Document 2R7BQrgOGxkQV07pVp8b3ZMYp

December 9, 1946. Or. A. J. Lanza, Aaaooiate Medical Director, ---------- -----------^-----------Metropolitan Life Insurance Comoany, Nev XorJc 10, N. 1. Dear Doctor Lanza: .............. 1 shall be reit glad to do vhat jerricI can in reading Roy Gardner1 s uncompleted report " on Aabeatoaia and in making auch sugreations as I may be able. He vas vith ua Juat about this time last year, and I consider his loss to-aoience is a major one ^ - ' With best personal regards, I an . SlAoerely yours. IHLikbp Eenneth M. Lynch, H. D.# Dean. 2 2 12 12 2rpria?*ntI CtudiB* by TS5 SARAXAC LL30RAT0B7 AA2AXJLC UTS, CSX TORI 247art to th* JOEJS-SUXTILLS CORPORATIOI ICT TOST, nr TCKT PLAINTIFF'S EXHIBIT 3*ptrfs*r 30, 1948 /x. jl'x.a 2. irtreduction 3. Asbestos VtLncrais ABSTRACT 17. CTSUZSIAL asbestosis Expcrlacntal Methods 6. Spocies Susceptibility ?. Peculiar Characterl?tica of Asbestos 8. Rat of Tissue Reaction to Asbaetoa fibers 5. labeet.-ala Bodies 1. URLUIIOa ECPEcLDOTS n. Ring's floats Aebestcs Dust 12. Dusting Material 13. Dust Ccapositicn lb. Dust Concentration 15. Reaction In Animals 16. Guinea Pigs 17, Rate end Type of Reaction 18. - Progression 1$, Infection Coincident eith Dost Inhalation 20. Infection after Dust Inhalation 21. Asbestosis Bodies 22. Rabbits 23. Rats 2iu Suoaarr and Interpretation u Fas 1 > 3 U s y 6 7 7 8 8 9 8 9 9 9 ID 10 U 12 12 12 13 to. Ousting 27. Dust Ccspoeition 23. Dust Concentration 2?. Sixe-frequencr of Dust 30. Reaction in inlmalj 31. Ouinea Pi^s 32. Set* and type of R-aaction 33. Progression 3U. Asbeetoais Bodies 35- 'tats 36. Rate end Ttp* of Reaction 37. Cate 36. Rate and Type of Reaction 35. X-raT' Chanc* UO. Asbestoeis Bodies Ll. Rabbits U2. Rate end Type of Reaction U3t lebeetoils Bodies LU. Sunny end Interpretation. U$. 100 Per Cenv Bell-edlled iabestoe Dost U6. Duet in; Material 17. Dost Coeqpoelticn US. Dnst Concentration US. Slae-frequenc?* of Dust 111 Ui 1U 15 15 -13* 15 15 15 17 17 IS 18 15 19 19 20 20 20 20 21 21 21 22 22 23 50. Rac-ctlan lr, Animla en _ Guinea Jl^s Rata anc Type of Reaction 53. Progression Lymph Node tnrolrsaent 55. AsbestosLa Bodies 56. Rats and Hies 57. 3unaary and Interpretation 50. Long-fiber Asbeetos Dust 59. Dustins lists -ial 60. Dust Composition 61. Dust Ooncmtration 62. Slxa-CnqQeaey of Dust 63. Reaction in Animals 6iu Guinea Piga 65. Bate and Type o Reaction 66. Progression 67. lymph, feds terolreaent 65. lebestoeis Bodies 6?. Cats TO. Rate and Type of Reaction 71. Z-rajr Changes 72. Rate 73. Eats and Type of Reaction lr ?cra 23 2; 23 2k 2k 21 2k 25 26 26 26 26 27 27 27 27 28 29 29 30 30 30 30 31 MAC* Reto and T"p* * c Reaction T'u - iarsiaiy sj;d -wterpvatAt.oa .:;jcru. :r.Jzcr:cN acPK-r.--r^ 7-. 'rvCratrac-'ca.i SrptriJMcts 77. Coopariaon of fibrous and N'on-fibrous I>zjte ?C. Comparison of lirious lone-fibsr Duata Si. Cos^arison of lone-fiber ^n<i Short-fiber fusts o2. Intra'rmous fhrperisients :*3. Ir.traperitcp.scl rperin=nr.3 C3xiv. vrsnzz zlzixis * C5. ProtectiTe Action of Alixs3 Cccctisrcia :6. Conation of Aabestojia Codies L\,rrr:. -sot? .* L'irfiT actic:-* Lnmii. o^uolte-ks :3$. Infection ?0i Suaceptlbliitj to Tuberculous Infection 71. Susceptibility to Non-tuberculous Infection 72. Neopiasw rcm. COHCUSICIS XCIV. T1BI5 XCV. FIIURIS * T Page 31 32 32 32 33 2U 3b 35 35 35 35 >5 37 37 38 39 U3 - 71 72-75 aabeetoei* la a TulscnaxT disease caused by the inhalation of asbestos . Ift aninals it it character lead by peribronchiolar fibrosis which o to b* the result of flecharilcal, rather than chemical, irritation of tho tissue by asbestos fibers. Only the Ion* fibers produce a typical reaction^ short fibers am relatively inori. "The filaaantod structure of the fibers is an essential factor in the rBechcaisa of irritation. A character istic tissue response can be produced by nca-eilicsoua as -well as siliceous fibrous sinerale. Inhalation of asbestos dvxrb apparently does not alter significantly the course of experioantal tubarevsloots in guinea pigs. 7ne asbestosia body, which is a specific concoaltarrt of aabeatoeie and forad soon after the entrance of the asbestos fiber into the lung, lx believed to present further dsrage to the tissue by the fiber and then to Halt prograaelon of the reaction whan exposure ceases. Altartrsa does not exert a protectire action against the tlaaue irritation of asbestos fibers as it dote against that of <purta particLee. if373YC "13 Introduction Asbestcsis is. a. fora of r.naunoconicsic rtsulti-v. ircn rvnj.oatcc inhala tion of anhcrtos dust. Tlua iwvas isbe3tos, literal!;' 'iniri/Tiacie." is not that of a particular tinoral but Is a tent applied .to a rriaber of different drierais whose characteristic feature la * structure ccninosea of long, parallol, fLxcitLe fibers. This structure la unique beuauso the fibers are capable of repeated longitudinal subdivision to unita yf salccular proportions. In length the fibers 'n'7 free a few cacrons to r.i/: or noro inches. Sams varieties are stiffer than others but nany arc sufficientlr flexible to '> ifpun into yarn and woven on codified textile raachir.or*/, 3* Asbestos Kinarals The asbestos adn-rais are r.ilicctes of variable cor.pc3ition and belong to the serpentina and the annhibclo >prTjps. Listed beVr** .ire the sore coimon varieties, Anthophgrllite 0?e) silicate isocriU (Hg, Fa, -11/ silicate taptiiboie (Ca, Vg, I'3, il, Ha, K.) silicate Treaolito (Ca, Jig) silicate Actirolite (Ca, Ug, re) silicate Crocidolit* (N'ur Fe) silicate Fe silicate fieroentina Group Chr7S0tilt U(j silicate (hydrous) -2 Tha balk of tha asbectcs of corrarco 3.3 chryo: ^ile. 3'5C.2Si.C2.2*20, which la alnwi lr. the Ihatford recion of the frcr/wr? c: C.iebec. Crocidc- lite and erodto are also csed coee.-jrcisliy' hut ir. sculler amount*. Chr78otil occur? x reins in serpentina, a fair,era! rr'i: 1q ciiarical coa- poaitlcn to chrysotiia tut T.tiich exists in n&ssiva X'arr. and is cade irp of nicrcacopic fibers without tha parallel oricrnts.ticn characJuristic of chryso- tll* Tha aaaeiva blue black eerpeaiir.e which i3 r.ooth -\r.d soapy to tha touch. Is traversed by rain? of fibrous chrysotiio varylas in width frosj a barely perceptible tin* to sir or joore inch. The fiber? run aeroas tha rein end not lencthwis* with tha formation. Attention is directed to tha sdnaral brucite, YrC.F.oO, rrhich is often found in the saaa formations with serpentina ?rd chrysotils nod aay be fibrcua in structure* It has no cccrsatrcial value at present J.^causa its fibers ara not sufficiently flexible to bn usee in textiles hut thsy ara capable of repeated lan^itudir-tl yubdirision. Unlike oth<?r esbostlfora minerals, brucita is not a silicate end for this reason it has boon a valuable '-col in an axpcrircatal evaluation of the action of fibrous cinersic upon 1-^ tissue. 17* sxpsmfgrcAL asbestos is For cany y&sra studies have been carried on by the Saranac laboratory in an tnvfstijixion of tha cszxss, nature and developssnt. of asbtstosii. The present r part is devoted to ExpsriasatAl Ishestos.lSo In it are doscribcd tha active! ex periment# with various kinds of errbeetnn dust, /-rather report, to bs pr-spars'd and if.jjvyftd liter, sill b* ccr.cwmnd th Human Jt^beetonia JJed rill cover ha ha* aspect* of sorters srtv> here b*-*n to asbestos dust in an industrial enviroooent _ . _. ^ ours ;"p*cie3 of Ant~-.* charmct-ar- iatic tissue change rtilch siaflsr to the lasicns of human aabeetoala. Siaca the Lif*--aroan of tha rprl;^nt-il ar.is&i is relatively short, it is not poaaibla to ia-rmirp the cnaract*ristic lesions in animals undar the usual industrial con ditions. Con*t3aiCTUl7'; to obtain a coarnlets evaluation of the tissue raepcose to inhaled particulate and fibrous notarial, it la rcessary to accelerate the reaction by employing higher coccentrationa of duet than would ordinarily be o> counters! in industry* While condition* of sacpoeure are thus different, tfw infera*t ion yielded by erperinante with aniaais la invelazbla in furnishing a better urxi eretending of the reaction of the huaea organ* saa to inhaled aeboetoe dust* 5, Zxneriaental Methods - 7or investigating the biological reaction of the experlaental arlaa.I to tbr various aabeatos xiaarala, ts* type* of technique hare been employed, ruoaly, tha inhalation method and the infection method. In inhalation experiaaots, groupe of animals - up to 100 or sere grrtns*. pig* and eooetisar* eoallar sabers of rabbits, cats, dogs, rtxt or idea - are kept for asht boors a day in a cubical dnrt rocs, eight foet in dlaanslon, in vfcicn a cloud of asbestos dust is Maintained. , it isterrals during the experiment, 4. fan? ar.iaala are aacri fined and the tissue snsdned to dxtsrntas the cstura and extent of tha duet reaction* 3oe enlaals are exposed for psriod* op to three rears. Tha injection experiments, in which the dust, either dry or fuspeodgj. .ia noddy is introduead into the ardaal by the intrareooua, Lntraperitcneal or irtr%tranfael procedure.' are used to determine whether or not a particular dust h* *. potential capacity to produce tiaaroe reaction* Long-tarr* inhalation fumiih infcrr.ition upon 'dvVch great raJLi- snca Is placed whan ecrtlxstinc t-h? negTe<* to ahich & cost might be hazardous to industrial rorkora. Whether cr not stoospheric duct, iireo tlvcrugh potentially dangerous. can be inhaled, pars the ruturil defense barriere and reach the pul- raonarr tis^ua In quantities sufficient to causo danesra can hs detemirc-i only by inhnlsticn procedures. Injectics experrinonta oro useful t-sreeus* in then contact between t` s dust partiola and tissues is assured and the potential capacity of the curt to produce reaction cun be eatisated accurately. l*hen dealing with fi brous ainerala like asbestos, the intratracheal nsthed is rslushla ticca it j-r- aita obferring the effect cf the fibers on pulcsoncry tissue. 