Document vbMQ1BEEVLvbB3GXo8wXd3R

FILE NAME: Metropolitan Life (ML) DATE: DOC#: ML DOCUMENT DESCRIPTION:^ZZ^ WZ B.liidgupOl" t, C\)!tn. Nov~~b~r 10, 19ZG Mr. F. H. Echluter, Prusid&nt, ~'hc,tr:loic1 Huui;I::.!' Co., TJ.~~nton, N. J. I (~ J .~... . " The wl~itf.:.r l~nd LIr. V\.,nc~1ver B.rv\,n, of .lohns-!knvill~, had h conft.:1'imCe y,ith L.l'. 1trl1Y Gnront::l', of fi~lr;-mac,N';.'\\ Y:)rl~, ;J11c! D1'. L~n~a onct tl'. :JcCo.tUloll, of thu Mctroi?oli thn L1\-,: Insurr.nCt'~ (;')., .ith refortnee to tile Asbestosis tltuntlon 1n t~o Asb~ntoG In~ustry. As you. no doubt i<:no'u, Johnfi-Lianv1110 r;nd=>ul':Hlv/J~j 1111ve blh.'n c.oln~ con~id(!:r'l\ bie \,,01'1(, in conj\Lt1ctiu!l \" i til t:'\(;~ Motropo11 t~n Lift: In!;urvnc(: Co., in tho V;llY of (~lininntlng l\.!:bf~~;tO!~ tUt-t in our fcc tOj:il::~, ~!nc.:. ,....:! !lU V~ made 0 Vel"Y S~, tl!iiri~ctory job of it. \;lJ lu~ve n.:>'!. r'\:'!uchcd the ?oint 'f;hl::I'r.,: \.,': CF1n c:lii11in~ to a l<lrb~~rlrt of tht:1 D\l~l t, but us yet tll'.VH no' deflni te' 1nfnrr.1;l tion n~; . to \tlHLt Asb:!'.ito~jl0 r.ill llHlcl ill'tO. Thty eJ.t:hl i t lmiCls to Tu1;~rcu l;)~is, bu.t \:.0 (i" not iincl this, to be t~c cn~l(:. 8t111, rit~Cr!.nnot go into court cnd ntl.! t~ ciufin! tcl~r ~nd zji6clficolly tlUI t i t \'.'i11 not co ~;). We do IJiO\'.' th;~ t A::1bew to:3 Fl bl'eG cc.n, anti 60 t gl.~t into the lunge, o.n<.l !;IUY Dt;t up li t'1bl'o~ls contil tlo11, ~h1ch, for ":~:nt of a b e t to!' lltl!=t~, so,no doc tot's havo c~..lled As bi1S toslr>. Dr. GU1"0ne:r ho.~; t1 well CliUiPP6d Lr.bor:::f:,'Jry, ~nd :': nll.~ber of Hl:.:parHtt',: lJu!.'t Chunbo1'3 in his Lnb:J!r.t:.),~"'Y l.\t fJ~"J':.:.nr.c, ond he r.nd hi:; t:~t:~octutc:; huVu bQt:n !;tuCiylng Vl.;r1.)\t::. t~':H:~ of Duct for n mnbCT of ytHtrS, in (.!,:mncction n1th Tub<.:rculosis, b\lt~l't:c:tiCtllly n')thi:l[j h:::.~ u(:i.;:n .~on{: v.lth 1\!:iue:;tos. In orG !.:l l' to carryon u 5yr.t! r;l:~llc t"unt inv\.!btlf;,'d;ion, it t~.::{u!.: rl'~f!1 tv...., to thrt;O yual'5, ::no thest; inVi!:; i..i~;t.U. 011~ t.il'''' i~Ll"'l.iral- 1.mit. 1y ;>:'i!O fol.' 1.;y lndU$\:'l'Y, r3\Jf.itly i.vl'ltintj ~!.~; II D""' , .l.. nJ" t.J'~.....l""--J C'_"..f.. "." G~(rl/~L'I,w (., 'W .i....."' .\..f),.v,.,....:.. t"o'lJ',HJ \')n " Y! .~H-..., ).l...O.. :\0',.",""" lc.'...:.LC l.. tc'll'(..'\""i J:,l,'3("", v'. 1.':t.' "I."L~1 J" J".J J.' ,\ ,1_"_;'1' .".ft('u ~l l' , t .,-).. .. ,~:. ,',)'I"ltV \;Y ~ , in OI"'v l~'.l.'. .to' t",'"('l ..".. '-p_ .., ~tll.t,n th:.\t iiil1. t tLl1Ci 11,1 (Iml uu flcc~pt(''ll by trw 1.:L'clc!~l fr:.ltl.rrl.ity . I I';., n,"1", 1t...I,,1~ lf~"'" ... 1 .... ' bJ" \.I~.L;t.". i.!.",,,.4'.!."'t'~. / / 1.~ChluteI'. 11/18/;:6 \'.or~ o~ ~.x)el'1:;1(::~nting v;1 th A!jbu!J. tos c t once, ~md hr..s sug!;estr:d to us th41 t tl'\c A!Jbc!:a tos Inc1u~ try tnlt\-) OVC1~ this Lust Ch&r:1bor G.ne employ 111m to- c~u.ri' on tho ~xil~ri~ent:l with g'.linoa pigs ~md rubbits. ThG 1d~u of t,U'. Bro\in nnd r!1ys~lf v,ould bt~ to .h&.vc four or five (or t;Vun uor~ if v.o could ~ct them). Azbc.stos l~Ulllufllcturers tf.l.ko OVOl' this study by Dub9(.rriblng ~n equal amount per yQar, tor threo years,. and th~l1 ,'.c could dctel'tJlne fror.l tlm~ t\J timo nftcl' the finding~ are Ulo.t1l:, ...:lv3thor '1.'0 wi sh cny iJub1icn. tion or not. i,f~' . or..n id ea is th"t it would ue u good thing to distribute the informatl:.:'n arJong the medical 1'rntc:rnlty,. providing it is of the right type ond viould I not injure our companies. This would. menn, 1f o~.lr of us v/ent in to curry on this v;ork, it ~\01.tld lJe~~l,n!jO.Oo n yoo.r foZ' each one of us for n period of threo yearn. If you.. ure lntur~i9tod ~.n this subject f I ohould' like to have & meeting 1n 'NGl'I York, on TuGzdny, lloveclber 17,' c-,; l~' 30 0 t c l o c k , ' f ut The Bilt&lor~, or .11' th.1.s 1s not satisfoctol"Y; con roak(J it nny place y~u care to havo 1t. I fit'l aSl,;11lg the i'ollov;tng t,o attend the ~oot1nfi,;, t Mr. V(.tndivor B:ro\',n, Johlu~-tIIan.villa, Inc. v Mt' .F. H. {~chllltor, 'lhcrrn01d !tubber' Co . " , Mr. At U. BJ.ar,rlen, K~t\5 bt!y &. Ms t ti son. Co Mr .. H.. lJ. LeMont, Asbestos MllTlufaciu.s:-ine; Co .' . th'. G. M. WilJ.ltlrJ:1" ltuSSGll Mnnufnct~ring Co." Ur. S. Sir.tpson, l{aybostos-Mr.nhutton, Inc., Is there bl'lY one' else you v:otlld S1.1f;,;cst? Very truly yo~rR, SS-G. Presid.ent , , . " ,,.' "'. NOTember 20, 1936 LTehReoySaUra. nG~carLdnabero,raUto. rDy,., Director, Saranac Lake, Hew York. or Dear Dr. Gardner % meeting yesterday attended by certain brake to present l1n1ng manuAfatc\&turegrrlo, u~,r.ofS1imnptesorenDatnedd I were able corporations the )ropqs41 rther ex;>er1- 'f to a that fairly one of large your du.ting chambers asbestos dust. be engaged for ,fu mentation with roposal was very well received and co1rtpo~e&:.Vt.y~e<a?rls!~. tha.t not The p less than eight, and ipate in financIng it'it:lreb~he pfsutrethneorarnezmxa~oearrneid,m~Dntr.s'MacloCnognne.ll w111 the l ~8rt1c ines d i s c u s s e d when we met with Dr. L '" . a lew days 80&0. Accordingly, you may considenrtemthpilsateldette~xrpearisll1aennts . authori~Eation 1th asbestos dtousyt'outorto thcoem:4p1u9rnpCoe steheotcodIetterilslinfAiYngunmdoerrestadnedfiinn-gitely si,_ wtthheatc, auamseosnganodtheefrfeqcutesstoiofnas swbehsictwhoin1gt: 1s ~tIci~ated these experi- ments will ~la.er, are the follo of dust 1s necessary to ~)rouuce (1) ,t,h'heatfIcbornocseinstroatfiothne lungs which is des1gnated al asbestosis. (2) \'/bether ex sis posure to without t as he bestos existe dus nce t will ,)roduce yreylous ound ainsbfeecsttioaonncedandhuwaahnethasebr etshtevsX1s-racyanchbaengr~esprfoduced in 1n adv animals w1thout infection. (J) Whether t hoeg rfei bs sriov se i st y ppreo, dut hceadt by asbestos 1s is, will the after ofifbrtohse1s,>rlncrea~e (on~Q it has started) t &9 ceased exosure to the dU8 11 If /Vl1 /) ~ /1L'.0-/I ' _ , '\ . /' tl"'lS'j;,/ ') ') 7 ).~. ".; ". -, .". ;: " , ,." :!":2::;~t;;:::',:,:;,;t(f.;~.~;/,:( ',,;": .' ~ " (4) Whether the fibrosi, resulting from eXpo!ure to i iii , ',I asbestos dust 1s OCQaSi0ned by tent or the asbestos or by 1ts the s1licon conf1brous structure. '/ (5) Whether the presence or 'asbestos bodie, has any diagnost1c,significance. ,will It is also our require approximately understanding that three years, whIch these ~xperiments .111 mean that th~ .111 that nthoetybwe iclolncclousdtedf5,OuOnOtIlaanbnouuatllyth, eoern8d-toof tathle oyfe$a1r 51,090390;. and out~lned w i I ll t is be our cons i fu de rth red e r th u e nderstand pro~erty i nogr that the results those who are advanc- ing anc\ the requir od. funds, ,who will in "hat mannbr they shall be determine whether, to what made public. Inthe event extent' it 15 deemed desirable that of your study w111 be the results be made submitted to us tor ~ublic, the manuscript a~proval prior to publica- tion. ' . accurately I shall a~preeiate your advising expresses the proposition you had ~e in if the mind. foregoing Also, let me know the manner in Tallced to you. WoUld whioh you would like to have, th~ you, for eX8:lp.le, de.t'ire to have runds'adtl.l50 paid quarterly in advance, or Ju.st what arrRngement Any method you suggest will be satisfactory. 'Would suit you best? ' tively larGeSginroceupt,heit exhapseribmeeenntssugaGreebseteidn&tl~utn,dearswraitmteanttbeyr a relaot con- venience, any communications aud I will, where necessary, regarding the _ork be 8ddr~ssed to ~e co~uniaate the contents thereot to Mr.S1mpson and the other parties. You by e1ther Johns-Manv11le Corporation or 1'111 be providedw1 th funds' Raybestos-!Aanhattan, Incor- ,>orated and we or tl.ey will secure from the othf.:r .>artie s their ;ru rata contribution. . I w1l1 advise you later of the names of the other con- tributing parties. . possIble I shall s~~reciate your informing me at mo;.uent whether the arrangement as outlined the earliest herein meets with 'your apyroval. ' J VB:T ZL'/~/3..~l S1n:=erely yours, Vandl~er Brown General Attorney .' ':I'M! SARANAC LAnoRATORYPOR TMB'STUDYOP TUBERCULOSIS ',;:' OP THE EDWARD L. TRUDEAU POUNDATION Mr. Vandiver Brown Johns-Manville Corporation , 22 East 40th street ' r! New York City , I Dear Iv:r. Brown: . Your ,authorization to proceed Vlith the 'i q proposed asbes tos i9 'experiments a t the Sarnnuc Laboratory :'1, is acknowledged with satisfaction. ,,' We believe that such eiperiments cnn be expected to furnish asnwers to the questions which you hove outlined. ~~e estimnted cost of $5,0009nnually for a period of three years, making a total of $15,000, is correct. t Your suggestion to make advanced qUarterly payments of $1,250 will be entirely satisfactory to the Labor~tory. If this is not convenient arty other orrangement that you may care to make will be acceptable. Tho Saranac Laboratory agrees thut the results i I I of these studies shall become the property of the ,contributors . ,i ( aanpdprtohvaatl othfe thmeancuosnctrriipbtsutoofrsanbyeforerepoprtusblsihcaatlilobne. submitted f~ I wO\1,lc. :'Gco~mp.T"n t.ho t the eXT'eriments be performed with pu.re ':~nudion t.sbo:3t.os fibre contllininG relatively little Sel"l:eHtit:e l'UC~ uust. '!lle "Kings };41loats" uaeti in our 1'irst exper1went w~s unsatisfa~tC'ry owine to the fact that it contained such a high concentration of non- Ii' fibrous rock dust. If this meets with your approval I would I sugeest that a sample be submitted to the Laboratory for ! chemical end petrograpqic analys is. HaviJ1B mutually satisfied ourselv8a as to the material to be used I wt:'Itlld request thht tre companies ngree to sUDolV' A S\1ff1~1.Ant uunntity 01' asbestos, p;round t.o ~he f'i He s t H'tl:t te 0 f 9 nud1 visi on po~ sible. 1 am .'lot. ~wurtl. ;Jl1~ thor any of the contl'l.Outurs: huv~ appl:1I'tltus capublt! of reducing fibres to inhalable dimensions. If this request should not Xlr. y.,tlrOWU, l1U V. Gv, ..L."::;vtJ, p. ~ ..- prove praotioal some arrangement for its final reduotion will have to be made by the Laboratory. But nt least the material received by us should be broken to powder. It is impossible to estimate the amount of material necessary for the experiments nt the present time 98 its behavior in our dusting apparatus has never been I determined. With the "Kings Floats" t6Sts approximately I l~OO oounds a yeor werA renu1red. It is conoeivable thut a pure fibrous UUDt might be dissipated into the atmosphere more rapidly and hence even a larger quantity would be necessary. .., ue are reedy to start the work at any time and II will be pleas~d to er.r1.rnine samples of Que t as soon 8 s. they \ ~ .can be procured. \ ~! '. 'l'hulIking you for your cooporation in arranging ir this progr&m, I am !: With best regards, il. i~; I Sincerely yours, LUG :cc ,\ I Mr. Vandlver Brown -2- Naturally, I ahall welooce any orlt1olse thnt yc~ C~ MY ot the other oontr1butora would care to offer. Shoulc! any c~ thec want to 'l.ou detalle, I. would bo pleased to ceet wlt~ :~e=. :-!ay I take thla op;Jortunl ty to thank all the D?OneOro tr.rout:: ;'~''; :::' the ,upport that "'a have had. -' LUG: :~n: Sino erely ..l0ure ~~ Leroy U. Garc!