Document jBvdvqzDpqYjmoaaoB8RLknp

nraxx Bzroxr maildx tsx wotnffKUL icnmY or uha aaff W te U--M TTTTinTfl SUSS COMMIT farm b uuuft UBUsas OCBKS 30, MU vltU lklU| C. httt, M. D. X. Satu, x. X. B. 000191 Asbestos Litig. Saranac Lake 1989 Depos. Exhibit p*78 OTBQOTCTIC1 Os* y*ar %*o, oa October 30, 1947, an intaria report vii ratalttad, eoTvriag tha profrasa of eart&ln anlnei axparlmats with Ltylo oTr * total poriod of 30 aootha. It vu MMttu/ at that tlna to raaocand further arparioaata nrwmtttf --i tali jdrrr~r of tho yooblMu A* jvasaat raport daala with tha final phaaaa of tho ar.niiiMat than in jrppaw tad vlth tha rally abswrttku wmim in tho now mtIm of nfarlmtu tha original axparlnaai hu ao* baam aoaplatad and tha aooalasiaas dmta ara baaad tpga tho raaolta of a fall tltraa jwi* ixpoaara to an ataoapharla aaapanaioa of Layla dost* ftmiaua azperlaaoa haa shorn that this la tha ro- qaairad porlod error aspearn to a daat of daebtfol Mologieal aatlrLty tat ha imotlnnol bafara final aaoalnalnaa ara wrntad. this asparlnant, in faat, aoostltntoa an ananplo of tho Inportanaa af soak pomloocad atady for, aa is to ba ahoan halos, tha findings at ttiraa poors vara atrllrlncly dlffaraat from thoaa at toe aod rar tiilf yooro and tho taatotlTO aaoalsatao wthal at that tint vat aov ba alt atad. Ana, at tho tlna of tho pmlaa lagart, tho arlilaiai iadtcatad that faylo aotod as an inart daot in aaonal rata and fillnaa pl*| raraltlag only in tha fezmtlm of alinvo of daat sails, althoot fltrals, laoaoar. It U1 ba ahean balao that Laylo in oapahla, an paoleagad Inhalation, of pi aliasing aabartoaia In tho 'f of goltoo fi|, and Iht it bo haoHlad lortaalilally aa a ho- sardooa daot* ispart **''* bo poooontod In fbor aootlan* as folloaot Am nnl sbsavmtloas, dost lahalatlno in aatnal rdnaa pig*. U BAaaoaatan. 6. fnnaloalona. 9. Provoao raport an nan aoriao of osporlaMto. 00019i Asbestos Litig. Saranac Lake 1989 Depos. Exhibit p.79 4. final observations. dust inhalation la nornal mines ;dg Reference to the Interia Soport of October }0, 1947, vill reveal that tvc groups of aaraai guinea pigs were plaoed la (bo dust room* one grcup in fafcru- 194} iad the wsnrsvl la iagoat 1945* The antsale mn exposed to taoapnsric an spensions of laylo cbut for eight boar* daily, fir* and one-half A.-js * vae*. throughout the experlmot. lb* dart oonoontratloa, watch varied aoaaviu.t froa tir,e to tins, ha* mn|4 lib partial** pr coble foot of air over the entire emroo of tha oaperiaoat to dais* 1 brief review of the utssi istiuas AssariW c page 4 of th* previous re port will reveal that up to thirty eeetti the mention la gulma pigs vs3 Halted to the nwanleMne of olonpo ef seoropteegne, oontstatTig duat pertloles, la groopo of adjeomt air epeoea. tifclla oomirtOHel mltlaaclssted giant cell* were aooaf there was ao aadaa proliferation of tisane histiocytes aq4 fibrosis vaa absent. 1 few mnlstafcahls asbestos!* bodloe ware Identified. Ia geor*l, the acwimtletloa of aall* of the types described above *ad their persistence as such over a fall three year period, wlthoot the developaest of fibrosis, has bees foaad to ladleata that tho ageot mspoaaihle for thaa is aot oapahla of producing fibreala. 3usfc ageata aw sow ooaaidered to bo *MaLogloall7 inert, sinoe tho eore eellalsr asonculatlce bee eat been stove te affeet pulwonary function or resisteeee to Itseise. Bnswr, of also sacrificed subsequent to thirty aeaths la the pre sent experimat, ell have dw dot mly the above lesions but also have developed tns flbreeia of a typo ekaraoterlatle of tho reepooes of guinea pigs te asbestos. This is a rather diffuse typo of fibrosis vhlah foxes ehiefly about the mail air duets, tots as brwoehlolss, free i*loh tho air spsoas, or alveoli, cf the lung arlso. The appended photonioregroph* ahow the saiaro of the lesions being dis cussed. This yttrium is Identical with aaboetosls as can be seen by eoasaring Asbestos Litig. Saranac Lake 1989 Depos. Exhibit p. 80 nr..'i ' UUUi.-* Flfiux* 2 vim Flyura 3. Tbo loaioaa La too tnchoobroec&ial lyaph sod** Bv#d no cotago botv**n thirty oairtha ind tfant jrv&rs. Chaoioil iBolyul* of to* lumgs of fnlmoA pigs tost bed lnh*l#d lojrlo duat Tor poriads up to 3$ souths yialdod toa data firm 1b Ttbl* X. It will bo uotd that s too poriod of wpoww boooaa Xongar too ash vulas gradually lo*w*eod, indicating am toewlatlom of alaaml aattor ia too lungs. Thorn vao a proaouaood laoraaao 1 too oillou actponsnt up to about 30 souths and than a alight dacnuM. Sm mm for this eoaditioa, uhish ha# bora eboomrd Is raporlomta vito otoar daat#, is not astir*ly la*r. disco <mlj too aalmla war* aaalyxod for sack orgoraro poriod, isdtrlduul vulnos vara oraasioanlly out of Uma but toa tfwurvl tmod vaa aloorly SadlamttoU tbs flaal obosavatlaso 1m this aaporisost alto laflo lahalatira ia vorml galas* pigs, moportod abara tad lUmotvutod im too figsran, prraa tor.t Kayla la osfohlo af pradsolng too oftwootorlatlo roaotios, tafcootooia. It is ovldaa*, thorafhra, that a miHiniKi portlra of too aataatoa oospoaost im Kayla moaino noahiagsd during tom samfaotorij* jraaaaa or, if It ia ofcaagod, tout too altomd prodtoat malmtalaa ito oofssltr to sum* fliraata. toils too Tstlnma p-to 30 aoatoo shorn* me fllwria, aortaim lipwti 0f torn vow oasjaUbla with 0 prolix lossy ta*v lm too ispilupasI, of aabostoats. tbsra aoyosta vara aaakod by tbs laart typo of taostiaa to too astorlals otoar torn aabortoa im toa dost* Iba oharaatoriatla oarly stags af too wotins to aabaatoa la toa pradllootios of too flbora to loaaliaa im torn Imam rat vail af toa oasll air dost*, fcsom aa tomtosi tooMhiolao, T*1* ia ia swat root to postioslato oatortals, toloh looallao tolofly Asbestos Litig. Saranac Lake 1989 Depos. Exhibit p.81 00019s in tii setual ir iptett, or slTacii. In the pp*s*nt *ip*rij*nt tae portion of ths ttvK.ifait, baiag partlsulats, lodged in tha nJ.Tso.LI end .xaaxini tom pwltrruuthlolar dsposltloo of tcm of ths fibrous swpcnoot. In rotroipset, it is pssaifcls ts 11 --rs that tiisr* is nor* **ld*asa of dust e*il activity in ths ratio* of ths bvonsfeiolss tins is oharastsrlstis of tha raeotion to an in*rt particulate dost* Little si gal fl--ns* * attached to this st the tins of tie provisos roport tmiw tkara vns as wlif of ths dsvalopsaat of fibrosis. BM differaaaaa b*tens ths aerly rssstlss ts hjrlo sad that to asbestos *7 ts litirprilst so a aartffiaetl -- of ths Isaloss by ths psrtisulsts eoapcneats of layIs* "Wadiflas11II* f sill--sis is sail raanfitltad when lesion* of that dlssasa daealap fsllsalag 1ahs1*t*1"~ of a atoad dost aestainlaf quarts teftthsr with aatsrlala sf a* issrt --a, east ma Iras wUs. It is of lapartaas* ts asts that tdrtls ths psrlbrrsohlulsr r--stinna ob served lasiialasla Kayla as sapsbls f jsodiisliif a*be*w*ls, they exalt** the yaniWIitp that it *y saaas rtllasrli, sinss, isr a fail thras yaar period, thsva la Is as sslaal a-- fsaas of byslias awtilir fibrosis ohoxastsrlstio of ths fosstlsa ts partu Nritsao*) it say bs edued that ths aoov no Vidasss sf ths tfps sf dlffass flbsaais vhlah has hssa ohssrvad is this Ubor- lUfy ts falls* labelstl re sf list--Mini sarth dost. Is regard to bydnUi a--a -Itiw alllaatSy a sajsr (aafitMt sf byls, it acy bs said that Sll* thsra la as jslitsd --id-- as ts Its sffsst *s pal--ry Uesas* there is saob ivjdisM ts As* that variety of till--tsef laaladlag seas forma of enisle* sllieatas, are hfelaglsally issrt* It mmm 11taly that tha aalsias silisats Is Kayla mold eeafara *lth th&s pmlas sprlMH. Sms ths pa--itnity triml ty Bast-- 0--ds-- is his sarly oossidsratics of this p-hl-t that Ksyle sight fltd-- tas ywsaeaadee**, asbostsais sad ailleo&ia vith ths rsMltaat SsfSty haassdsf has baas Sdaqaatsly studied, UNI ionlira ov*r SSSSSTiiS19- 1989 Depos. Exhibit p.82 0i92 lattar condition ean bo dlsaiasod* forthar oonaidomtion Bust to ivn to isbsstoalj, howsmr* fiw laboratory hat rssinUy oaaplstod a l*rf* lacruot of wort vlth asbonto*, vhlch has hsoa reported to eertela other mppertlag eoapeaiea, but sot as jt fufcllahed. The followiag jlmniiat t the problaa la dram largaly from th.it vork, tad ve maid request that these tmti bo ecaaldorsd oocfidsntixl. It la fait that the follevlay lafaroatioa aj bo of aid to ttaa Omns-Xllinoi* haalth departaoat la fenalatlay a safety psuyfa*, vhiah eertalaly la aeoesaary la ris* of tho Toaalta of this Itfla pailasst* >ihsstosla both, la oaa sad amiaelt, la a tfcrmle, *lowly dsweloying pori- brwjahloTit fibres!