6. Speclea Susceptibility Unlike free silica, esbreto* doe* sot axert ita specific sffact in ail erg-ms of all species of antoaJL (Table 1). Injection of fine quarts into various organa of the guinea pig, rabbit, ret, cat, dog, chicken and ever. tadpole will produce silicotic cedulas. Kc/egrer, sisilar iajacticna of long or short fiber asbertrs h&T resulted in L flbrcm* reaction in tho lung urd, to a leaser extent, in the perltcneua but net in ether organs. 7, PecuHa- Characteristics of lebeataa Experience has dsewtsstnted that asst of the psrticuiats sat ter inhxlec into the lungs of asa sad la ID oleroas or lass In ecslxun disaster. Larger particles apparently are axcialsd by the protect If? w*--h*.ni.ra of the upper rasplr- atorr tract, la the cam of fibrons sateriftla, benr^rer, this restriction dose &="- ppiy end fibers 100 end srsn TOO Einrons In length hare been found In the torsoc-- al air apece* rf huaan Ijags. In aaall laboratory aclasis expceed to aabasto* dust the langth of fiber fortnd in the Iun rarely sxcasda 60 cicrona. Rot every kind of flbrouq eaterlil is inhale ^th e^zal raadi naas; for exastpL*, the synthetic fibers of glass ^ol apparently.' are too inflexible to pus easily throurh the nose, pharynx, trachea and bronchi and celdon roach the terminal bronchioles and alveoli. Inhaled particulate natter cooes to rest throughout the teraInal air spaces (alveolar duct, atria, alveoli) la all parts ->f the luarre; inhaled asbestos fibers are first retained in the respiratory bronchioles. These very smaLL tube* are Ismablately distal to bronchioles lined by ciliated epithellva. Their enro essen tial lining la s las echoidsi type of epithelium but, as their name 'allies, they actually function in respiration through lateral alrccli given off as pouches along their vails. Either these pouches, cr the abrupt change in the character of the l i-iing epithelium, or the decrease in diameter nf the tube, or perhaps the crgfalhation of all three i'actcrs is responsible for local retention of the inhaled fiber. Only after asbeatoeis is veil established are appreciable numbers of fi bers carried into the sore peripheral air spaces. 6. Rate of Tissue Reaction to Asbestos Fibers The rate of tissue reaction to asbestos is nuch zore rapid than to on active dust Ulc quart*. Evidences of tissue response appear as eoon u fJbers hare localised in sufficient concentration in specific areas. In rit# receiving asbes tos fibers by intratracheal injection this evidence is rirlhle. as early is tvo wok* after lAjectlooj fer quarts dust, ths Latent period s&ght be tvo re-.ttw or eerv. The behavior of Una tiaras reaction to Inhaled dust After the Unairution of ecoorure 1* not the same in rUlcceis as in asbeatosis, In silicosis, the young nodules becooa larfsrj in asoestosis, young ecar tissue, that nsy.hare fo'.mjed,cootracts and becomes acre dsns* tut the are*, of inrolTea*nt decreesea in site. If exposure to asbestos dust is tsrcdmted after a brief period, the recently-inhaled fibers in the lung zs? cnusg the fibres tinrae rc3pou2* to continue :or * ahorc tlj; or,til the fibere h*re bean coated. TMa orogr-ision is ct only a alight degree And of Little significance. 9. labostogia Bodies Tli* pecuHtr structure tonro 53 the aabestoaic body or curious bodj- is a specific eoncositant of asbestosis. The typical bc-Jty is a gaLden-yellcw, beaded or haustrated rod which ssscr be sdther straight or curbed. Often ens or both ends are bulbous Hies a duab-bell* The bodies vary cons idarably in length, and di ssensions up to 250 dcrons hare been recorded. It la beULered that asbestoais bodies are evio to a deposit of protein and. iron pigsent upon the surface of inhaled fibers. In guinea pigs they for* after about 60 dar* ef contact with the tissue. They are abundant is nan and tha guinea pig ($ Table l) but are ouch larger In the foraer, probably because thsi largersited air tube* adait fibers 0" greater diasnslon. In cats, rsbbita and ssioe is an atypical coating of a few of the fiber* after auch longer residence in the Inns*. In rats arsd dog* no bodies could be discovered. 41though the rrldaca is inconplete, it appears that the fanra.lion of the asbcot-osls body prrrsnta dcrags to the tissue br the fiber. 2. DIUIAIICK E2PEUHSHIS ?cur cgarirahsoalT* inhalation erperiraortta here beer, conducted at the Saranac l*l>ort;rr-rith. rtricus feras of asbestos dust. In each of these irrewti gabions nor? than 1^0 eri.rj.if- rtrs t^d ar<t the sxpsriaanta carried cm fer pariodo ranging frra ? tc asare. this 5 ptsra. The fo** Vlnds of s^beato* durt c3pio7?d are ldeotLCUd as Ir?*o fl&aU, ahort. fiber, IDO par esnt baUj&llsd, acid long-fiber asbestos dust. 11. Inhalation &roerlr*nt vith "Xlrur's floutsisbestoa Dust The first inhalation -orpcrinent conducted at the Saranac Laboratory rith asbestos dust was begvsn Is 1/23. Aairals inhalwri the dust far periods up to nearly three yuare and sea* guinea pigs lived for about four years after their first exposure to dust* 1 preliminary report jiving oboervatioas after 29 months of exposure appeared in the February, 1931 issue of TK3 JOORRAL OF INDU STRIAL KTuIENB.* At that tine observations covered a period of only 2-l/U years and the conclusions as to the ultimate effects of inhaled asbestos dust were provisional. Results of the completed study shor that most of the conclusions drawn in the preliminary report vers substantiated A complete review of this experiment fellows. 12. The dusting saterial vaa a cocrvercial variety of asbestos dust Vcnovn as Sink's floats and rue ccomposed of short fibers and particlas of variable size. It was obtained frees, the Thetfori, Quebec plant- of the Asbestos Corporation of America,. 13. The dust cocaositing (Cable 2/ reveals that the amount of fibrous chryse tils mu only lu per cent, a rather leer value. However, there was suf ficient fibrous material to produce a characteristic fibrosis. lit. The dust coocectratigr. at first v*s quite lev and f<rr irpingsr ssapiss taken toon after the experiment v*s started, ths average light field count- by the standard technique js only 6.0 wHlion particles per cubic foot of air. An appreciable amber of ler^* partAelf* (or filers} also wre present, c* STUDIES OH EDraUkDftlL FHCacCCSICBIS. 71. Inhalation of Asbestos Dust., Gardner. L.U., crai Cuaatngi, D.E. J. Ini. Hy*., 13* 97-lU, 1531. shown by n average count of 0.8 milion far particle* greater than 10 nlcrons. After the inhalation axparixant had been under way for about tro years, the epaad of the rotating paddle in the duet inf aachlna wwa increased and for the rameinuig ? or 10 souths cf th* arpericoat considerably cwre dust waa dispersed into the ataceph-re. Average dust counts for iitpi/iger sssipla* collected after this change were 53.? Billion for the usual light-field nethod, and 1.6 oillion for particles larger than IQ edemas. 15. Reaction in Anlaala to Inhaled "King's floata* Asbestos Duet. Esuite of the investigation, briefly aassaariied in Table 3, show that inhala tion of King's floats asbestos duet produced a typical peribronchiolar fibroaie in guinea pigs but not in rabbits or rats. 16. Quicea Pigs, iersn croups of guinea pigs wsrc n*-d. In three groups the effect of a continuous and of an Interrupted dust oposure i*as studied; in two other groups th* r slatiocs hip between infection and dust exposure na irrrertigated. The resBinirg two groups were infection controls. IT. Fate and Type of Reaction. Qcinea. pigs Inhaling thin dust for period* up to 33 souths dvr-loped a characteristic fibrosis occurring in conical patches about the respiratory bronchioles. Daring this eepoeuro the peripheral alveoli were not ir7rolv*d = The particulate elacents in the dust wiera transported to the lycphatlc ajzUsa. where they caused no signi ficant reaction} the fibrous eleaanta ressinsd flari z\ the site of original locaiitatlou and wwrr seldo* detected la the lyEphoid tissue. rLsurisv and fi brosis is the septa were ct#erred only whan infection cccplicated ths procaaa. After exposure of opprmdLjrately a ywr, a snvtJLi aaount of cellular reaction had beta produced about ary respiratory bronccdale*. As tern dust was inhaled, it continued to accurnlato in the sacs location, and later stages ef the disease consisted of extenaions of the original lesions. Him ?u*oaL5 not l/irolTotj* Appereatly, the inhaled fibers rre caught in the pockst-lika alreoll that aro given off from th# lateral walla of the respiratory bronchioles. There they *ur phagocytized and cany of then were carried into the -sull by srlgratory cells. libnonuclear leucocytes attracted to the area caused i appreciable thickening of the bronchial rail. After 16 nonths a delicate fibrosis -bade its appearance. The process evolved so gradually that uitotic division of fibroblasts could rarely be discovered; nevertheless, the msaber of fine intercellular collagenonr fibers (fibrosis) steadily increased, As this fibrosis contracted, it partially closed the alveoli, and with this atelectasis the epitheliua assnned its ofcT7onlc cuboidai fora. The result urns the aderwca-Uke appearance that 'Billis described In guinea pigs inhaling silicon carbide. The longer exposures resulted only In acre thickening of the Trails of the air spaces, largely due to an in crease in the osour.t of fibrosis. The fibrous tissue always regained cellular and never showed the hyalinisatiou characteristic cf silicosis. Ifl. Progression. Tha reaction produced in exposed guinea pigs did not pre- gress significantly during a subsequent period of 37 rertthj whoa the lived in a aontsi atroephers. Betxeem li and 11 oonths aTter exposure ceased, the cellular reaction had been cocpletely replaced by thin strands of flbrcua tissue. Observed still longer, the scar tissue decreased la uaoorrt bat in the last entail sacrificed, 37 acevths after discontinuing dust exposure, *a*e flbroala vms still risible. 