~er. ~. D. Dlrec'::or ...... L I........... I _ .-.ol. _.... __ ._ '_ . , ......... THl SMANAC LAaOItATORY FOlt THE STUDY OF TUBEACULOSIS , Of. THi IDWAIJ) I.. taUDlAU fOUHDA!10H s.u.vv.c LAu. N.Y . 1 ~;. '" ~r. Vandlver Eroun Jotn,-.onvl11e CorporRtlon 22 Eoet 40th Street New York, New !ork Dear Mr. Brown: ~ . I have at last .uccee~e~ 1n a::alj':l::;.- :::st of C~ v~~nous sxperlcental data .n~ asaesalne the reoults0 I r!a~l:e tr.i'("" tr.le stould havs been oompliltec. betore th!s, but tr.e flcer~er.::: tao lett 01 .hort-handed ln the Laboratory an~ aleo neeeselt6:e~ =y ~01::S' a good \leal of extra trAvel1ng'. I hope that tr.e spo::eo!"e c~ our .tudy of aabeetoe!. w11l be ohar!table and reall:e that tr.! ~:~~ hae t&r exceec.ed 1t. orlilnal .cope. Ve have done over 40 dlt!erent axperlcente, ca~y 0: ttao d!v!ded into aeveral parte, vhich l~volved exposure ot a~~=n:s tor 1 to 3 year. to Tarlo~s dusts. The bUD!nees of prepar!nE =::~: Gcep!e .eetlona an4 oheclcally analy~lng the tleeuee on core t~a~ sao an!:ale has been a Job in ltself. ~y tl~e tor a:u~y!~~ eec:::~s ar.~ ar..aly:lne data haa been 10 l!.~l te~ thAt "'e are behlr.c!. o.:r e::-.e':' ule. T h~ve .tl11 not had t1cl to ~rlta a ,full report o! tr~s ~:r~ wr.!cn ~!ll of n.ceselty be conograph!c. Eowever, tor the b!r.e~!: :: the cont~lb~tor8. I &C lubclttlne table of cer.:er.:e a~~ an ~~ nc:a:e~ outllne tQ lndlc.to conoluelo~8 an~ the l!::e 0: arEu~e~t :~a: I w111 be eeveloped. The latter itself occupies 15 pares, :~: : ~:;e the), \~111 t1r.d 1t .uft1C 1ently lntereot!ng to reed. I s!:a~l wc~!. ::-. . tt, tlnal ca~uecr1pt aa I have opportun!~y. p~c~;eo8 v~1:~ f There ere a to'" experl:ente et!ll ln e~::'Jld be c::=j:)l et edo by the Uco )!e are ready ~C-:' t!".e::. .. he wo~~ c:: !I cet~o!8.of dust ~eter=lnAtlon, I oonslder l=j:)o~tant e~o~:t to 1~ cluce in tte study. The que.tlon of cancer 8'Js::e?tlt!~!ty now eee=E i c~~e:!l[sur.!!olrCatn!ort!:raneploa~aldr~prltevflrOcU!l't'hle~ca~n1c~ed. Is be~!e!e Inca::. oe.a... ,,:-. I~ . . . . . . e!' re eer.... c rou ,... he t. it !t w111 ta:<e h'o or three yeare would bttter be oeltted troe to oO::j:)lete the preeent suct a study, rerort. It 1: ID~::~e:::!~.. e . I: beco:e poselble to cake ttl. etudy, I hope that I 8:Y :our.: C~ s:=e 0: your ce=ber8 to sup?ly ae w1th tnouet p~-e, long fl~re ae:e6::5 I for tte pu.rpoee. ..._?....1..-.:.\.l;.-l:1 ' ............ -'.... '. '-:-'-:. - ~ . :":'..-- '.--'" .. ~ ~ ii .. PLAINTIff'S I "I .EXHIBIT + i~ , J i i I ." '- ... ,' . '.' . OU'!'LI~:E: .Q!: PROPOSED HC~;OOiU.?H .Q!! AS9EST03IS SArnnnc Lfiborntory S~'Jdy un~er Grant ~ AAb,eto~ Areoo16t12.!} I Human P4tholo~y - & stu~y of 25 autopsy ,J4ee~ Illuatrated 2 X-raj Patterns in ~bestoe1s, Illuatr4ted 3 Ash and Mlneral Values in Hucan Asbestosll 4 Co~plications of Asbestosis (a) 5usce~tlbl1lty to 1nfectlon 1 Tuberoulous 11 Non-T~berculoua 111 Cancer ot the lur~ ~ D1sabl11ty, causel B~d cocparlson with silicosls 6 1'1anosls (a) H1s~ory of ' adequate eX}OAure (0) X-ray tile pattern (c) Physical ex~cln3tlon (d) Asbestosis bodles in eput~, their slen~tlcan~e i'~~)..t.;,-...'. -J.. ...., ... '. , - - "0 _ 0- I }tethoda Ca) (b) (0) IInnJheaoiatitoionninatxopolouunrgee tothrpoluagnht dtruascthse. a of pure cl Injectlon of pure clnera18 1nto other organs. ~er41, 2 6,eclea Susceptibility Man, g"J!.nea dogs. pies, rnocita, oats, .... h i t e cl:e and ra:f 3 Peculiar Charaoteristlos of Asbestosis Unusual Rate ot 10ca11:alon of chr]soti1e resultant tls&ue reaction flore in l~n~a. core r~pld 0 ouart:.. t~an to cReeaascetslo; nagtoalnchtrhyeeortelvleereneotopf rothgereoasitluvaetiAornter . eX~08~ro Ascestosls Bodles in s111cos1 - .1 11 C O ocpoalti ccurence o n in and dl f c~thod8 ferent s o p r e to cie r s : . a t l o n . 111 1v OForra~dautallodniedaopepseanrolltncpearaatltleerl developeen: or tibro3 exposure oeases. 4 Cooparative Effects ot Dit:erent Aabestitoro clneralo . (a) Canadlan Chryeotlle. ( b) (c) Ar 1 tona Chr Ysot !.1 e, Crool<io11te 1 o~" 1!" ~ r 1 11 Bo11vian So~th Af 8?eol rioan, : en, sor t stlr a~~ : an~ elae~!.c. rlexl~le. (<:1) Antr.ophylllte (e) Aaoelte. (t) Tremollte. " ~ Effeots ot Control Hinerals (a) Orann~lar Serp~n.';ine, chrysotlle. . suee o~.eclce.l co::;~osi~!.on as a or ((00)) OB81rllau1socsl~tWe,ooal, fibr8oyunsthecta~ec~eo8l~~l~lcahtyedrorx~cldrea. al=ost ~ree 6 Chec1cal Cooposltlon Irritatlon., ot Aabestiror~ oinerals in Relation to (a) Nothing 1n cepac1.t:r. coc~o81tion co~related wlth relatlve ~rr~:at! (b) Prellclnary acld treatcent 1 Hydroohloric aold 11 Carbonl0 aold . (0) Effeots ot Aluclnum ~ 1 Phl,loal Properties 1n Ro1at1on to Irritation a) Length of tlbre b)trreot or Cru~hlng l 0) Heat treatcent 8 Nature and Slgnifio4nce or Aobeatosi1 Body ( a ) :'a r::la t 10 n (b) (0) UPlr~oltQeactteivesoelufrbeiolittyprienv~ntitslsnuge rurther irrltation 9 ThoorlC1I or Action of .\.abestlrorc l(1nerala (a) (e) Checlcal - M~oh8nioal r~aaons tor considering invalid - expericenta1 deconstratlon of. -' 10 CC::lp11cationo (a) (b) Infecti Cancer on o~ , l tu~eroul081s and o ung - exper~Qental t h d e a r t a var au ie gs tie est s lv e but not proven. , 11 Disability 12 Essentlal Featurea ot Hatar~ous Exposuro (a) (e) Nature ot duet - fibrous cooponent and elte At::loopherlc Concentrations - probably lo~er ractors t~~n :or quartt . 1 Inadequacy of standard lr.pl~er 8a=p~lng =e:hc~ which does not ool~ect the ~~.erou8 flures 11 Eleotrostat10 precip1tat.,1"'sa::;:>lIng pretera'::e '0'.1'; cethod cuat be coditied (o)'Ouration of Exposure 13 Rceecnotcraoet ~lodantsl' oonfeABfobers taoaNewDueSttandard of 5afe Atcospherlc CO~ 0: (8) T!:h)~er cQu~a. sit'-to. rflc18l standard.of 4 to 5 011110n part!c:ea (0) Work upon better cetho~ eacpllng (e) r1:neceecspsliotYy 8f!os r ooopa.rlson of results wlth X-ray tlr.<!!.:-~s 14 Pr!ventlon (a) CheQ1cal ceans not.pr~otlcal . ". . .._. ". -... .-.... - ... _._._......- ., .. 1 Ac1dosis neoeSSlrr thAn Asbestoe1s to dioDolve tLbre in lungs ~orQe '- 11 111 CAlhu1ce1rn're~11Tahnocrca p ys t 11 nl la pup~lolno a~bulaet preve~t1o epe&idl ecphaols upon the fibrous n wtth oocponenta " ... . . , ASSS1'CSI ~ A.:li:C'l';I) oUtU::t , n:OICATn:O R::S:.:t::'S '- PA1r 1. - Htr.L.U{ ASe::STOSIS I Human P~tholo,'Y ~ X-rAJ PAtterns - Desoript1on Baaed upon 23 huesn autopalos 2 A!!l 6r.<! H1ner8.J. Value! 1.n Hucnn lunge. 3 Coo?11oAtion ~ A8b~tgel (a) Susceptibility to Inr~otLon 1 ~Tuupblelrccautleodusi-nHsluenrvelynsc1o~ofnoAe=eirnlcEanngPlliashnte~.xperience r.ot Available ectlon of autopsy statletice ~aterlal. deceiving because of sel- 11 Non-Tuberoulous~ The sace reason probably applies should be aenteeiea c a he eo o n k g e d, as by be s ann tos l ys18 work o er t s . n b - 111 Cancer of Lung Ditto, but ~here are caces ot. lung cancer nov on record 1n asbestos 10 Co on =pared aeccs t to oo l th a, e t t h ot i0 nl 1 n n o u:ber ldeneo ot is vorke~s. auto~sies Rr ~8o111scuoc0h1efr~quoenthcyerhtaesrcbeeeon t ~lpscoveer~ecdeoeilnv( a18 act exoe~t .4ve ore tte A s. . . Scr~eeberg ..he eVidenc e neuco:~n!o c~nea of ~e~!ois but not concl~elve precipitate the ~e that sUEteetlve asbestosis ~sy susceptible velo~=ent lr.~lvl~uals. ot can:er in - 4 D1eab~1~ty ~Calninlf1ecoatltde~b'yOerlieesnsce staruigke,i"nesgt8Xt-rhRaYt de~ree ctrh'.a1n1ygeac11theaabnllangooArsrbeeesptoo~sdlls is dis 4n e s ase 11 of "'! , 8i11co~le. Su thin tl".e lune:s c h an d d i s n ub ot lll to t y ~n aobe secor.c1o.ry etoole heart 19 due ~lsel ~g to ~ c.ls8a!:vi1leicrt0lyt8y.1so, 'f:'a~trs.eoe1dauteet dfipburlocosnisarywilthnrreecs~ullo~na~l:ncraececeeenatutah1tEie!oen.a=0ou~:ar.: study ot here puleo nary Undoubttd1y, 1fu8 nucrtelo;ennt 1nneeadsbteosrtoasisoaorfetvual rypihnygsisoelvoegrilc~ayl. disaoility. there Are cany diagnosable cases with no 8!.gnlt~ca~: . ~ D~e~nO!!.8 depends u~on three faotors. (8) tHioisetsorylono~ftra,deaqtua~toerke~wp0h8eurree,bouthsutahlelyco6 ntc~en6tryateiaors, 80=echarActer of the "asbe8tos" 4uet are ha:ardous. n and I II - S~e-cle9 ..... .. .- .: , ~" ...... . 11,~t' 1 . .. ~b) I. ' a ohara:terlstlc X-ray po t ~ ern. '~''::' "a (c) .A phy s 1c 01 'Jxac1n on wh1ch reveals c ertaln c ~aroc ': er~ .... t1 . slena and CQy reveal -. ev1dences ot disablllty ~t present . ( c1) Asbestosls bodiea l~'th~ 9r evlous.t'aotors are' all 8~ut~o are =,oslt1ve. conrlr~atory HO'rfc\'!r, the when the' boc.!.es ~'. cay 'be abs ent.: pQ.r~lculo.rly 1nfection. . '.. 1:. t~e aosor.a e 0 ~ brcnc~.l t 1 a " Asbestos"bod1.es unsup:,orted 'by othor ev1.c.cnce <10 r.ot . ::nko. . a dlaenosla. 'Occaalonsl onoo autopsyapeclceno ot poraono heve wlth been round 1n aoc~t 15 no known expooure a~~ ~o tierosls. prob~bllot~non-ocoupD.tlonD.l orlg~n " t ~ " ~. . 0 . . . . . . . . . . . . . . . . . . . 0 .. .. ':.. .... . ... t to. : .:: .' : I .............. n ...... ~ ~x12!rlr.".lOta1 AFioestoe'.G ' _. t~.';' .'0' .,..'11 I.' .' ,~. : . ... II ,',' II, '. a'-' , II ',',. 1 . . _ " . ;.\~.:~...... ..~:. .... .,' .. (a) InhE\lat1oo " Ey.po~ur('A .... ' I ~ . to '" ". )'.. .toPIMt Ou:s:.t . ~.. .' .;,.... '.' -:Spcc1fl0 _. :, t!.oroels.i.n::: lungs. 'aut no ohar.gee ~l~ew~ere. ~ .. ..' . . - . . . :::.~::.; (ll) . ',. .. , . t . . , . ~ In1e1et1ons.211 Ruepenelon,t ~ ~ H1nerale into !, ',rr-: ; Treot':.ea.~';~ .Q.,lel ar reau ta. . :.-. .'. '... ,'. ~.:... .,' " ~ . ',' . .. ' .~ . : . . : :..... .~;.: -:; ........ s.....: " ;.: . ;'. ~~.~. /~ . ': ti~ ~.<' .21 I. (Q) I n l~c t 10n Bus oen e1Qne P'irrr" H1r.erAl into 'other orZ!lr.s Flbr! tined s t d o l ssolved; no phygooj'to81~ a s a b n e d s ' toelB bpdles; enoapsulat~on tiGa~e r~B:tlc~'c~: . Co:.?o.ro the .~;:::\::.: asbestos cpl"t\1 or hu:.4~;aubjoct8 '.. . ". . ' '.. . ;" :~' .. ., r. '. I.' .:,:\... to 4 e'. :' r to' ;:-:' :.' :::.:':' ..;'. ..: e S"'ec 1 s Suec e ;')t 1'0 111't'I '. : . ~ .:'"~.1":: ,., - - - - - , '0 .'e. ~ ~ ::~:';:.:~ ~ ~t' .. :.~ 't... . . '. ", \.:: ./.};(.,;~. Unlike tree . ~~:,;; 't,: I ... .;;.. ' ,. .~."J: 'to,,'. . . !' .: .... , , ..:. ' .. .... 10 'tj r_:-::: _, ..... , .-,: !'\ . : . . . t ... .. . 0,0'1" ',a . , .. .t..-..::-.\.;.~... al11o~,.aebe~toft~doea not 'croduoe its opooltl0 e~:ec ot. .1n any organ ot ot.'" the lungs' 4!l)': man -and speo1ea.ot. tnoca 'anlcal:::>"It'oauaeo t1broslo'onlr' !ew,'Q!.-.the opoc1esteste<1..::~::~A . . ~..J'J.:.' , " ' t.- , ~. .",,_ .... .~,"1.'!:-,i......-.~.t . .,;~ ~.' :. "-,.-.'.:;.."-,-.t.;'0'" .,,-,~. .'..~ . . '0" ", ... ~,. , .. ' .1 ;,.\ .. .,! .. . ...... ..... Ftbroals Aabetos ao..dleQ..:.,!,'~. ~I ~~~:~~8oec!e9~ -, .. F1broDta '." ~ ,,- .- ..- A9~!e;o~!c .. .' !t .... (' 4+ ..S.: . :.'..,'.,..'... , ..... : ." ,.".~'~t l J. ,: . 4+ '. :: ..... ... ... C'lt +- .... . ... ~"" ,... .~ :. t ""'::".~.\f',' .~.... . ~.: :0 ~ ~'''..,:..'.;,'.''''"....i.','-,. . . . . : , - .. ,J. , ..~. ~.,. -. 4 ., ~".,:.'~''' . : ,,.. ..-,,:.. . I ,. .."'