*, shialt la lata atafaa artsad firm tha original alto of lnmTImtlns larta tha amremdlay elmsU tha brssahlnlT Loealisotlc* la sppsr- sally has to tho fibreas aatavo of tho aUwral. fayailaaatsl stadia# la&lsata that tia shiaf wa& of ostlaa la hr aoohaaloal irritation of tlasoo by tha fibers, tha treatora of thooo ftban, sod tho oapabdlity of ropaatad leogltadiaal dlfi* sloa to aalaaalar strands,!* lagartist la tho asahaalm of setlea, aiose tho solid flbars of glass wool sro aet oapablo of prsHnsIsg tho fibrosis* Qtooioal settee la of lltUo a* ao tagsrtiaos la snalng Toostlos, slaoo etayaotile ren dered perttealste by adthy md sspsrattm doaa aat laitlata fibrosis. Certala TMsslIgsHi-- tevo Isdlostad that a ssaalucJy sayUgiblo proportico of flbroas sabsstoo lo saftlalaat to twhii tho sberaetarlstte raaettea. Ban, sa 4-*-- ittfli ssporlnml ms serried aat eith ball-arm ad sabsstoa la vhloh aa attsnyt a* mdo to t* all flbars fM tha astorlal* It mo found to bo lapoasiblo to temk ? iU of tho fibers aad aboat aaa par amt of tho sir ***- pmdsd dast saaalatad sf fibers* tts aha rootart stls porlbrmablular fibrosis dsvolopod la tho -nr"" l>1` f*rty onolbo thaa, it appears that rory Asbestos Litig. Saranac Lake 1989 Depos. Exhibit p.83 00019 suU Boater* of fitera in eayabls of produslag astestoals, *1though tti* dorol- opawnt of tte losioaa is dalajad, Tte profoot axportsant vith iaylo is *_Loo ns saspla of thli fit* tt* important aattsr of pncrsssloa of rssetloa *ftar oxposur* to asbestos dost nuM has tea* saEtassiraly lo**tlafiod. Tte rsmlt* indieat* ttet In con trast to aillsools* bsr* peofrosalo* Matins* for sqm U, thsrs Is ao aigni.- floant dsfrao of prugrusioa la satoat of tte loslnao. latter* tte sis* of tte iooloas itsorso sis la asbsstools das t* tte tsarfsnsy of tte flteoas tlssoo to contrast after tea stlaalaa to Its protest!oo is raaosod. tte Irritation of tissue tar a astesto* ftter is apparently arrsstod within a fsv months after it satsrs tte long tr tte f*--+*-- of tte *sstertosis tedjr* (a moating of tte flter by ircn- oonta1*lg aatorlal), with tte malt ttet tte existing fibrous tlssn* oontnots. ttetter this soatrastioa snart* a teaaflslsl or dslstorlona offast :( funo- tloa is sow aster isrostigatio*. ffif**ln--l*tj, tte stsdiss site sstestso tete aot so y*t ecsplataly clarified tte problsa of Its sfftet oa ssoosistsd tatemaTmis lafostia*. Zt appears ttet Laris say accsst ass asited sdvsrss tiffin--** oa tte iafsstiea than tess pars astesto*. Tte diffusa** *ay wnll te das to tte pgosouss of tte i--11 iwad of o*ort* la Isyls or ysatep* to otter 1 notteats'! fs*tor. Oas psrpoao of tte sladlM as* adar ay is to alaxlfy this prolisa. c. Smiaaiamr 1. bfls, teooooa of it* ssotoat of aa aM**slaU* anai of flteoo* tefaUls, is s*paMb* of yrsd**lin asteotoois aad atenld te handled as * tessrteos lsrio*trial d**t 1. Karls teas sot proteso sllloools la minis. Asbestos LitigSaranac Lake 1989 Depos. EKtaibit p.84 00019 3. l*yio dooa not prodoaa tha diffuao coliular fltrosi* of ths lunga no*. rvsofoiaad aa roaaliinc froa Inhalation of dioto- D* ?EMTt *apogt_m n* flM of cg^wt. tea thxas jfcasas of tha rry*rlant| aa oatlliiad in tha roport of October }Zt 1947 and la a lattar dated March 3 1943* ar now vadar aaj. tells littla of aignifiamaa haa dawlapad teaa far, a rrrlav of tha vo*k is praaaatad hero, frogrsaa aad rosalta to date af teas# ajrpsrtwta ara flaw telov undar tha tills of asah phaaa* (l) Tha affast of Itfla lahalatlrm a taharsaloua lafaotioo laitlatod *t tea ooast of fast uicwi, telrty- axparlaaatal varo imfsoted with tha sttaataated rtrala C*l) af tohaul a haaniaa aasd la tela tjrpa of azparlaaat aad vara jlaaadt la tea dash raoa tea aasst d^. teirty-thraa austral aalaala vara Inflated ah tea mi tlaa aad kapt la aaaaal air* Of tha axparlaaatal aalaala, ate ara mm laid, tao hstlad baas saarlflaad at tea aonths, too ah foar aoctha aad haa haring dlad* tea otesr saa aa raasah that aaatlMB has* aot yat haaa proparod* tea Tillnt ah tea teawd laatoaa soaparabla ulth ttesa la tea aootrola, hate fraaaly aad rtcrsaaaplaally. tea aalaala 44 tear haaa aah haaa atadlad nlaroiaoplsally, hah ea cross iBMlaatlM tea * appaar ifadUr la tha too {reaps* (2) tea affast of layla Inhalation oa rvfraaalnc taharaolaaa iaalma la f*Lasa pdf*. Za tela {haaa af tea arpariaaat, teaaty-flva alnaa pica vara latestad, aad troops af teas tan kapt la aoraal air for tea, tear aad six Asbestos Litig. nnrv-iA Saranac Lake 0U01vt< 1989 Depos. -7- Exhibit p. 85 aooths bafars being la tfas dust rooau it the prefect tla the first two (roopc ban beea placed la the dut rooaj the third 1* to go la on Seceeber 15, Mid. Qmly two matimmic of the first jnv base been aacrifleed ta jet, iftor too mnttt la tiw dost* JUcrsecople obHrntloa* lun act bees made, bet la tte grace, tba litlnw vr MpintU tlwn la central (3) Dm effect cf accemlAted Xeylo lm the Image cm a sbeec\mat taberealcas lafcctlMu Dirty eared frtm jtyi cere glicsd lm the dost reoa cm Hay 12, 1911, sad cm tegeat 12, 1941 **r* imfactcd elth the attaenited tubercle WITH* flee ami--la wore Mcriflccd at thie time for cheated analysis tc establish the ins--t f dost Itedsd* Ctmtrsl calm Is sere lafeoted on the same data* am* accrlflacd lacsmtly, tea scathe after infection. Qrecely, the leticca lm the aepcriacctal sad teatral aalmele verm enepercble, hat agela alarccccftic clsai ictioae hews mot team made* She resalts ta data lm tmie aeperiasai are cf little ei^lflaanec, since the discerns la a atarada eaa amd acy Assess tea ta tea 1she!aline of dost cf say actors are fcasem ta he else* Xeaeecr, it earn be said that the crycriaaot le grogreeaisg eary aatlefecterlly, sad that sa aattelgetc asms tf the esapllsaH nat diet imterfered dth tte latsrpeetetlem cf the ysscisas smpariaaat lm regard te the effect cf Seyla cm iqirliiitol tsha rail ids Asbestos Litig. Saranac Lake 1989 Depos. Exhibit p.86 00019S u s* l<k la ttdw 0002eG Asbestos Litig. Saranac Lake 1989 Depos. Exhibit p*87 71. 2 - UrlM Itealatl--, 36 wrtli. 200 tte twwMal.i ia ttii ujii^ Is jst terra tern it* 1M te tei if Ite alteaU la aaapar- law lte 16m ten tel alar nils te flem 1 ate 5- flaw tlwMt t fltea-- tlaan h te mm tet tet tear *ra aor* ?irte<>rii5iffte?^JSirii<?ijiM?>Tir<<fct ^ ^ 000201 Asbestos Litig. Saranac Lake 1989 Depos. Exhibit p.88 fl(< 3 - ukntM 30 MiM* 200S Ik* liMiitili U tki* jk*kwrtwcrk 1* Jaa* hot* and to tko l*f% of HMr> M* tk* ttMnlai sf iu wU a* la, tfea %k *1al ti 3t i--itha., struda of fltma ttmi 0a Mpmt itttli tka mil of ttia hwwuu, aa mil a* la tko lijaat ilaalw mlla* 00020i Asbestos Litig. Saranac Lake 1939 Depos. Exhibit p-89 0002CJ, Asbestos Litig. Saranac Lake 1989 Depos. Exhibit p.90 la loailktlMl, 00020-, Asbestos Litig. Saranac Lake 1989 DeposExhibit p.91 T*bl 1 JL5JU.T9E3 '* UJWS 07 OUTSSA "I0S zx?otK> to curt iv immoi exp a ram am cost JUh Pbt Cm4 of Dry TIsmb MilMl of f kmbrnr Dry Tluu SIOj C0 M*0 P Mt JBT OBBI* 9or OBB* pw OBB* 2 2 *M, S 10 4 IM, 11 4*42 4.94 4.4T 4.42 0.24 0.20 o.xs 0.10 0.00 0.04 0.00 o.os 0.0T 0.0* 0.0S 0.0* 1C 1 w. IS 4,12 ,n o.xs 0.20 0.00 0.10 0.0* 0.0* u M, H a 10 BM. 64 a a U (Hi 4,St 4,2* 4,St 4.S1 4.St 4.SO 0.21 O.xs 0.42 0.41 0.S2 0.11 <M2 0.11 0,14 0.11 0.14 0.1* 0.0* 0.11 0.21 0.1* 0.1* *.** t ss IS M, 10S U MB, lot 40 St M, so 114 XT m. 110 71 9 BBB. Tf 111 SS MB, 122 90 M M, T IS 4*SS 4.9* S,U *.** s.ot 4,n 2,12 4,10 S.SS S.SS S.70 S.SS S.SS S.SS S.4S 0.1* t.tt 0.04 0^4 o.** 0.40 o^s 0,4* 1.22 1.12 o.rr 0.1* 0.** 0.ST 0.S4 0.0* 0.2* 0.IS 0,1* 0.1* 0.14 o.u 0.1X O.U 0.12 0.12 O.U 0.1* 0.11 0.1* 0.2* 0,2* 0.11 Ojl* 0.04 0.0* 0.1s 0.12 0.0* 0,02 0.21 0.17 0.1* 0.IT 0.14 ?wr C**rt of iaH 310^ * p*r Mat f*r o*nt pmr sent S.ST 4.25 1.36 1.23 l.=9 1.92 4.s7 1,99 1.99 4.42 1.99 l.