15. Infection coi^idsnt with poetInhalation. Of the group of LO guinea pigs infected with atten uated tubercle bacilli (R^ strain) 31 died or were sacrificed before two years of dust exposure and were reported In the paper b7 Gardner and Cvisaings nentioned above, Seventeen .cf-these died fron intercorrent- pTwrurttnii. Briefly, the re suits -nr* as follow* t 10 revealed soue evidence c' * pro id ;f the tubereuicrus process; is 6 of these it was confined to the lungs Aid in the other 1: the ebdostlnal rlacer* also were involved. Usually & slight local extension of the tuberculous infection had occurred 'out subsoouant hsoling had resulted in fibroeis of both the puiacnary lesions and the secondary lesions in other organs. The healed pulmonary lesions showed acre fibrosla than is characteristic of either tuberculosis or asbestosis alone. The 9 animals switch ware still alive after two years of dust exposure were sacrificed at intemlf durinc the folio-wine year. In U of then the primary foci of infection had healed with fibresis and ren calcification ?nd there wus no rrideace of progression. In the other 5 the tuberculous foci shewed rrtdanca of haring previously spread locally: in U of thacs it had healed, by the tiae of autopsy, with excesaiT* fibrosis i in the othsr animal there raa a generaliaoc chronic tuberculous pcemonla in one lobe and isolated primary tubercles, ebich were still active but had not spread, in the other lobes. Evidence of extension of the infection was first sasn after 7 months of chartinhalationj during the rwrt 20 months dott than half of the animals shoved an actively spreading tuberculceit and in 3 of thea small cavities had devaicrped. During the last S aocths so animals exhibited any evidence of active infsctica although in half of t*vsi th* haaLcd fibrou? scars cf previous extensions verc ob vious. Sixty per cant of the guinea pic? with oprsading puiaonary tuberculosis showed tuberculosis of tbs spleen and liver. 20. Infectiom Saperlrpoeed Upon an Satabllshad jabortceis. Ibraire guinst pigs, after in haling asbestos dust for nearly 26 months, vers infected Kith tubercle bacilli and then reacred to normal air. The subpLsural tubercles in the dusted animal* wrs t.7 cere nuaercua than in non-due tad oruvirols, but a considerably runsiXL- zzz<:. found in the depth* of tbs lung about foci of asbrsiw-aia. The reaction to infec tion showed only slight local extension atout the origirsl cites in the i-jne-e and tracheobronchial lyxph redas. " *7ris oMoninal viseer* nare involved in only one aninal. Gacettion was found in tubercles 1-1/2 months old bat by -1/2 nanths it had ccnnpletaiy dia%rpear<rf. leaving only scru* tissue, ?ne latter still persisted in the last aninal, which wae VrIliad lb uonthe eiter infosticn, 21. Aatostosis Bodies.. Ibdarit* mtebers of asbrtosi3 bcdlos occurred in the lungs of the guinea. pigs, bscoring saa rusuai-ou* and core distinctly aesjaented in later amthe. 22. rabbits. Rabbits exposed to the &ebeatas durt for poriedo up to 19 nontha developed a low-grade foreign-beefr type cf reaction tut no fibrosis, Although 1-hair, lung contained particulate eleamt* of the dust, fibers were rsert present, irdicstlng tfc*.t t-b* upper respiratory sajchiMiiaa of the \ rabbit is adequate to cjcclurfs fibrous foreign bodies. '!vro rabbits, after inhaling dust for 6 and lb .-aonths, lived La narta&i air fc?r or* than tw yssrs., it autopsy neither anisai showed sny eridence of cellular rttniicn or fibre-a in L tic tazurlnai brrcchicl&s nor rare there y fesbeetc*a bodiM. 23. Fat*. ill Lb* Thj.be ret* had. acquired an ir-factionf resulting Lr. tha fomatlco of pueonacy ihaciww, before they cas* to autopsy:. Apperently, sc such h**T7 tocos obetruoted tfusir bronchi that vary .Cr* fib-ers could ha** entered Lhsir lusgs. In & ff?w of hhp ?its} an uccasiojuu astoatoe** body wts discovered but there *u no fibrosis. 2ii. Svamarr gnd Ictertrrtatlon of Inhalation Experiment with Xlrg(s floats Dust The findings in the erperlwint xi.th King's floats dust can ha suxaar- ized under three headings. A. Effect of the inhalod dust on normal nnlrAl_i. The ling's flcata dust caused a charfl-c- terisrcic peribronchiolar fibrosis in guinea pigs bat not in rabbits or rata. fibroai* did uot progress after the dost wrposure was discontinued and the guinaa. pigs transferred to noraal air* 3. Effect of tha Inhaled dust pn tuberculosis in trainee nigs. In guinea pigs in fected with attenuated tuberclo ucjcilli snd then placod in tha dust roce, the results were sorts Turi&bi* than in usual in an erperinant of this type, l few cr.laiia showed no sign of progression; ir. rawt of then there was oridsneu of teaperfiry progression rlth r-ubsequent healing; in one animal there was continuous / pro gross ion to death. In contrast, when guinea pigs, after being inf acted, are exposed to quarts instead of asbestos du.it, the infectious procasa corrtinusa to progress and e rwr.tufl.llr reuses the death of the aninals. Oo the other haod, ex posure of infected ani.'Bftl* bo a hamlees dust liVw ralcit-a or gjpsua doee not lead, to any progression of tb infaction. Chsinaa. pigs infected with attenuAt-ed tubercle bacilli follcrwlag tha termination of about two Tears' exposure to aabeatos dust did net dwrwlop prograaaire disease. The cnlj modification of the infection was in its Localisation, a few bacilli being retained ir, tha fibrous tordinal bronchioLsi and foroiru; tobwrclos there in addition Vo the usual foci bsnsath th* pLaura. In rierw of this rarisbilitj, tha unusual oatur* of the response and tha high propertlcm of daaths fma lnterciJrrwifc pn.rznouda it ix felt that deficit* conclurtonw as to the Infineon* cf thix jfcsafc on the course of tuberculous infection are not Justified. C. iffact of tuberculous Infection on ths rrar.T-lo;. ?,<; ihaleddujt. Infection cccplfcatlng ishoetosis accsntuat^d the teaiancy of the dust to produce fibrous tissue. This charge occurred ohc-her or not the bacterial lesion vaa in contact with tha arse of dust roactioa. 25. Inhalation Ercarlaeot with Short-fiber Asbestos Duet. Slaca baxsa dons duets Uics quarts ere aoct effective is producing fibrosis den the perticl 45 are 3 aicrcns end l*oe in size, an inhalation experiment vas carried on to determine whether thin condition is true also for asbestos duet* It was thought that by using a short-fiber uebwrtos dust consisting alaort entirely of fibers and particles smaller then 3 dcron* an accelerated tie rue response cigri be initiated and an advanced reaction obtained in * short tics. Trie previous Inhalation experiment with Xing's floats asbestos, -*hieh ccnrvUdasd fliers iron 1 na. to 1 derert or lees 12. length as uoll as a great deal of particulate natter and which produced a typical peribronchiolar fibrosis in exposed guinea pigs, eerrod as a basis of comparison. 26. The dust lap material for this uqjuricst Teas foi-inardsci from tha itarrille plant of the aohn-Jstrri 13 r, Caryeration. It =us th* remains 01 fibers collected in dust bins after a carding opcraUxn and ocrwnad to pass 200 nesii. Since the wateri&l as received caataijvsd rarrf 1xsj fibert, l.t m grouiil In a eteel bell gill to reduce practically all the partideg zo 3 stereos or Leas in size, then used *loo in & rtaaiard dusting Hachirst, this flnfely-grtnird asbeeto* tended to pack In the hopper and it b*c*n* nscaaitrj to dn ana vclsss of lhe un ground saterial with three volcostf cf the grmi to goraravi & satiafactarv dost dead. IT* addition of the *fil quantity of unsrcunl a*b*rtos -rza, -srJbrt-imtt because it confused the istarprutstioc of result*. Probably the sincr cactast of reaction that developed ' ' i ta the Lang fibers in the edxtttre although the data of 1&3# erperia*. do not. prcrrs the point. cogporttdcn of the hort-fib*?r oobestes tvs raceiv-d lc diicicsrd by chaericelspd petrographic analyses given in Tafclo U. Sables taken before endeafter jrisSHaag yielded about the zaaa roiuea on analysis, indicating that thers^ae no coning*-*nation froa the aill cr loss ox* water content. a 28. drat ccaragatration variod soaestmt during the experiment and light 4 SUrtd counter Tor atacspheric sacpiea collected inside the antral cages with the hunger sppenrtus ranged from 63 Billion to 182 aiHion. The average of 6 coats was 20 rdllioB foz the first year of the eonperinant, 13l million for ttai * second ye fnd LuO afllioo for the third year* * 29m 53ay e-frag nancy. oaasnrtaenta of air-floated dust froa inside the cages at. a signification of 13CGX rerrtied a great prapcmderanca of fine par ticles (7abJ$ 5). Nearly 90 per :wi of the particles seen were eaaller than 3 aicronso . 