nw aat ti oat aa.t am LT no CL* P*rst*lr Defer Mw '.i iao IL* - aa U4 as U ta tt4 I 6B 0023602 r. APPENDIX C T 'HT\ 235 \ 1 *3T JI Amrhic.wMkhicai. Associatidn 535 NORTH DEARBORN STREET CHICAGO. ILLINOIS fiOblO Nl (3123 527-1500 . TW* 510221-0300 0. auaaar aactviat. ao. Mlaa ? cjunk Sam "* -- i-km* Dm Jon B. TM.R0TT. as. Naa turn a kmAi am****** ORCar Ihmm iiaiM Cam wu o. aicatT. --WI Cam Robert T.P. de Treville Mellon Institute 4400 Fifth Avenue Pittsburgh, Pennsylvania * 15213 acmt m. mcerasti-'-.. vf., ^, v *%' IMwCL R. IS. *y MuL. aOTai. 0. R**-i^ *. Mm. C. LACv. ao. It. La* KMT 0. M, m. Sat AM* L. laaarao. MO. aataaa*. Tm. C must HIU*. *. Im*- M. f*"^ C/3 ----- | - 1 Dear Dr. deTreville: The enclosed copy of a letter to the Editor from Dr. . TThhoommssoonn. Since. I did not forward (probably an error) your letter to him, I believe his letter should be published. I believe this interchange should now be terminated. I trust this will be agreeable to you. Sincerely yours. DMA:eg Chief Editor Archives of Pathology THIS. DOCUMENT WAS NOT A RECORD OF PPG INDUSTRIES, INC. DID NOT COME FROM IT'S FILES AND CANNOT BE AUTHENTICATED BY PPG INDUSTRIES, INC. 1 BB 0023603 J 4897 Hsyly to Dr. de Triville'i lsf.er. To the Editor, - In ay replj to i)r. Cross' suggestion tht non-amral fileaentous dust particles could fora the cantiv cf asbestos-like bodi*s, sty coaironl was that "unless. on* can suggest an inhalsd astorial with tb fsaturos of an asbestos fibro insids as asbsstos body with a length of to 15QP dnd a thickness of or lsss, as Sr. Cross has failed to do, It would sssa aors logical . and practical to regard asbestos bodies as Barkers of asoestoK Inhalation, however unvelcoae or inconvenient to soae that conclusion may be." Sr. de Treville, Archives of Pathology e2i 4V6 - 497 (Kov i960}, m reply to this, produces photoaiurot,rapes of .* non-asbestos fibres ith thicknesses of e and 3*4b> on ibis concludes that ay opinion that "non-aineral fibres in aabisnt air are net aufficisntly fin* to fora the ceres of ferruginous bodies (asbestos bodies)" is thus open to question. tty opinion, -of course, is still opsh to question, but the average thickness of the asbestos fibre in the centre of the asbestos body is 0.u, * without considering the ainiaturs asoestoa bodies deaonatrated by the electron kleroaeope, and all fir. de Trevllle has done is t fail to find any non-ashestoa fibres in household dust as thin aa thoss in tha centra of asbestos bodies. THIS DOCUMENT WAS NOT A RECORD OF PPG INDUSTRIES, INC. DID NOT COME FROM IT'S FILES AND CANNOT BE AUTHENTICATED BY PPG INDUSTRIES, INC. | BB 0023604 | DOCOWENT _PORO 0^ ^ from PPS WDUSTHES, INC. - 2- Dr. de Trtville next 4ceus me at attesting to op*** for tho profession wh*n 1 say that pleural plaque* are now "accepted by soot" *.* resulting fion th* inflation of asbeelos. Hi* only support for this if to quote a paragraph froa tho monograph by Meuraan stating that pleural plaque* woro about a* frequent in * diftrict in Finland with no sabesto* aepoeits and no partioular 'O :.U -J asbestos industries, an in a district with an asbestos mine and. Bill. Tbia it preceded by a *tat*a*nt that "Meuroan conclude#", but tbo quotation if froa a summary of bl* finding* (page 53) and not froa hi* conclusions which ar* given lat*r (pa*;** 97 " 99) und*r th* heading of General Summary. Sr. Meuraan naturally diaeuff** tho *wid*nc* for and against th* ralationahip b*tw*n aab*ato* inhalation and pleural plaques, and it is an**aay natter to select froa this discussion (pages 67 - 9b) opinion* against that association. Meunsan'a opinion on th* relationship between a*b**tos hodi** and pleural plaque# is verg clearly stated *: hia aimmary. "Plaques were observed in of the urban population and in 31.c& of th* rural population. In th* rural districts cases with bilateral plaques were sore frequent than plaque-free ease*, nly . in the asbestos mining comaun* and in on* of it* neighbouring oomounem." "lobe*to* bodies in th* lung* and pleural plaqu a occurred sort often in conjunction than separately, th* difference being v*ry highly significant". "The present results seta to e -indicate that pleural plaque formation, in particular when it is bilateral, and the occurrence of asbestos bodies in th* lungs, have tea* aetiological facnor in common. The oust that induces th* formation of asbestos bodies do e u t, however, soem t be the J_8B^0023605~7 4899 elt e*uo or pi*qu f re*Hon", 3o*dir of idle corri.ond #eo */ jud<f for tataioiToo wMtLcr a?, da Troriilo'o quotation fro3 Vojrsan giro* * correct or incorrect iaprctoioti of Jr, H^are*. *s opinion on tho T*l*txon*^tp betcocn to* inhalation and aebootoa plaquou. ' J.o. THOGOX, X.J. Kodioal School f0 Capu Town, South JLfric^i ' ' \j ' THIS DOCUMENT WAS NOT A REC6R0 OF V,PPG INDUSTRIES, INC. DID NOT COME FROM fT' FILES, AND CANNOT BE AUTHENTICATED BV PPG INDUSTRIES, INC. 4300 Noli* on copy oi 1 ranuctionjf: appendix d Dr. Anm*viin- -- Plt*ac Kct- p, 1 1 I (ttr h pic Iun* ui * fiTni^numH body pruduci-d by Or. Crodu. 1<TIJ UoT. Vure^ li 196? Dr. D. Irfurray Aageviae Chief Editor. Archives of Pathology Department of Pathology University of Wisconsin School of Medicine* 47C North Charter Street Madison. Wisconsin 53706 Door Dr. Aageviae: Kegardiag Dr. Thomson's reply* by way ef review. it should ho re' called that the following two hosic assumptions la his paper (Areb. Path. 11)458. 