-79 S.SS S.SS 2.00 2.44 2.30 2.19 4.44 4.4* 2.TS Z.4S 1.77 2.41 10.12 S.42 10.00 10.2* 12.27 1T.S* 12 >4 10,20 12,70 12.SS U.S* S.SS U.S* 20.2* 17.10 11.00 1S.10 12.42 S.9S 3.04 2.20 2.SO 2.17 1.SS 2.0* S.SS 2.90 2.54 2.92 2.27 2.41 t.S4 2.2* 2.2* 2.2* 2.as 2.11 2.24 4.30 3.02 4.44 1.40 5.31 4.S4 2.0* 1.42 1.20 l.TX 3.7* *.04 0.92 0.S1 *.77 S.2S 3.2S *.17 2.2* 00020o Asbestos Litig Saranac Lake 1989 Depos. Exhibit p.92 HTSXXX ttTQJCT IPBigTmO BBC KintQffTCiL igriTITT or uso mtr rw-- TTTTWTH &4SS COKTiXT ano nx tiiiM uuacB vctcmi* x, i S l^s vltki mu# c mtt, x. d. ft. ' LX. 000191 Asbestos Litig. Saranac Lake 1989 Depos. Exhibit p.78 uraorocncB Cm yur afo, os Oetcbar 30, 1947, u latorla rapcrt v* aubaittad, eoxariaf tha yrofrasa of cartels aalnal a^rliwti with Liylo owwr s total parlod of 30 months. Zt u mmMary at that Um to rsaniMaml furthar axparlnaats aoaoamiaf ssrtala phaaaa of tho problaau Tha praaaat raport daala with tha flaial ;feasa* of tha mnrliiaot than la ^opM ud with tha aaxly obaarratlaaa aada la tho nan aarlaa of axparlMOta. fiio original axpariaaat has aow baaa aaoplatad and tha oooalusion# draws ara baaad apoo tho rssult* of a foil thrao yamra* iipanw to an ataospharle auspasaloa of layio dost, fissions sapor! anoa has ahoaa that this is tha ra- qalrad parlod osar *^<0 azposoroa to a dsat of teubtfol Moloclsal satiTity out ha bafsra flsal --slitslums ara marraatod. fills axparlnacrt, in fast, soostltotss am sasaplo of tha Inportaaas af sash pcrolotad atody for, a* is to ba haw talov, tte flndlxs at thro* yaar* oars rtrtlrlncly dlffaraot from theso at too asd aoo-fcalf yaars and tha taatatlwo aaaalaalaa rontesd at that tlsa oast nov ba altarsd. Zhas, at ths tlaa of tha provisos impart, tha iH--i 1 Mirratod that Kaylo aatod as *a Isart test la auad sots aad raLasa plfS| raaaliiac only la tha foxaatloa of aliaps of daot aalls, olthoat flteosla. hiwTir, It will ba homo balow that laflo Is ospshlo, sa prolong* lahalstlm, of pro teal 14 asbartoais la tho loses af foiiao pd, aod that It should ba hsodlad ladastrlally as a ha- Ihls rspart ho naswlul la four aootlaos as fsllaosa U Final ahaortatloos, test IshsUtlno la aacoal fslaas pia. 1. M assist ao C. fnaslssloos 8. frogass rsport aa soo aarlaa of upsrlawts. 00019i Asbestos Litig. Saranac Lake 1989 Depos. Exhibit p.79 4. final observations. dust. inhalation la normal, rnin 8ifintM to th* latoria 8*pcrt of October 30, 1947, viil reveti tint t>o group* of aoraal guinea pigs --r* placed la the dust xocau one group in rafcru- **7 1945 iad the wcm--1 la iagust 1945* Th* aalaal* van exposed to * tsosjawric sacpeosioa* of Layla dual for eight boar* daily, fir* sad nn*-bn7 f <.-75 a vae*. thr--ghout tiio nptrlwt, lb* dart --ooeatratldo, mi oh varied aawvo/. t fron tirve to ti**, hu averaged U& aillloo parti*!** pr cubic foot of air over the entire eoors* of th* sxperi--nt to date 4 brief rsrvioo of th* ub--rvatlnuJ described qb page 4 of th* previous re port el!! reveal that up to thirty aoaths th* reaction la guinea pigs vs 3 Halted to th* --latino of elacpo af --orophagea, --ntalnljig duat particles, la groups of adjaooat air apa*ae. ail* oc--viand altlnacl--tod gloat cell* vara M*a, thara vaa a* ah* prttllfaratioB of ti*a* histiocytes nad fibrosis vu thuat. X tow a--latatab!* a*b*to*l bodlM van Identified, la gaaersl, the aroi--ilatloa of *11 of th* type* described above aad their persistence sc such over a foil thro* year period, with--i th* develop--nt of fibrosis, ha* beea found to ladloat* that th* agaat reapeoaible for than la sot capable of producing fibreala. rfriah ageats are mow ocr1rt*red to be Wologi--liy Inert,* cine* th* aare aallalar aoc--Hati-- ha* aot b*ao ahovm to affaot pulaeoary faactlon or realstaao* to ill*---- However, of ala* col--la --crlfload enheoquaut to thirty --nth* la th* pro tect experta*at, ail ha-- --ova --t coly th* above lesion* but also have developed true fjtraela of a typ* charaotorlctlo of th* raapco** of gulua pig* to aabaatos. This 1* a rather dlffo-- typ* of fibre*!* ehlah form* chiefly about th* laall dr duet*, kam a* brwnahlolea, fro* ehlch th* air spaoea, or alveoli, of the lung arise. 1b* app--dad pfaotooiarograph* hcw th* --tar* of the lesion* being di*- cuaoed. Ibis ewMttl-- la ldeatloal vith aebeatod* a* can be seen by ecacxxing Asbestos Litig. Saranac Lake firM ' Ui/Ul- - 1989 Depos. -3-- Exhibit p.8Q Ftgur* 2 vlth Flgurt 3. The lasioa* la tha tnehaotaroBChlal lyaph cod** *hcv*d no ehaag* botvaan thirty oostha *nd tfar*a yaors* HimI*.! umlycis of th* longs of gain** pigs that hd inhLad t*yio dost for pariod* ap to 36 aostha yialdad tha Act* glraa ia T*hl* 1. It vtll b# notad that t* tha p*ri*d of u^mn baoaaa ldsgnr iba ash nlu gradually luntavd, Indicating a isnatlaUa of ataml atttar ia th* Infs. Thar* na a ?ro- aonmod iaar**ca la tha aaapeoaat op to about 30 Months aad than * alight darraaua. Tba raa if for ttll aoadltloa, vhieh hu tm oIhitiiI 1b nptriiMla vlth othar darts, la aot aatiraly elaar. 31no* only tvo *ni**l vara saalyrad for task axposma joriod, ladMial nlMf oar* ooeaaloaally oat of liaa bat to* goaoml traad a*a tlaarly ladiaatad. Iht flaaX obaaraatloaa la ttii aiparlaaat vlth Ujlo lrK*'l"M'** la aonal gnlaaa pigs, raportod abar* aad lUostrotad la tho flgoras, proa* that Saylo ia aapabl* *f j--a--Ut ahiiaatarlatta gmottno, aabaatoala* It ia ovldaat, thoraftra, that a amaldarabla portlaa of tha aabaatoo oaapaaaat la EayLo ranain* iiaah**gil dorlag th* mmftotorl^ jaaaiaa or. If It la afcaogad, that th* altarad rroib--t aalatolao its aapaottg to aaaoa flbroal*. Mhil* tbo 1**1 no* p-to 30 anatbi riwvad ao fltraala, aorUla aopaata of tboa wra aoapaUblo with a pralilMiy stag* la 1b* ianlapaoal of aabaatoa!a. Tbaaa aapaota mi mafctd tp th* laort typo of raartlao ta tha aatorlala *tbar Da* aabaatoa la th* tut. Tbo ahanotarlatl* aarly atago of %ha raaatlno to aabaatoa la tha pndllaotlao of tha flbora to looallaa la tha lma* ** mil of th* aaall air dmts, tawa aa t*maai bmnaOl nlas *** is la watmt ta parilaolota oatarlals, shlah laoallao ohlafly Asbestos Litig. 000194 Saranac Lake 1989 Depos. -> Exhibit p.81 In tb actual lr upte**, or lrecli. In the present xp#rl.oeot the portion of tbo ^T'K*1 ** dust, belfly portloulate, lodged is Uu alTooll and :*Rdi:ed Um peribronchiolar deposition of inrnm of tbs fibrous oanpoaont. In retrospect, it in possible to 11 mn that thorn In norm esileum of duat coll actiTity in the ration of tbo branofclaloo than in abnrontnrlntin of tbn mention to an inert pertieolste dost* Little rfytffmnor non ettnahed to this at tbo tin* of to* proeiwm report bemwm thorn non no eeidenoe of tbo demlopmnt of flfcreeie. Jho dlfformee# ktww the eerly mention W leyle sod that to asbestos 007 to interpreted ns ilifiwtlM of tbo Ionian* by the portinuloto caopos*nt of Knjln* HostfTmtlim" of sill pools in mil rtsocnliid dm loniam of that 'ill nonM 4omlm folloning Inbelntlon of dM dost eantainlag qasrtn tofether nltb natorlnZn of n Inert atbn, eon* os iron oxide. Zt in of < i ~lonoo tn ants thot nfciln the pnrlfcrmofcioler reactions cbaorrod Inwlnlmlo Inyle on oppotto of prodnsl iig ubodsdi, they nabs* tbo ponniMlitf ttat it an? * dlimili since, mr fail tbrm ymr period, thorn in in an mini beta of by lino portal ir fibrosis ohemetcrlstio of tbo roostion to ynrtn. Fnrthccmm, it ny In added that tbo mimls scow no midenee of tbo typo of diffboo flhmoin wblab boo boon otoormd in this laboraUcy to roller Inhalation nf Hit--nonim wrU amt. In rqut to bydraUd mm sol si-- nUlontn, noJoe oonetltamt of byli, it ny bo mid tbot mil* tbnro in no pointed ewMonm on bo ito offaot no pnl--iy dim, tbom In mob irtbm to nboo tbot n mrloty of nillootoof including mo fans of oololm Himtoo, n MrtfjnHy inert* St oomo llkdy tbot tbo wldn slllmte In loylo ffrnli iimfun with. tblo jndow rporl--. than, tbo ponStbllttr Mgroonod bf Idstar Qudnor In bio ooriy oannldomticn of thin pooblm, tbot byU night yrnrtmo bn yooomoaoiaooo, aiboatools and tillooala. with tbo mmltiot mfotr boo sdoqmtely stodlod. m our Asbestos Litig. Saranac Lake 1989 Depos. Exhibit p.82 00019c tee latter condition can be dieaiised. foarteer aoaaldervtion aust be jivaa to asbestosls, howssr. tee laboratory bat reeantly oo*plated a larye amount of verb vlth aabeato*, vblcb has baas r*parted to aortal* other mpportlay onpaniao, but not as yet yiMI ^had. tea foiloalay diaeustoa af the problem la dram laryely free that vorkt aad ve vonld request that these esmanta ba considered