30. Reaction in to Inhaled Short-Fiber A-ahrstoa Dust. Four epecie3 of-ardnals - peine* pigs, white rate, cats and rabbits - were used in a this experiaent. The result* of the dust exposure, which arc girawtaed in Table 6, will be considered sore in detail belew. 31. Guinea Pitre. Eighty guinea, ptga were originally placed in the dust roca : but 21 of ttuss were later eUrinated fhea the erpartneat and killed beesnae of enlarged lysph nodes, Of the other 59 animals, 1*6 regained in the dust rcoa until they -ware sacrificed or died free natural csoses and 13, after being epoead to dust for 20 aonths, rare transferred to a noroal atcorphsre. 32. Rate and Type of Reaction. The type of tissue reaction to the inhaled short-fiber asbestos weta essentially the saoa as that already observed fa tYm axperiaent Kith Xing1 c floats Acbecton. The rats of reacti.on also was approxi- ciately the scoe bat the extent or involvement uith lha snort-fiber dust was very mch less sad after 16 to 2li couth:* of exposure only a vary few <ma'n feci of reaction, which generally required cicroacepic wrerination for detection, were produced in ths CKtuaa pigs. Until exposures had continued for approritaatsly cqo rear, thers was little tendency for dusWcntaining phagocytes to collect ir.tc ebsapa. By 16 aonths phagocytes had begen to collect about tho walla of a few of the respiratory bron chioles with a little proliferation or infiltration of nonenuclear cells La these walls. There were!*lso sons traitlnuciaatsd calls but they were always of the inert forsign-body type. At 20 to 2li oonths the cellular eiueps were sonatinas quite narked and soostiacs change3 In the epithallvia resulted in the edenana-Hka or "tdanorfetoid'' appaarxace previously described in Section 17. la nost of the subsequent wabers of the asries, the reaction rocaiaed oellular in type. la a fee, howwrer, fibrous elaacats docii-ated the picture. In the latter case, the collagen was \al3 in color and tenuous with no hearry swollen hyaHnization. As ia the rats described balsrx, tho alveolar walla sight be tauie up of a baal of collagen supporting a Layer of epdthoLust, but with m contained capillariaa. In the tracheobroocfcls.1 lysch nodes? the reaction wss eors pronounced in this experi ment than ia the prerio^a cess with King1 a .floats asbestos, probably becaaee of the transportation of r> ccceag of fins particles t-o tho nedss in ax-r-als inhaling abort-fiber asbwwto.e, Ths reaction rrsjt ^sasntiaily an increase in rsticxiu;, rather than, a fibrosis- **ith prtserration of tluj original cells bsbwewn t-hoi thickened reticular fibars. Clffua* chronic plour* Ltaout rridsnes of palccnary Inf set ion wa present In a far js. rrcfrwgicn. *n trm .^:/u cn:.ns follcrriag ti>; cassation af 20 ooaths' exposure to dust-, urogressinn of disease wbs not definitely daaonjtrat-frd but neither cculd it ?*e absolutely disproved, awing to the varia bility of the response i_n differor.* inihw. ' it the end of the iu-t exposure of 20 2Jontha tire pigs wre read as * and ons as 2-*. .'0003 the 13 removed from dust the findings vers variable: in 2 the reaction vtw i; in li it was *; in 3 it ** J*l in 3 it was Uvj and in one animal it was $*. It is quite possible that those with the oost narJoed changes had already derniopad more reaction than the reoainder tv the tine asposure coasted, Since the mors ssvar-e roactlcns occurred spora dically and bore to relationship tc the Length of tine after ceesstloo of expo sure the differences were attributed to variation in individual scjcaptlMlity, This view received support frea the cheoical analyses (Table ?), which often re vealed comparable aawunts of ash and oilica in lungs with widely different mounts of tissue change. For example, the ash and silica vsluas were quite eintlxr for three anioals in duet 20 sonths and thoo in nomal air 13-3/1: nonths, yet the tis sue reaction for one anisal was L*j fee another, *j and for the third, only t, 31. iabestoeis Bodies. The formation of esoestosie bodies wa *t first ex tremely limited* After 5 nontbs' exposure only a very rare short body could be found, usually inside of cells. Around the finest Intracellular pertislee there were yeHot depoeita haring the sacs* color ea the asbeatosle body. Scpocur* of one year had psnxitt-sd tn acdnsalAtlna of aany longer fiber* about which the asbestos Is-bcdy coating devolopod. toot cf these ware still short enough to be partially or antirely within phagocytic cells. Dy the 20th oouth and thereafter, they w*re comparatively auasrcua although still rare in comparison with the findings in the King's floats expertaant. ^1 35. TTKitjr Rata. SsTenty-thrcre white rata w-ore axpos^d to atoospharic shortfibcr asbestos duct for periods up to 32 norths. Sacri ficing duri~ tho flrot ID tenths wo rade bitentHy and for the resaindsr of the ax-parlacr- <e.t lass frequent intervals.. 36. Hat-a ard Tyne of rUactloo. The dart calls until 8 aonths Tars widely scattered and acd-rted in foci only a poradi cally*. Ksactiac vaj Halted to occasional slight thickenings of the septa about mall tCQiWiIall oas of dost colls. In & few rate at ID months, there was a sugfestloQ of esriy fibrosis but the change was so slight that It would probably be overlooked vittout the clrnrp cf dust cells to attract attention to the area. Only ID animals were exposed froa 12 to 32 nonthe, In each of then the lungs showed s&nuta patches of well-defined fibrosis distributed like that of asbestoais but without asbestosis bodies, wxe lesions, visible only at a signification of 150 disasters or care, consisted of patches along alveolar ducts in which the walls of the sir spaces were vary thick, due to swollen collagen framework. Comactire tissue and Foot--Dielschowsvd silver preparations revealed carpla to loss of capil lary bed locally. Outaide the collages was a thin layer of epithelial cells. This did rot retells the 'edasacaatoid'' change characteristic of guinea pig os- bestosis. Uo plerurl*7 was present. Hoar the lesions the air spaces were filled with phagocyte* containing gray' to yullow particulate dost end a rare long naked asbestos fiber. Careful search failed to reveal ever, a suggestion of aa aebesto- sis body. The trscheotaroachlel sodas shewed compact focal collactlcru of oooo- cytic calls at 12 south* and, et 20 amths, soee diffuse thickening of Vn* reticulaa. In a few rate there was definite fibrosis along the margins of the node and extending Into the nodiartinal areolar tiesrue. Compared with the response to active dusts like quarts end chert the reaction to rticrt-flber asbestos was negligible. ----- ------- Result* of chAsicil analyses roce on the white rats are given in Table 3 and the average values have been tabulated in Table 9 Tor comparison 'rdth siatlar values for rata inhaling other dusts. The concentration of atmospheric particles to which the anicals were eoeposed wnj approximately the saae for asbestos and quart*; for the j&psvra-qusrt* sixture, it was about twice as high and for chart five tines u high. It ttUH be noted tliat the percentages for asbestos are lower than those far quarts or chart but are similar to those for the gypsuo-quarta mixture, in 'which atmospheric agglutination tended to reduce the anaunt of dust inhaled. It edght be inferred that the total.quantity of asbestos dust inhaled ns low or that it had been eliminated from or dissolved within the lungs. In the present state of coir knowledge evaluation of these hypotheses is not possible. 37* Cats. Twenty cats -wars used in this inhalation experiment with the short-fiber asbestos. Eighteen were kapt in tha dust room until death, tha exposure period ranging Iron one month to nearly U--1/2 years, and two, after a dust exposure nf 31-1/2 months, were rwsoved to normal air. One of these was sacrificed $ months, and the other 2lx nonths, later. 33. Rate and Type of Reaction. The reaction was essentially that to as inert dust, even after mors than U years of espc-- sure. The tissue response in this -pecioa was confined to microscopic foci of fibrosis In the vails of groups of aufcpltvral alveoli, rather than ir. the peri bronchiolar areas. In one animal the change vs* extensive enough to be risuslixed on gross inspection of the section. J9. I-Zxt Changes. Only In the animal with tha longest exposure did the I-ray reveal definitely abnormal shadows. After 29-3/i* cocthi the picture was negative} after L5 dotthe a faint mottling could be detected tlirou^hcut beth lunge, it autopsy, S months later, there was only microscopic fibrosi.3 ir. ths subplanrai. cons plus h&.rrr lyuphccytic infiltration about. szzll bronchioles. fcO. Asbestosls codiss. On prolonged search a fsrw yellow atypical asb . os::s bodies, eaooth and without vsu3tratiorui, *rt; fours! in two ar.l.