1966) were challenged; 1. that htetcpathologists today do not believe that the asbestos body may be nonspecific, and 2. that It la ase accepted hy most that pleural plaques resnlt from Inhalation ef asbestos. 2a a paper given la October. * D. Paul Grso reported early findings of hie research* on production of ferruginous bodies with non-asbestos fila mentous fibers of respirable sine. Scientific questions are properly s etlod by consideration of such data* net by opinions. The eery enistaoca of Dr. Groe research is adequate proof that Dr. Thomson docs not speak for ail hist patheie gists today concerning specificity of so-called asbestos bodies for asbest s in halation. hieurmen's findings, mentioned by Dr. Thomson* are la ace rd with those published earlier* by Dr. Kenneth Smith, who said. "If Inhalation of the asbestos fiber aloae eould cause pleural plaques, one would expect to find plaques wherever the fiber Is used." Meurman'e conclusion that "the dust that induces the formation of asbestos bodies does not* however, s im to be the sole cause of plaque formation" does set appear to bo consistent with th second assumption of Dr. Thenvson. further work Is certainly needed to shed light on this Important area* %s the occurrence of ferruginous (so-called asbestos bodies) has be a f und THIS DOCUMENTvWAS NOT A RECORD OF PPG INDUSTRIES, INC. DID NOT COME FROM IT'S FILES. AND CANNOT BE AUTHENTICATED BY PPG INDUSTRIES, INC. 4SQ1 I BB 0023607 | Lr. & J. urr*y h-arci. B, 1-67 Pag* is almott halt (43'.*) of tha IndiTiduala studied at aatop* y in Montreal by Thurlback.** .fortunately, plana for auch ara being made through cooperative alforta involving ladnatry, government. univa-raitlaa and private inatltuti na. a va painted od la a recent meeting bald by lnduatriai Hygiene rcuadattoo IDiT and reported ta JUT Medical Sartaa Bulletin No. 11 entitled "Aabeetoe Bloeflacte Reeearch for Industry. ** A limitad number a/ copies a/ this pubUcatl a will ba made available ta raadara ad Arehiraa of Pathology epoa roqua t with out charge while tba supply la ata. Slacaroly ywora. daT;aJe ~ cc: Dr. Paul Croat bcc: Mr. . K. Davia on Mr. Hugh J ackson Robart T. P. deTreville, M. D Managing Director "L'VC 1. Transactions of Industrial Hygiene foundation 31st Annual Meeting. 1964. 2. Industrial Hyglaaa foundation Medical Sariaa Bulletin Ha. 11. 'Asb at a BlooITocta Raaaareh far Industry." 1964. 3. The Paeonjocoaloses. A. J. Ussa, Editor. Gnat & Stratton, lac,, Haw Turk. 1963. 4. Tha Zscidaasa of Aibecioe Bodlas la tha Lungs at Random Nacropaloa in Montreal. Lily AnjUvsl and W. M. Thurlbock. Can. Mad. Am. J. 95. 1179-1132, Doc. 3. 1966. j BB 0023603 | Amrhica.n Mkhk \r. Arisori.vnoN 535 NORTH OCAfcHOftti sTHttr . CHICAGO. IUINOI& MolO RHONt (312) 527-1500 Tw 10 2?tOJ0O A. MUMAY MCtVWC, 110. Cm* (w APrcNDi?: e IKMI * rttkfcBCT imw hui AaCmf n. A*CM MPMLTHtt rtkiwp^. n>. u it- , t. IWVU R. WCM. U*. A>w, M-vk. RAUL AOTm, ua, fc*U. M. Raul L. lacy. mo. to. i v- *" . TALHTT. MO. 0tCH Lumm Rmm.cjmm DOt AT . MATO* luurn* IUu(a< t*m MUP a. AKKY. `iv* * April 4, 1967 Robert T. P. deTreville, M.D. Managing Director Industrial Hygiene Foundation of America, Mellon Institute, 4400 Fifth Avenue Pittsburgh, Pennsylvania 15213 Inc. Dear Dr. deTreville: ** I wish to thank you for your letter of March 6 together with enclosures. After careful consideration, I do not believe it advisable to publish further correspondence on this matter in the Archives of Pathology. It would seem that after the initial exchange of opinions in print that further discussion should be by correspondence of participating parties. 1 assure you thet this is not a deliberate attempt to curtail debate but rather than a continuation of it may not be of large reader interest. Sincerely yours DMA: eg la!?, D0?UMENT Chief Editor Archives of Pathology 4203 j BB 0023609__ APPENDIX F INDUSTRIAL HYGIENE FOUNDATION OF AM ERICA. IN C. Mellow Institute, moo Fifth Avenue Pittsburgh, Pa isaia July 19. 196? Dr. D. Murray Angevine ,,Ui Chief Editor Dept, of Pathology WOT .mvi w.,. .. University of Wisconsin Medical School 470 North Charter Street Madison. Wisconsin 53706 ` -- - Dear Murray: I am enclosing an original and two copies of our manuscript, . "Pulmonary Ferruginous Bodies: (1) Their Development in'Response to Filamentous Dusts. (2) A Method of Isolating and Concentrating Them, " together with two sets of illustrations for your consideration for publi cation in the AMA Archives of Pt.thoiogy- The work reported in this paper is a logical follow-up of the cor respondence between Dr. J. G. Thomson and our laboratory that was published in the Archives of Pathology, Vol. 82, in August and November, 1966. With best regards. Sincere! PG:ejd Enclosure Paul Gross! M.D. Director of Research Laboratory 1 BB 0023610 | mi HtotuTM or woutmi *o* tmc Owwmcsncmt or mcmThtul APPENDIX C INDUSTRIAL HYGIENE FOUNDATION OF AMERICA.INC. * Mellon Institute, aao Firrw Avcnuc PlTTSSUNOw, Pa imam PULMONARY FERRUGINOUS BODIES: 1. Their Development in Response to Filamentous Dusts 2. A Method of Isolating and Concentrating Them *y Paul Gross, M.D. * Robert T. P. deTreville, M. D., D. Sc. * Lewis J, Cralley, Ph. D.