confidential. It la fait that the foUssrlay Infamotion say ba of aid to the Ovaaa-Ullaoia health depertaanh la fiumlatlat a safety jnilMf vhl ab ssitelalj la necessary la Slav of the remits of this Iayla anyorlaant. ixbarWdi, bath, la aaa sad miauls, la a dnala, alovly dmloplaf parl- hriaiteluln' fibrosis, teiafc 1* lata stays* eitende fboa the orlylasl site of lnosllmlian late tea aaiwadlai ilnall* 9m braaahl iiI i localisation is appar ently tea to tho fibrous antum of tea alaeral. txpatrlasntel stadias indicate that tho ahlof soda of nation is lr ueatenl aal Irritation of tisana V tea fibers, tea stiusluio of tboaa fibers, aad tea oapalility of rapestad lonyltudlsal divi- nlan to aalaaatsr rtr--da,la lapaotent In tea aaahaalas of action, alaao the solid fibers of ylsaa nool am aot anpabla of gradualny the fibrosis. Chemical nation is of little or aa Inpartaans In snusiny Tuaetloa, alnoo ehryaotu* reo- demd partloalnte by satilny sad separation doas mat initiate fibrosis. Cartein Isessllyetlma hate Indiested that a aaaalnyly aoyllyibla proportion of flbrona aabaates la snfflelant to pvodaas tho ahamaterlatla raaatlon. teas, aa Inhalation experiment one earrlsd ant rite ball nilTad oabaatoa in vhieh a attempt ana ante to allniaate all fibers fra* tea aaterlaL. It ms found to ba Impossible te break ay all af tea flbara aad aboat aun par aont of tho alar *- pmted dast tiarlelr* af flbara* tea sternatarietta poriteonahInter fibrosis teralopad la tea Tj.irrr-1 after forty nantba. tens, it apponra teat vary Asbestos Litig. 00019 smell number* of fibers are capable of produetrg ssbestoels, although. the devel opment of the lesion* la delayed* The prevent experiment with laylo is 'Iso r-n example of this feet* the Important setter of profreeaien of reaction after exposure to eabestos dost aeeeee hes been extensively investigated* lb# remit* lndloete that In con trast to aiUeoale, where pmyreeelc leetlense for torn tine, there le no signi ficant decree of {mmde la extent of the lesions* lather, the slee of the leelena decrease! In eebeetoele dm* tn the tendency of the fibroma tlism to noatreat after the etlanlfta to its {redaction is reneveit. See Irritation of tissue hf a eeheetee filer is apparently srreeted vlthin a few monthe after it enters the lent by the fti--4**^ af the ***bo#toeia body* (e Boating of the fiber by ironenstelmlsf material), with the reenlt that the existinc fibroma tisane eontreets. ibethnr this weiinttin enarts a bammfialel or deleterious offset on lung faaotlon is mow ader Tire*U|e >1<n. Ihfwbmtsly, the etadlan with eebcrtoa hrw not as yet eospletely olarifled the prefclax ef Its effeet an asset!ted tahemelM* lafeetlen. It appears that Kayla mey exert a olifhwiy mere marked adverse litffnamse en the lnfeetioa then does pore eebestoe* the differmas my well be dae to the preeanaa of the saell aneant ef qpartm la Ksyle or ysihape tn ether Inaldental featore* One purpose ef the etndien aew rodmr ny is tn elsrify this problem. C. jatidflSHr 1* byle, bsanmne ef its eeetent ef an appreciable mmm% of fibrous ftiyxllls, is rf*k? ef yrihmlng esbeetoeis and ehoold be hemflsd an s baeardame Liidnnlilal. Ant* 2* Kayln denn net predmne atlleorfs la emtmals* Asbestos Litig. Saranac Lake 1989 Depos. Exhibit p.34 00019 3. 1*7la doaa act prodaaa tha diffusa eallular fltros-i* of tha lungs book mapl<d os rooulting trim inhalation of ditto-- iumu oarth. D* -gPMm Soport oa aw *arlaa of rnaonimnUm Tha thpaa ffeaaaa of th* p*riaaat a* ootlinod la tb* ropart of October ;'T, 1947 uA la a l*tt*r datad Xuate 3P 1943* ** aov oadar wf, thil* llttla of slgBiflaaoaa baa dmlipaA thus far, * rrriav of tha vox*, la pxvaantad her*. Progr*#* and roaalta to data of thee# axparlaaata are *iv*a below under tbs titla of **oh r*---- (1) Th* offoat of tajla 1ah*1*t1-- aa totemlan lofertloa loitlEtod t th* eaart of dart expoeara. Jhirtgr tzyiriiHUl --nn iofaatad with th* etteatsatad atrola (*i) of taborele taenia* aaad la this tjrp* of azparlaart aad vara plaaad la th* dart raoa tha ant day* Otirtp-thr** aoatrol aaloala vara lafartad at tha aaoa tlaa aad kept la mmtmml air* Of tha arparlaantal aoiaale* ds ora mam da* A, taa hovinc b*ea aaorlflaod at taa aonthj, two at fart Mtta aad too ladaf dlad. Oh daatk eaoavrad at flva vaofcap da* to Istaiauxraat jnwmli, tha other vaa aa raaart that aartloaa bav* act y*t taa proper**. TO* miad at taa aoatha aheaad lasloaa HiagirmhU with thnri la th# wtml a, both irmly aad ricroaaopiaally* Th* aolaala at faar asatfco boa* aat baam atadlad oiaroaoopically, tat oa enw HHlaatlm tba la alma appear dilUr la tha two troop** (2) Tha affart of lajl* Irtalallna oa rofraoalac tutornlnao loalon* la alaaa jdga. la thi* {hart of tt* oxporlaoot, twaatr-flv* gala** dd* " lafoatodf aad pwpo of ttH var* leapt la oataol air for twot fOar aad dx Asbestos Litig. Saranac Lake 00019c 1989 Depos. -T- Exhibit p.85 noctha fcaforc b*lnf ,&caad is th daat room* It tha pro^oat tia* the first two groopo h**a ha*a pteood 1m tha dajt roonf tha third i* to jo In c 5aoah*r 15, 19A3* Only two aainnln of tha flrat troop fc**a baaa Mriricd fat, after two anotha la tha dost* ftlafaeaapia ob*mUoa haw not b*nn nada, tat la tha {TOM, ilk* laaicoa vara aaaparabia vith those in control oianls* (3) tha afloat af laailiUtf Xayla la tha baga aa * eaheaqoaat tabercuioos lafwtiM* Thirty anal |dM plf* ware gltaart la the dost mow a Mby 12, 190, * aa Jagaat 12, lttf ware lafnetad with tha ottaaasted tetania teeffll* flan aalanla warn mmittmd at this ttaa far atertaal aaalraie ta aatehUa* tie mbI of daet lafealad* Coattrai aalanla now lafaatad on tha mm dkta* ftrtaata warn mmitSm* mwtly, tve aoatha after lafaatlon, dranalr, tha laataaa la tha agpartaeatal mat naatrnl aalanla wart eoagarahla, ta* afala wlawoaagla ataaifatiawa tarn aei tana aada. jhn fwaalta ta data la thla aaparlaaat arc f Uttla d^lfSaaaaa, iinat tha dlaeaa* la a nhaaaie aaa aad nay nhnageo dan ta the lahalntlee of tMt of say safinra u kaaaa ta ta tlaa Imm, It aaa ta aaid that tha aryarlaaat la jrwln* wary eeUafaaterUy, aad tkat to tatlaigete aaaa of tha aaapUaatlaoa chink laterfated altk tha lataryaatatica f tha yeneia-- aayariaaat la rafard ta tha offaat Asbestos Litig. Saranac Lake 1989 Depos. Exhibit p.86 00019S OODSvO Asbestos Litig. Saranac Lake 1989 Depos. Exhibit p.87 71* 2 - tcjrli InhaTiU--, 3ft wtti* ZXH tto toioahfaU lathis jiHwiiwin^ U Jvst ttan ttw lla Xmm md ttot tf lb* idjitwt *liwll is mmt> im o aaiiiff iu a nm ii3. m* *tm<i f OlM UaM m a iwt ten, M Ut rt aon MtoafttaHH 1m 4an la Hm m *t a rifct f a CUM ftn ffWlrfl to WltoU to ilmlir Ui, 000201 Asbestos Litig. Saranac Lake 1989 Depos. Exhibit p.88 3 - liktitM 30 awOa* 3008 to* brai*lt la, tkia jtolwfwtTijh 1* Jwt aba* ad to to* Lift *f Mtar to* ****--*> 3f 1U wall ** la. to* K^la ala*l tt 3* ifitht. Stouato of fih Ut-- tarn **atat vtUia to veil f Ula tevauial*, t* ail m la toa *J--Ml Uaito **11*. -41- 00020i Asbestos Litig. Saranac Lake 1939 Depos. Exhibit p. 89 n*. 4 OOOSCi, Asbestos Litig. Saranac Lake 1989 Depos. Exhibit p-90 Fif. 5 - &U Om3A +mm m lm lasgltaUml, uiinn mt mm mix mt ttw liwililn, mt tte WiM>laln la flpm 1# 2* aa!4* M ate tta -13- 00020-, Asbestos Litig. Saranac Lake 1989 Depos. Exhibit p.91 TifrU 1 ASJU.TSES 'J LUVOS OF OTISSA IJS SCO* TO COST IX m*UTIO SXPSSIHI51 'TTH LITLO COST SmtlM Kaimml of A*h ?mr cm* of Drjr rtiiw of W hyowi Dry T1om sio. C*0 0 mouth* F*r om* ? m4 for oat P Mt l 1 Mi. S 4.42 4.44 0.24 0.29 0.00 0.00 0.0T 0.04 10 4 AM* 11 4.4T 4.4* 0.9 0.14 0.00 0.04 0.00 0.9 1* 4 BM, 14 4.1* 3.H o. 0.9 0.04 0.10 0.9 0.9 a4 34 4.M 4.34 0.9 0.24 rt.14 0.11 0.9 0.11 4 i1 3a 43 4.44 0.44 0.14 0.11 M 4.41 0.41 0.11 0.14 44 12 M, 44 4.44 4.44 0.4* 0.U 0.14 0.14 0.9 0.9 4T U Mi, <4 4^4 4.4* 0.9 0.44 0.9 0.9 0.9 0.3* 104 9.1* 0.04 004 o.u 104 4.24 ^4 0.14 094 44 9 Mi. 0 9.04 4*fl 4.44 4.44 0.1* 0.U 0.00 0.9 1U IT MM. lit 9.U 4*14 0.4* 0.O* 0.14 0.14 0.1* 0.19 TX 44 M. T* 9.49 4.44 1.14 1.U 0.14 0.1* 0.9 0.9 U1 34 MM. 123 9.W 9.44 0.9T 0.9 0.U 0.1* o.u o.ir 90 34 Mi, r M 4.94 9.44 1.4* 0,9 0.4T 0.44 0.1* o.u 0.14 0.14 0.1T 0.1* ?WT rot of 310j *0 x<0 par MBt p*r jt pmr cr 5.ST 4.08 1,35 1.23 1.5* 1,32 4.T 1.99 1.99 4.42 1.39 1.J3 8.4* 9.