-uLs erpcsed for oore than a year. ill. Rabbits. Eight rabbits were exposed to dust fer periods axteeding Croc one to oora than fira years. Tha last anisa&l was renewed fr tha dust rocss and left in norcal air 6 souths b*far being sacrificed. k2. Rate and Typo of Reaction. There was nerer enough fibrosis to be de tected grossly and there sms ao chronic dhasire plsuriy/., llicroscopin errldcnet of alwecLar wall thickening was first detected after about 3 years of ezpcwrs and was seen in all fire snisals examined thereafter. In cm aninal that died of paralysis after nearly four years of ex posure the reaction was sxten3l.r* enough to bs risible on gross inspection of tissue sections. The possibility of pulccnarj' infection in this arlral could not be ecrelwiM. Kcrarer, ir. another animal. dying trr- years later tha fecal fibrosis was not nearly as afrrlsus or as adrwnced. Areas of irrrolvencnt, which ware Largely vlsuallMd be-sns-t of phagocytic reaction within tha air spaces, tended aicroacopically to become aora fibrous with the passage of tine but there was r.rrsr sauch ncroaciuwnt upc* tbs luwan of tir rpacs* and the axrhltecturt of tha lung was pre*rrad. U3 Aabggtosla oottLss. Aabextn* bodies wure not detected in rabbits that died early in the axpariaant but ^en seen in all fnlnAls that had bean deposed to the dost for tort than throe years. l*ii. Sucnarr and Intgrnretatj on. Th# original purpose of the expr-iaont was to <rraluate the chemical thoory of the pathogenesis of asbestoais. It was felt that If the tissue reac tion to asbestos were chaoical in origin an i. Lerated cr accentuated response would result frca exposure to finely-divided asbestos, u ii the case with quarts. This experiment, in which the reaction was slower and less extonaiwe than with King'* float*, indicates that the reaction probably is not primarily chaaical in nature. Of tho four species exposed in this experiment only the guinea pig aod rat reacted with characteristic peribronchiolar fibrosis. The cat reacted with atypical rub-pleural fibrosis and in the rdebit the fibrosis which occurred could not be positively attributed to the dust because of a strong possibility of pulmonary infection. to. Inhalation Experiment with 100 Per Cent Sall-milod Asbeatoa Duse. In the inhalation experiment with ahort-fil-er asbestos dust a small quantity tf uaground aaoestos was nizsd with ground material in order to produce a suitable dust cloud, when evidence of a dust reaction appeared in the guinea pigs during the experiment, it was not clear whether this was a tissue response to t'ns number of long fibers in the unground asbestos cr was a delayed effect of the core abundant fine duet. Consequently, another inhalation experiment was started in which no unground material was usod. iib. The dusting material was the ground short-fiber asbestos used in the previous inhalation experiment but no unground material was aixvd with It. To obtain 4 sufficient usdurt of atmospheric dhirt, th design of the dusting apparatus was changed to an open type of hopper and fresh dust was added daily. Crrtrv? to tha tendency of the cstcrial to Com ssill sphsrules which. prevented ouch of t-h* fibrous portion fvca floating out of the hopper, the dispersal of the dust -mo r.ot entirely aatiafactor*/ and after 7 months of operation, the dust in? rr.ci'.i'in v&* ucerrrorted to its original doaiyc. To prevent "pilling" or the fonsr-.r-ion of spherules of asbestos. Steel wire broshe3 r/ere attached to the in- . sice eurface cf tha hopper and to the rotating naddi. This arrangonett gave satisfactory rerule- and was used for the rexcalning 1 Booths of the experiment. U7* The corgosition of the r.nr raterial (short-fiber asbestos) and of atxaosplieric dust liberated froo the ball-exillad product in the dustlog ea ch ins is jiven in TabLa 10. These values are based upon petrographic study and X-ray diffraction arm lysis. The atccspheric saapl* was collsctcd r.ith aa elec trostatic precipitator after wire brushes had been installed In the dusting machine. Previous to this, the chrywotils content of the air-auspeaded aaterial was undoubtedly leas than the IS per cent value given Id Table If). In an IntarIn report, it rae stated that tha air-borne dust contained about 5 per cent of chrreotilc before t a wire brushes were used cal up to 8 per cant afterwards, but these raluaa were probably lew. Quantitative; estimates cm bail-alllod asbestos dust nay be soagwftat inaccurate because it is difficult to derter=ce how nich of a dust aaaple is Xlbrcmi cfcrysutils and how tauch is non-fibrous serpentine. US. The dust conoogtratiou for the first 7 oocths of the experiment was about ICO cLUioa particles per cubic foot of air. Alter the vtro brushes had been lcstalled-, tha dust counts were a littla higher and the overall average for tha first year was 1D6 aillioa. Tha average of courts for tha second year w*s 163 nillion and for the third 7oar 1U5 million* L$>. The gia-I>raeacr of t!v- rccpcrests of atioepheric dust collected inside the nitr-al cures rrith `-it: eLsctrcccatic apparatus is reported in Table II. Tnc oaapljrs wor: taken. om before tr.c '.Tire oraches more installed and one aftar. It *112 bu noted that aftor the irir-j brethes wtsre in uuo a greater proportion of r*r/ fine port idea and also of longer fibers was released into the air. 50. Reaction in animals to Irnalad ICO pgr Ce;n: tiali-Ulllad Aco^stoa Ou.-yt. Guinea pigs, rato and nice rcre used in. the inhalation erperirent with the ICO per cant bell-rcilled asbsstoo dust. The results aro surzarised in Tabic 12. Jl. Guinea Piga. Toe e*periacat true started with l0 guinea pigs. As the dust, oexorurc proceeded, tharc \rcru 39 accidental caath*s 32 of pnetconia in an cpidcoiic. ilftcr 23 deaths of dusting the 16 sumring guinea pdgo trere transferred to noraui .xir.- Hate and Type of Reaction. For the first y-sai* of exposure practically the only- reaction to the dust v-uo the pre sence of scattered phagocyte* and an occasional ninuta as be 3 to sis body. At 16 and 20 cenths no groaa response *ao risible an the tissue 3 actfar. but ricroncopiciilp parforcochiolar foci of inn.legatory cells could be s*=n. At 2U mentha thers wss utill no ch*ng j* mcnpn to be scan nlth a hand lens although rdemstopic axaatination rerealed cellular accunulutioas about tordinal bronchioles and r;&sxy 3n asbeetoat* bodies, chieflr within cells, Chemical analjssa of the lungs (Table 13) rsrssl that in spits of the Halted tissue reaction carnidarable oust had been retained in the lung. 53 rrogreagion; The lungs cf iinimaifi exposed for th* lull auattr- period (26 months) and then livinr in renal air for 2 months revealed the changes dascribed abo^e and also Tory alight peribronchiolar fibro sis. After 0 months in normal air the findings tbit sjctlar but at L2 coathr of h antrals showed grsasly-rigibLa chargeteariertio peribronchiolar fibrosis with adanemteid charts. $lu lynch Jfade InTolredant The taraohoobrTOChlal nodoa tsare wsentially oajutivo until cccposrre had been continued for acre than t wear aai a half. sacrificed at souths and 15 eontha rvrealad a few rinut* collections of phagocyte* containing particl*a tat pr*e- ticolly no fifcoro large enough to be recognised ts such. Alter 20 coa-ha of srpomre nary Eonocyte* filled Kith yellcnr granules tbt* present* It 30 months there had boon a slight increase in reticulum but na fibrosis, No further changes occurred la the nodas. Isbestoois todies w?re not s^en in the nodes of any of the guinea pdgs. iabegtosla Bodies. lUnuto ashes to3ls bodi*n ture obsarrad sc early as 3 rsonths after axposura began, -rut they did not be- ccra* ssaarcus usstil IS osniba bed elapsed. Tha bodies tsts abort and practically all iwe intracellular, although at 20 senthe acre were long enough, to project beyond the call borders* It i* important to cote that la the later souths of exposure there raa c, dis tinct increase lu ths tsssbar of long fihens fa? to 70 sdcrona la. length) in the lungs and that after oeposurs cessed cbar&ot-eristio 1onz asbestos!* bodias wwre sees. $6. White &ata end Idea. In this parint to rato were exposed for periods up tc 20 Booth* and 2ti ad.ee for periods up to 12 amthe. Neither sped so developed ct.-,- a rocgosticn cf anbootoeis and reaction 1 to hhacccrtosis of inhaled particles -rj vlueir-acattored duet calls rhtd; rsnainad froe in air a paces or irara transport'd to the tracheobronchial Irnrh nodes. !Jd aabcatools bodies trora found in v rats but in the oic* there W8 a very for small ncu-hausrtrated forma vithin phagocytes. la 21 nousa lungs sectioned thorn were 3 instances of pulsenary adenema. (115}. 57. Summary end Interpretation. Tie tissue reactions observed in this arperiraat -cere orach less eztensira end slower in dsvelapsant than in the previous investigation with short-fiber asbestos. Since presumably there vrro fairer fibers longer than 3 microns in the nat<rial used in this experiment, the results tend to ccnfira the interpretation cade in Section Hi of the short-fiber oxperisont that the reaction probably Is not primarily {Tiedcal in nature. ` The finding cf long asbeotosis bodies in animals inhaling the ball-rilled catarial is an suiapla of the difficulty of coupletoly eliminating long fibers free an asbestos preparation In regard to progression cf reaction after removal froa dust, *hch tras ob served in this experiment but not in the others, ths foilowing interpretation is offered 1 Hian the reaction is velL-developed at the tcrcinatlon cf axposure,tha contraction of the fibrous tissue would obscure toy pcsnibla progression. In this erperiamt, however, since only the earliest stage of reaction was peasant at the ttm cf removal froa dust, its subsequent progress was apparent. It should be noted that the degree of progression wus so slight that it can have little, if any, practical significance. 