....... . ~ulnea illg 2+ Rabolt + _ '0"':' ; ' .t.:...:' -.......'.i:i.-.:~",:v..i....~.~."'..!" ' ' '' ', '- 1"~.'~'J'~'R~'aI;t"""'~" -.:Oi. ,'.'; '. '. I . . , ., .,. .1 " v -..~ .. . , .... t- . '. 0 .<~ .(1'+ I II Pec:(ual)larLoeCotttohraa"1r'1a:eo1t ~r1"1e01b1ndt'..'e'u1ote(Qt",t;'.0tt"'l9"plbl1agr.ro.sthu1ls,o0l,"e1.,,' remeiat~f~..!<."tl:a'.I.l.~a.~..1~..'g~~n~'~:~r~;.~~:g.~'.~" .~~:l..'t..r~.~~8. .tr?~,_~...0},::,-!:~:j.'~::~..-:.>~'.:~-~.. : YerI e~el' " ' ..' . -,:.',' ." " 'J' A'.. II.I.,. eo' ': t : I : .\,.1. .' : " " ,,. ' ., .,.-, . :"'~'. 't_ \' "'. ~ ".. ., .'- .: .'., ':., .. ... ,.."",.,.:,., " DOff"""r?:~::---.~ 0 . ~..'!,':' ii" " ~ ) .' .. t. " 't "., ,' ' .; ',..".'.f.~..:. t f .~' .. " ' .;... "0 -i ,. .". !,.. . .... ~ ." I' ., I !. , ".- I ~..,.." ~~_. ~I ~, .. t %0. ~ran~lar '.":':J.".,'('...".:.' t'.' ....' ' ...-1........ ... ~:~:'\ ~.~::::~.;~:,,;I .' . t " ............, I , -,. ."":;''''~''.\~'':''~ .;'!.'.~" ,.," , ,~'. ... ., " . , " IOf . ' :' "., .. '-'~'.1.'.,.:'., ". tf' '" !" - " . ... ' . " , , .,...... \ .. . . . . . . . . . . ,,; , " , : .~:. : . ~. ."":. i . , . ' t : , " . , t . J "," . t . . . . . . . .".... t. ... .' " ...- ,'. '. ! c: ~ I," 411,. _ . ,' ,: .; " ... _ , .~" ~ , , ~ .....~ to. 0 '....... ~ ';.~" ....... t. ,.~_. ,.r ~. .\'.~0' , _ 4Ift. . .~ ,~ ' , ~. ... o' .:.... , _! lA.' ' ; ' :,.,.,. .......... : . ,~ ... ......... " .~.; ...... ,...... ~) .'!'::',.l.... :: . to . - . .. ,.: . ,.I .'f ;'.... til ' 0 ,'~'L....,...:.' .\ . ' . '... , .., ..:,'.,. ~~ E .-:' .. ~, J '.,., ... ,;> I" ....' ..t'. ., ......" . ."," .' . f..;,.' ' . .:~. "~.1,i . ....: ..... _, -~ . ..., l. 1 aFnldbreeslalsltkiceiothyryaao~ou:clulelBtheavw1n1etha oert41n degree of !le:cl.b1.11ty ] dteure:tin'las l oaa1rrr1eedpaofeuarther on and i1ns thweidfellnl ~ostoa4tt1erretdubters.:;oUgOrhnnuthlae~' (b) Rtoataell o4r cttiisvseued'Jroet4olitk1eo.n. qUtollraobeeto8 10 ouch oore rnpld t~on ad 'in 800n as speoifio aaurfefa1s0;iewntithooqnuoaertn%ttt.ratlEo:-n/ldoetr.cfoisbroers fOr::1&tlon A.~oea: han looaltte~ oonthl. ., there 1s a latent perlod of (c) React10n to 'ure. J:oung Bascboresttiosssudeoeotr.natot progress on oeasatlon of ex?os Sbeicteo.ceaInco8re11d1ecnosso1sb, uttheth.eyollrmeaayohf avinevoflovreomede,nt oontracts decroaoee and In. - exposure oeases. ung nodules becoe! larger Arter - (d) pAnseb'e~ootcoo!nl1a08B1o8d.leoT3herye II 8~~oltlc are conco~ltant of ttls foro u~on afte r t h a e b o su ut r fa 60 c e d a of ye in of due to a haled tibr~e. oon d epo In sit gu i of nea prote pigs 1 n th an ey d ~ i ot ron ant 1n lar~er 1onanthaendfogrur.itn~~raprpol~bsn,tao(Steewipthnrathgernptiheo2uaeb. ovTe)hebyuot r:eucaobr~ur.!- s a dci typ t l c lar~er ol coa t tibr~8. ing ot a In c bl at y o i b ec ra n b us b! 0 t a t h a e n d l a c r l ger ca, few 8,1 z'f'd there air h tube a cdoenvceeredin. thireoQlunpeAar;ag1ranphra2taotanthdedotlgesrenoo after ouoh is lon~e~ bodies co~ld an res!- be dis de7o.e?s!rin~oetntlp.artahlelebl oddeievselhonpv:een1mtt e~1~0 ap?a.rent that tloroele. In t~elr occurence l~nF lnjec:~on , . ~~al.l eeveral p.~r.!ic years e a d. ft e r The nU:::lber ex;:oe'.J..re c ~ e t a ;:.evelo~ed. bod! es s e ~ntf'- eea tv 4f~~c;C~rre!!l8~'e:r~s!.a ses. " C<;::;:,:e r l\'6 E~:~otp.2.t. D1r:~r~n~ ~":eo-:Jst ~~~np.rele. (a) Cana<!!en 10 .' t,;hrr6?t11e - highly 1rr!.:at!.ng. (b) ArllOr.A ~hryeotl1e duces Just. at' oAny a(slobwestions!1ron) equally l~~l~otlnv ar.d O~~ with over 11 tl~es 8e ~uch .s bod!.es iron. ae tr.e Car.ad!.arl p~c~'J';;~ (c) Crocldollte nsbeatoe!.s. - The Only S~uth African 8 ll~ite bluQ ~sb~otoa is known to rf.oorn~-rwrnoojuactvla~lelnebxl~ee, rlc~oent d of n~ Bu~ply it W09 u0o: eJt'~oisarl~!A.teerri1onl trI.en :aUQe pure "o tests cause oinf toitathehielhun~peu,rltay.3e0.11vFlaonr vthaerielatytewr aecrsltuibcsotll:ul:neJdcctr!:..tonin s:!.tfer Perhaps bliencdaucsoereofelathsetalce thaInta thteibrceoattowr.eyre!3couucthh pec a~ra1eh~er':,eAfrlc.:ln vnr~ reactlo bc~1~8 ns bu t co~parable did not lo to ca c ll hr :! y ullorlt ooti1e. l e s, It lt has not Slven produced aabeatoGls p~y. fatntyrlcfalnbrocrsoiac.idoTlletsata'W~iothw in be1nr phy the te~clnal r~~eQted with al~ a t tu~e8 yplca l nor So ca uth u s e chryaotlle. slcal cr.arl\cterle~lca a~',J,latlne ',: - L: l: l3) ...... -4- , ,'" .' " '~'i~ , J ... -:-" (d) Ar bo .tho dles o hvlllt torcs e , -'s low tl ly t t, bu t atr no a i l ght ooa fib li:s r t es lon ~ o aty~loal r tlbros1 a a o be in s tool0 ' lung~.' (e) A:~o~ 1~~ - Ditto. , . 'f " (f) Ar.lpblbol~ - D1tto. .. . . -. (e-) Trp.ooll~~ - Ditto beoing but vory fo'll oont1nued. sebestoola bod1es"':' ~' Obl5eM~t!cn . o!. . '.', . ... - . ' . . ; ~ . V Control ~1n~r~1 . . . " ~. '. \. ,,:. .' e' .' ' (s) GrAnulqr 10 inert S~rn~ntln~ csusing no of oaee f1broois chemioal in lungs ; ' .t.~.~~ oocposltlon ae ohrycot!ll or other organs. dt attraots iron troe the lunga but ot oourse, no _~~:, abo~les ,davolo~ (b) OlAe! 'dool(s synthet10 silicate) tlbres are not lc..halabl'o ' .. tro:i a(tihr-ebodrinaecesteursp1e8nsnioont sr,esappopnasriebnltelyasbeoaoomueseuooetd thwoerler stittoeo8 . 10al t~n'~~ 1 cloro 100~11t8 n 1 t~lok) n t~e a l On r.t lnJ ube e s ot b io ut n a 1n re t o w the 1del y l ucgs soat , t o t r h e ey d. do not '/ .,'" Tbe1 o~u~e no tleroo!a. Atter J or 4 a tew ~lass tlbres take up contho 1n oontaot with l~ fluid" lron but recaln Deooto. They nover show the swollen ende aseeetosis bodloa. and lateral projoot10ns " ot the true ',: ... (e) Br~c1t! tree ot ot lnterest because it 18 a tlbrouo al1104 (o.9~). Cryetallographic~lly cln!ral praotlc3ll, the arr4ngece~t ot 1ts~g and OH groups 1n cr:ysotl1e. The sAcple oaoh usod un!t also oell 1s Dic~lar oontained about to that in lS~ !ron, ~rc b n a e bly edle t r l oo 1k ~ont~~lnating e.' Observ410n a ~enetlto. not yet o o The ople t fib ad res but are at!tt an~ after 2 con:~9 1n the yet no 1~np8, tlPlpal tleroeis. .he Asbestosis bodles ~cvelop b~t t~ere 18 4! t1bre are l5olttered t::rough t~e lung lr.nt~. roet.aobtel.loung",,.0.l.o0 cCaulrlltea'droulnn0d1, delnsthteeadteroCt'!lwn1stlhainlrthtuebetus :eansd. tiosue . 'II ~~e!':1cpl C~!:ooE'lt1on in R~lat~on 12 Ir-rl";a~i:n (s) l:o~.!.ng related in the tollo~:lne cheo!.cal co=;cs 1: ~ons ~ith varlations in oa~aclty ~o ;rovote can :e t~seue ccr-- reac:~:~. (See :abls Next,Pa~e) ... _...... , .' , .f, . .o. .' .. : .. '~~' /~'~ ~:', ' , 0. . . . . f. ... '. . . . . ' . . . . ',1 " ~ ..',. "', ..; '..,~!~:.' t'~ '" ,," ,'.~. ~ .. ' 21'. '" ..... ..c..c.7"..:.:.4\....-.2J........ _.. .. . eM,.G- ot1le Crooid011t ... ..;'f,..:.-.A.".rc,'o..o..1_t:o.,... ':.h...... I., . .. -r" -. " ... ,."t ~.n tb.o-+~ ~A::phl~:b.1.tocoll:Q p,:.eNo~to~ ~, "" L , . . . . , ~.~"'I",t1. ,'" i ~"''.' ''- .... .,~ ~.,., ~_J .... . . ,..;,. ~'r.t~""'JI"~.(~ ..t:Al~.. ...~...:,,1",p~1?.~.~ : -',",,-.,.,'. ,.: .,., . . . ... ............-~:-'....&. ..,}: -oC4"" 0' " '.:,. ~: . ( ~ " , ..';t .. '.J ~ .... .... t.' . r..~ :~-:( ....., . "~ , .: II;t '''C\''!''J, '~" . .'.'" .' o\rJ ,".. . "-"':'"-,':" .....~ .'. l'~ \ " ......... ,... ,,~r.:' " . It ' . "-1 .~r ....... . . . . t . ~. ." ~. '. 0,r.;',,_ FS.,i O:z 0c- ~A. 0 :'7. ,,~ 2.~5~ 0 ~1,9~ 15.Z7% 4.29~ . ' n.OL1 Q '7 ...~...... :-. '. ' .... !.QS% ,,~,e~ .. . () " .. " ' " , . , A 1."~ O.~6.:c 1. os:< Q.25~ \.O~ : ,"1.#', Q.15~;" C... 0 ""~O ~~O "~O 0,05;; ~e.77~ 0,29 0,09 0.7<J~ 1;?2~~ 6,92 O. ~7 0.14% 2g.~.~ O. ~2 O,l~ 2,Ob.~ - "Lg9~ Oji}3 0,10 12.2~ " .' Q. ,\0 O,l~ 6,7~ 0,99 . . 0.9l ' . ' ... .I Q,15 . ! ,to;.'\;' I ... l.~..J~ L..105 4!~0 >105 14.92 0,02 2t~8 0.02 ~,1\2 0,8a . ' 1.01 ..' .... 2,79 O. .. ~~ ,0' .,. 1_ II ". ~a t 8 .;~:.' .=~' I ' I. <'f' ..: .I'" ... ,," to' .,..~tf.~:' ~ 1 --ZC:"':' '0 "1' -,',- e' I .,' 0' .~! (b) Ac1d treataent .ot ohr1Gotl1e . '. '., "f, tlbr'D :.~:';: :....:.:- 0'. ' ... /' " "I. :. :';" . ::: .;:: 1 One hour 1n d1lute or ' ; ::~"'::'~'.' . t oonoentrstedHCL dotu not .al~:;'0-'.,,- a.p,".: pearanoe or rior~ but solves and disappears attar suoh treatcont !t rap!~11 ~1! on inJ eo t 1ng 1n to 11ving t1s 8uea ~ . .' ,:!. 0' 11 Trl!!ltcent "ith sU8pens10ns ot C02 bu'obl~d tr.rough \iat~r' 0:" l'..lr.g 0', Ju!ce chr1sotl1e tl::-aa cauaca pa!"~lal .oluticn ltlth l1beration ot 811104 and c.lgnes1a. . ..... (c) Colloidal allum1na as 1t does qUllrt:.. does not r.eutr~llte tte 'e~~~cts or On 1njectl~~ ch::rso<;!.le s'Js~e~!e~ ae~e5tc in aluc1nuc hydrate solut10n fi:roels !lop at the usual rate. it recs1ne taon~~ea=cot ensstt oraotcto~~r1.eeet~~eer~t : tlbresbeooce o04te~ with a h., ~een proved 1n the case later of al~~1r.u: conor.i~"a:e of q~art:. t they hs~e, t~e ae coa does not sfreot their oapae1ty to irritate tis9'Je. ': , . . ".. Short 20 to ohrysotl1e flbre,un~er ~O cloron fibres cauee ~ c1orons ore p~act!cally ~yp~cal !lbroals. lner:~ The effects reRsons. ot ,longer ones coul~ not be tested tor tech~~=al . (b) cChruryahalontgileo.om~~llettbelylos~ee'torto1sstruthceturf1eb, ro6u1s1.osatrpJacct1ut1retootl:ri~dte!. d1sappears. :~. \ . '.~, .;: . 1 . ~ VIII ..",.t. ,'!T..;..tn.,.: ......-". .. 9r1g ,Bg..",l".g.f..t.... . . 4:.': .:.....' ... . . .. . .:..; -. ...~ /'?\ ~y . f' . .. "ti' . I,ur\." ' ;-:I!I~.:.".) .. :r' .. ,.. ".. , . ""~ ~"".''''',f'O,. .~,......... fa ". . ~ V-;.J I'".,:....~1I,-~_,~'"........f._.,.'.'-'.'\-;''.',\...1,r:~~~.....1..' " ..... to '\ ~""'.~.:,.'.',.-.. ....;.:.t--.".~:~:W.: .").\r .:~' ~...l.."',,.,~.r.....t- :.-;.:SP'...~.:toO.,OtO..\..."~,..,...,4.,i,.....'..!.-., .. 'f'i .... 'V .~\',~:'.~;J. ~\!::rt. ';.'.a~!~.t.W(.~ol,~:....1'",'''!.r~.t'!,~I...~ ff ; ~:',I.7~,:~;.oo-\...~,~.:.;; " ;..~" ' .,".r".~":;;ht),: ...,..~. '~:-;'~:t.,,..J . (0 )."': At '.1.gn.1t '..~...,I.~' .. .. , .....!."'~,.~ t':~'., H~t\) ! ~..' - '. ".'1' ....... "f," ...~_.~....t.........".,. '!'f'v I'~~~lt-.' :.~':.. ." .-_:..t.~.~..~,."~,",../-f. ,_..;. . !On. t or ~~ccp~rstu.r~I: tftl " . " '~~/ ..t... , .. ' : " . ' fA' . " . It',4.-.'."...':.::.'.1., "''."'1_'"r' .'\,.", " ". . :'r'" . ~ 18 dri v~D~oit~.but:' tho e~;.:...~..~.'.;:'"" ~\">i .... ~~ (lbrewstruoturo'10 th~ pnya1ca 1 oh.e.~e prcsorved.\~:~rlbros beoolto e%tr"Q~11' &U. tore typlol1l 10oll11ta t10n" vi th1n cr1:ttle.: tho ~~~':-=~:'.~ . . lungs. no t1broe 4 s dtyeloplS .'~ reaotlon '11m1 to~ to No asbestos1s bodioo' tormed._ ,~',::':.:. "~~.;,;.:~~:~l':t phY~Oo1toola'.'" r,' ~-i.'~':~'.:" Natur~ ~ ,Aab.,,,t ~1E:n\rlct\n9!};.21 "",.\"t~o,,.,.,.,('l,il,t,.,,, ",' ~ ," ,I,t'" " '; ' t , ..,I'!.It~'I,~,~:,,.c.~ ;I,\.. .<~ ~'r".,.,. f ~ J ~. .:\-':f~~~."":. (a) Bodles. probably I' I a'.i""II' r~;'ult' .\. fr " om ,dfq"~,o e' l. t1'0, .n.I ....L. ~~i-.o,~,.~tt , ';1,. f'r'''ont \t~."'.:.~d.I.,,..o1'rgo.n!.o . . .~.' o... .. Datter ot the on a 1ron oloyl,. d1aool'Tlng :tlbro .or:ad'be:ltoQ.~,.: . !ho aou:oo . . 10 tloro 111:011 to :})o ,tho lung t1aaue .th.o.n'the clr.o!"D.l clnerala 1 t 0 a t elt l~ co ir tho on' o 0011 t1r~I:1o ootont.:,:t8 . :-.]uot upon. 