*e 2.00 2.44 2.00 2.19 4.44 4.4* 10.14 4.4* 10.9 10.24 2.TS 2.43 3.04 2.20 2.9 3.1T i.n 2,43 4.30 3,02 4.4S 1.40 I4.*y IT. 44 l.*4 2.00 9.31 4.S4 IS .44 9.9 14.9 12.44 U.tft 9.84 19.9* 9.9 IT. 9 11,9 19.9 14.44 Ml 9.9 2.9 2.94 2.9* 2. ST 2.41 2.9 2.9 2.9 2.9 2.9 2.11 2.9 2.0* 1.44 1.20 l.T* 3.TS S.0# 0.9* 0.91 S.TT S.9 3.29 3.IT 2.9 00020,, Asbestos Litig Saranac Lake L989 Depos. Exhibit p.92 unsixEm produced to eagle-picher IN LITIGATION DEC l984 KETLLEniC TET EJCL0C3C;i ATTITITT or eiilo wst to tb* cvxsi-Ciirois gust- co*G*iri TOLUO, QEIO fcr d Slcl&lC LfBOHUOKT GLL&UUC UU2, ITW 2Q2S OCTCEL- 30, 19a Art&ar /. Tcrvxld, 1C Clrvctcr Th* tMrd 1m Tradm Fwarfitiai la coopers tier vt:i Philip C. frttt, X. TE^klc K. Dart cl, X. I. lathoe^ 9< tfcieiitat p.0,r*r.^tr t)01l6D Cto# t**t ea October ?0, 1947, aa laterla report m ff^bxUUd, ccrtrLa^ the pr&iT+tM ef cert:. Id aaJLfcsl tx^rlaectj vith Ltjlo orer tottl period cf J Booths. It vts stMUitry at th/.t tlvi tc reecaaCLad furthir arperiaeaW concerning eerteln phase; ef the problem. Tfe* present report de.l' Vlth tb fJitBgg flf t.V <Tp-H-tn4 iS** > f." .n< !.>< t>.. tf-Vj: cbscrritloas Bade in tis cev series cf experiments''. The experiment tut ncv been eoopleted mi the eorcluricnG dr*v- irt basal open tb* results of s full three years* exposure to an ttatsjhcric tntpenslca ef Leylo bust. frorioue expert we* hti above that this If ti>e rs.'olrei period crrr which expcrun* to t dust of doubtful biolofiod acUeitr aost be continued before final ceoclusio&s are vvrrtutcd. Tale axparlriit, i:. fact, coutltotOE an example ef the importance ef rash prolcscei study for, t. it t be shots belcv, the finding* at three jitri vwe rtrlfclacly different 'ree ticct e.t tve tad oaa-htlf yaert tx-1 the tantatire fceaeloaice reached t that time sra"! a? be altered. Thus, at the tlx* ef the pretieux revert, the rrldeace indicated ti*i a?lc acted it as inert dost In &er*cl rata cad plw pies, resulting caij la. the formr-tloo ef clup cf dust cells, without fibrosis. Severer, it viii t* ahavn baler that t* elatleo, ef produclaj; efbc.vtocii. Is the lanes of grui ria fix*, thd that it should be hutdlad as e hi- sardoua dust. This report rill ba prs*eat*4 la four eeetie&s as foXkarai i. final eb* errs Vicos, dost inhalation ie oaratl juIjum *1*0. B. Jleaussioo. C. Coaflnrinoa. P. Progress report on nrr aeries ef aiperlseats* i. flat! cb^err^tlcng. da^t lnblgtlon ip porex! rul-Bee clr*. produced to EAGLE-PICHER IN LITIGATION DEC K84 heftreoce to the Inierie iepcrt f October 3C 19Z7, vill rereti tbn* tvC groept cf ttcrxil guinea pigs vere placed la th* dost room one grosp Li Fttr--- X7 19Z5 and tbe second In Zugnst 19Z5* The talaris vere exposed to itrorparric euspenslonc o? LljIo duet for eight hour* dully, fire ur.i can-half cLyr c v-t;'; througbcut the cxpcrlaentf dcri ------ to ti*r, has arerrged 116 cl 111 on particles per coble foot cf air ertr the er.iire coarse of tbe experiment to date. l brief rrriev cf tie obaerrttieoe described oo page 1 of tbe prerioat rt'port vi11 retail list up to thirty months the reaction la guinea pig: v-? te tbe aecnmulatlon of clun.pt cf cterophsges, ooataSalnc dart particles. Is groups ef adjacent elr epaees. Vbilc ccesionsl esltlaucletted gi.-et etiir vt-; teen, there vae ac undue proliferation of tit rue hlatiocyte? end fibrosis v*r tbeeut. A fro unci stf.Li bit eeVertocis bodies vere identified, la gcaertl, thteccoatlttlwi cf ctlle ef the types described above end their persiateees sr over e Toll three year period, vitheut the denlojacat cf fibre sit, h*s been lean! to toilette that the agent responsible fer then It aot ecpeble cf produei.*:?; fibresit. Sunn agents ere nov considered to be Sbiolcgiealiy Inert,* sine: t_ wn cellular sceusulstlna hxt act bees chavs to effect yuinsnsjy feactict cr re pittance te ditam. Eaveeer, efalneenijcels sacrificed cuicc^oeat to thirty noothr In tha pro* snot experiment, all here sheen hot only the abort It alone tut cleo hero dorsloped true fibre ale cf type ehamcteriiUe cf the response of guinea pigs U ebstot. Jfcis is e rather diffuse type cf flbresle ehleh form* chiefly shout the tasll air ducte, faurw u brooch!oIm, fire* vMch Ue elr spaces, cr elteoU, ef the lung B appended photcalerogrephs shoe the nature of the lesions being dle- custed. Tbit ood!tlac la idsatiesl viU ssbesterta wb ceea b? capering rtjrar* 2 vitb Tlparc 3* ''luu'UCED TO EAGUE-PICHER IN UTfGATlOf* DEC 1984 Tii* lesions In the lr*cb*obrooebitl Ifn^b nodes eh.*,v*d do then** Wtvem thirty sceth? tad three yrirs. Qieaieil Mu,lyels ef tbs lva^s rf uir.<x, pips thct b*d Inhaled Ltric- ta: i for period*, sp t? 30 nsstht yielded the csV. firta In Tstir 3. It v!ll t* Drti ihil er the period of crpcTare'h^eznr> Isa-r^r tao cgh~r?tlue r-d:n.LZy`it)crE?tti, indict tin; tn eecsacilttioD ef ndberel su.tter lb the ltmjv. Tberr Voe t prc- aoaaced iaeretes la the fillet esspobent np to shout 30 scathe rad then * elirh*. decretse* The r*i*Ncn for tfci* coodJtlci;, uhiet bt hera ctMrrrd in eiaerisrsnt- vitb other dusts, 1* ns*. entiraly tlt-r. lias* only tv leIvI* ver* sbclyrTf fer c/ch upeaarc period, indiriia-.l value* *r? c-ecsrioo'Iir rut nt Jibs V*;t t-ie jaer*I tread ** elerrly ladle*te-d. E. Elrcaeslor.. The fib*l hecrrstieni In this crperlsest vith Isylc lnhi.lr.ticr, in ttrt.'. rslnee pl{;, reported ebore end illartrsted In tie fifures, prove-th-t jjylc lr. ceyblejof prodanlcd the chtrecterlstlc reaction, tsbeetotle. It le trident, therefore, that * coaslderihle portion of the asbestos eospoaeet lb itylo rj-is:~ uacruaced jorla^ the Jniftcturibg process or, if it Is changed, th*.t tag rlterv. product lb teles lti^ cepeelty to exuse fibrosis. hhlle the lesion* up u. j~ booth* shoved do fibrosis, eerUlb aspects of then vere eatpetible vith l pr*li.*>liuoy ttc* la tbe derelepaaot of esbeetosi*. these upset* vert aabiied by tie Inert type ef reaction te the setrrttls other then ubeiioc lb the dost. Tor chnnetcrlstie early tUpi ef the reebtloa to ashes toe is the prcdllectloe ef tit fibers to localise lb the loses sad veil of the caell lr doote, Isaeva es ttrxlael brcsuiiolec. This Is in wrtmi to pertieulnte ceterlsls, vhicb loeellM tZLefly Eagle:.PiCHEn IN LITIGATION DEC /S34 in the actual air r aVreoll. lr. Via present experlMt the rrntaft pert ice c: the inhnlad dual, being psrticulata, lodx>d In the alveoli tai w=r.Yr-j tie peribronchiolar deposition of scce of th* fibrous oaspoaent* la r*irc;,*tc`.f it is possible to discern Uut there is sort evidence of dust call tc'.iriij i;, tbs region cf to* brcuehielat than is cLrroetcriatic cf tht reictior. tc m inrrt pariieuiiite cunt. Litila significance vib btttched. to_tiit,x\. tht tin z: t:r. previous report becouso there vt up rridrnce of the drrelcn*eat of fitrorls. Toe differecett between th* esriy recotlco to Ltyl uaa that to tfb*stcr sj.y be interpreted si t aodifieatioa cf the lesions t/ the particulate tonpcaerAi of kkjio. *Kodifititioo* of silicosis is eell recoculted when leaicr.s cf Vcct ilwtrt develop folLovlcg inhalation of olxed dust containing cusrt; tsfoV.t? vith tu terlala cf u inert nature, such sc iron oxide* It is of isport&ace to cote that vhile the peribronchiolar r^cticnr cb(erved ireririnite Kcylo an(ccpcbltjof ^producing csbestosls, they exclude tiw pcibihilit? that it sj-7 enure silicosis, since, Ter c full three year porioi, thnrt is in no anixcl ey focus cf hjTJLin* nodulxr fibrosis chareeterictic cf toe reaction to cuartn. furUisnsoT, It a*jr be sdoad thtt the sniraj* sasv u. vi^*uc of the type cf diffuse fibrecin union tuu been observed in this lifc.:story to follow inhalation cf distoosceou* earth duet* la ragutt to fcrtKj-ctleiux silicate, e Major constituent of icyrle, it aey be said that utile there is so pointed eridenes si tc its effect on polaoaerjr tiara*, there Is Much eridense to ebwr thst s cartel/ ef cilice tat, including soae form c: esiciur silicates, ere biologically locrt. It coext likely ..thet taa ctlciun eilleou in LayLo should ocoform ultb this preriotu experlrace* fhus, ths poaeiMlity expressed V Coctor Gsrdnsr in Ms early oasidan, ticn ef this problem* thst Uylo Might produce tvo yaooxcclo***, esbeatoais end liliso: vith the resultant safety hsxirda, bis bees eds^ustsly studied, sad concern over r.TGDUCEO Ta z vgle-picher: It,' LITIGATION DEC 34 tie Is tier condition cjlb b dlraisetn. Turthar eoul<Ur*tlpa Mu*t b* pi*** to eibestorii, bcvmrr, too Ubontcry hi* recently oosyleted * large uaouct of vorh vith oebiatc' -which his been repoirted to certain other supporting cospenUs, tit not tr yd published. Ta* follcvtng dlccuaaloa of the prcble* le Arsvn largely fr?