53 * iKfta-i-atlcn Ebrcori'aar.s -with Long-flbar ksbestos Dog'S. iftar anisials inhrJin/: short-.rber asbestos cHurt for sorr than a jesr had failed to develop sign* r.Vr.r.nt. ruction, tho hypothsois that asbcstosia i* pro duced by tho nechardca- irritation oc long fibare xw given added supportjLcc th# King's float--; asbestos. used. in tha first inhalation nrpcHr.rnr. ;(d a rather law content of fibrous chrysotiLa and contained considerable erpentina and other irspurih.i nnt it, ras decided to oiaiuct a tusv inhalation eaperixont elth a purer form of chrysotile uhleh would be richer in long fibers* 5? The dusting rater!al aaslored in this issruotigation wax obtained from t&a Uarrvllle plant of th Johns-^wyiiia Corporation. Saatples of **-- Tarcl rari sties of acboetoe duet 'mrn first, subpi tied to the S*ranac Labora-tocT for ssaairation end on. kind, identified .. Lot B, i-Xich vas lav in eagnotite C and chrorsita and had & fibrerae content orat-ina-tad to b about 7? par cent, *a selected wt cvrwrt s\?it-sb.le; Steal wins tantsfcos rcre fastened to the imida $\rr-- fane of th hopper and to the rotating paddle ii> order to open up the bundlei of asbestos and liberate sore fibers into the atiaosphem- 60. The octrees iti on cf tbs lons-.Cibrr isbwctoi used in this ccpuriusnt is indicated b7 tb* chaaica.! and r^Lro graphic aueiyss* giTen in Table liu It appears that this asteriai -3 * *r>voh piorsr fora. of assertso than th* sheet fiber dvrst ussd in othr 'sqx'rirsrit?., Thi g 1.- bora- out by coaporiag the approx la&t* ?aslypes of the lisig^fibsr and snort-flbw ttfurt in Table 1?. 61. The dust c-cncsatratiors a r*rrr*J.*d bp inping er' ws=pla e taken inside the irlsai. ca^gsa we ouch lesrer than th* concentration for the srp-srlsanut with ahrrt.-fl.bar or bdiJ.Kd.lled For th* first ptan of the erpartnant with lonf-fiber Mbsstn* the arsrttff of the lieftt field cw.tf n 32 willionj for th* ner-ord yrar, U9 Dilllor.; for tho third 75ar, 3? riilion; and far th* fourtu year. l3 cilllco- Ssasanaticn of the iropincer cacrpl?8 with dark fisid illunir.r.ul.rm disclosed. t'rufc many fine psrtlrlm less then one rdo'on in lire accecpanioi the larger particles *na dark fi<jld ccum.ts m?t8, cd the arsraee, about < or 6 tiroes largrr than ths light field counts. o2. The 3 Iso-frequency of atzrosphorio oaaplss of ths long-fiber xsb*sto* dust and of the ball-el Hod dust is shewn in Table 16. Beth sanploa awr* cnLlentsd with the electrostatic precipitator. It will be noted that th*r* wus far acre fibrous nsterrisJ. in th* long-fiber dust. 63- Hexctlon in inlrrcls to Inhaled long-^Tlber asbestos Dust. Guinea pi g*, exte, rats end dee wr eseployed in the irJialsticn expericent with loTveH'.tbsr asbestos,. Results af the exptsrirnt* rjastriisd in Table 17, are described in grater detail below. 6h. Guinea Pigs. The experiment was started with 100 guinea pigs. Alter srposurs had been carried cm for a yeer, a. sereru spidssic of pneissaoiA nroxr- in h<s dnst, roors p.rri about one-third of trie ardnxls died cr were, killed. To replace tha; .>3 Phr* gnln** pigs wru added to the sua-rtrir^ * Eryup in the dust nxs 6<. Rat* end Type of Reaction. Histological sxacrir.fit.'.on. r^rexLrd grossly risible la airnr i_a the lung a xftftr *3 oonths r.f tsry?jrir t-5 dust, coreletlng of cellular .inflitraticn about th* terninxi hrorrhrniea, is, 12 months,, ther--* sw.ts ?d<T>.o?ixtot.4 thongs;. in the air apinai i:A nr th* 1.6th rrer.th & defied.t flbroKla ?s prrtent in th**? rr**3 in half the oatealx., Th* fibroox lefton cotIG be eerm ucrocopiciiljr 2C eoaths. Proa this tin* on the- increased in srtsnt and In the ssouct of collagen cn.1 t7 the 3iith SOTth, it had firmed out into the parenehTnc. The lesions -mere rather sharply localised cmc the extensions free;i different bronchioles showee no tendency to fuio, t*ven in aniaals exposed for the r.-cri=um perted (3 years ). Although the intra-puL-w-ary reaction 30.notL.-13 reacncd the pleura, there was r.o invclraraent of that embrsna, Uo eraphTaeva was risible at an/ point, foxo thickening of the larger bronchi frith a chronic inflnmatory infiltration was re-- railed, but it probably rma no core than would be produced by a siniLar exposure to any dust. For the first months the phagocytes consisted of rxmocytas or very small giant cells; later, giant cell formation ras acre preninent. liter 16 months the giant cells were large, filled frith rellcslsh-brcB'Ti ptspent and scoetlaea vacuolated, An occasional animal shored an .vinixturs of pol./norphoruclcar Leukocytes and, in guinea pigs exposed fer a coc.v.dorabla period, eosinophilea. Tho reaction was at first entirely cellular but by 15 months fi brous tissue fc mation was dofinite* However, it never atta'ruxi a stage of h7al.lniiA.ti0n suggestive zi silicosis. L noceratc incivLiuil variation occurred saong the exposed 1 /"ala. Icth in the rite of developing laaioas and in the stage of davelopcuint attcLred at c'rx end cf exposure. Analyses cf the Insjs (Table 13} disc La sod chat although the tissm response was ouch greater in thane guinea pigs than in those exposed to either shear-fiber or ball-allied asbestos, the aour.t of dncrsl os.t tor in the lung ash was Lee. 66, Progression, In guinea pigs exposed to tho dnsi for 20 rontr? and u \n rtBored to nomil air, there tms a marked tendency for cellular irdTUcmatory reaction to clear. This affect, accompanied by contraction of tha fibrous tissue, resulted in a diminishing slao of the focal lesions. None of th*se sric3-s. Itillr.d at var'.oiis pericvle ;ip to lli rort.'u sSLer expo juts, lc5.3T-t 9-9 !r* s* tho an i:; tho jrnap r.'icrv'icri at i>z *rr; of r.hs ZCw-'cont.h crpc-sure pfrn cd or those Li nio>:k!l= rhich rc^.-ti.v.d in the, dwst rooa for corn then 70 nont.hc* Fourteen mnths after ruat c urs ceased, the foci in four of the *ix rsrT^Lcirj does flir.-i `-cire sc, steal.'. tr only with a- hand lens. they were t 15ibis fviiacti:.: in the tf-otrp kt0'^ -"or 27 r.onths ari Vr>nr. transferred to a normal aterschore w-^ quite einilAr to t-ha re.cpcn-Sft J_r\ the i?0-nonth 'reposiire acisais cent lor.od abyre, Roenrver, snail foci -r.-F*re nlracys risiblo on ^ross inspection cf sections o.f all piss of tha 2?-<rcnth aeris.*: bni in no instance was there aTiceoce of srtervaion of the reaction. 67, Lffnsh Sode Iirrclraoent, Ra5.cti.0n in the tracheobronchial lynch nodes was first risible el the third sonth of <rz~ roeirre, At the 6th wroth. patches of oallv.lsr cnnoftccivA r-i?*';* begin to appear in th srstallA &nrt by thn li;th month rcost of the aodu had been replaced by CftlLi.Ur corre'Tt.tTe tis.ei;?. This picture, ntvich rese-roied that in early silicoals, pfsmPieted to th end of the cp*rtncnh. .Aojm anicils, is t variant, enroll heery sheets of diffuse no&ocTt** and l?.rgo roti.ve (yUnt o*l\ birt there nerar any necrosis or hyalin*? .fozTfiti/n The spicdle-ehjfqyod new cells were yuUorLsh la re-lor fin* p55^rtt jraTPil*? th?.t r,t.?innd fr iron. Ro fibrr- or ajb&stoeisi bodies *W 4MA, 65. Asbeetoals fellies, ilthough A.o!>t^sip bodii- m*r- seen it enrly as one camth niter sxporor* began, th*y nr rare and hard to find. At ^ conihr rort rrrn Tisiblo. chiefly coi led inside giant cells, arjd at 6 ornt-h* r^iny hodI#* srwre .free in connnctiver tissue, Thor became fairly abundant. e croeirr* although In sosm later stjdffitlJ* tho e.Hboobos.la bodies only noderately mansroue. 69, Cat-a. Four rat.5 inhaled the ianr-flfsr asbestos f^st for pariooa cu li, ?S, 33 and i'-2 months, raspeetirely, and -rer* L=nfraL&tly- sacrificed. Two other catr alter being exposed to dust for 16 txnthr, lired lx a normal atcospnere Tor an .^ditiooal 22i Booths. 704 Rate and Tyre of Reaction. Exposure for IL souths irax flufficier:*. to produce cellular accumulations of phagocytes around terminal bronchiole* ana peripheral artariolea together with compact col lections of sisriJ vr cell3 in the tracheobronchial lysph nodos. It that tine there ware no typical asbestosis bodies, but raocth pointed Tellcw fibers e-re seen very rarely. *<ith continued exposure, up to U2 tenths. reaction in the locations noted progressed to the formation of cellular connective tissue which aade Teil-dafined sheaths about the respiratory bronchioles end arterioles, wrkod lymphoid hyper plasia and lymphoid infiltration of brouchio'Lsr rails- The bronchiolar epith elium rae leer and flattened, giTiaj the tubes a aaooth contour. Typical aabestosis bodies were not formed, although there nae an occasional relloe, ssooth, pointed fiber, Ko pleurisy rea present. The reaction vies siniLar ir. location to that in the juinaa pigs, but fibrosis exe cuch slower ir. deveiopoent and had not reached the aarae degree of maturity, (A. Jk-rtay uvangee. Roentgenograms of three cats were rede after exposer* periods of ?A, 33 tnd k2 Deaths, but tiseu* charges were not dense encugh to be seen on an I~r*y 2Lln- 72, Rats, Although 20 rati were placed in tha dust roots, aany died from pneu monia and were net ardtable for study. Five toJLmals, of which oz3 was exposed for 19 tenths and four for 2$ nonthij, were fra* fbta pwlsuary infac tion and offer a basis for conclusions. . 