** and THIS DOCUMENT WAS NOT A RECORD Of PPG INDUSTRIES, INC. DID NOT COMg PROM IT'S FILES AND CANNOT BE AUTHENTICATED BY PPG INDUSTRIES, INC. M. G. Davis, Ph. D. *** * Industrial Hygiene Foundation 4400 Fifth Avenue * .Pittsburgh, Pennsylvania *** University of Cambridge British Asbestosis Research C Department of Pathology Tennis Court Road Cambridge, England ** U. S. Department of Health, Edhtation, and Welfare Public Health Service National Cent r for Urban and Industrial H alth Occupational Health Research fc. Training Facility Cincinnati, Obi 45202 ? .4305 | BB 002361T7 tN0U3?l*iAk MVQICMC rOuMOATt N Of amciiica.inc ABSTRACT Formation of ferruginous bodies should not be confused with patho genicity. Failure to understand this differentiation may result in the erron eous generalization that all fibrous dusts share the ability of asbestos to produce lung damage. 5uch materials as fibrous aluminum silicate, silicon carbide whiskers, cosmetic talc, and glass fibers produce ferruginous bodies experimentally which are indistinguishable from those produced by asbestos fibers. A method of isolation and concentration of ferruginous bodies from lungs of animals and humans is described. Ferruginous bodies from as- * bests* fibers are much more pleomorphic than has been described (except by Gloyne and Merewether, International Labour Office, Occupation and Health Supplement, Asbestos, January, 1938, page 7), casting further doubt on .morphological distinctions used in the past in separating so-ealled asbestos bodies from pseudo-asbestos bodies. ' i.TM 00 23612 i IMOUSTftlAl MTOItNC rOUNDATlQN Of AMCftICA.INe Introduction ' Worldwide attention was refocused on ferruginous bodies by the publication of Thomson* * who found this phenomenon in the lungs of more than 30% of unselected autopsied adult hospital patients in Capetown. A ported in Pittsburgh and Montreal are possibly inherent in the more intensive searches carried out in these cities. These bodies are similar to asbestos bodies though the nature of the central fibers have not been identified. Asbestos bodies are golden-brown, ferro-coated formations found in the lungs of persons who have inhaled asbestos dust. They are gen erally described as symmetrical, segmented structures usually with clubb d ends, 3 to 5 microns in diameter and 20 to 50 microns long. The core of these bodies is composed of a transparent colorless asbestos fiber, although this fiber is not always demonstrable. Pseudo-asbestos bodies are similar to asbestos bodies, but are formed in the lungs in response to ixhaled non-asbestos fibrous materials. e .Apparently the only difference between an asbestos body and a pseudo asbestos body is that in the former, the central fiber is composed of asbestos and in the latter, of material other than asbestos. RECORD OF ivS2S;EaAND cannot be C0fcl from , by PPG INDUSTRIES, INC. AUTHENTICATED I Bff00236ll"7 r. tv1-' IMOUSTftlAi. MVQICNC rou0*TION Qf AMCAlCA.lMC 2. Since asbestos-like bodies can form in response lo respirable, trans parent, .colorless fibers deposited in the lungs and composed of materials other than asbestos and since classifying these structures based upon identification of the central fiber presents difficulties, a generic term, "ferruginous" body, has been proposed for all bodies formed in response to the presence (in body tissues) of a broad spectrum of fibers, including asbestos. Davis and Collet^ demonstrated by electron microscopic studies of macrophages that ferruginous bodies are formed intra cellularly by granules of ferritin or a ferritin-like protein that are precipitated upon and around some foreign materials. As asbestos body, therefore, is only one kind of ferruginous body. one in which the central filament is an asbestos fiber. As will be seen later. the appearance of these bodies and their dimensions are so varied as to defy the reasonably short description usually employed. The problem now confronting investigators concerns the significance Of the widespread finding of ferruginous bodies in the lungs of urban p pulation groups. The solution of the problem is. of course, linked to the identity of the central fiber about which the ferruginous body forms and which is at e present unknown. It is hoped that recent analytical advances, such as lectroa diffraction and microprobe will provide techniques for definitive identification of the central fiber. THIS. DOCUMENT WAS NOT A RECORD OF PPG INDUSTRIES, INC. DID NOT COME FROM IT'S FILES AND CANNOT BE AUTHENTICATED BY PPG INDUSTRIES, INC. -1 * IMOUST*tAb HTOlC*C ^Ou?<3ATIC*< 0* AMClCA.*C 3. Up to this point, the identification of ferruginous bodies in the lungs of unselected autopsied hospital patients as asbestos bodies* has been based on the hypothesis that transparent fibers of respirable sixe composed f materials other than asbestos either are not encountered in industrial and community environments, are not deposited in the lungs, or do not result in the formation of ferruginous bodies when inhaled. 7 Respirable fibers, however, are apparently ubiquitous. They may be mineral, animal and vegetable in nature and from both natural and synthetic origin. They are disseminated through industrial processing, community activities, personal habits, and the action of natural forces. Also, we recently * reported that a ceramic fiber of respirable sixe, composed of aluminum silicate, resulted in the formation of ferruginous bodies.