'as' thaa hCllvY':'on ~ .high: .1 ! n 1b 1r rou on. c .: ::'. .':' . .' (b) : The etteot ot 4!Sbeato!3ls' to ~.': .~. . ' ~ '.,,o:'-.~,~,I~'!.''1\"I."#t.~...\..,.~.~. ':!.:":'~J~~ .. ,,'':..::.~I:,:- .: ),. '.. bod1~.tor,o.,4. t1o,,.nlo .l80UllOd be . ~:.,.'! , ... pro-j. tect1ve ttnough q D.1~hougb uan t1 t1 lt ot. t 'ha he o CSt not atr b u oen. otur p e o o o a1 in blo .un ;to. al to 1eol rad'. at to o r: : 4 , t lo. or r g . 3 ::~' ........ ~".~ pur?Ooes ot test. j at:ooth~roundcdtJnd,~pre:1ent~db1 tho bodles ....ould not 'be ooo~o~~ 0 '" . "'. r..: 0 .1r ,. r 1 t~t1ng :0, .. ... ;;!r.:'..:"~.;L:;-,:: .. . f "'1' '~ ' ;"~'. (c) It they .... ere ..... ; ' I ' .~t'.;I:;~'" 4 " ',~ t,".... '.:""', ~.; '. _ I ~~ oa;>abloof caualnglrrltatlon.l,thotlbroo10 1n . , t:o lunes should progress a t t a r ,,-o~poouro.oell8olS.~h1ch ., ,."", . ' ,'t', 0.. ." . ".,,:, .., ..".. " . .' 1t does uot.. . (4) .! The :!"90,c!~eil d184~p!s.rQno~ ot .}jod1ee ~ ~'... (rind'w tlbres) long e.!ter . ': ; " ex::osut'e polnts. to ul tlcate eol'Jb1l1 tl ,. 1, :\J tlo. suo tl. ulds.' " (e) The bod1 ea a c!use ot are probably a tortul tous oonooI:Ci tant rn ther th.:3.o' ., flbrosis.' do . (4) Che~!cnl Theee e~perl~entB not oont!.r~ tho t~eorJ t~n~ a8~es:o~1.a 1.s ~erely a 81l~c~ 11~e~ated 1n the torQ or e11icosla ~eo~l:~~g r~= solutlon ot A silicate col~cule. ~~:~ Ir th1.s ~e~e t4n'J oreAn t~ue asbestosJll~e of ony 'specleo tor ouart%J,hcu11 cnuee rlbroals in ~r.e exper!.::cnts hLlve e1:o....n that lnJec!ed aDoeato8 dlaoolves 1n theee 10cationo. if~ not. c~uoe such reac~lon 1~ en'J locatlon but aovcver, 1t the lU~Bor ~ L"- species ,. . '~e 41..,"e pro~o81r~ the tneory of Cle~r.l\nl~gl 1::-1 ~Rt~on lihlc!l 10 oonlteet!d on11 in the lU~E8 b~cnuse :h1s o~an ~g the on11 :~e "o,hoQbGle11ntOy.:-::l!ilx~pehryls=leonlto9S1dceasllg1n\1endot1t.0o:18prolnvve otlv~;9!.4ncr:.!e.shsltI!yee:!-Oe~e ot :~:~:~ in ~hls tissue have talled for technlc~l reD.BOno. For fibr ~t1s es be t heory conce to ntr b! ated a) 1 ? n l l t c h a e ble tL , ; . e 1t 18 n!c ter~lnAl a aa al a r r y tu tta bes t . t~e It has be ~n . erO~:l ra~~~a8 the t hA pr t o on per l y p h o y !'-.:y ao slC31 t 1 o 1e ha ot rao tr te .e r1 ae atl bea o3. t t 1 o f ore clr.e~.11J lns~e such t~...:.s 10ca lone 11tat enou l ! o h n. b e t I o t r e 1 s ~t also essttr ~ls!~lves l t1a in l t that he:lu 'the nga f!.bro s~..9.11 ~erc!.so; ot ap3cles l~~e ciee. rats,+Go:,,'. lt !Xert8 no 1rrltat10~. ~";"':Ir~~!:!.:r ~lc11arly d1oso1vod 00 rnpldly :hat it rApl~. ~01ut10n coy explain in pnrt. the lAc~ ot flbrosls In or~an8. ~t~cr than the l~n~a. '0 ," ; . (. \. ..' " .. . ,.. :.I,... . , ~. '.' ; -7- , ,.. '~" .. '.-, ":-'.':-' ''''',-:-' . .- "- 8Tuhrerof~lrblrdeead roun bm'uJa,t~~b~ec.Olo?yng enol~h eo th Obs SIJ! e d, rv a brok tion en ha o a r tda w deooil i t ~,lcoella h the de 1 whlch'\aot:ot~hled 10ate y p Oannot reVent be e coo?l, aWl1lt.hnetahep1ogt!hetrre!alstebde O tro ted '.11 th lone; of th stlfor thflnotrethcehacereylcoloandolut~ipoonratlnnreoont:h~nceac~t.t1c (c) It e prerequisite t~e 't.c'ereclnlaccr~ta.llang thauadt otlle nnd rhioovo been tlbroo!.o tes-ed telob.l':r1eooc1h0e1:.:rlr1lctaal tiooonoi'woselr~e10cnh'eclcal. tlne tlbrosls ee s d;veiopt thnn posed intact to Tfhiobrcersu.shbeedo~c~hryaos octlh1reYQ~ohtolulC~1 8rhp~eunltdlnte'..o.wvehlaclhso~ t~r~t~artt et.e n b ebcoodoy ! 1r l uc1oda tae.d wOnootheot88th0ueo~rtroioantQrhaVoeurtbnoooon 1':10re nr~na tleroals a~ch 1~ tsh...o1uthld 0b0e11d0e1sdtarol iatlhu.calnvue:1ryhythdlrnoxlatyheart ooht raysl~~~l1:1.e~ (d) ,.t not the case. 4~e heav . yed 1t the 80t19i"dew, ecreapacch!e. tcylc.atol pprBorceanbtllyy ydocsosateintogp rteissuslutelng tro~ 8soe8tos (e) Heat suf oeehanioal for rearseoancstiocn1tebdu.t 1s here tbhOe~je rt:oerc=at a~~o~, tthootirarlftraeftieoiebnutt to 1t aallatoeracheoloal str~etJ.re X Cooollcntlor\e et locall:otlon l o t f e rs the eaeo flbr ntl co al in p h d ys i es oa t l r ocyhQarepce~wee, the luncs. ( a) ~'J ec ept 1b 111 t '( 12 In reo'; 1 .Tthuicserrceulous - 1? n Asbestos n~tlve !eotlen se~ueacetept&lnQ~11n1ntty l1tokbeehea~vaerst"t:iwkehic=hosst other =~~edr.nai:-)~: f 1 b r o o l s ca a y c c spr ent ead uate t s o r a t~a the t~~e tubercle but th~n b a?ceicl l1urs~.cal7!1h l al~:~e h ~~ il iHnohna-lTiunberoulous - ot no t cauaed by :he oe~an1e6r.ol T:hle~rree.e~l: pneu~onlga C1etho~ dust occ s u r ot ln ot o h u e r r rreater kindo. Oterecqaueleoncy s d n~ than 1n 6nl~Rls in unexp"oosetdhoaunsllnegalar.athe~rBtthornootoos. dubuett; t~eleaepalrdee~~luoen ot to 111"'Ca nc '!r !t1 Lun"'Q they ~ Qls~ oeo'.,;. fc~oerteaxi?nerelVoeidnetnscewere~.~-dt:e(s"(i4E-1n,ed to avor 1 de?elQpment 8outgeteus:toarat~int aseblueectlod6o1to! t~!a cay pol~: su act tut I a n re gui ra nea re. pies. rnbb1 ts.' rat scept1ble 8?ec1eus.ally 2 When h these .peole 8. Os ta and dogs lur.g t'.l::o:-e waaslant1o0t ninootreaaasboede.tl08wedreus8t.ubtJhoeotiendCitdo 2 to 3 years In I . ,- ence of lung - tu=or . . .".... " ' ." " . . . ' '. ...; ~ ..'...~.. ," , ,., 3 Soce stra1ns ot whito cloe do ~evelop tucora V1t~~ut ~ apparent oause. , 4 ~uch a strain ot white_c1co vaG unintentlonal11 uaed 1n three inhalatioh ex~er1bents w1th asbestos. aOtd1e1veclolopeed1cnah1ailglnnganlt2ntugcoflrabr1,n aethbee1ortoisuntgoor 15 to 24 and e or conth :c=~ hod tuoora 1n other organa. ~xce~elv,. ~ lnold~n2~ ~ ~.~ 11 e Of 12 22 cloe 1nhn1ing ~ !J,br~ conthn only 3 dO'lolo-ped lung Qobeatoe tw:lora. .fao.a,r..un1o,Lt 61%0ngor tc. 7 As oontro1s, we have dust experl~enta. only the experionce w1th cloo 1n ~ othe ~ ,hort 2!r1bde, there were 51 cica ~x~oQed kin~a ot ~~st tor 10 to 12 months. Inc1denoe to ot 4 oth~r lung t~: 1.9%. For lon;; kinds of i2~r1ods, there were 14~ mice duot, inolud1ng pure quartz, e,;poaed to " d1tter~: 23 to ~l contha. all was this eroup 13.B~: the ot cloe highest the averaee lncldenco at lung FOl tUQCr rate (25%) was in a aubgroup expose' to tllnt dust. Th~a the \OIDS over lnoidence of 16 tl::es the lung canoer average tor in the lng tlbre 4sbest08 etoe cloe lnhallng other duets tor cOQP Hlce orable p ex~oaed erlo to ds th e and pr 4 o 0 ver t1o 3 Ql l t1C~8 y lno r t t h e cax oh9r~ 1 cuc tlbr f e o r a s any bes t ot os herero shoved u ; fewer l~~ tucors to other dUDtS. although 7 tlces coro than those ln ahort expoaur 1', . heee observat10ns are sugreotlve but csncer stl~ulnting ,aotion by asbestos not conclusive evl~ence dust. They are open to ot 4 several oriticiscs. asbeetoa expericent, The atrn1n of clee was not the IS 1~ ~any ot the othero oited; s~e in the Q~pnrently the tthoer~edr~stwetroe run10uno~uea1r1ythl~uaotheeptll5b1me.onthNaot apenpoaurgehntalyn1ncae1csesssaurryvlvtoe~ ln pro~'Jce cany tucors. stra!n and age ~~d no .I.here were no un~]:"oeed. c:)ntro1s ot the ace 41~11ar oontrols exposed to other ~usts. It 1s hoped that thia c:)ntrolled condlt1ons exparlcent Can be re~eated under properly to deter:lne whether sebesto! actually tavers cencer.pt the lung. XI D1sab1lity Cannot be ~etercined froc the SA~e ca~8es 1n ani~a18. cet with 1n the acciden:al deaths ~ere a:l our dust ir~alatlon experl- cents. \ . XI,I ,i~"e!'!tlnlr(!~ t9r9 .2l (a) Nature ~ Due) . '" 11 .The long (1 breo Clue t be th1n eno'..lgh (1-3 Microns) and s!:crt ;~~ enouih (und.er ~O lHcrons?) to be lnh41ed.. .. . ' 111 Verl short flbre. (under 3 Microns) Dre practically i~ert. (b) AtooQph~rle Cone~ntrAtlon Stlll-under 8tu~1. Apparently this factor 10 lOlier then ln the case of d'Jets ooc~o8ed ot granular o1ncrals but cethodo of estication are 019 leading. , ' ' , .,:',.',: 1 The averag8 standard Publl0 Health'Servloe l~pineer co~nt ln the long flbre aab~sto8 duot rooo'vas 40 011110n pnrticles per cu. tt. ot 41r. ~a18'cono8ntrQtlon:oaused tib~oeis vleible to the nAked eye 1n 20 to 24 cJhths. For cocparison the averaee lopinger oounto ln an experlcent with pure quart1 vas 120 011110n pnrtlcleo per cu~ 'tt. and tlbroe1s developed at about the 8at1e rate. '; ,; ~:~. "":. ' . . '. '. " .. . ! : '1:. : 1, ;-'. . . 11 Ho~ever, 1aplnfer oounts ar~ dec;ptlve because by thla method ot sampllng verl te~ tlbrcs. vhich are the slgniflca~: elecents ln the dust are ooll.o.o,ted.'," .~.''~,', ,',': " . 111 Sacpllng vlth an eleetrootat10 pr!olpltator 1s a c~ch ~cre efr1cient ceano ot colleotl~ fl:res troe air-borne o~s pens10ns. Sacples froe o~r long flb~e aobestoo r:OQ ohowed that the d~8t in the air oonta1r.ed J2.5~ of f1bres rew of which had been oolleote~ or counted in t~e i=~~i.~er seeple. The latter eac~led largely the 1nert ~on~lar par:~- olea.' .. ,,. " . lv As ordlnar11y ecployed prec1pltator eacples are weighed n~~ the reevlt8 expressed 1n mg. per cub10 toot ot air. There 18 no ceans ot oonverting such values 1nto nuebers of particles particularly when these vnrl 1n 811e, e~~e and '-speclf10 gravity. ,"'. " . , . "~I' ~ . ' to , . . . . . . . . ," v Slcultaneous aocpltng \11th precipit~tor and 8tD.r.~ard 1:- pingsr ylelded the respeotive values ot 0.65 cg and 60 =1:- 110n , , part101es per oubl0 to.ot or air vi 4heoretloall, the beat index of ha~ard would. be either the nu=ber or weight of t1brous elements ln the d~st. -,----------~ ----_..-.. ,~......... _.. _.. _. -... ..... --.-~ -----. - - - - - - - '. . - ..... .'.. 'o' . ... ... . ,.,.... . , I,: . . :. ' ' " ~ .~~. ~ ' . (, ", ;.'-; ... '",'~ .... . .. : I 1 Fibrosis viLlela to 1ncreases 1n extent th! naked ele in oU~8equent l atta p,! r lc~-.~ .~.,n ontt ~.. 8he7. .~O '..j' 8'J.!"~e o.1 . 11 ," ~he the 8~an ot lite of our coat E'ulnt'4 pig has ;Jrevttnted I BU8ce~tlble lAboratory . ~ antesl . : ....... , ,.:f' ~;. . thr st.!\ ee e:e p yea of rs. 'as b e In oto thl0 s18 per h:\Ve lod ,be e c o n ontlnul nly' tt.e ' ~roduc r ,; ~X;Jos'Jre lon COr.lp~rntlvely c.:er ear - tr l/ . ' i ",;':'::::/' .,>'.l"'~.:~;. 1edce thst we hAve dlsea8e could hEve g31.ned, been c::d.~ it 10 prooC\ole til:h the kno.'. ' that Clore ext~ne: l'k.:\'.':;'.' . :: .'~,):" chrysotl1e. fortunately nToht ee~lsocnePetll~i.v~peer_do:.d""upc.eecdl~)181tthllakep':u~:c:-erts,lonc.to:e;et'luorr-ee ur ~:r:\'l';' ,:.' ~'!-~; ~:, .,'. 111 . Fol" theae reasons 'X-ray changecs hOve 'been c1nlr:o I::~'~ i!".:" .~_._ . . . . . ~' \' gwrearme . no t sol e to fulf.i.l' l on.e..o.r. th'.' e'.:o.'b:J;"eo~.~tl. vee ofl athndl Ii....-pero~ r~':~"'"~'.x.i,i~' R:~'o=~t'ndetlon f~'~ 5t~~dart1 ~l1te"~t~o"onh~r10 Conc-:nt:-(\~~o ".'. '.21 .4;: ,~.,A,''''--'! -0-, AS \w00 es t ~ (1 ~ US. N',,'! " ,'. ~ fW. .:~."':. '~'ir~c1t\1 :~~8'nd f ,(s.) 'ft'hl1, there 11' no . .." . ........ ... ' ...'..,.'":'~"'. - . . t~7;}.~:':: ,:.' ~U~~tt~. pe~ tlr<1t t~e~"~~nn1t'~~t1v~:requero.~t~.Y ?t ~. ~ ~. t' .. cl1:!.lon pa;tlclee cublc foot . 10 one .' ' . (~::;. ,.thrFlll~bla b~ L: :. ... ;" (1=) This 18 probably :'~.. cau8e {'.: .' .::._ r~ "'1 t~ C~!" a ot 8 tnndard l:l~lne;er ~'hl.oh ve the t'lb:-es the.t are ~he lt :'1'8; based upon sO:::!,lln2: h(lv,r Dr-OWn does not collect ; t:: .,' (0) I, ':Ie no'" t~!.r,k ~hl\t a at~n<!.lrd sO'J.rce ot.:hJi:.arc!. :0 t~~:" colcl.ee:tteerd~llnJelthreaAdn ileyl~ctr~8tat:'sohopurlpdclb~1e.tbla\ateo:r! ..!pon al!.