-*:. *- i Yer):, end ve vculd-r*..ttsit-th*t-th e pc -oegaents-be- cens idc rcd~r~.rfTTT~t~n.~~ Zr. 4a felt that the following inforaAtion eny be of eld to the Ovens-Liilacic LtzlL1-. depertaext in fonolttlnf * safety progrut, vhieh certainly is neceacgry Is -ric% of the revolts of this Lryln aipardjeaat. isbertoyia, both In bad end enisals, it e chronic, elcvly derelc/iir.r yrr.*brcnchiolr fibrosis, which ir. Into st&;e; extends fres the criminal site cf lcctliaet4.cn into the rurroundi-ng eiret-li, Tbe brDCehielxr locrUctticn if. ty.r.r eotly due to the fibrens nature of the Mineral* Erperinestcl stadias ir.dlcii-' that the ehlef node ef action if by nechtnictl iTTiUtica cf tissui tj- the fiber: Tr.e structure cf thee fibers, and the capability of repetted longitudinal diriion to Molecular strandt,!* lportent la the *eehanlta cf aeticn, since the solid fiber* cf (la.ee vool ere not capable of producing the fibreeia. Corniccl action is ef little or no laporUnce In causing reaction, eince chrysi *..'!<. re:-- dered partleulAte by cutting and separation dote net initiate fibrosis* Certain int*tig**lion* hare indicated that a secMingly negligible prc;crti:r. of fibrous aebeetoe la euffielent to produce tha characteristic reaction* Thus, an lnhaletloe uparlMat see carried out vith bell-*illed eebestoe in vhieh to attempt vu Made to aliainate all fiber* froc tha Material* It vu found to be Inpossible to brack up all cf tha fibers and about oe par oect of the air sus pended dust consisted cf fibers. The charuetarlsilc porlbro&chlclcr flbrvaia dereloped In the expoeed anlnalt after forty ooajthe. !ta, It appear* that eery EAC-L E-Pi CHEFS IN LITIGATIQbi DEC 1984 s.iaII anbrrf of fiber? tre ccpeblo of prodocic^ tfbe*io:i.'t altheac'. tot d*Te.puect cf the lerleos Is deltrad, The present experlxeat iritb Itylo i* c.lre iexerylc of tbit feet. Tfl* important sitter cf progression ef reaction sftrr exposure to teb-;'!:dust ceases be.s been extenxiTelp iarertigntei. The rtr.ults indiert* !; t i;; c-,i1 iTi!t*~tc EilieeriK, Vhe?t pFSjresrian ecttlcyes for rets tiucv tArr; it tc fieest degree cf progression ia extant cf the lesions* Esther, tir* sir? c! V/ lerioac decreases in eebeetoxle due tc the tendency of the fibrous tii*oe tc esotrtet after the H!r.i1r. to its production is rootti. Tj? irrit'.ti^r cf tl V mi asbestos fiber is apparently arrested vithln a fev mssths after it ea*-r~* the lung by the forwtien cf the *esbt*stosis bsiy* (a testing cf t.V fib-** tv !rv eonivining arterial), vith the result ta.*.t the existing fibrous tissue tre*. Vhether this cntr*etion exerts a beneficial cr deleterious tffctv c;. 1-r.v- ' -ir.-tlsa it nev trader inTtstignticc. Eafortunately, the studies vith tsbesics h*.ve act a* yet omelets!? cirrifi e the groblea of its effect on associated tobereadout Infection. It appears the*. i--" 1 J>yiesay exart c elightly aofe narked edrersa influence \oa the infeetierl Uirr. door. pure atbeatos. The difference aip veil be due to the presence <S ins itscant of <putrtx la layl or perhaps tc c-ther irinldeutel factor-.. Out ;urfc:. cf the studies now under vty le to clarify this probless. C. Coo-clutloo*. 1* Lijls, because of its eooteat of aa appreciable aaouot cf fibrous ehiysotile, leW^blsNpf producing estsetecic and should be hassled as a hazardous indurtrlal dust. 2* taylo does not produce rlllooctf la talsnlt* ' --uced ra RICHER 1:< litigation; DEC 1934 3. Ltjlo <Sc>*t sot produce the diffuse c-*11ulLr fltror.it of Vat long* csv r*ooEl**d it rerulliag fros lah*l*tlca of dictoBiceoa* etrth* D. ProgTca: Kesort cu ocv eerie: ct o.terlacstr. the Uutt phases of the eipcrlssst, ** outlines in Vat rccrt of Scisb::- ' !Vi7 d to k letter"dtlcd K*rcii 3, 19i/ire ~i^'ubdF\xf7 ~thIi^ lit\ie eifuificsnee hie developed thaic fir, * reriev of the vcri. ie prer-ento;} her;1. Progress eoi results to date of tSr?e experiment* ere files bclcv usder vir title cf **cb phase. (1) Tfc? effect of t7lo lnhr.lr.tles co tuberculous infection Inltiit*.; - \ the cruet of dust expocure. Thirtj experla&str.l minis vert infected vith the .ttertu- tr J rtmic (E]_) of tubercle bceillur usee is this type of experiment ucJ irrc plxcei in the dust rocs the next dej. Thirtj-three control mincls vers, infeeted et the outs tine mi sspt is norxvl sir* Cf the experiment! 1 ml rj.lt t tix or* bov deed, tvo haring been aecxifleed it tvo Booths, tve it four Boathe tod tvo hiving died. One delta occurred et five vaefc;, duo to lstercurrcut pncuxcr.it . toe ether vie 10 recent thet section* htv* sal jet bees prepared. fits aniselt killed it tvo sooths shoved lesiooe comparable vith thoeo Is the controls, both groeslj isd ricroieopicilly* Xho talmal* killed it four aenths hire cot bees etuiied mlcroeeopieillj, hit os ersts exmlnttiaB the leeiooe ippeir eiiliir is the tvo groupi. (2) The effect of lajlo lnhnlition os regressing iuberculcm* Issioat is guinea pdgB. Is this phase ef the experiment, tsestj-fire gul*** pigs ver* infected, esd group* of them vere kept is nonel eir for tvo, four *d<5 six _*r. I.AC-LE-PICHE = )N LITIGATION 0C 1934 sextos toTer* Vila* pieced ta to* doit root. H tor ?rr*tcl Ll.w w firet tvo fT^rc^a hjTv b<tc pLtcod 1a to* diut rooa; tie tiiLrd U to ft Ll or Iterator 15, 191e.. Cal^ tvc tala*. I? of tit flrct cron," itrj boon tterlflcoi tt jrt, eftor tva mcato* It tic du*t. 5^cre<itc^ie cfc'vtrT.* tioa? irtr ott V/: aide, bot It tie croff* th; Itrinas v*r<e con^r'-hl* \Ltl-. IVr-rr-ln c*r.\r~-.' itislt, (l) Tbs offset of fceetatiU.t*d tejto la tit luo* ea i rube* utr.t tubcrc-lru. Infection. Thirtj turrw.1 fuia**; r^f- **r* placed la lit dust rccu cr, S-7 191R, rr-i 00 August IT, 191? rt Infected *lth tit r.tteuu- tof. tuber;If b-icllli* me tniirjls v*r* eoerifietd rt toi* tlr.* lor cirric-i tailr.-'.r te ft*tilth tho tssast 0? dust labeled. Control talar. It vrr* isfeci"-' or. toe e-jst dttf. lalasla vtr* ecrifle*! r*e*sU*f tvo strati' after lafti:a. Ircftaly, tit leoicnr la to* zp*rlacUl asi Control aaisrli vtro eou;'*j-.til4, tut rLln alercacopie ebstmtiocs btre aot tooa aed*. The rorultf to datt la tol* tiperisaat cr* of Utile tlgalflceoet, *icee ti Jirtt-st If eiroaie oo ud aaj cb*agc5 du to to* iah-U.ticL: of uutt ci jl-.-l. tr* toervx to to aLev, Bwmtr, It e*a to **14 tb*t to* **i>*ri2*3t Is progress! a* T*T7 Mtlsfectorilf, tad that n taUtiptU aea* of too ccapliettioa? wica iaUr- r*r*d vlto to* laUrpr*uUoQ f to* pr*Tioas azpvriwmt la rtgerd to toe affect of Ltylo oa xprla*Btol totoreulosla* r---DUCES TCJ r /vjle-picher tN LITIGATION! DEC ^ Fif. 1 - ttylo iainlatlor,, JO Bcatoa* 2DC2 C jfeerte bc*n * tarns tactlca of * Iccotololt Jut *.bcr* tad *U^btl7 to to* toft af tsstor. Ci* other ip*t *r* let* the ierk mrtf rithin ** of th* aaseitor *P**d*llj to iho rl^ht of to* hreoeMoio. th*e or* too Mcrg^ufn cad ultiwctoctod cleat cilU, demerits', to to* trrt. Soto to* totoc**a of to* otll of to* taroatototoj it 1 TirtsalXf Bomtl m le oppeneat ca oos^wteoa vitb Hew 5* to **b*atol* W7 1* proaoot to tola ftoto, *ad to mUaf to fl^sr* 4 at fclaT ijiiifie*tie6. PRODUCED TO F.AGLE-PICHER IN LITIGATION DEC 1934 Lstflo IshtUtlca, J6 acaihi, 2wCJ Tio broochials in tUs pbotaalerojreph it Jcrt ebo^i eni to the right of center. feta the thleiaese of the Uf^c befcv-een its lusaa ui the! ef tb* tijteec* tlTx>li la eca:.iarJLxir. vith the brnsehieler vails la fl^ares 1 ud 5* flic tnfcir of fibre'.is tlssu* eta be eset berc, Vat tbey r<* erre AjjAxeni, because less 4e&str la the mi t the rich! of iu field y*r* fibrosis ii( extrdei te edj*eect alreclsr vtllr. produced to eagle picher IN LITIGATION DEC Tit. 7 - llUlUt 1H*JiUm, }> xcitia. ZZZ. Su trerwiMfil* la thi* FholealcrofTfeph lx jut *.be>T* tad to the left of enter. let* the thick#tine cf it? vtU in the l*yio esJLntl t ^6 au;th. ItrcLir of fibrout tlxfu* nr# p?cr8t ritLia the -nil of thii brocthinl#, u nil ne la the adjteoiA vlreoUr PRODUCED * EAGLE-PICH; IN UTIGATIC QC 1984 Pi. 4 - tvjlc ioZ^lotiCO, >0 OOOtlU, 12071 Thin hlfhw m^cniriettloo of pert of Vs* fltl4 thwn 1b Tifro 1 rmtii & l^pleel form of 'wbefteule body,* la>* Krr*t 4*rk #loc**t*d ftrMtor* to tb# ri<tt of tst*r. T . .EDUCED, TO .