^ The latter were indisting- uishable from some of the asbestos bodies isolated from an asbestotic lung of a known asbestos worker. (Fig. 1} Although non* segmented, they were golden*yellow, symmetrical, clubbed bodies, staining deep blue with Peris' test and exhibiting a .central transparent filament. This paper discusses our further findings as follows: # ~ a. Ferruginous bodies are developed in the lungs of hamsters in response to the presence of "biologically inert" filamentous aluminum silicate, glass, and silicon carbide particles. 1 BY PPG INDUSTRIES, INC.' *OUSTA4. MTOICNC *OU**OATION r AMtCA INC NOTfL*, TJ 1 " 'V T-f Tr I^ '"N * * 4. b. A simple method is made available for isolating ferruginous bodies and bare fibers (inclusive of asbestos bodies) from lungs. The method is given in detail and the results obtained ` described briefly. The Production of Ferruginous Bodies * Croups of 12 hamsters each were injected intratracheally with 3. 3 mg fibers contained in 0. 5 ml of aqueous suspensions. This was done under light ether anesthesia with the aid of an illuminated, self-retaining speculum that made the vocal chords visible and allowed the insertion of a long 18-gauge needle between the vocal ehords under direct observation. All of the following -were injected: 1. Ceramic aluminum silicate fibers. This is an uncoated ceramic fiber with a media.* diameter of 2. 0 p. Fifty percent of the fibers were under 75 p. in length and many filaments were shorter than 15 p,. No free silica was * detected la the fibers. . 2. Silicon carbide whiskers. These were 99. 5+ percent SiC. They had a range of fiber diameter from 0.5 to 3.0 p, with a fiber length that ranged from 100 to 750 p. 3. Class fibers, uncoated. The fibers had a mean diameter of 0.4 p and a mean length of 4,4 p. THIS DOCUMENT WAS NOT A RECORD. OF PPG INDUSTRIES, INC. DID NOT COME FROM IT'S FIUE&AND CANNOT BE AUTHENTICATED BY PPG INDUSTRIES* INC. 4210 I BB 0023616 1 not C INSUSTfttAb HTOiCNC rOUNOATlOW or amcic*.inc 4. Cosmetic talc. Fifty percent of the fibrous material in the talc was under 0.2 n in diameter and 1.0 u in length. 5. Attapulgite. Fifty percent of the fibers were under 0,1 y. in diameter and 1.0 h. in length. 6. Chrysotile. Most of the fibers were of ultramicroscopic dimensions. Isolation and Concentration of Ferruginous Bodies Samples of lung tissue cut into thin strips three to four mm thick or fragments about 0. 5 cc in volume, are placed in clean glass or plastic __ # containers. ?o the tissue is added about 20 times the tissue volume f com mercial 57* sodium hypochlorite solution. This is allowed to stand undis turbed at Toem temperature for several hours until all chemical action has ceased. More hypochlorite solution is then added at frequent intervals until the tissue has been digested. For small lungs, such as those of rats and guinea pigs, the frequency of addition of fresh hypochlorite solution and the amount should be such that all lung tissue is digested in approximately 24 hours. For human lungs, unless quantitative recovery of ferruginous bodies is desired, complete di gestion is not necessary.' 2n the case of human lungs, the ferruginous bodies and bare fibers are often associated with a sticky lipidie film adherent to the bottom of the container. The stickiness allows one to pour off all the fluid and undigested lung tissue without loss of the bodies and fibers. Because of the presence - . imuusiKIts, INC. IJECOk-D OF FROM 'A t ED T BB 0023617*7 . 4911 IMOuSTftlAL HYOICNC rOUMOATION Of AmCAiCA.INC 6 of anthracotic pigment, the film usually has a dirty gray color. The film is dissolved by vigorously washing it with a mixture composed of one volume chloroform and-two volumes of approximately 50% ethyl alcohol; the total volume should be the minimal necessary to remove all the film. The wash fluid is centrifuged for about five minutes. Because of their high specific gravity, the ferruginous bodies and the insoluble mineral particles settle to the bottom of the tube. On the other hand, most of the carbonaceous material collects at the interphase between the chloroform and the aqueous alcohol. If too much alcohol is used, the carbonaceous material will lose some of the water that lowers its specific gravity. As a result, there will be no separation between the. anthracotic material and the ferruginous bodies. In such cases, rehydration with water followed by the addition of chloroform will usually effect a good separation. All of the fluid and solid material above the sediment at the bottom of the tube are discarded, and the walla of the tube are cleaned of the adhe rent anthracotic material. The sediment is washed several times with water to remove all hypochlorite and other water-soluble materials. It is then stored in an aqueous or alcoholic medium. When smears are made of the suspensions, it may be advisable to dehydrate the smear and use a mounting medium to render much of the mineral dust associated with the ferrq^inous bodies less conspicuous. The naked fibers remain visible. NOTE: TIE? NOTCCNl INOUSTI*<Ak MTOiCNC rogMDATlON cr ApCSiCA.INC 7, Jn the case of small animal lungs, chloroform and (lie supernatant fluid were poured into centrifuge tubes in a proportion of 1:2. After centrifuging, the supernatant fluid was carefully