~;;1.e9 if 1: 1s feaa!.:~e r r.:rte:-!'Al. ~ . :,. .. f the r!latlve pr:por:lon or.tl~rea :.~. :.,:_. .......,:..... ~~ 6~:~ (~) ~ori. 10 st1ll in pro~reo8 u~n'tr.e l~ttorpol~t . ...... .. . . (e) , '-\. '1'0 't:.e ot .valuethe ne'," 'with the. X-rl'j " '. stancUlrd ~~:-:", '. "'.',:'',,~,,........". \' \"ould"h!ive{,to::be . correl~ted. . ,~ . . concer4tr.:! :10tl9 flnc11.ngs' of dust. upon"(lc~lc1eeQ ~cxp'osed "";.:" .':t':. ' ..'. ~~ ......~.~.. "~ ":':" . . t o ' .c . a : ! ' e : - e n t ' . ',. ". Ce1o .. , . .:. X!'! F"t'v('r'" en 0" .. - .j --!. f f ,\sbes .. I ,..... w__ .. .:;*l. .~.,.! ,. It t'~" _ I . ~._ '~I' . . . . - ...... .. ._..'> 11 "'\ "It. ~-o' tt. '~\.i:II.~,, .til.....,;.,.'-"" . . . , .:.~.~:;.~ .';" "~ - ~;. '.. t -I .. ' '..... .. 1:.' t, ~~ :~.;' ~ ~ :.,'. I " . ! Tr.e e~~er1~ento r.~eLlns of neutrA l h:vet l:.1nv a t. l1e he d a . ,t ct . ' t o develo~ J,oH'ot fl' brousiQ .e.nye~~..",p_\r'' '~:R c' t.. . 'lcR.:..! . ~t~~lcal ... ," "so' 'It . .... (8) ':0 alter fiere the ." huc,An, 1.1'.u~e: " . ,1, th ' " . 4 , t _ . , . , .~ scec:os.., ,,,,.,.J.l..(.'f... :"di,t',1"ciolv~''''~t.'~c'ct's,:08 s rp creatl~r t '.e tl" .pl an 1 d l, a v c l l ! l. d k e e ls a rE't wtloh , ",ould necescl.~".te.' h.; wou~d.be~~o~:~.~~4~ - i'66CO: .. } tte~e~re;to l .., r 0 s !. . ',. ...~':'. ~.. I~ , . . ..', ."' .."' _....,.'.ir..'.. , I,'..":,..'" ' ",'..'" . of .. , . :"'.... t . . .. .. . '.. .... :',! .. ;: '~'" I.' .. .:.,". &.ic ,,~ ' .. .... ~.' ~ : . 0. I t' .', ".-. I r , ".,\-, ,.: ." " . ' ~ t '" . ' " '. ~\ ~: I.'" '. '. .. ]i.." "\ ..:i; , .', ..:--..,' til " .. 'i.: ,: .- , : ~ ,,,.' '0, ~. I" ~: ~_~ ~: :. , ..."'':. :' I . '': ' ../, i ; ' - ': 'i ' ...'. '"" \oo'~f t ~ : ' .' . . . "':' .,' , '. . . '. It :.~. ~~.' ". ' , . 0' t I .' .o ',44.,:. . \. ",.., ( , . ...... .-. .. ..' . :_.It \' " " ,'a. ',' :,' . , , , ' !, . , ,', ...,,,, ..:a -~ ;- ;f . ", ,I, \: , . .' .: \ 'f . ... " :.,' " ! '~ " ... .. " ,e. . I."~! '-, .. . ' . .' t ~ ..' .. .' ,', l' , . .. .. ... .. , ..... ! ~. ' , " '. ,; I,' I. . ., ..." ~ , . . , r. . :,~. , , . .-,, y. ' " .' , ",' ~ -"" ...~~ .... ". ."'i' I , " EXHIBIT ML- 1905 LeRoy O. Oardn.r" M. D., D1.r.ctor, Tb. Buanac ~borator7, SUI.D.&C I,.,Ue I H~" l'ork. it a ~eting yesterday &tt'nd~ by c.rtain br~. 11n~ manufactur.r" r. Saplon and I wer. able to ;>re nt, tq & tairly lare' (rou? ot 1nter'lt~ cor~or.t1o~ tht ;ro~lal tha t one at your d~ t1.a~ co.amber J be enga,.d tor (urth.r .x~r1- .entation ~th a.be,ta, d~t. lh. ~ropo5&1 WIS Tery ".ll rlc.iT.d &cd it a~~ rs thAt not less thAn eight, and ~brnAp, tin or more, corporlt1c~ w111 ~artlclp&t. in tL~~c~ the,. farth.r '1~.r1m.nt' .lo~ the ~e. dlacU3sed when ". mtt wlte Dr. t&~a and Dr. ~cConaell & few days a&;o.' .1c:-ord1n.cll, you ruy c~ld.r tt.1. lett.r as IJl autr.ar1~at1on t~ you to eo~.nc. the contemplat.d '1~.r1~~ts wltb asb.stos dust tor tb. ~ur~o ot d.terM1n~ more d.ttnltwly the ca~.J LCd .ttect, ~t llbe,tolil. It 1s. &1 underJt&~in& tt&t, &:ong other q'~st1onJ whlch 1t 1, LDt1c1~&ted th.s x~.rl ~ents w111 ~ r, are tb. (ollo.10&' or or (l) ;t'hatconcentrat1on du.t 1s n.c.ssary t.O .Jrcx.:uci the tibros1. the lun&s wblch 11 d'li~ated asbe.tosl " (2) (J) 04037063 ..... ,.. . -- -_. '. , , I ~ ,~,.,,' .,. . .-c a .: PLAINTIFF'S I EXHIBIT ! 3 lQ05.0 -2- ! ~o+;L (.4.) Tbether the!'1brol1J re3u.ltin& 1":04 upOlure to a:sb~3to.s dust 130cca..t10a4K1 by the 1111con content of the a3be.ttOI or by ita (1brou. Itructure. (5) Theth~r tte pre3aD.Ce ot ~3besto3 bod1 has LOy dl&gno.tic ,,1gu1f1c&Dce. a.. It1l a.lso our under.tAadint that these ex?er1:ent.s w11l. r ~u.1re ap tlroxi.a.&t ely three yea.r J, ..hich ... ill a..n tha.t t.h.-y will cot be co'ncluded unt1l about the end of the year 19)9; a.nd thAt they ..11+ co.t t5,OOO annUAlly, or a totLlo! $lS,OOO. '. It 13 o\u" (urther understa..od1Jl..g that 'the results outained ...111 be considered the' property ot those .he are adTanc- 1n; thAI requir-.:1 f\.1lldJ', who Till detera1.o.e ..hetter, to wb.a.t extent I.l..lrt in >ltu, t c.&nIlt:r they .shall be ::ade pub11c. In the 'Tent 1 t 1..s .~ \ '.~. ' deemed :.,desira.ble th& t the, ,re sul. ts ,be ...de ,Jublic", the C&llU!lcr 1;l t .c!',:your'::3tw1y '...ill. be, :sut:a1t t&d ;,Ul.u,,::!or a ;;jJrOTa..l;~;>rior ..1.0 ,public'a.- .~ ~ t1on. I shall a~r8c1&t. your adT13~ ~t i t the !or8,~1n, (. accurately ex?rtsse. tbe propo:s1tlon 10U had 10. mind. ~lsot let 118 x.n.a... t.tle !Moner 1JJ -.blch you ..ould like to b.J.Te the tundl a.d- TLCC~ to you. Would you, tor e~ple, desire to have tl~SO paid quarterly 1=1. a.dTance, or Ju:st what arrl'\ngem.ent would Juit you best? ~Y ~thod you :sugge.t w1l1 ~ s .. t~fa.ctory. Sinc. the .x~eri--ent~ are bl1n& uodlrYritten by .. relat1Tely lar &e grou;J, 1t has .been J u"es te<1 tl~ t, as ~ :u.t ter ot CO!l'TUlienc~, ar.y co:u;unlca.tion3 regard1ng the wor~ be ..dd.:-~5sed to :N, and I w11l, .he:-e necI.sa..ry, COBJ..W11ca.te tht, contents thereot" to ~. S1aplon !Uld the oth er p artiel. You will be ))rOT ided ...1 tll ('.J..nC.J by either J~-~T111e Cor~oratioo or Raybesto!l-Waor~tt~, Incor,)orated a..nJ we or tI.e), .111 .secure rro~ ~lle othert>a.rt1e~ t..'>leir ~ rata contribution. I will ad'T 1.3 e you .La. t er ot the 0.&..:l1lI a o t t..~. other contr1buting ~arti.s . I .shall !~~rec~t. your ~or:in& :e at the earliest ?01~ible mow.nt whether the a.rra.ngetnent a.s outlined berein ~et" rt th you.:- a;>))rOTlll. ' .. ; 'G:T ::}i " 51.n.::erely yours~ -/',,' I ' j~ ~~0ure~ .(j~f-Y'_ Ya:ld1vlr Brown General ~ttorn.y 04037064 -,. .. -,"",'- ~j IJ 't ; ...: oJ .. >. ..1.I . ,. , , \ , .. , .. I TlI!! SAIV.NI\C L\~ClV\7CilY roll.. THC STUDY or TUD~!l..C~LO:'I:l 01' TH:! I:.DWI\RO t.. 1ii.Ubt!.\lJ POU~bI\Tm~~ c.<. - - ~ PI.AIHT1FF'S 1 EXHlsrT i \S D<O ~. , , 2.i 1.1:--. Vo::c!.i 'I'~r Or07:t1 J 0 !'\.'1:J -!:G.n,~ e C or;::oro. ~ 10n 22 Za:J~ ~C~h 5t=eet lie',,. Yo:-k C!. tJ" B r o ...n : ) pr~~o~ed Your o~~e:Jtcsi3 o.uthQrl=nti~n to p~occcd with tho eh;::eri~~n~:J at the Sar~~uc L~bc~3~C~7 ;.:. .1s aC!CC~71c~6~d. tv l.th S[\.t.1;J.i~ctio::l .. ne pee :~d. to furnish beli~ve 8.sn;ror:J that ~uch ~~pcri=ont~ can bo exto th~ qUO!l t1on!J which you h!l.-o ou tllr.et!.. 'l"no 'e:.'tir:ro.tec. of th:-eo 7cc=:J, mak!~o A CO.:Jt of ~5, Oc.~n=.uc l i j " for n. por1oG.. total of $lG,OGO,.ls cor:-ac~. I::o:r pE\:.r.:(~~t:l of Loboru~o-:-7 tr.a ~ :JOU Your :n.!r::c:~::t:1on "to t:I~l:o nc.'"Tc.ncoc. ~uo::,~e-:-:7 :S1,250 w1ll be C3ntiroly ::lot13f'llc~o:-; to ~hc Icuf~ethit3o =isukcnowt iclOl :1b'Je'on8i.cc:1ct~potnaybleo.the:- ur::'!l.ne::e::-~:lt of' thO:10 one! tr.ut o?pro;ul . TI:o ~o.ro::.nc Lc.br)l'a.torj o.g:-oe:l thut tho r~!lul:~ 5tu.d!c!l ~hull bocor;e tho propt.!rty o~ t!~ t::o.nl.!!lcri~H3 ':Jf [m~i rtJport:J !Shull ~ho cor.::-iG:..lto:-::: bo !l\!b:::ittod of the contributor:J boCoro publication. '<"'~' '.~ .t.~ fc:;; 0" ' ' . : . '.~ ", '" ,. -:~:-rorr::.ed 'i71th I woulc! =ccc~~n~d that the ~xro;{~ont~ ou.r~ ':c\:~t.<!ion ::.r.~C!lr.o:l r.lbr!:t' contn!.nin bn i;,~:,~~.j- l.l.ttlo 3~!.~:~I,t.ir.~ L'U\..:/' Ul.l~:.:' 'i11O IIKi:1S~ G rl!Floot~" . ~"':L:. r(JI:~ 1n ou:- l'1r:Jt ~T.;J':!r'~=::cr.t 'fillO Uc\!lnt1:lf'l'::;C:-:: oni~::; tr.ot i t contCl~r.p.d such n hlc,h conco~t~ution.or to t110 f1.t.rcu:l ~u~r.f)!Jt r~c~ CJ.:Jt. _If th~.:: ::-.net.2 'tIlth you:- ncr:a?p:-cvnl I wcu'!.d th':..1t a 3e.~~lo bO3l!r.i1::1.t~od to t..'1e L!lcer-Qto:'; fc:- cr.or:llc!'.l and petroe::ro.j1h.!.c anul:r!ll!l. tr.c n:otor!.ol to be I-in'7~r.c::; U313d I =..!~uI!.111'sat1~!,!.t,)d 'I/:,uld rp.que!lt th!l'; cnrucll':!):l D.!l to tho cc~~anl'~!l Ilo:-o~ to !lu~)o17 n :Jurf.1,.\nnt:. L!Urtll';l.:':' 01' a:lCo:ltou J .c:;::'OU:1c. to c.:~CJ f'j"O:lt :ir.... te:of !511utll'11!3i,)n ?u~~l~!.C. or en:! o!.. th., l!Ont:.l:!"O~~..J!,,:J huv<; a\Jp"I'utU:l 1 O~ ."lot cu~nbl~ uwur~ "i.tj:r.o::roc.tc !.:-.e:; r~b~on to :lnhalubl~ di~on~lon~. If t~~:l roquost ~~OU!.~ r.ot .,!..~,,,,,' . . ......... \ .. I- : t; I< ';"'- .. ,.., .. ... . .,. r, .. ,(' :--,.~ .. '.. _1. _~ : .......-"-"..",'\ . ;.n,'. 'r. ' f(I ., -.".. . M . r. V' f:rO'itn , Hov. 23 ,19:36 I p. 2 .\ .... :) p:-c':e !=l'"c,ct!.col 30:::0 wl11.r.o~e to bo ~~co rna terla 1 rucei vod b~i orrRn~crr:~nt fa;" it:s bj tho Labo~ato~7. U!J ::Jhc:iuld be bro%cr! flr.s.~ recuc~icn But ~t lou:s~ tho to pO:'IC.!c:-. mater!.al :It 1!J noce~!Jo~J l::mo:J::!.ble to ~!lt1.::oto for- the eT.por1cc~t3 at the the s.=ol.:.nt pro!lont oJ: t!=o S!J It!l ocncl-J'!.c:" i., ou:- CU!Jtl~o Oppc.rClt'.l::1 hos novcr boon do tor::!::oc!.. 'r11t h tr.3 "Ki.nt;:l Floo t::11/ tt:.!J t!J 0 npro7.i.r..!l to l:r l? 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" ,........... . , '0 I ........ . '. " " " - , . j, .. --~:-.:,':~ .:.:. .;.--.:.--'. " --;~.. PLAINTIFF'S EXHIBIT !/QJlf:O m. - ~ a1 . ~ J. LJJ1J. D. m S!J..N1 07 DU!aUCJOO1 lJ.19 DOI!~. J.I ILI'tlJa ttJl) em !lJ ncxn !lIP !O !D I 41 J11C IJ.JaI.J.!'atl' .:,. 1'1"tJu'\ Y'N r .&.. :. Lda. ~I .. mI-i', " -: ~ t. I ' ~ . 1. Y. 1.... .L. I. 11aher .I.. I. n ..:aW1 T. O. r. 7. I. J.:osnroa& H. ~" .1&4k.Ma I. 1. !aaUua J. P. Y10 4..a..r1!. :..:.... tu , h. Y"'-a..-4 .1.r'T"M &I eh&1nw.a d ."UAC. PLAINTIFFS EXHIBIT I:1L .. 'IOLl/ -,' !2a.a hK .Ni1lac 'YU ....uN ~. .n ~ ....t ,h.t t, .riar u.erllT a:t1u 2 lit iz..r pr1lta.ril1' h.&Ti:l..r 7.x. b"1 1& '&'.1. w 71ahn' trio.. y~ ~ & ~n .., h. ,J.. :. Lng. a! 'ba )(ri1"t~lltu Lit. l td. f tr the ya.r:po It If b..u..: ~ Iuuru..c. O~t IUUZh1.:1( tu F"a.. ,~ t1 ,~ ~,. rit)' llittu.&'ft' ...nA ..t th.e 8a.ra..u.o I.a.Untorr. n . U , 4 aha.L......a .,1IJ'a..<l viU, .. HT'1ft ,.t b.G COTt1'M U &. prnlou auH,..,. ~b.I aM b:!1dr1al q(1u..a pnU... ix-rU .... ])r. Lu..J.& h (iT. a d ~ocs rlpln of yA1ol1. tu 1"Hn.' Won.d loa. .vh1ah ha bAoi raUl-uN. oa hi, ,rip h U. Sa.:&1AC Lt.Hr&~'rr. itpOM )r Dr. Lull '" 00011Hf)() Dr. LuS!. z.morand.a. N'por"tK thd Lnr~ hil racISt Tid' ..t 8.&ra..u.o h.t bd hat uc... and. noh. l.ft 'oT th.t lat. Dr. G1I...rd..ur. &ad he hal. h.lkl<l yUh to all ~h.t 'TerTbo~ there vho yu eo1l0tmlN "Uh t.h.e "112:. pra..oUea.ll.T loriu:A.d.lT. llr. Q.uU.ar hd. ha.4 a TerT Tear ea,?abl before t a hA eerlh.. d.iK. l 7. 'i lnlt hlle t '&!L!ortuz:.&hlT har OY1t. knoYt..4t hI . Ad. ....rke4. t the ezp.T tor 1aa h.1Jl h (1 n 4 J.r ... , app ~ r u : i a . a h l T OlU , euthadartliahe1.reMIvrxup ahelIr.uo4.auah.bhlvA.iTttIAoaUptrObN.'Tari.4"a:.t.t~rl.r.,tUh.ap' .t' ltTl"r"T.'hu1.ll',dCu,Uba.tubW4 .lrLaaq.pUc.eods. 41&vbeobaacn'k.hc1Hi>oq11lo1lJ&L1y4"ith ...u ... Zarlltu"n'tl0T1l. MDbr..]GIat.rhU.e.r heal4.t"pl'..azm).,:nta.nbH..U., .,Ia'; o.-prehaui" &1'1141. os J...buhu 1h })i'o.b.ot 10. pre'lnl. tk. e..trol .t Au. 1.& al 4UtlJ"At rllab' : ..MZcA proU.... k1nU er 1.Kll.'r1tJ. ,laat It .te. Re had pra.oUeallT tUi.he4 th.e p&rl .'ot MI ta..at oa lma.&..a b'..iA&'t &.u. hM. "'n.O,t,.d'...M...... ',t~ repon 4&&1121.