73. Rate and ?rne of faction. All fgut ar.irala sacrificed at 25 tenths showed a well-marked peribronchiolar fibrous. It,\ Uj 15-wnth anisal, reaction vus just beginning. isbestesla bodies were practically absent at both 15 and 25 aonths although two small 33100th bodies war* found In the 15-sionth aniaul after z long socrch. Thus, these anlnala exhibited fibrosis without asbeetosis bodies. 7U. Hice. Oat of 20 white slice used in this experiment, 11 lived & year cr aaro in chirl and died or were killed without showing an appre ciable degree of pulmonary infection. !$ Rate and Typo of Baactlon, Reaction was Halted to phagocytosis by oonotrueLear colls. Usually these were wide ly scattered through the sir spaces j & liadted nintsar were grouped about the ter minal bronchioles producing son* thickening of their walls. There was no sug gestion of fibrosis. The striking feature of the experinant was that 9 out of the 11 nice (82 per cent) exposed to dust for a year or care showed pulocmary turners, usually adanonetoo- in type'. These lesions did not contain dust or esbestosls bodies. Numerous asbestosis bodies wore observed in anir.au; killed late in th experi ment, Thus, these aidnilf exhibited antes to sis bodies without fihroeie. 76, Suaemtt and Interpretation. The perpeae of this experinant was to evaluate the Importance of long fibers in the tissue response to inhaled asbestos* The results indicate strongly that long fibers are chiefly responsible for the reaction. Thus, in guinea pigs react ion developed earlier and became acre extensive than in previous experiment* in spite of a ewaller concentration of atoo spheric dust and a lower ninaral con tent In the lungs. Furthermore, a. typical peribronchiolar fibr< ------1 J in cats aithoucn in a previous carp^rinsat with 3hoTiber dual it did net develop in this species. Tho cause of ths cellular fibr03ls in the lyaph ned.ee cf the guinea pigs is not clear. It did not occur in other inhalation nxperiaents with asbestos. ann. dtjectiow eifcirrents ' In crier to determine to what extent the various fibrous minerals possess the capacity to proves tissue dsaage, jssaerous injection experiment* were per formed. la those experiment* guinoa pigs sad rabbits were used and the mineral dust ices injected try the intratrachealt Lntraperitcne-il and intravenous tech niques. for the purpose of simplification the findings in each series of test! have t>eer. condensed and reported in tables, to which reference will be* cade liter. 75. Career leant3 Ifeing Intratracheal Technique. Since the asbestos xintrals do net cause a typical advanced fibresia in extra-pulmonary tisane, the intratracheal becy-xJLqu* is the perferred w?y of in troducing fibrous dost into the animal. In this sathod the duet suspension is injected by nean* of a special needle or catheter deep into the trachea. Cram which it flow* Into the lungs. 7?. Comparison of yibrous and Sor."Fibroua fusts. ?<:- -leasrustrats that tha ability cf asbestos to produce fibrosis raaidw in its fibrous, char trier, the swriw of injection experiDsnt* reported in Table 1? ware peri'orasd. Th* test* *srs made with unbeetod long-fiber chrysotllo wad with chrynotil* that had been ignited to dartroy ita fleccLbls structure or ocll-rAiiicd to reduce >.? h ; iber to 3 nicrcnc and less, At the 3M tics centre 1 tost-". werf - v; : tine, which has the 3arc chemical composition cS chryro-'ile /r,v l-.- r.cr-' ; c revierr sL' tha findings reveals that only tbs unhented lorg-.C?!.er- c ry: a produced fj.hroals. Fibers subjected to ignition or shor-sred by bali-<n:_ - i~ r. hxd lent choir capacity to cause serious tissue damps. Iedition produced . taut chen^-s ir. the chry- sotila fibers, among the* being lose of -cater, an el (-re.ti.ou Cram a flexible to a brittle structure and possibly other changes. 30. Comparison of 7arloua Long-Fiber Dujts. 5o:a very interesting findings * n-c disclosed by the results of the expcricents included iz. Tab In 20. First, nil c u lon-i-fitsi- asbostos minerals tested, -with the exception of anthcphyllitc, produced a typical fibrosis. It is not entirely clcer Thy ar.thophyliite b6iu73d differantlv from tha other asbestos minerals. Unfortunately, 5 of G .vt?.la died of rnouxenia within ths first two Tre'KB of the experiment ate. ths rorainir.g aniuilo ware sacrificed at 1, 3 and 12 months} thus obserratioru ?*sre non .ends at the ortinun per?,oca cf 2 ard U sentha. Second, with the ainex-el. brucitc, chlch is not a silicate but i.'i a fibroua for.i of magnesium hydrmzido, a characteristic fibrosis Ills that of the asbestos minerals was obtained, finer ths brucito usac contained only C.?0 per cent aiiica (as tn impurity), it la sbriccs that a siliceous component is nert an agential factor In the development of acbestosie. Third, no fibrosis resulted fro- ths injection of class wool fibers, eren 9 though glass wool rablet> asbestos in soon ruy*. There are f'u-jdanental differ ences, hoewrer. k glass wool flbar 3 microns in diaxaetar la a solid red and, in short lengths, is fairly rigid, while an asbestos fiber of the seme ctlaxnatar is a bundle cf artremely fins fi.laosntn which impart to tho fiber a high degree of flex ibility. It would eeom that this structure And the associated flexibllitr am important f&cxcrs gore mine the capacit7 of a dneral to produce peribronchiolar flbroarit < fli. Conrariscn cf Lor~ -"Iber ar.d Short-* tber Dusts, With quarts durt It has boon daoonstrated that the Trailer the parti doe. tho acre intense is the tissue reaction, and that there la Little reaction to particles Larger than 3 a&cron# In disaster. In tha c&aa of asbestos, bereersr, the reverse is true and apparently only long fibers hare as? specific affect. 71us is conf lrrd by the data of Table 21, la which a series of testa with fibrous minerals is reported. Hhan tha Injected duat consisted of fibers 20 to 50 nicrons long, all the el nereis tasted (except anthsphyllite, as noted in Section 80) produced a fibrosis) rhea the eaterial w prepared by first grinding the fibrous durt until the length of fibers ear reduced to 20 d crone and leas (cr, in soae cases, 3 aictms and less), none of the injected slnsr&l dusts ernsad fibrosis* 62. Srparinents Using Intravenous Techelons. The experiments, described in Tibia 22, in which the intravenous nothod of injection war aeplcyed, sheer that the asbestos xlrveral* ere far difforest froa quarts in their action on tissue. It has been repeatedly doBcnstrited that intra Tenons injection of quart* particles } nlerana and lees in disaetar Till cause a typical tissue reaction eith the development of fibre si* in extrxpulaceury sites, such aA the lirsr and aplest. Asbestos tcLnerais, fccwrrsr, on intravenous injection Sanerally produce only an inert type cf reaction; s in revealed by the results given in the table. The reason for the early death# in the experiment with ehrysctile pertlclae 1a not clear) It nay hare been canned by silicic add liberated by the finely-ground sineral. 03. r^crwiagtitg Ualrj IntrapcrltonttAl techniauQ, The rwulta of injectico experiments rith the intraperttoneal technique ar* girn In Table 23- It -rill be noted that the long-fiber dueto producer! c. fibrous reaction while dust* cospoeed of particles 3 crLcrona and less in else cauaed only an inert typo of rerponae. These esperiaeata indicet* also that the fibreala LaitLated by the irritation of asbestos fiber* La not restricted to the lungs, a* was forwrly aseuned, brut cas be produced In the peritonaea aa trail. UTH7. cim gnsssyrs ttith ir^srta khtouls 1 uussber of additional experiments nro conducted to throe sore light on specific phase* of the aebeetodLa problem, / l C5 Pro tec tire Action of nnminna Cogpotinds. Intratracheal infection of a snapwaiem of long-fiber ciaraotile to ehich colloidal aluafnaa hydrorida had been added revealed that the addition of the luslnua ccgpctBd did not prevent the tiasce irritation produced b7 cfcrysoLile. If anything, the acute isflenwmtcjy response to the injected fibrous mineral was accelerated* One sth after tha last injection cf the duet rarpecLsioti the bronchia Litia cu beocedjnc fibre**. 