removed and discarded except for about 1 ml left undisturbed on the bottom. The film os the bottom of the original container in whieh the lung tissue was digested, was then removed as in the case of human lungs. This fluid was added to h pool of whatever sediment was obtained from the supernatant fluid. The subsequent procedure was the same as with human lungs. We have worked with formalin-fixed tissue only, but there appears to * be no reason why this method should not work equally well with fresh lung tissue. Results Paraffin Sections Initially the ferruginous bodies were sought only in paraffin sections that had been stained with hematoxylin, eosin, or Peris' test for iron. Be* * cause of the paucity and small size of these bodies in the sections, the hems* to toxylin made the search more difficult. Subsequently, replicate sections that were given the Peris' test only.or slso lightly counterstained with eosin and cleared, proved to be satisfactory. The injected fibers generally were confined to the air spaces where they were associated with free macrophages. Some of the filaments passed THIS DOCUMENT WAS NOT A RECORD OF PPG INDUSTRIES, INC. DID NOT COME FROM IT/S FILES AND CANNOT BE AUTHENTICATED BY PPG INDUSTRIES, INC. I bT0023619^ | - 2j313 iwOusiaiAi. "toiChc rou0*T,iON a*c*ica snc a. through the bodies of one to three, and even four, macrophages so that these cells appeared to be impaled as though upon a spit (Fig. 3C). When the sections had been stained for iron, the dust-containing areas-, under low magnification, were usually marked by a granular deep blue coloration. In sections of lungs of hamsters killed one month after an intratra cheal injection of aluminum silicate and glass fibers, occasional ferruginous bodies were found. These were non-segmented, light yellow, structures with bipolar clubbing and a transparent central filament (Figs. 2A, 3A). These, subsequent to the Peris' test, took on a deep blue eolor that often obscured the central filament. Very similar non-segmented bodies were seen in suspensions of isolated and concentrated human asbestos bodies derived from an asbestotic lung of a worker known to have been exposed to chrysotile asbestos dust for 30 years (Fig. 1). The ferruginous bodies that formed in response to chrysotile asbestos were smaller than those that formed in response to aluminum silicate and glass and also different from the latter two in being segmented (Fig. 4C). The ferruginous bodies were more readily found in the lung sections of hamsters 9 injected with aluminum silicate filaments than in lung sections of animals injected with filamentous glass or chrysotile dust. No ferruginous bodies were found in the lung sections of hamsters injected with silicon carbide filaments at this time (one month post-injection). kBX. PPG INDUSTRIES, JNC. MFV? S lJ J i iNQusrmAh MYOiCtC foundation or auckica.imc 9. Examination of lung sections of hamsters killed six months after the intratracheal injection of the filamentous dusts revealed no more ferruginous bodies than thos'e encountered five months earlier. No segmented forms were found exeept in association with chrysotile dust. No ferruginous bodi s were seen in lung sections of hamsters injected with silicon carbide. Dustcontaining alveoli found in sections of lung from a hamster injected with talc were easily identified because of the blue coloration caused by the presence of iron; however, ferruginous bodies could sot be identified. Similarly, no ferruginous bodies were found in lung sections from hamsters inject d intratracheally with attapulgite. Lung Digests The smears of the sediment derived from the digestion of the lungs from hamsters injected six months previously with aluminum silicate, glass, and chrysotile, respectively, consisted largely of naked filaments, but many ferruginous bodies were also seen. Although most of the ferruginous bodies that had formed in response to aluminum silicate and glass fibers were non* segmented, a number of segmented forms were also found (Figs.' 2B, C, D; 3B, C, D). A more prolonged search of the sediment from lungs of hamsters injected with silicon earbide waa necessary before several ferruginous bodies could be found. TKs search was facilitated by applying Peris* test for iron to the smear. The bodies were mostly nonsegmented, and exeept for the * clubbed ends, the coating on the filaments was thin. One silicon carbide . fiber waa found with a club-shaped coating at one end, a fusiform coating nea; THIS DOCUMENT WAS NOT A RECORD OF -srowisn 4915 IT>? INDUSTRIES, INC. DID NOT COME FROM 1------------------------------- IT S FILES. AND CANNOT BE AUTHENTICA i EO BY PPG INDUSTRIES, INC `E INSuST*l*k MYOICNC '`OUNOATICN Of AMERICA IMC .10 the other end, and a very slight thickening near the middle (Fig.4A), Two segmented ferruginous bodies that had formed around silicon carbide fibers were observed. Unfortunately, the diffusion of the blue pigment of the body rendered its outline fuz2y (Fig.4S). The sediment from a lung from a hamster injected with talc was com posed largely of crystalline plates; but upon eareful search, a number of n nsegmented ferruginous bodies were also found. These too had a transparent central filament. (Fig. ZA. 3A) Because the Prussian blue reaction for iron had also been used in this smear, the outlines of