( "itA the eft.o' rHt .t 1t, ,"be rou&h n.o'~1 .f a.b..tt. aM, c01l::1uh. . . . . . .. '. . . tTa..ah a' r. Luu wrOh II. allooiatt4. ,. Dr. rcndll yUh the 1&\1 .Dr, tba Ke41cal School ilL Ch&rl.dOJlt 5.0 YM hat Oarh.r and. h1a.tlf 0lL &. lot of the aa.r11' yon: 01 ..b..to. ca... ,:' Woraed. hill ot the Iitu.&U.oa al he M4 tOUllJi U at Sa.ra.uc. w, a. !a.r Uu Teb'1tlh1.&J laab.lte., Dtor. porn-.i..drd..ntlr Ir IaI ~Ufltrc.atp~i,_.__'rY..U. J. .C..O..B.elnlld. h14 h1a U ha.4 bin. &rr~eci h , , -a- ~ Exhibi u 'rr u.. ~. y., ...... w.nH Dr. l.fu.h 'W 'hi ...~e:rl.&1 rill " ttrn..rt.M. t. k1:a U HH U 1t 11 ..... al&:p.e It UlII.\ U W NOt1TH. )..I rlll & NJl1 M~ haT. U h Uu aft"" h .... i~ 1..W 1&... flr. ~I, hl.M:n1H~: tka\, &.t1n Dr. Lr'I4i. M.a bt u ~rtu..1tr e.DJIW ,h. U . .l'1&.1, ~lh_ltla t.ft. AI r l l l cLthn.w yt.. t h.u U 1& ~ II i u ~ JIlL' U hpthal' u .: ~ '. Q .1 lW' I-A' -e.u., Pr. X"ng, ,la:u h 1"" A a 'riJ h 'M r.d a~' ' u t1,N, d ....T 115 ... l)r. tru.h ,hat lao rill ~ It p.t"i\1, h Lan U~. "\ru&rr aM ... t.re ,lwt,\ 'ta., )ct. Un.l.t U 1.s.c Pr. Lc.a.sa. N ~ tlM:a.. it Yill N aakr1.&l h k.1a ..... traua1.t1et unnbel..a.l. Irr f 1 .... tQ&.M 1., Jr. I,pg aU M n'Il..l k ., 12 t01lAh. rl'll I-X a'~....' ':UI, o..elnLa. hi e:aa ... y1tA '~u.hrUl.. J. .'Ue( U.., UII. &lM a\n\ 0&, Dr. ~ aM. .., 1..... ' ,be 'N.I1..e pa..r1-'ha.' .h.ai'l YU (a1h a 4..ul11( Yit). tAl dtu, .t uhn.. tu, 'It wH'i&.l ~ ha&a NUp-.M:aM. h M t ..1rq c-p.l.n. aM. u kl1ITM ~, n.U~. a "' 1duht7npu;. u.... auu ai' ,MtM7. ,fl.l Hh.er.nn. r~ X en ....r...~.. ,u. -Yohf.lta.\.~ nl)..rte ..h..t.t71~. ,~ Pr .t.rua woU! ..tt." " pnotut CJ.Oue:rtnt-o Hl.T n ~u pu1 Ualu., rl\k t:l' b.a.I. hM 1:ll bL. 'J' Yilt hAl' b.a .-n.ll ~tH" . t U\'ltOI R b:u.u. N1ica: a1is.t'odU..1...I.U....n. ~vN. b".le.uhI.a"t l r~~ e1-. o1l.inMcihtiA.tliduta..r.i a- n..,.., .hW 4 YI UPl-l.I.oLprauc,h1whUOtlal lLl OIt tuidt Lct.GlU.4.fHtt .1pqt t . , ,.nl tu Wr. Jrn:a h~ Hf.rrM. 0. hU. h tw oeMu1t4. at rl'll ........h. yAUA .la.a )(at, .u. ta. Xr. ltl1u.l, .t 14't, u.t ~tM ""r~ln_ ~1!. tu,\ D:-. ~ ai.dt1 w).1u uk. 'I." It At U &~. ,)..I Wtr..tl0 )t.&1..J..M t. u.t.u1akt. Dr. I-ua tra. tlu .. h.h, 1s "," ...'U4. A,(NM 'lIA' U,U .~\ \. t.a. ~ ' th.I nrlt i... ~. l1al:Lu r-tU,.';;1Id. tJ:.i th.t ~Pd:l :u... a ut1Uh Jt\ t. u is {'.Auh " .nari ".u uu d!c.;J\' .t .. l.~ .t l!""",&1'uh~ It u'b.t., ...d;u"\, u.4 u upr....<i thAt ha.I ,b.t .puiol. ~b.&' a 11 NaUn. h U ha.ratIl l"fP'In, it prl'p-&J""M ~ Dr. atfNh ~ otllpD7. . ~o~ ,h.t 111.. "UUM., Yftl4. l t aahr1l.l WJ ... 'k. -'-- - ( - I.ttu-ru.r t. ~. Ltuh' t&t_nt '0 Dr. Lua. \h&\ AI wnll IH U th.t uhr1al i lla <'>4'U4 N l"t uh p:l\l1ahail.' t.ra. Xr. Y. JI"O'W'& ca.llM aUcil.on h 1:& rcu" ~ d 1 rl U. t lLa 8.az&.ll.&4 1.&\0n torr Yh1..oA pm 14M. 'h&\ ,UpUat1u. p&\11ut1aa U ~u Z"lnlh .t ~lS.ta w1\h.n.i RZ e.fl....i. 'haN Yftl4 N at !.t ..,.14, 1! U 0 .. ~ It" oui no1 h \t the 1.n.elu.. U'1 t! rer>tn v. wtrall N ,la.d. t t. baT. e\J..oH.4wlt "'u1.al 1"l"n n.r ~'~ F1\11ahM, ha ~ Pr. I.ruh Yn.l.l It T1w, .... t.r I%..IZpl., u:r r.a- 1"04b.... t 10n b. h-. ell &.H to. "lU~ , u to thil in hit .ou~a:p.h. u.d. o.u..o no, h a.dd..M.., tla' nil. t 'b..I r It n:AC. wh1ch l>r. 0t.ri.1.I:r ha.4. u.d.I ~ Z"1'p4" ~t ..1.ut .ca.... tb.a.' ...... In't ,to-e taTor..bl., trOta 01U' ~1d .f Tiw. w hrW nUl wOlll.l4 pro'M.U.1" YUBs h haT. it pub11ahK btU:l1t .f tu Ns..afU h \, P~ tr:n 'boa 'l>e' "'~. tf tu ~n. pDreurp\.lolIMa..h..np au4. r ...l.l~ .u..r.t.cbS~ a. rKlP.r.r.l:nLTnUh'hv,ndl4tutir~rhiabte entbt1bU.t e.4taht_laoh' luil-lKqu'UTUdl1.o. ."YteUrt.hMa\ UUe1' ,i:....;... 00011997 pKUr".c:l.'ah~hper.nO.OoS'l.l.estMa.t.hnaUt hoAlU"4nlU4A.'.~.1ydult~cl~.uo,\ .c..alvl.irYrh1~.crh lhaAM \u ..,'But .. IOU \h.naaa4 Mea fU~ ~ilI.rl oo..-pa,q at \lu"1)n. ~" i.bu", iur~ ~h.a a.n.4 oOD.dtd ttpo. pal" tvo ~hl t'w or thrt. r..u"","".,u.1 ot that \hh cp.1ek &.otic. whiah hd. \ta. Y1~ r'I"PH' h 1"QJm.6.l"U7 all .1drl a)ef-\ tiehn. he.UL..I"NO h.a.4)lh..an.4. U to.. dcToe04r... . .tttot vhtrt C01:GJl1ty opuloa n..i oouerud, ... thl re- }fr. Vood...e..r'li ,raa&ri:..&d th.&t thl, ll1l1th e&.. , hovtTtl", haA. turud out quih d.1!:.rerllr 1A.c. H dIT.lol'M. th.... t u W1Tid'a.a.l 1.nT01Ted. you H'Porhd. to M-or_ . . .----,.. Exhibit /' "'"1ac ruua rr- Ou ten 1rl at t rn.Ut 1:& 1>Dt<n 1D1 al o11M ltd ta.t.4~ ...-.rU. U u.u rlU u. l' qpe.railT rt d ' . .1. Y1U en1M \M aa ... rul IU e9'J) U'" U 1tr " pl'lDtn..i& Dt U D- ,,11... J ~ U M 11 \U t 1l"1' MEa~ aX q t .b.('Ln, lJ.4&. " ft.il"l YYn nUl n.n1.TU, 11 yUk U ,~ w. UN n.t. ...... IMStU arptRN, 1-' rlU. T -.u ~r 'WI' t .... UJ1 u Inc u .Ua ,ra.rl1a&Ut tar & rtM:r t:! lUZ- t... tdf~ . . we '.A..n at' 10 ..ai ltt ~ An tlLe San wm liiM'" ef tU 1s.M earU. " " ' . . U:tWh f1\:rub U U... l'II:I.CSt 'N.t a 'D" n'l tu.1p ~ H&.ot In yUk cbroJl1o 11t1..&..a.&tio. a.K W:I..Hkl tha.' ahuc'fl 1N U tu ~14. """nM .b'\a1aM tro. the ret. 'Mot a t1lrtll.l .t \k. !ha IW- .11.; tno ynll 1&, c:z ap PNI'. laxu.rr. a.d . 'a 1'"", u... ...~a\l,.. o~. rut on.eatnt14u uu ter U yu wn iun&H4. t~ rlt~t .:t ..~ : . , p&r.::U1i& YU t"T'U. u that ,boa U3.(n' .t Ou ku4r14. &U tin.1S Mn rUua ]I ~ n.n 11.4 ..... u'. 1_' C, ....u.c 'Is.JMti.oa ~r1M:1tl .1Jd..t utuJa.. ,~, 11. Wn:n:uu, ~t 11'ra~n..eh.a.l. aM 'iu~. 11~. u.. tk,q h:N..ri t wa"'I a l l o.lCpl~ M. u.n Usa, ".. rw 1M Mrtn.l 1..1.4.anil.. Mr1k ~ no ~. ~ c:allH. a ;-tuh (~rrtWh). nu ..u ... " btu( n Ua ~. yUU C".... u.a o.-pldM YIN u.. b\alAU,. ~. rlu': /- .. ra c..l1h .. a..~M o.h.&:.ct. ~ J~ UJMtM yare &bd trn. t hi. UN ..1~ & JdU ~ c! h.Mnl.e." Cl'Ir1.:M:a ut at 'n4 ntrT t. ' . , 1 . . . . eszLM qr..... t . . . .- .. ~ ~ Jr' 1:IJ Nt i.o.J. 11 art ~1antl uu( oal.a11.M. (linM. ., ~ I ...I ~ Rrfi.o. Nrlk ylU1. U'n'n~ .. ' 'ki. than 24~ 'rrr1.k1.U.. rul n..a U .. -rq Nt'n.41 U::a ariAK~ . ~ e:ale11M yUk. ..... ..,. uA. hlt.h ~. I%?t J'LN U o.J. up U'ua:.h nT. ,. nHre.l. U1wi ~ oanh4 n &.lUC r1U viU (l.1.u.I. p14. J nriA.. hl.rcl. is!""1u.. .... !b.. trw.." &t1-tr up. Art ,. n H.role W~ t 1.01. c:q rill on~ 1D..t fu a\ lurl fU ..r. T'Ml'J &lJt h'tahUa upul1ah vi~ .1f!1.t rlt~~ U1 aUK W.o11u. '!he UJ.1eatio11 a.r. ... tar ~ha.' ir.tlt Ha.l.&h, ta.krclt W M H.a. , It Ye.I felt th.a.t tlu eaulu10a rNC.hM d n ... Qt.. h U .. attHt \ha.\ ,ht ue \h&t E:rflo aUmulat .. hl.bercl. U!.cUoa. YU :-&thoU' ~tuU.AC u4 inticaHc:u x.ua of the T'port ib.d _4ht ,iT ..... t-OK. c.a.o.rL lbt. yu tM p&M yu uIc..t t~ h1a qi1i..d AI to hoy lrUeh t1:u vou).d b. rlC[1li:rt-4 Nftrt & "tlUt .n.aluloa C01LlJ. \. rNO) .... About thil, vnJ.' tu tho~ht the u.4 hi ttahd. 'hid tecbl1101u vho h.u U prebe.\lT ohare- ot the \ab atU tari~ e.t u1wtl. eM rl 'lu vnll han J'MZ: h M on hi' .xptrulllh fir thl Nit ot th.t f'M.!'...... ~ ,be U u 0&rTT ~. ~ \M pathologiat yill UT. \ ,.t. u. H.e ad.~t ,hat YAn h.e &\1. t. O&hl~ 1r:p yUll JL1, \.uk tr_ U. \r1, t. tahfJma'101' .t Y, Oout. a~ \la. tl&.t tl1.4..t t1rd 01 lUll', h. would. l1k1 h CO k.ci: ,. !a.n.li.&o. U cut ,j"I1..t "a-.t PZ'f.C!'~" hAl \ . . . 1LIIoIl..e. .00. U ,..111\1. altet thAt, ~ fat . : .. , : :-:: ".:',;.:\~. t:, ~: .:- G-t...rdn.,. !o u u.quirr ma Kr. nlll.wi a.s to rl1lrul.&tt. \'Il\erolt W.oUu. r va.. thl vht\h.tr "lit s.d.l~tlou a.N"#'~1,ru 1ah Dr. Gt.rdnlr' .,WOll. Dr. 'Lau ~tp11K thl.' it nl ut. \!Ia.~ thd it YU )bot Dtltl\ul , iaJrudoa. a ' . : -..DA. thd u i. :'. contider.4 & Tlrr t:tperhnoed Y8.0 a.:trf eT1d.AAo 0 Ua~ Dr. U1. Kr. nln\ari ha4 r e.a.cht<!. UT 1a.quire( further Yh.ethlr th.aH n.cA 0010.1:"'1 Los h1llIlU I aM. . " Dr. Luu. anAvti-t-<i 1.n th.a n~t be. , . .' . -. -~ Xr. n ..abu~ &.1 ... rt!UT.4 to & prfTUUI r.qul~ 1f ~ .. 1\la. .., I&.roua.t Po U:~. tL.ri be a:p t:T1ltd h.e b&.t IIILU. \4~ Pr. L.u.u. wek. u N.r1 11 n.1.4lL W &.oa. tNa t e. r h.a.rt h rlU & J..ct'N..cn rt. I, wiiU UJqIl, t.! nl ! cra4 ,1.&hn u ..... t. i.&..1.1 u ai.rTtu" Ulh t aM "h.1.Ih b.i PrM:1.o-M uu n, ~ u..t r..rp. e w a.lIJ.pp"- 1. tua.l t 1 N J)O"ri nlh U..t t. 0.. r hM. Q& uo.t Dr. ~'. ,MIa n'l.Llo4 ul41.1.M ILAt.rUl '0 & t ~ U"'I aM SM . . 8A. u lt.&.rl. ft1 h.u WTt2' I i i~ .. hai U'T.r tU pu11ow.l&z ...-ple .t uhrU.l 1.1 t1L14h ~. GuOa' t" f.U it yu .1 11t aNn h IAhnliu f1N' 4.ri'ctM olLr7'1h"UUI, ~~ &114 n1.c11 .t tJul NI )tr. nlf'1"o.&I~ Pro-Itt", at., .9l-. hU .~ u t. ~'. u,~. yM1h.t1' Dr. t.u.h Ad tflU.t-UT rrl.~ II'pl.. h U ft.i.a u lAa Pr M . Lau. ~~ riatM. th&t U y..u. . . wil . H l . M baA u U!t1nl~ t t Mq &il u un" i , h ...u a oU4k .'n.&.U ~h.t n ~hil u:a;U.a, ~ YJ'it U, h '1Z'a..I.G, U t bq :PN\&\l.T on.U proT1U U t:.. t... 1l'M W.r6.Ua. tU H<\It ri 'hq k~ thin .t .aNn MTarl.1( U. t1.!t&HS~ uapl.1 uM 11 ~.. '. 1":1" na J&-. 'hoe )ron u:p r......d l.O'I.~ t h&~ PI'. O&rclur hd. ...ph 1:A (I.... U..... !M' e. nu;' a.asp 0I.ZT1..M ts ttf tut inc ., t%j) '1'isa' wU A 1rp t u.t .lu., 11..1 baA. aulTt M ..... ~~ le ha4 ,bu, k1:a the elu ....., 1.1!tll 0'IrU.l t1 u:.tod e.aJ. IS 1.u4 u t trl.al aM t ou4 rl-u.H.al pc eu.i&.. et oUr I i .. U U. 11 U. X. kuw, ~'l'Cnh,~9 t.! chrrno)Ulh, tut At haJ. & '\.&4 a.c1.r. & ).e toou.d. a&112' ia.l. rl ~ thll n u s X l ' . I. u.t .... a. M.rl u&t .ad..M... hoYn no t t It.a.t aUrl'fthId, 0nil han )tea & \ hi e.. rb&rl _ t t1"i.&l- i4 YkieA. & u:a J1"'OG.4 t .f U.!!a:rm prtl'm 1.. tn. l.Mi). R:Tfi,. '1' tu I7!l" p-uc.n1"", .t c.hrr.t.~UU. U o.u.tau....! .4k' M" aM fer \M.a r.uu. M 'hliATM U 1xporlut \4 tJ7 Hd ~tu h ert&)11" t \lI&1 1J. n . ~ aM. r1,t 1J. .! t u o..rhart MIq1l. ... !I.l' U ~ ....\.r1&l ....... ca.e us.N.., Xz. n ta'a. a1 ~ n ... tu 11 ~ Yirthu IF u\ pl:rIhl~ t:tt tot t.. CZUK ~ 1\ ah..a'a.ll .... H'1 a.~ p&l"'t ~11 I i tu 4::u t 1.1U.lt4, 0 l' 'r t ~ ~ 1W :uk1-'1:1.P t1 t h.I a.t u ial. " t.! Dr. La:ua .\.. ~ that 'ht ~Hlhi p~\ :pl"'ttbD" the dt'.o1 a~M,,1eJl~. Tl ' A u.h r1..a.l.I th.d &.N u..1 M 11T a.o t 1TI, UVIT 1.1', M 1&i4. 'hi t 1.ur n.q I.H, , M u.. "'1" &.ei i '" ~ hIT ITfl.t pnti.I.r Ju" Xi I 1.lq!:r. II id 1rLI 'ha.t t hi hei:a.io ~ d !&.N..u.e taL" t h.I &.. hi He.1T. U tna Lo.p o-c (vk.1.U 11 the H('Il.l...Lr ~ cra.d..t). &M 1h&i U h.u UXT pa..r11..cle .1u. 1.1 1'. If'e ial J.t pr-..hM, honTu, ,. nU. to n:., 8a.ru..&4 &Ad 1.r..q:u1.r. wb.n..ar U yu "'1 ed. Jut u. it YI.I HM 1T M., '1' U 2' D:f u .. yUehf"ApfoIt frttihsAhc&dah. Tb~.a~lal'.u~ l.Adi .d. to dt.o,l,'ehpi..&1t 1.r&t.~&it. l1..u.n-4M...'IhI.I t1t !!ti~ 'l1d1&.p&.aY..frtt.1lJe.l.Z"dftU ~ wI 1U1 It.:."r"i truw.H.iun.t !411ef ,hi., efftct val e.rcr ....d, ~yfT.I',1 ill c~1.J.& th.e Ublt1'W I 'hi d.ri .ra1.u.U..n, .t n..c). hr,1.au PNu.... d ~ !&.ri I .. .. yau.l4. - _ hne .. sa.d., at S&l'&nAC. ).0'11 !u. a..a..t ou.!tU aahrial. u, '1' tM &%;Ilrallth UToln4. is lha pM..la HUe &It eot ~ Loapoo, a.aA. it va. f.lt tha' at 1"u.Mhar t1Ju ...4. b. 101t U. coau& to & a' uc1l1oJl. U to wh&' ....., 'b. d..os.. h oolltnl'the tut t1tLUioa 'h&~ l'wt. hl, Cl B.for. lUTil4: ,h,a V.., eo.u, ~ ~lu ~tu~.a.aP.rrl . fvLaur..u...aottfh'aar.t04RleUYI U'..Wni.1e'.1.lN1.21ouf :trhec.a.epo.a:a..-opU.ar.J.wT'.bidl..a.o1sH to ~. a enpttu.