66. fornatlce of labeetoalj Bodlae, The iron in the coaling of the aabeetoais body appear* to be derived Crcs blaod cr tissue elaoent? snd net,, &g has own suggested, frsa the aiharai fibrr. fallowing subcutaneous ibjiKrticn of t-ao Vlnda of chrynctila into the groin of Ctdnoa piga - on* bind containing 2 par cent and the other 0 J1 per cant Tts^y- the tebactoeie bodiae ewr* equally mossroue at both eitea of injection. / / // V/ Ln attempt to produce asbflfito?t3 bodies in c'~-2*'Vi*3 by ixzalantation of y .thr*t si_LSc ba^s containing fibrous chr.yaotila. vas unsuccessful. On# bag plant,od subcutaneously in the abdominal Trail diaapp-srad; the other tw bags, placed in the peritoneal carityt prcducec ^ little foreign body reaction but no asbeatosis bodies in a yew*. Intratracheal injection late guinna pigs of aabeatosin bodies recovered free. huEaa lung tissue railed to produce the typical tissue reaction to anbesto* fibers. The injected caterial -was obtained by digesting with sodium hmacMorite .solution lung tissue renoved at autopsy Crca an aabeetoa warlcar. The aabastosia N bodies could be seen in the guinea pigs for at least a year after injection. This experlseirt shew* that the asbestesis body has a rather resistant coating ' which is not destroyed by cod erato hypochlorite treatment and nay be maintained in Tiro fer a year cr longer. LXXS7H. TH50P.T OF miTA-VT ACTIOH 0? JLS5SSTCS ULVc^JLLS Two hypotheses hero bees proposed to explain the tiscua irritation and reac tion "**--<< by asbestos fibers: the c headcal and tbs awcbsnical. In tba chemical theory, which is based upon erperieno* with quarts, it is assumed that tbs a>beetoe jdT^qrula dissolve in the body fluids and that in this proceae their bases are leached easy to Isare silica in ?. fora capable of irtitating tissues, accord ing to this hypothecis r &xbestoei.t mold be merely in indirect ai11 cos la. Setaral facts nakn the rhd<c?0 thry 'intenable 4 (1) intratracheal injections of brucite fibers, which. had a silica content of only Q.9C par esat, caused a typical fibre* la like that produced by the mbeeto* aintrsli} (2) free--allica particle* increase in potency m the particle slsa becomes lest, but asbestos fibers shorter than about ID to 20 citrons are relatiroly innocuous 1 (*) elnHimr* ' V/Craxide neutralizes tha irr Inc effect cf quarr.z but not of asbestos; it doe- :'j?t product tha sene '.ULnri o reaction: (f) there is a. ^bde rar.q: . the cbonical cocpooiblcr. of the aircrals Tinier, do cause asaeatosis (see Tbie 2ii). In Tier of this erridanes It seats raore likely that asbestosia is 4 caucid by en ur/isual mechanical irritation Iras lon$ asbestos libers. Probably this irritation is related to the peculiar filagjntcd structure of the fiber er.d the associated flexibility, shied are poesesssd by ro othor foreign body. Fcr crancle, is lition of chrysotile fibers changed their structure and mads then inert while the same fibers, before being heated, would produce fibrosis (sea table 19). Further support for the theory of rechcrical irritation is that asbestosis occurs in an organ of high nobility - the lune - and that a fibrous reaction can be produced by injection of asbestos flbors into the peritonsrua, where chare is also a degree af Debility, but not in* other extrapulaonary organs. The expert anntal inrcstigatiou. with asbestos dcecrals was concerned pnsarily with the effect of the dust os noma! tissue but soma attention na given to other phases, such as susceptibility to infection era occurrence of nalignancy. 09. Infection. The only experiment in which the effect of inhaled asbestos dust 02 & pul- nonery infection wa* studied was the first Inhalation uxperiaont, carried mi with "rdne'e floats" dust. It is, perhspe, unfortunate that infection studies were not cade in the other Inhalation experioents also 90. Sviseyrti'aillty to Tuberculous Xnfflci.xon.. "he davclopicact of a tuoerculcaa process initiated t the 'oeprinnitv,' ef ecpceura to isbectos oust. ar.d also of an Infection supcri-rpoeed upon an established ajboatosic, mui de-crlbc>d lu ooctioi-. 19 and 20 of thin re port. It will to notec that asbestos, ihen classified according to the effect of a dust on tuberculous infection, rould be placed brio- an active dual lila quarts but a'oov inert chiate, such as cnlcite and srpsun. In anirala infected with attenuated tubercLa bacilli, quarts dll cause the infectious p.<accss to progress until the animal dies of tuberculosis. Inert dusts will hare no effect oa the infeetioa and the lesions rail usually heal and the disease disappear, isbostoa dust is in a different catogonr. <>.9n tho fibrous dust was being in haled during tha evolution cf the infection, thoro ras a spreading of the tuber culous process far a tiao but usually the otiaaiuo for continued proliferation of the tubercle bacilli ms not sustained, the progression vas arrested and healing followed. In guinea pigs infected with attempted tubarclo bacilli foUcrring the cccplatloa of nearly three years of axpoccrs to asbeoto- dust, prcqreaaive disease did ixit develop. The only modification of the infection. n cue of locs-IH*tloa, a few bad Hi being retained la tho fibrous terminal bronchioles and forcing tuborcles there la addition to the usual fod beneath the pleura. Such tubercle* healed in a fww aonthar and there was nothing to suggest argr influance cm the course of the di irea.se, 91. Susceptibility to hon-TuborcuIous Infection. Thsrs me no pointed ex periment concerning the effect of inhaled asbestos duet on norr^ubcrculoua infection. Intercurrent pneu monia among animals exposed to aebastoa durt wen rather cosoca, the frequency* in guinea pigs exposed in the four inhalation experiments ranging from US to 39 per cant, This incidents vridcr.cr * no 3-355 ."tlity of an effect of ajt-astoa c*iat on non-tubarculcus icr.. ii'-vsrthclnss, since such epidcnics arc not uncoscwu tn ishalaiicvs sx-T?r-_.-e*r.; -.rich other duotr and even in the eoicr^ of norsvti cwizzls, It ic fell ere i:jhalatlon of asbestos dust decs net exert a lir> specific experirsnib res conducted to datoredx* winthor tha inhalation of asbestos furors the cereloerrant of neoplastic disease but certain obeemetions on this subject r*r record?-.", in the outline of tha proposed son-^aph on asbeatosis subdttad by tho late uc. i, d, Gardner in February 15U3. In :V be called atta in his arpariafectai net as. hooarer, he rnferr**d to these icsionn is adencras. There is an ioportar.t distinction bet,*#eer. adcnctsi and cs..-iccr itiic'n should b? made cloer. A canear is n tvenr, or neoelasa, capable of local in vision and co~ gtrenn to produce isolated foci. frer. 'rhich rct tutors drraiep. Thi; phcncronor. of disaerination is keem*. as netaatasls and cny tuscr 'which exhibits it is a calignaat growth, of xhich canear is om typo. An arier.ona, cz the o.her hand, is a so-callod benign or noa-ralijpant tuacr (ocoplasa) 'which ncy. or aty not be capable of local inraaico but ,shich does net nvetastarisa. In order to clarify the eract nature of these lasirr.s the path 'logical jnaterlal is being carefully etr^ned. Since it is folt desirable to har*. the benefit of Doctor Vornald'a judgaent, a re-rie"* of the data on this subject \a being post poned until after Mx return free Europe, Rather than delay the eal're report, further discussion LH be reserrod. for a supplement to bo issued let v. to the vacu Eraunt ci da-*. ire.Vrio-.' ir. .-' it r'*p*,,:n : f. s`-crs .v-'si ccnvcni .-*, to a Wee toe or.ciusiona ;lri\*o;J i.-jr hr.-* irr.'-'oti-ation at. i . *n-.t'.r. r.ceocanry, folios' earl ono sith a bri'l ram:': c-f i!; evidence. A. ''ariocs fena- of csbestos fi!;r-rs pvtf'jrc c. peritt*-.:c"Ac'.-* :i ivesi.*; cl iur.ns o;` pij ;*h pi<jr, rate, cat.': ?_~d rabbits art n<.*t of irf.ee ind <i<?cs. Both InhoXiticr cad injection ::zvlscnt8 prcrri.de mpie rappcit for this nonelesion. ri:;vrcs 5 ard 6 Jhm* the reaction to tro different idr.cir of asbestos rsincrtl. a. 7c* rede of -tetion tppe pvirnril*/' rcehaniccl re*.:ter than chcsdcsl in nature. The eridc.ice is ivcn in scctirn LfTTT.TT* Figures 1, Z, L arc*. ? illustrate the important points. Ibe fibrcris filaaen'.fd - structure of asbestos appears to play aa essential part in the Arritatinp action, rice* the solid fibres si -L'?? rn-i co net produce fibrosis (see ',-L~cre i;. C. Slusrt tabeato# Tiber? do rot produce fi'oro3i3. The oonciieion is larliad ir. the .r-l.or.na ccntitred in pcrc- CTph B doera. Erp-irl7.-4-.t3 Tbish further aup.r.ort this fir.sir.- are reported ir. Tablej ?1 and 2;.. D. Typical fibrosis can be p.--zinced cr an atoocxheric ruspension of asbestos duct contAinir^ only 31 extrcnely snail prorcT-ticn of lens fibers. In the Inhalation erperioe:r-t with ICO pr cent ball-oilled asbestoe dust a typical, though delayed, fibrosis rma ottair.cd 'cor Tail' ii) cc. )\ lee.' \ . ' ;cr zzrt, >.* J.:zn.1; .V.:`-C duet _*i`M nicr.^r.c, -roe c'.1. i.' J.r, i.-ikO i;. -'.v- irtvc- o/rorl.Ti;:.w -rich fior c:'-:t>svja roict tciiiir-; nr: floors U- prod*'-.?:- fi'iroeis. fucu Tai<l: '1). Inlialaii'jn c: sabeiTtns riui.t rircrvr.ti,* .Joes r.?t altar i*i;piif;.c:''-.tl)r course of err cvimeutal tubercvdooic in ^oir.ea piss. TMs conclusion is tentative 3ircc the evidence nr. rfticr it in bcj'jd docs no* conform Trt.th cur usual experi rnce. 2cf*:*- e.*cc `-o labia j Trill sheer that ehen infection v./is cninr.ifcrx "ih q;wc; t >' .'h'xr'u ccr.scrJT? inert raj trupororr p'/nf^rc^oi^r. of the dioon.-m riih subsequent hoalirr; nticn infection rao irJ.i.:.airxi After 2u J/l. ZKcr.?jt of cox exposure: Vat covrae c:' 'V.e tubercrulo.:s uiJesse vco rot e.rcrrc.i.ably altered, In centrist, i*. has born roserpni in crperineuts 7.-it.*. r.ixc.d iota wntririrt quart7. V.-.nt ii i.nort ir. a aUi'bt pronroscior, ?: c-.r ;:.-rrv- loatfl 7rteu ininctioo And dint exposure arc coincident, IM 3 effect is roro marked (instead of less, as rath 1s.best.03) 'r-.cn infection is initiated after a period of duct ex.pc.vore. This concltciar. c^ncrnrisflr.ct of irhnloa 3SM-.<tr dust on tiformilosi: sec-os justified rcc-voo*. ir '-M auro sv.V:.tins test (infection ini dinted after a r^ricc of dust erpe rirn) there ,-*c to eriprcciai'le increase in nusceptilvllit-r to the tubercular-: infection. !I'rrB7er? since ilia findings in the Asbestos pcvg7 dc net ccoi'ara wi.h previous ccpurianca, ard ?in t-ho dwtlinf. -.r.V r: ... r. o: *' ' " ' * Turthcr i T.'oat4. *d.l -r c.: ti in ~ -n.'.r. 7C- - c- c*-r.- r fijrar.fLon >;* rir-'.u'.ov.'..- r-.-r." " o:.. t rv.;.I.l ?. .Terrs ~ril in vi' '..V.t7 <> :reJ':c> .Intra.tr-ic.ical In.locMon nd? m r,.J.V:6 tc prcd-ica tie tjpical t-isuix* rc-uc ;irrt vjaa r-:.i"-Lvr. ii). Ti'.z cosaatim of projjpis-v;r r.-ict.tt.n >.> aEtcoton - rern al'icr * *:r Jue to tf.c oi" i'.vrrx ;it l:cci-.n.