^GLE-PICHER It'i LITIGATION DEC B84 fit. 5 - Jforui pit laa** 2X1 tali field above tec brescMelar, c&e it loo^Itudic-.I, to* other jjo croee eretioc. The mlII usoei^ted blood Teapftl le oeeu ikr the feraer tavpchiolg. Ccs.pr.re the thietse** of the vail of thM broochicle*, vith tht of t&t broseoiolse In figure* lt 2, &ad 3* Sot* alee the aspty alTvoli thi alreclar *'* W T*b3* 3 i/jai!2S W LU3TC3 Of CUHtSU riCC PRODUCED T' EAGLE-PICHEr IN litigation DEC 1984 ixpcsrt- to dost ir I7a IC8 UPO-TUTT; KITE UTLO DOST Owratiec 4th Pit Cos! f Ptt tli rut AnitiiJ of of Suaber tjpoHzre l>rj Tilluo *102 CftO --watRf par crET" per east par cart par east m X Mot. c 4.94 0,24 0.10 0.0$ 0,06 0.C7 0,08 10 4 Mt, 11 4.47 4.42 0.21 0.17 0.09 o.oe 0.0? O.OS 16 6 not. ie 4.U 4.74 0.16 0.10 0,06 0.10 0.05 0.06 25 t It 4.W 4.34 0.31 o.;t MS 0.11 0.03 0.11 43 10 mob. 66 4.66 4.81 0.45 0.41 0,14 o.n 0.21 O.U 43 11 wa. 46 T 16 MO-t. *5 4.65 4.99 4.63 4,90 0.13 0.51 0,19 0.66 0,14 0.16 0.09 0.10 0.22 0.05 o.u O.U 105 11 Ml. 106 49 14 m. to 114 IT MM. UP 6.11 6.14 6.01 4.n 1.13 4.76 0.64 0.14 0.6$ 0,60 0,82 0.46 0.19 o.u 0.13 0.14 0.14 o.u 0.11 0.05 0.06 0.06 O.U O.U Far Crr.t of it'- Si02 C*0 *r* per erst par cant per cc: t ** l.fi 1.23 l.rl' i.c:. 4. "7 4.42 6.66.3$ C.64 .4r 10, u e.4i 10.80 10.25 1.9c 1.6? 2,0z.c: z.t: 2.<: 3.0< 2.2: i.tr 3.17 1 ie' l.f .r; .1* 9 * 1.* 4.3* WV6 4.66 l.CC 12.27 17.68 12.64 10.30 i.c: 2.06 3.65 2,00 5.31 C.i-C 2.01 1.42 U.TO U. 62 2.64 2,92 1,10 l.ts 15,93 9.65 2,67 2.41 3.70 s.tt. n 10 Ml. n 121 BM. 122 90 16 Ml, ft t* 8.61 6,13 1.70 l.M l.4 1.36 1.64 l.XO 0.97 0.89 0.16 0,67 0.64 0.14 0,11 O.U o.u O.u o.n o.u 0.05 0,08 O.U 0.17 O.U 0,17 O.U U.M 20,15 17.10 U.OQ 16.10 12.46 .9X 2.66 2.21 2, t,u 2.89 2.11 2,86 0.9? o.si 3.77 6,25 3.20 3.17 2.3S 06^ IUTIJUM RZrQHT jtd THE BIOLOGICAL ACTITITI OF KAILQ DUST ' to the OVE3S-ILLIHQI3 GLASS COKPAJTI TOLEDO, OHIO' lrr THE SAEAH1C LABQRAICE] HAEA2UC LAJDE, HEV IQBK 0CTOBIS ;jQ, 1945 by* ^ur J. 7orv*!d, N. D.-, Director ^ Idvord L. Trudeau Foundation In cooperation vitht Fhllip C. Pratt, H. D. Thox=e H. Durbtn, H. Z, Anthony B* Delahimt "C IKTRODOCTIOB Cne year ego, on October >0, 1947* an interim report vua submitted, covering tha prcgroo e of cortuln anlnal experiments vith Laylo over a total period of 30 months. It va* necessary at that Hao to recocraend further axpsrisaata concerning certain gixe.noa of tha problan. Xhe present report deals vith the final phased of tha experiment then in progras a and vith tue early observations nade in. tha new series of oxpsri'ceatxs. the original experiment has. now been completed and the conclusions drawn are baaed upon the results of a full three years* exposure to an atmospheric ruapension of sylo dust. Previous experience has shown that this Is tha re-- <{nirad period over which exposures to a. dust of doubtful biological activity aoat be con hi rated before final conclusions are varrentod. this experiment, In feat, constitutes an example of tha importance of such prolonged study for* aa is to he shown belov, the findings at three years vere strikingly different frost those it tvo and one-hnlf yean* end the tentative eoneluaioa reochad at that tine sust nov altered. Thus* at tha tine of tha previous report, tha evidence indicated that Win acted as an inert dost in narael rats and guise pigs; resulting only in foxnatloa of clumps of dust cells, without fibrosis* However, It will be Jhcvn below that layIn is capable, on prolonged lnhalatloa, of producing asbaa tools ta the longs of guitoa pigs, end that it should be handled induetrinily ae a ha~ *<tdau3 dust. This report vill be presented in four sections an followst i. FlntL observations, duat inhalatioa in norxal guinea pigs. B. Discussion. C. Conclusions. D. Progress report on nev series of expericanto. Final observations. dust inhalation In aorsul guinea ?l=ra. Ksferenc to tho Interim Report of October 30# 1947# vill re reel that tvo .~oup3 of ttorsaL guinea pigs vere placed la tho dost rooai eae group la Jabrult7 1543 and the second In August 1945* The anlads vers oxpaaed to atmospheric suopeasious of JCaylo dust for eight hours daily, five end one-hal days s veal throughout th experiment. the dost concentration, voich varied eoaevihnfc frpa tir, Vo tlx, ha2 avoreged 116 al 1X1 on particles per cubic foot of air OTer the entire cmr rs of tho experiment to dote. 4 brief revlav of the observations described on page 4 of the previous re port vill reveel that up to thirty sw>nth the reontion la guinea pigo vac Halted o the tccurmlatioa of cluapd cf saacrophages, containing dust particles, in roup* of adjacent air spaces. Vhila occasional aultinucleated giant cells ver *, there van so undue proliferation of tissue histiocytes and fibrosis v&s ^ot. 1 fsv unaistalnble asheato3Is bodies vere Identified. In general, the -emulation of cells, of the types described above end their persistence as such Ttr a full three year period, vithout the development of fibrosis, has been 'cod to Indicate that the sgent responsible for them, is not capable of producing Ihrosls. ouch agents are now considered to be "biologically inert, sine* the cellular eccuualation has not boon shown to effect pulmonary function or ** la tones to disease. Severer, of nine mtisutls sacrificed subsequent to thirty soothe in the pro fit experiment, all have chovn not caLy the above lesions but also hero developed '5* fibrosis of a type characteristic of tho response of guinea pigs to asbestos. ie s rather diffuse type of fibrosis vbieh forms chiefly about the snail air *l% fcnovu aa bronchioles, from which the air spaaee, or alveoli, of tho lung The appended photomicrograph* ahov the nature of the lesions being dieThis condition is identical vith asbeotosia os can be ee*a by comparing /lfure 2 vith figure 3* Tta Lorlcnj in the teachaobronchial lr=ph coJoe chovtd no change botueaa ihiriy ccntho and three 7nn. Oaeaical. coalyela or the Xun^ja of guinoii pigs that hnd lnhnltrd Xhylo dust for periods up to eontha yieldad the data given in Table 1, It vill be noted tta l ta the period of exponura beoano longer tho ash value gradually Increased, Lsdiexting an accumulation of ninerol anttor in th lungs. There via projounced increase In the elitea component tip to about 30 non the And then a alight .'creese. The reason for this condition, uhich ban been observed in experiments Hth other dusts, ie not entirely clear. Since ouly tvo enissls ver# analyzed for atch axpoaux* period, inolTldUKl Taiu.ee uere occasionally out of line but tea general trend va clearly indicated. t* Discussion. The final observations in this experiment vith leyla inhalation In normal ^ina pigs, reported ebors and illustrated in. the tigures, prove that Eaylo la *pabl of producing the characteris tic reaction, asbestosis. It is evident, ^refora, that a considerable portion of the esbsstoe component in aylo reoalne ^^htoged during the etcnufaaViriug process or, if it is changed, that the altered n^0t Eu.lQ.ta.ioa Its capacity to omia% fibrosis. Vhlle the lesions up to 30 ^th# thovod do fibrosis, certain aspects of the* vr compatible vith a prollrvt<r7 stage in the development of asbeatosls. Thee* aspects vere naalced by the Urt type of reaction to the aaterlala other than asbestos in the duet. The l<r'atsristio early ataga of the reaction to asbestos is the predileetloa of th* to localise In the ltxoen and vail of th* snail air ducts, fcnovu as teralns 1 1>tchiolae. This is in controet to particulate nat*rials, vhlch localise chiefly jx the actual ir *o*es, or alveoli. In the present erpcrl-wmt tie greatest pert Ion of the inhaled dust, being particulate, lodged la the alveoli and acaked te peribronchiolar depoeitloa of sons of tha fibrous coapocent. la rotroopnot, Ik 1* poafihio to discora that thsr* is stort* evidence of oust cell activity 1a tho regiea of th* bronchiole a than la characteristic of