these bodies were fuzxy because of the diffusion of the pigment (Fig. 4C). . Unexpectedly, ferruginous bodies were more difficult to find in lung sections after chrysotile, than after aluminum silicate injections. The same finding was observed with the eoncentration method. Although few in number, all asbestos bodies were segmented (Fig. 4D). One of the most interesting observations was that, when stain d for iron, filaments that passed through the bodies of one or more macrophages showed a coating of ferritin or ferritin-like material only on the intracellular 'portions of the filament (Fig. 3C}. The sediments from the lungs of hamsters injected with attapulgiLe revealed no ferruginous bodies. The failure to find ferruginous bodies in these sediments may be interpreted as a negative control to indicate that our positive v% * findings were not attributable to the accidental inhalation of fibers In the ~BB 00 4S1S JOUST*)**. HTOlCHC rOUNOATlOM or AMC*)CA INC IX. `The sediment from the human asbcstotic lung was a rusty, red-brown color; in the smear, a wide variety of asbestos bodies were seen in addition to innumerable naked fibers. As previously indicated, a large number of the asbestos bodies were pale, thin, and nonsegmented. Also of interest, was the fact that many of the largest bodies did not have smooth surfaces, but were spiculated. The spicules were often coarse and had e squared-off ends. A few of the bodies lacked symmetry. Some pear-shaped bodies without a central filament were also seen. Although most of the bodies were more or less rectilinear, many curvilinear forms were also present. --* Some of the latter appeared to measure between 180 to 270 degrees of are. In the larger spiculated forms, the central fiber was often obscured by the thick, dense, red-brown coating. Some of the very long thin fibers (50 to 100 (i) often had segments of ferro-protcin at either end with relatively long stretches of naked fiber in between. Xn an attempt to free asbestos bodies from adherent fine csrbon particles present in an otherwise "clean" suspension, it wj subjected t ** * ultrasonic vibrations for a few seconds. Unexpectedly, only naked fibers ^.remained, and no asbestos bodies could be found in the suspending, fluid. Comments Because bodies similar to, or identical with, asbestos bodies have been found in human lungs about which definitive knowledge of the identity 4317 i.L002J623 i INOU5Tl*t HT6ICHC roi-MOATlON Of AMCmCA INC J \ u. of the central fiber is lacking, the generic designation of ferruginous body has been proposed to cover both asbestos and so-called pseudo-asbestos bodies. The distinction heretofore made between asbestos bodies and pseudo-asbestos bodies may have been based in part on what the observer believed to be an appearance consistent or inconsistent with that of asbestos bodies. More often, however, this distinction was based on the observer's knowledge that the host had or had not been exposed to respirable asbestos fibers. Consequently, it would probably be correct to say that the erueial point of difference between a diagnosis of an asbestos body and one of a pseudo-asbestod body is the observer's knowlcdee, from the case history, of whether the central fiber could be an asbestos fiber or not. Regardless of the nature of the central fiber, the bodies that result in response to the presence of filamentous dust in the lung have as a * . common feature a coating of Iron-containing protein (ferritin or ferritin-like). Furthermore, it appears probable from a study of the pleomorphism of human asbestos bodies, which was so well illustrated by Gloyne and Mercwether, ^ that differences in size, segmentation, or other morphologic features of the ferruginous coating would not serve to distinguish be'tween ferruginous bodies of asbestotic origin and those of non-asbestotic origin. Thomson has proposed to differentiate ferruginous bodies into * * ... asbestotic and non-asbestotic ones on the basis of the transparency or opacity THIS DOCUMENT WAS NOT A RECORD OF PPG INDUSTRIES, INC. DID NOT COME FROM IT'S FILES, AND CANNOT BE AUTHENTICATED BY PPG INDUSTRIES, INC. iMOUSTftlAl MTGICfcC *OU*0*TlO* Or AMCItiCA-lMC t* ' 13. other then asbestos ere capable of producing ferruginous bodies that ere indistinguishable from those produced by asbestos. At any rate, it is obvious from the production of ferruginous bodies in hamsters in response to respirable, colorless, transparent filaments of aluminum silicate, glass, and silicon carbide, that such bodies represent a general reaction to filamentous particles and are not a specific reacti a to asbestos fibers. To what extent our findings may have application t the ferruginous bodies that are being found with increasing prevalence in human lungs remains to be determined. The applicability depends, of course, upon the identity of the central fiber in the ferruginous bodies. The meth d ' of isolation and concentration of uncoated fibers and ferruginous bodies from human lungs described in this paper may help in the study of the nature, identity and prevalence of inhaled filamentous particles and associated pul monary ferruginous bodies. It is highly probable that the composition of the ferruginous body is altered by the method used for isolating them, since it is not likely that with the destruction of