\ TuHla\1oa ~1n.e::' a\ I.~o. W a.n.d. 11t Xr. nitJl'b.u t b.ow 1..! h.I .. Olin I a..cro aa X. "14 h.t would. a.ppl1.c.ui Yhn ha kt., e ta1. u r ~~ u.... O1lll ~ PLAINTIFF'S EXHIBIT onn19.nnn Ii" ,.. .. ".--- . -'- t 'en,rt.... r.... w. l'lI.d - t 1..0& n. ..u t 'M ~ Y'i1U yU.l t.M.l rlU. 'll...1.eHi.', aM .. w:h1c.i. Jr. J.hu,.. rt hctl.., i.a tlT ~ U Yritbc, Jr. W:ua I'1.&.tM Ud ~ ~ Pr. l.b ... v.ll a.t Ii,n:...,h .. w...u ti.caul rltll lL1a. d J.a..cw.l ... U. %"'Hnl ~ 'ba.t .. FtriLI ftr U. )Mk a:q aU.rl.t.l . . ~...... MT1A D.1.U Y'I k:'Jr.M h h CIIUIIt. :f' Jtr. 'J-Mra fIIU.rl M ... 1"1-. Lara 'ltd, Uftll M kTl ..au in. t4 ~ rttlt. Jr. hart -s.e.n 1& LH .b(U.. , lu yut t.. tUC1UI riU kilt a rHGt "~r~ he lsM tu.l.a .t a u..r sa... YMr. U H 11..n-M. 4.1&, ea&.c' 0'& I t&r1 h h&.t hat ,be eltH1 t:! rri.&:rt1.q. .r ucl d!, 1~ pn.c:n.. t h'NrN.. Ii. 11 & H.r1a.il1. W-lrli:ul. va., it M W kG a:a u.t. .ri1Ju.rT o&u, vnlt h&T. ,ted. .., .. II&C.A eul1u thu M '14. "i 'u '"" Ir. ke. ..ut h.t MJ.... Pr. LAn y...u Ti.lt I..-pte briJc u. T1.J l' t. a..u1. ,lar. Luu. URrN h.1a U~&t he ~MtM at 17. l1&ls.u, AU"~'" tha.t, Ua Aa Ti.a 1i. tH -,lu.t. hi .11 Lra aU 'aJl: tnT 1Kut r1&l liIrcUu ...t,1.N pcl"'HMllT "UA Xr. Vutuat. rath.ar U:u. v1tll a crn:p .1 tm tl' .1% JffJl.. lr. y..tan' , be ~ W a IH" Ui ilia, ...... tMrnP nn1..tc-t at uLt"~Uc t.t the ".Ml.a InU. whiell h.t o.ut H H fr iJrp,&rl is & CUTtru.' ita al ou wi U" Dr. t.u& 'M.I. M on.ll i t & l u I u Un:)I WH callM u.. J.NII' Rr. Lua u.k..M ~ cs i:M Xr b.. . r na u.c .u\ u... . u1&' h". r W )'& in M K t:! r. 1 V.. tau . \ra.&J7. t ,AI., U )rla.1lT TrLlJ. rhU Xz'. YoMut .... nrM "Dr. Lou. ,hat all ,baH jrr...st talt (LU, hl1.nM. ITer t"hl ill hi W lea aU. h .WkU rrc. Dr. Q..e.rb.u'. IUH, u ...u ... ,be r~ .. ,.1 M.t a.td.t n. tAl np ariMai. is 1'",,"'" ai !ualu.4, f.r .1, uY .--..4 q-pt.:' ad tMi tM c,apur yO"lll.4. ~ 1callT all ~Ut 1~ h9.lt ha" re\ Mt .,.. Gud.u rut Lied, u.e~t, .! OOtlrU, h.1I t'n. I::.t?fM Uh..rYT.~d10'1 ot \u U:i/uUnH r' 0' - 1'-:- r\.A\NTlF~S EXH1Bn I\I - - _I 0001?nn1 . : / . "' "- THE SARANAC LABORATORY OF THE EDWARD L. TRUDEAU FOUNDATION SARANAC LAKE, N.Y. LaO., U. GARDNC.., M.D. DIMCTOIt February 2~, 1947 Kenneth M. LJIlc.i:l, M.D., jJean Medioal C::>llec:;e of state ot South Carolina, Charleston, South Carolina Dear Dr. LYllOh: Dr. Lanza has askad me to bet toget~er and send to you all pertinent material in oonneotion with the report Dr. Gardner "as preparinB .tor Johns-Manville, and this I ha.ve attemp ted to _( do. In one folder you will rind probress reports that have been made from May 5, 1~37, tllrou~h February, 1943, when Dr. Gardner submitted to JOQns-Manville an outline of a proposed :nonobraph on AS.3ES'I'OSIS. Attaohed to the :mono~rap~l are various data identified witll: it. I have oopied f'rom Dr. Gardner's notes his oomments on papers on the subjeot 0'1 Dr. Gloyne and Dr. 1!erewether, also two outlines which may be of interest to you. There is also enclosed a draft of a paper by Dr. Gardner and i1Ir. Donald E ~ G\.UIlm.ine;s; apparently this 'las to follow the 1931 preliminary report referred to whioh was 9ublished in The Journal of Industrial argiene, Vpl. XIII, No.2, February, 1931 (reprint enclosed). c r have included considerable data on the susceptibility ot animals to lung tumor, since this has a bearing on the ASBESTOSIS problem. Dr. Gardner intended to carryon further investit;ation in this oonneotion, and undou.:ltedly his suocessor will wish to do 30. In a seoond folder are a number of reprints, and in a third folder, the illustrations Dr.. Lanza used in his book. "Silicosis and Asbestosis." All; of this materia~. of oourse I \~e would eventually like to have returned to us. gap There are many s , r lmo~, and i you 'Ili1l call on me from ~ime to time as the need arises, r will try to provide any additional data which you may require. CC: A. J. Lanza, M.D. Sincerely yours~ R:u' ~.~ (Mrs.) Lillian R. 31inn secretary to the late Dr. Gardner P.S. The above is lJeille; sent to y.;u by Railway E~..:pre3s. acknowl~dge reoeipt.,.... - ?lease 't.,L \').. , Progress i\sp'lrta - :lay 5. 1937 April. 13, 1938 Dece!%lber 9. 1938 De C8::l:JOr l4, 1939 liovember 30. 1040 Dec~r 4. lJ40 Propo,s"d. IIcnograph - i'e~. 1943 (accOlZl'i'an7i~ data) ( Dr. Gardne r' a comcenta. on ;lap era by Dx-. l3~yne IU'ld Dr. lfarewe thar- two outl1.na s oraft or 'a. ;aper bY' Dr. GardnEar and i.tr. Experimental. data ( '. Pa1lrua.t?' 2(), J.g47 EnclOsures to Dr.. L~ " , '. P1JbJ..1c Heal.th Bulletin Ilo. 241. - It. S'rJDr OP AS3E37~SIS I!I 'mE ASIn::SroS 'mXttr..~ I!lOUS'rn:c Special Bulletin 10. 37, CoQM1onJIealth o~ Pennsylvania, Departcaent o Labor and Iadust17, Harr13burg~ Per..Da., October l, 1936 - AS13EST'JSIS - Part I Special. Bul.latin 110. 42.Com1Cu_.al.th or Pennsyl.vania. Depart- - ment. or Labor and l.93S - ASBC;S'40SIS n Industr:r .. - Pare Harrisburg, Penna., and Par~ I I I September 20, . rrom. Baprint Iro. 1665 tba PubllQ Baal.tll Reporta, Vol. 50, 110. l, J'aa:nsl'T 4., 1935, pp. 1. to 12 - EPPE.C'rS 010' ~ I!HALA~IOB OP ASBESTOS ms~ 011 !'UE LmrGS OP ~BE;;)'l'OS \10~ Reprlnt - 'rBS IPtJUA'r!OB OP rE ASImS~IS BOD!' III !Ui.: tom by s. RooCllouae GlQ1tJ8, K.D. (reprintod trum. ~borcla. June, 1931.) Beprint - THE KJBBID AljA!Jfa .em HISTJLQaY OF ASBEST':'>SI3 by S. Hoodhouae GloJ!l8 D. (reprinted'rro: 'ruberollS, J'Ul1, Auguat". and. Septe::2ber.. lJ~) Bepr1llt - A EJIOaA.3Dt1JI 011 SIES'.r:)SIS by E. B. A. !larewethor, M. D. (reprint.ed. .t:roCl '1'Ubercle, lIover=ber-Dec8C1ber, 1933, JaDUa:r'3", 1934)" Bcokle~ - THE PROmJC':IOll AND OlLUDIlIO OP As$~ 1'05 07 Jolmson' a CoZ:2p&t17, 'tbatrord JI1J:l.ea. Quebe c. .;anaaa llaprint - IA.=tTI:. JPl::llATIOlt) U?BA3~ Il1OOS1"RI.AL ann.lIZ ?RJ3~l:!S OP A.S3ES:OS IlIDOSTRY (repr1nced. from !be I~l~ls, tabor &.LUetin.. Pebru&l7 28" 19~ i.aula) , Paper' - AIR SAUPLIlIG 01' ASBESTOS Ol1S'f, COMP~ISOH OP IJI?IBGEB .ABD ELE~OJ~IC PRl::CIPlTA11OR IIB".r;lODS by J. 11m. P.hlle~ (given or bltore tbe bentJ'-tourtb. A"ma.l t1ng or the American .l.aaoa1at1on InpU8tr1aJ. P!l3'alc1ana and. surgeons with .Aalu-ican eonrentnC8 011 Occupat1onaJ. D1seases and IM"atr~ HJg1ene. Cleveland. ObJ.o. Jw:Ie 5-8., 1;939) Il.luatratlona used in 1:ook. Sll.lcoa1.a and. Asbostoais- b,- A. J. I:.an LD. . h~ 26. ],;47 ~l.oaure8 to Dr. LJncl1. , , March 10, 1947. Dr. A~J. Lanza, c/o Metronol1tan L1~e Insurance Company, 600 Stockton Street, San Franc1sco 20, Ca11t. Dear Doctor Lanza: I have reoe1ved the material trom Saranac but have not yet had t1me to even review 1 t. I 'shall do, that as aoon as poss1ble, 1n relat10n to the present verT pressing aeason, and shall then ,- . let 10a know my thoughts on the whole pro~os1t1on. \... W1th best 1;)8raonal regards, I am Sincerely yours, tenneth M. Lynch, M. D., Dean. DIL:kbp. ce: Mrs. L1ll1an R. Bl1nn SarAnac Laboratory, 'Saranac, No' Y. ( " THE SARANAC LABORATORY OF THI EDWARD 1;. TRUDEAU FOUNDAnON SAaAHAc LAo. H. Y. LEROY U. GARDNU, M.D. .; ~. DIMc:raa !larCh 18, 1941 c Ketmeth M. Lynch, U. D., Dean lC4ehda1rlceasltoCnol1le6g, eSoout ththeCasrtoaltienaof South carolina. Dear Dr. Lynch: Enclosed are. copies of an exchange of letters with 1Ir. Vancl1ver B~ ot the Jolms-Kanville Corporation, which I believe you rill .rind entireq selt-explanator,r. Iou have no idea how grata.rw. we are to you tor a.cced1llg to Dr. Lanza's request that you undertake to bring Dr. Gardner's notes on asbestosis into transmittible shape. Sincereq yours, Or~:,..~U~..d~ c.~ MB:AD ene 1lan.tred B01Id1tch Field Director ,. - THE SARANAC LASORATORY OF TH1 eDWARD L. TRUDEAU FOUNDAnON SARANAC LAKI, Nil Y. LaROY U. GARDNER. he.D. DI. .c:rolt lIarch lB, 1947 Than',, ~ tar '1'O'Q'r lattaz- o.t U:..rch 12 I SIll T pq with 7JU:-- suc:est.1on 6:11 am c!oitJ; so' bT ,..".,1".c \ ot your latter aad~. ilZX1 ot this rtlt~:--- Tbe d.1.stinct:1aa. 1Ih:1.ch Dr 0 ~ to d1.Sc:usa ::e ... 3,1nJ7 that. bet aa t1browl r..cd parti azx1 b1s col..l..eag'tZes rater' those dee1pt.1cms ~ DOt clear ,:.,0:- _ toe dust" 1It\ereas Dr~ . JUSt ;.nat thC7 . . : by me! I. rUd that ". de ao~ haft t.ba ol'1giDal. parer.. l1ng tor m ezt.ended stay ami I all sura that" tbis . . or:. 01" ec:ta OD 1Ib1d1 he a::d t:-. Ciardner- CItCh.aIJgecl. acta,. tb.crIzP the ~ ~ ~ sub:1ttaci Cor.' pabl1c.t1orL be- tore Uz:g lett. _land. I _ taking ~~ a COPT o~ the ~per" '. Dr-. Oardzwt,. in Dr. ~ 'mak~ t.he .L.O-"~~: ch haTe~ trauac..-ibed and seat to c. ~ abcmI quot,at1Cft11. rroa Dr.. C&K!Daz-'a. note. ,;uoe. ii"ND Im"'el.T !or the ~ or thia COilWPtit.aee aad ahoald.. not be rep.z"ded aa ~ ~re. To ...nat a t a t tbq aT be a:xl1!'1ed. iii. the ~t o~ othar Llnd1.l::lgs. ill the !1!uL Hij5Of'tr r I 1 ne to be ..eo. . METROPOLITAN LIFE INSURANCE COMPANY Om: MADISON' AVltNUE,NEwYdRK lO,N.Y. ANTHONY J. LANZA, M.D. AssoctA'l'Z MlmICAl. DnulcToR BlUU.Tl!I AN1) 'W1n.l"Altll June 25, 1947 Dr. Kenneth M. Lynch Dean, lIedical College of the State of South Carolina. Charleston l6, S. C. Dear Dr. L1Ilch: I haTe f 1na"7 returned from J1I1 stay on the West Coast. I am planning to go up to Saranac on . Jul7 8th for a couple of daY's as I am eJ;1Xious to conteI' With Dr. Vorwald.. Before I go up, I would appreciate it U lOU ""ouJ.d let me know what the going is with respect to the Gardner material. Is it work- . able and 1 so, when do lOU think a report will be ava.1lable% Jfith best regards. Sincerely yours, C:. ~ --... <:::I,p. A. J. Lanza, M.D. . Assoc1s.te Medical Director ,. June ;0. 1947 - Dr. A. J. Lan%a, Assoc1ate Medioal D1r9otar, Metropo11tan L1t. Insurance Co 1 Mad1son Annua, . Nev York 10, New York. Dear Mr. Lanza: c Follaw1ngour previous correspondence I rece1ved Gardner's JIlLter1al and as lieU as I could, during the- extreme pressure ot working on a large legislat1ve program here, I examined 1t. in re- lat10n to the expressed desire that 80me publicat10n should be made ot 1t. p0881b17 eTen & monograph. . . I came, to the tentat1ve conclu.ion that the more ambitious type o~ publioat1on aa a real monograph.1s quest1onable, but that the part1all, completed manusor1p~ v.b1ch Gardne~ let~ could properly be published as a t1nal report upon the experimental program "hich 10 t~ as the immediate problem' vas aono~rned, had been oonpJeted. r 'Then go;. involved:. in f1nishing up the rear's etto~ and de- c1d&d to delaT M1 decis10n unt1~ I could reT1~ the quest10n. Your letter came Just. as I vas turning the matter over in mind again. It appears to me that to use Gardner's material in a monograph 1n wh10h the wr1ter would haTe to set torth his own views and add material. o~ his 01fll would be ne1ther f1sh nor tlesh and might be toul, ( to use a bad paraphrase. Although Gardner'. material would be used, the 'Y1ev point. would not: be- his and the vrl te~ might no~ be able to accurately repre8en~ him, t~ as he might.. Also the addit10nal material nece88al7 would not be Gardnel"l. In other words, to collaborate v1th &Dyone, poathumoual,.,. w1thout: that one' haT1ng .nn contemplated 1 t. perhaps vould not. be proper.. On the other hand to subm1~ his lD8l1u8orlpt tOl' publication practlcallT &8 he- has 1t written, with an explanat1on, 'Would be to properl,. represent him. Be undoubtedl7 meant to add to the manuscript, bat 1t 18 vorth1' aa lt Itanc1a. : .... .r -2- D~. A. J. Lanza June ,0, ~947 Xl present. idea 1& that 1t should be sent to the same publication as Gardner' a f1rst report on this atud1 and ent1tled as a t1nal report. Please d1scuss this Y.1th the people 1n Saranac and let .e know what lOU ~h1nk and 11' an1 dec1s1on 1s reached. Slncere11 lOUrs, renueth M. Lrnch. M. D Dean. ( ,. A. J. LANZA. M. D. ~ MADISON' AVElro1!: NEW YORJ[ Dr. Itermeth M. Lynch De&l'l, lledicaJ. College State of South Carolina Charleston l6~ South Carolina July 2, 1947 ,~ . /. .