the reaction to on Inert particulate dust* Little algal Cleanse vaa attached to this at the tine of the previous report because there vaa do evidence of the demslopneat of fibrosis- the dlffareaces between the early reaction to Kaylo end that to asbestos ay be Interpreted a o codification of the lesions by the particulate ccQjoaeats of foyio. *1Codification* of silicosis is Veil recognised vhea lesions of that disease develop following inhalation of a nixed dust containing quarts together *itb Materials of on inert nature, such as iron oxide* It is of importance to note that while the peribrenc-iielar raacticnn eb'ved lncrlgJLnste ftylo as capable of producing asbestosie, they exclude the Risibility that It asy cause silicosis, since, over t full three year poriod, ^sre is la no Sniaal soy focus of hyaline nodular fibroeia eh*rcatarialia of reaction to quarts. TUrthareore, It nay bo added that the animals show no rrid*oc of the type of diffuse fibroeis which has been observed in this labor Wy to follov inhalation cf dlatenaceoue earth dust* In regard to hydra tea ca--calolua eUULsate, a najor eenetitoeat of Xaylo, it any tr said that while We is no pointed evidence at to its effect on pulnonary tissue, thero is such rldeoc* to show that a variety of silicates, including uorvo foms of eoloina beaten, ere biologically inert. It seests likely that th calolm ailioate ^ylo ahould confor* vith this previous experience. 'Ihus, the possibility expressed by Doctor Gardner in his early consideration problem, that t*ylo night produce tvo pneumoconioses, ssbestoaie and silicosis, ^ the resultant safety ha turds, has been adequately studied, end concern over tf 3-0Iter condition can bo dlcmlsued.. further consideration oust bo given to Toatosls, hovorcr, Xao Libara tory ho a recently ccmpletsd a. largo amount of vork vith asbestos, iblch has boon reposted to cortaln other supporting companies, but not as jet 7iMJueiiod. The follavlng discussion af tho problen la dravn largolj frau that roric, end vo vould raquaat that th.esa ooaseats be conaldorod confidential. It i felt that tha folloving inforaatloa nay be of aid to the Gvone-Illlnoia health partaoent in Xorouinting a so-ioty pxogrva, vhich certainly la necessary in vlev t tha resuita of this faylo experiment. Asbestosis both In nan end enirsals, Is a chronic, slowly developing peri-- rcschiolar fibrosis, vhich In late stage* extends fror* the original site of -filiation into tha surrounding alveoli.. The bronchtolar localisation is apparUy doe to the fibrous nature of the mineral. Sxperiasntel studios indicate the chief node of action Is b7 mechanical irritation of tissue by the fibers. * ftructura of those fibers, and the capability of repeated longitudinal divi-- ca to molecular strands,is important In the taachanlna of action, since the fibers of glass vool are not Capable of producing the fibrenis. Chemical Uoa is of little or no .importance In causing reaction, since ohrycotilo nmr'd particulate by cutting and separation does not initiate fibrosis 1: Certain investigations hare Indiantod that a eSemiugly negligible proportion fibrous asbestos is sufficient to produce the eharacterlstlo reaction. Thu a, halation experiment vao carried out vith ball-allied asbestos in uhleh an **Pt van cade to eliminate oil fibers from tlio material. It vis found to be '5#ible to break up "* i of the fibers and about one per cent of the air sua- duet consisted of fibers. The characteristic peribronchiolar fibrosis Pd In the exposed animals after forty months. Thus, it appears that very pr.ll numbers of fibers ere cnpsblo of producing aabeetosia, although the duralcpscat of the lesions la delayed. the present experinant vLth. laylo io also an t(iapia of this fact* Bio important aattor of progression of reaction after exposure to asbestos kil cease# has been extensively investigated* the results Indicate that io coatn,rt to silicosis, vhara progression eoatlouoe for cone tins, thora is do algal-- fletai degree of progression in extent of ih lesions. Bather, the slit of the Utiess decreases is aabontoaia due to the tendency of the fibrous tissue to totrsefc after the stlnulua to ltd production is restored. the Irritation of tissue V *s sabsstos fiber is apparently arrested vlthin & ferv souths after it enters long by the forustica of the *csbe#toeis body* (a coating of the fiber by ironeaUiniog naterlal}, vith the result that the existing fibrous tissue contracts. ^*th*r this contraction exerts a beneficial or deleterious effect on lung fono- t is nev under investigation. SafortuiLataly, the studies with cobectea have not as 701 eoapletely clarified k* Rohlea of ite effect on associated tuberculous infection. It appears that *?lo nay exert & slightly sore narked adverse influence on the infection than *** I*1*1* ashes to*. The difference any veil be due to the presence of the naall 53=5quarts in Esylo or perhaps to other incidental factors. One purpose 1, " studies nov under vay ia to clarify this prohleni- Ssgclusions. laylo, because of its content of an appreciable amount of fibrous chrycotiis, is capable of producing esbsstoeis and should be bandied os a haxardous industrial dust, laylo doe* sot produce silicosis in animal*. 3* lajlo does not produce the diffuse cellular fibrosis of tho ] irn 71 ncv recognised as resulting fron lobala Lien of dlato-- saceous earth* ), Progrenc Resort oil nn aeries of SKoerlnanto. The throe phase of the experiment, as outlined in tho report.of 0ctoboi*30, 'li7 and in a letter dnkrxl March 3, 1944, are now under vny. Vhlie little of djulficance has dawlopsd thus far, a reviov of the work is presented horo. rrefreas and results to date of these experiments ere given belov ucdor tho Ulle of each phase* (1) Tbs effect of Ksylo inhalation on tuberculous infection initiated at the caoet of dust exposure* Thirty experimental animals vore Infected vith the ettoatuated train (of tubercle bacillus used in this type of experixent and vere placed in the dust rooa the next day Thirty-three control anlaalo vers iftfocted at the some tine and inapt in normal air* Of the experimental aninals, six are now dead, tuo haring boon sacrificed at tvo nenths, tvo at four souths and tvo haring died* Cue death occurred at fire veekap due to intercurrent pneumonic* the other vaa so reseat that osctioaa hare not yet been prepared* The nninals hilled at tvo souths shoved losiona conmu-able rlth ^hose in the controls, both grossly and rlcroscoploslly. The cninala It tied at four sonthe hare not been studied microscopically, but on gross lamination the lesions appear similar in the two groups. U) Tho effect of fnylo inhalation on regressing tuberculous lealona in guinoa pigs* In this phase of the experiment, twenty-fire guinea pigs were ^ected, and groups of thora vere kept in normal air for tvo, four and six ieotha tofcrv being placed la the dust root*, lb the pro scut blue tho first tvo groups have boon placed In tho dost roonj the third le to go In on lecaabar 15, 1913, Oalj tvo unlselc of tho first group har boon sacrificed as jet, eftor tvo aonttu In the dust, Microacoplo observations hare not boon aide, buf in tho grosn, the losinas vere comparable vith those in control iclmls. (3) Tho effect of aecux&iLited Lxjlo In tho lunge cn a subsequent tuberculous infection, Tlilrtj aorul gulden pigs voro pieced in tho dust room on lioj 12, 1948, and on .August 12, 1943 vere infocted vith tha attenuated tubercle bacilli, firo animals vere sacrificed at this tine for cheated onaljsis to establish tho amount of dust inhaled. Control infault uero infected on the rAsa date- InLatin voro sacrificed reoentlj, tvo nonths ifter ir action, Grossly, the lesions in tho experimental and control snisils were cc-spireble, tut igoln aioroacopio observations ham ot been aide Th* reeulta to date In this experiment ore of. little significance, sinco tho is a chronic one and ictj changes due to tho inhaletion of dust of. any nature to be alav. However, It can bo said that, the experiment la progressing ^Uafftctorllj, ind that vo anticipate none of tho ceaplicationa vhich Lotor- ^ *Uh the laterproLotion of the preTiooa experiaant in regard to the effict Wlo on 'aoatal tuberculosis*