proteins leading to the liquefaction of all tissue elements in the lung, the protein in the ferruginous bodies should be spared. In all likelihood, the protein constituent of the bodies is destroyed and only the iron THJS DOCUMENT WAS NOT A RECORD OF U^002362r7 4313 orMousTi*k N*o*e*e * ouwoati n amcmica <nc and oUicr inorganic components remain to retain and maintain the firm of a the bodies. The fragility of this chemically altered ferruginous coating is indicated by the ease with which it is removed when subjected to ultra sonic vibrations, thereby rendering the central fiber naked. This may _ further facilitate the identification of these fibers. There appears an increasing tendency to consider all filamentous dusts in the same category as asbestos with regard to their pathogenic potential. This reasoning is probably based on a mechanistic concept of the pathogenicity of fibrous dust in general and asbestos dust in particular. Such a mechanistic concept holds that the pulmonary fibrosis in asbestosis is the tissue response to mechanical trauma produced when pulmonary cells are perforated or impaled by the fine points of the asbestos fibers. It need only be recalled that a similar mechanistic concept of th pathogenicity of crystalline silica was abandoned many years ago because of overwhelming evidence against its validity. Just as the proven biologie . "inertness" of diamond dust was the coup de grace for the mechanistic pathogenetic concept of silicosis,^ so should the proven biologic "inertness * of filamentous aluminum silicate^ have done the same for the mechanistic S* pathogenetic concept of asbestosis. Extremely thin flakes of glass may also be considered to have sharp cutting edges; yet, this has also been found biologically "inert" when inhaled A or injected into the lungs pf animals. Silicon carbide, noted for its hardness THIS DOCUMENT WAS NOT A RECORD OF PPG INDUSTRIES, INC. DID NOT COME FROM IT'S FILES. AND CANNOT BE AUTHENTICATED BY PPG INDUSTRIES. INC. ]_B 00 23626" 4320 /' f INOOSTMlAl. MTOlCNC roUNOATlON OT A*4C*CA INC 15 as well as sharp edges and points that make it such an ideal abrasive, when inhaled as a fine dust or injected intratracheally, has resulted in a pulmonary Gaining increased attention is a newer concept that the potential of extraneous trace metals and other materials associated with fibrous minerals can cause the injury previously attributed to fibers. The respirable fibers may provide a transport mechanism for dosing tissues with injurious materials associated with the fibers. Gralley et al., ^ have shown that asbestos textile workers, in the past have been exposed to appreciable concentrations of nickel, e chromium and manganese associated with the fibrous mineral and abraded from the alloy metal in asbestos processing equipment. They state further that vlere is evidence that this phenomenon exists in relation a number of other fibrous minerals. There is also some indication that the biological response in the formation of ferruginous bodies may be related to the nature and extent of the layer of metal solute surrounding the fiber. Additional research needed in these areas is currently underway. Unless the above facts are kept in mind, the finding that ferruginous ' bodies are formed in response to aluminum silicate, silicon carbide, and glass filaments in the lungs, may be used as still another reason for erron ously classifying these dusts with asbestos in their ability to produce lung damage. I_^002362'T7 4221 INOUSTVfAfc NTOICNC ^*UJfO*T 3N or AMCBIC* I 16. Summary * The mechanistic theory of pathogenicity oi dusts, which in the ease of silicosis long ago proved groundless, nevertheless has again been raised with regard to fibrous dusts such as asbestos. Reasons are given why the' formation of ferruginous bodies should not be confused with pathogenicity. Failure to understand this differentiation has resulted in some instances in the erroneous generalization that all fibrous dusts share the ability of asbestos to produce lung damage. Such inert materials as fibrous aluminum silicate, silicon carbide whiskers, and fibrous glass produce ferruginous bodies experimentally whieh are indistinguishable from those produced by asbestos fibers.- Details of a method of isolation and concentration of ferruginous bodies from lungs of animals and humans are described. With this new , technique, much more extensive studies of ferruginous bodies found in the lungs of asbestos workers with definite asbestosis (fibrosis of the lungs) have been made possible. Ferruginous bodies from asbestos fibers are * much more pleomorphic than has been described, casting further doubt on morphological distinctions used in the past in separating so-called asbestos bodies from pseudoasbestos bodies. Attempts to identify central cores of ferruginous bodies by analytical means such as electron diffraction ano microprobe techniques are underway. DOCUMENT WAS NOT a RECORD cf ndustr-.es, INC. D,D.NyT.^!JlKo :1LES AND CAN NO i BE AlO t .^A. PG INDUSTRIES, INC. l~BB_0023628~] 4S22 f IM3U$T*I*1 HTOICNC or AMC0ICA INC NOTH: NOT 17. REFERENCES * 1. Thomson. J. G.; Kasehula, R. O. C.; And MacDonald, R. R-: Asbestos as * s Modern Urban Hazard. S Air Med J _37; 77*81, 1983. 2. Thomson, J.C. and Graves, W.M.: Asbestos as an Urban AlrC ntaminant. Arch Path 1*58-464, 1966. 3. Cauna, D.; Totten, R.S.; and Gross, P.: Asbestos Bodies is Human Lungs at Autopsy, JAMA 192 ;371-373. 1965. 4. Anjxlvel, L. and Thurlbeck, W.M.: The Incidence of Asbestos Bodies in the Lungs at Random Necropsies in Montreal, Can Med Assn J * . .95:1179-1182, 1966. 5. Davis, J.M. G.: Electron-Microscope Studies of Asbestosis in Man and Animals, Ann N. Y. Acad Sci 132 : 98-111, 1965. 6. Collet, A.: personal communication. 7. Cralley, L. J.; Keenan, R. G.; Lynch, J. R.: Exposure to Metals in the Manufacture of Asbestos Textile Products. Presented at Annual Meeting of American Industrial Hygiene Conference, Chicago, May 1967. JAJHA, to be published. 8. Gross, P.; Cralley, L. J.; and deTreville, R.T.P.: "Asbestos" Bodies: Their Nonspeeificity, JAIHA, to be published. 9. Gloyne, S. R. and McreweUier, E. R. A.: "Asbestos", Internati nal Labour *e Office Supplement, January, 1938, p. 7. THIS DOCUMENT WAS NOT A RECORD OF . PPG INDUSTRIES, INC. DID NOT COME FROM IT'S FILES AND CANNOT BE AUTHENTICATED BY PPG INDUSTRIES, INC. __________________ i-TM3629 J . 4223 NOT OU.:IH0USTWIA4. MTOtCNC rOUHiATlOw r AMCW'CA.IMC " 18. 10, Kins, E. J.: Yoganathan, M.; and Nag else hmidt, C.: The Effeet of Diamond Dust Alone and Mixed with Quartz on the Lungs Of Rats, Brit J Ind Med 1^: 92-95, 1958. 11, Gross, P.; Westrick, M. L,; Schrcnk, H, H.; and McNcmey, J.M.: The Effect of a Synthetic Ceramic Fiber Dust upon the Lungs of Rats, AMA Arch Indust Health 1^: 161*166, 1956. 12, Gardner, L.U.: Studies on the Relation of Mineral Dusts to Tubercul sis. Part H. The Relatively Early Lesions in Experimental Pneu moconiosis Produced by Carborundum Inhalation and Their Influence on Tuberculosis, Am Rev Tube re 7:344, 1923. " 13. Gross, P.; Westrick. M. L.; and McNeraey, J.M.: Experimental Tuberculopneumoconiosis, AMA Arch Indust Health 19: 320-334, 1 THIS DOCUMENT WAS NOT A RECORD OF PPG INDUSTRIES, INC. DID NOT COME FROM - ,T'S F,1-ES AND CANNOT BE AUTHENTICATED BY PPG INDUSTRIES, INC. 4324 \ * UOTE- v'\r'19 THIS DOCUMENT WAS NOT A RECORD OF PPG INDUSTRIES, INC. DID NOT 00ME FROM IT'S FILES AND CANNOT BE AUTHENTICATED BY PPG INDUSTRIES, INC. fy.Z 4325 I BB 0023631~7 r zo. this Document was not a record of PPG INDUSTRIES, INC. DID NOT COME FROM IT'S FILES AND CANNOT BE AUTHENTICAl ED BY PPG INDUSTRIES, INC. . ______ 432S I BB 0023632*7  MOUSTMIAk TO)*K 'OUMOAIlON QT AMCMiCA IMC 21 J.ucrnds of Illustrations FiC. 1 Asbestos bodies from the lung of an asbestos worker to illustrate some of the more simple forms that may bo found. In addition to some apparently naked libers, there are pale, nonsegmented, rodlike bodies with bipolar clubbing. The dust was probably chrysotilc. Concentration rig. 2 method. Smear. Unstained. X 1100 rerruginous bodies formed in response to the intrapulmonary presence of aluminum silicate filaments in a hamster killed five months after an intratracheal injection of 3.5 mg. of the dust. These are pale yellow to golden in color and transparent. The central filament is visualized with difficulty because the index of refraction of the mounting medium on the slide is close to that of the filament. This can be appreciated in D where a naked filament sbout 1 p in diameter traverses the approximate middle of the field, and a 3-ji thick fiber cuss . aeross the right lower comer. Concentration method. Unstained smear. X 1100 rig. 3 Terruginous bodies formed in response to the presence of filamentous glass dust in a hamster killed five months after - an intratracheal injection of 3.5 mg. of such dust. These * bodies a p pear to be very similar to the more simple asbestos 1 THIS DOCUMENT WAS NOT A RECORD OF PPG INDUSTRIES, INC. DID NOT COME FROM IT'S FILES AND CANNOT BE AUTHENTICATED BY PPG INDUSTRIES, INC. . 0 23fiJ}"7 4S27 "----- i `* NOTE' Tw? notcc;.--.. f fNOUSTMAi. HYOiCMC rOUNDATION or AMCftlCA.IMC J 22. bodies pictured in Fig. 1. Bodies in A, B. and D Are unstained and are found in a smear of sediment btained by the concentration method. The ferruginous body in C is from a section of lung from the same animal. The section was stained for iron, but is otherwise unstained. Four macrophages are faintly outlines. Their cytoplasm incorporates portions of a glass filament. Only the intracellu portions of the filament arc coated with iron. X 1100 Fig. 4 Ferruginous bbdies formed in response to other filamentous dusts in the lungs of hamsters. A, B, and C are from smears of sediment obtained by the concentration meth d and stained for iron (Peris' test). The central fiber in A and B is silicon carbide; and in C, tremolite (talc). The body in A shows a dublike thick coating of iron at the lower end, a fusiform coating near the upper end, and a slight swelling near the middle. A blue coloration of .the surface * of the fiber extends throughout its entire length. The body in B is segmented, but is fuzzy because of diffusion f the Prussian blue color. The other two fibers in B are uncoated. A similar fuzziness is seen in the tremolite ferruginous body in C for the same reason. The ferruginous body'in D has a ehrysotile fiber in its center. This is from a stained ' sccti n of hamster lung. X 1100 THIS DOCUMENT WAS NOT A RECORD OF PPG INDUSTRIES, INC. DID NOT COME FROM ------------------------------ . J IT'S FILES AND CANNOT BE AUTHENTICATED BY PPG INDUSTRIES, INC. 492S