\ ) y 'J ,y I'I/1:':-1 :,. '. - C.l c Dear Dr. Lynch: I am V8r'1' much obliged to you tor your thoUghtw. letter o June 30th anci quite in agreement with what 70U 54Y'. I am going up to Sara.nac on J~ 8th and will. spend a couple of da7s there during which I will bave the opportunit7 of cl1scussing this subj ect nth Dr. Packard and. Dr. Vorwald who bas taken over as Dr. Gardner's successor. I then hope 70ur suggestion tbat Dr. Gardner's manuscript be published can be accomplished within the next few months. Tllere i3 a situation here which has given me and others who are interested in the successfuJ. continuance of the Saranac Laboratory, considerable concern. It is almost ten years since various industries began making annual appropriations to the Saranac Laboator.r.for research in the effects of asbestos upon human beings who inhaled it. In that time, those of us who have been following what was done at Se.rana.c and. who have bad the opportunity of first-hand clinica.l information, have learned quite a bit, but there has been no authoritative pronouncement embodying the resu!ts of the .Sa1'8llac research. This state of affairs is nobody's fault, but it is quite uni'orttmate. During the war period, as you know, Dr. Gardner lost, through death, three of hil chief a.ssis~ts and could find no replacements for them. His efforts to carry on with all the added responsibillties due to these deaths, I think, were largelY' responsibJ.e for his Olm death. In the meantime, there has been quite a stirring up of activity on the part of State Industrial Commissions and similar bodies in the United States and Canada., nth the result that there has been threatened legislative actions or procedu~es based upon assumptions as to "the effects of asbestos which mayor may not 'Qe correct. All concerned are looking to Saranac for a replY' to their questions and it would be an immense help to both industry and constituted authorities 1 they could believe tba.t some of the fru.its of Dr. Gardner's activities will soon be available. I will write you again as soon as I return from Sara.nac which will be about July 11th. With best regards, I am, Sincerely yours, A. J. Lanza, M. D. __ .... _ ~:~- __" _" ._...:..l._._~ .. - ... - ...._ ..... __..__ ._ ... METROPOLITAN LIFEINSuRANCE COMPANY ONE MADISON AV1!:ln1I;NzwYORlt lO.N.Y. ANTHONY J. LANZA.M.D. AssoCIA2:1l: MlmICAL DmZCTOR B::IlALT:K AlfD W'ZUAlUI: Dr. Kenneth M. Lynch Dean, Medical College State of South Carolina Charleston, 16, South Carolina July- 14,1947 ..- .(,"~ ~I.,. _,.,~ ' - .- 'I=-' .......'.."... . \ ... . : -.;~" .to 7" ,- 7nr ,,, '~~ I Dear Dr'. Lynch: With further' reference to ~ letter of last week, I have just returned from a trip to Saranac where I _ discussed your letter of June 30th with Dr. Vorwald. t think we are all agreed thet it is desirable that as much of Dr. Gardner's material as is workable be presented. at an early date. It would be best if you could give _us such excerpts .of material as can be presented in one article dealing with asbestos. Please let me know' if this idea meets with your approval. With best regards, I am Sincerely yours, A. ~. Lanza, M. D. Associa~e Medical Director .. Ju1723, 1947. Dr. A. J. Lanza, Assoclate' Medical Dlrector, Metro~olltan Lite Insuranoe Companr, New York, la, N. Y. Dear Doctor Lanza: I. all lending herewith Gardner's manuscr1pts 8S I have- arranged. Joined and t1tled them ~ a proposed lingle publloatlon. !h.~ ezper1menta~ repor't. 18 len as 1't was, exoep~ tor the head1ng. Pleaa.. paas Judgmen~ on the t1tle: and tootnote. - Hl. aonograph outline othuman ~sbe8tosls contalns 11ttle' 1~ any signltloant material. No one else can vrlt. wha~ h~ intended without lt becoming the wrlter I a' lnstead o~ Gardner I a. On" the other hand, the outllne on experimental asbeltosia 1s more than that. It; 11 real17 a summa17 ot Gardner' a oble1"l'a~10na and la nluable and publ1shable as 1t stands. I haT~ pu~ a' heading on that part, deleted seotlon 1, on IXethoda', aDd renumbered the other sect10ns. tlon, but r !he whole makes somewhat ot belleve that 10U can induce s bDlkT publ1cathe Journa~ ot Industr1al H1Blene to tale 1t 1n this torm. Ir not, let's split; lt 1nto two. ~ am send1ng the detached Part I ot' the out~ 11n.. a15e, ln orde~ thS1: 10U maT I.e what I mean ~ Pleal.. oon8ul~ w1th IU~ others at Saranac aa 10u should and with the Absestol people, 1;( that ls in order. 'eel, tree to reject aJl7 1dea ot mine 1d11ch .-." does not seem best and cr1ticize treelT. With best perional regards, I am Slnoere17 foura, ./ . IKL:kbp. fenneth H.: Lrnoh, H. D. ~L1.P ... ':i- .~ Dr. Lanza, Page 2 - Jul.T 23, 1947. p. s. I am reta1ning tor the present the other mat- erial. sent me. Can someone at Saranac redd117 s111'p17 the reterenoea In. the manusor1pt? I am a bit short on t1me.. Should Cummings be- 1n this? ( tHL. ( _._.- ..... ~C<OP;7!: ,. '" t. (From Dr. LeroY' U. Gardner IS OUTLINE SUMMARy OF ASBESTOSIS) 9. Oomplications A. Susceptibility to Intection. i. Tuberoulous. Asbesto s behaves like mo st other minersls in this respect not like quartz, whioh specitioally increases native suscept1bility to the tuberole bacillus. This intect10n may spread tor a time, but then heals. The resultant tibrosis accentuates that oaused by the mineral tiber. 1i. Non-tuberoulous. Ot no greater frequency than animals inhaling dusts ot other kinds. Occasional epidemics ot pneumonia occur in our dust rooms, but these are due to methods ot housing rather than to dust; they also occur in unexposed animals. ill. Oancer of Langs. No experiments were partioularly designed to elucidate this polnt, but oertaln evidence suggests that asbestosis may aotually tavor development ot tumors in suscept1ble species. a. In guinea pigs, rabbits, rats, cats and dogs, lung tumors are rare. b. When these species were subjected to 2 to 3 years inhalation of asbestos dust, the inoidenoe ot lung tumor l. was not increased. o. Some strains at white mice to develop tumors without apparent cause. d. Such a strain ot wh1te mice was unintent10nally nsed in three inhalat10n experiments with asbestos. ,. e. Ot 11 m1ce inhaling lang t1bre sebes. tos tor 15 to 24 months, 8 develo~ed malignant tamors in the1r lungs, and 6 at them had tumors in other organs. Th~ 1ncidenoe rate, 81.8% 1s execsssive. ., ..':/.. . \ ..~ . .,. ( f I ,. ., . t; ( (, (2) t. Ot 22 mice inhaling short fiber asbestos tor not longer than 12 months, only 3 developed lung tumors. Rate 13.6%. g. As controls~ we have only the experience with mice in other dust exoer1ments. For short ~er1odsl there werf 51 mice exposed. to 4 other k1nds ot dust tor 10 to 12 months. Inc1dence ot lung tumor 1.9%. For long ~eriods, there were 143 mice exposed to 4 d1tterent kinds ot.dust, includ1ng pure quartz, 23 to 31 month~ For all this trouo .ot mice the average incidence- ot iungtumor was 18.8% the highest ra~e (25~) was in a subgroup exposed to f11nt dust. Thus the 1ncidence ot lung oancer 1n the long t1ber asbestos mice was over' 16 times the average tor mice inha11ng other dusts tor comparable periods, and over 3 times the maximum tor anT other group. M1ce exposed to the prao~'.!3~1:1.:1_. 1ner.~_ltl!Q_t..~_O~u a~:t;u.t.o.. showed tewer lung tumors, artnough. 7 t1mes more than Sse 1n. short exposures to other dusts. These observations are suggestive but not conclusive evidence ot a Ganoer stimulating act10n by asbestos dust. They are open to several criticisms. The strain ot mice was not the 'same in the asbestos experiment as in many ot the others c1 ted; apparentlT the tormer wwre unusually suscept1ble . Not enough an1mals survived in the dust tor longer than the 15 months apparently necessary to produce many tumors. There were no unexposed controls or the same strain and age and no sim11ar controls exposed to other dusts. It 1s honed that this e~er1ment can be repeated under properly controlled condit1ons to-determine whether asbestQ.1s actually ravors oanoer. ot the lung. . .. THE SARANAC lABORATORY OP THI EDWARD a.. TRUDEAU FOUNDATION .. ......... ~ ~ DI_1t SARANAC LAKE. N.Y. August Kenneth t-i. Lynch, M.D., Dean Medical College of state of South Carolina Charleston, South Carolina ..' "' ~ .....' ~..-'...~. .' / ", ~,' " .. . "': '-. 1 'C ..~_ ~~.". ......,.....~,. \~ ~ \--" \ .~'"}, I~' l~~'~ ~ ~~i~.; ~ .~';.-to, '. " .t.:' ... , .... " ,. .. " / ~... .f. ,,"--. .: . .... ,",,, .. "....!.~ !: . :1(:,-/' Dear Doctor Lynch~ As you perhaps know, I have 'been released to inactive duty after f1ve years and s1x months wi th the Navy. During the past (. two years of ~at duty I served as Director of the Medical' ~ciences D1vision of the Office of Naval Research. In tha~ qapacity my oft1ce enjoyed some correspondence .with you. Now, I have returned to Saranac Lake as Director of Research ot the Trudeau Foundation and Director ot The Saranac Laboratory in an attempt to discharge many of Dr. Gardner's obligations and co~tments and to accomplish much' of what he planned and envisioned. That task is indeed a tremendous one, yet my prewar years of association with him afford at least some background for the solution of the problems and 1ssues confronting the Laboratory at this time. One of th~ problems relates to the collation of c11nical and experimental stud1es of asbestosis accomplished by The Saranac Laboratory. In reviewing these studies and related correspondence, I learn of your kind efforts in editing Dr. Gar1ner's manuscripts and recorded writings for purposes of a report and publication. This matter has been discussed with' our mutual friend Dr. Lanza, who has kept the Laboratory infor.med by copies of corresponde~ce pertinent to su~~ publication. In consequence, a co;y of your letter of June 30 to Dr. Lanza and his reply thereto have been forwarded to me. I recognize your concern and appreciate the difficulty in presenting adequately the interpretations and views Which ,Dr . Gardner recorded before his death. The manuscript which he was preparing constitutes a significant contribution. Its publication alarms me, how~ver, lest'other ev.idence accumulated in the past several months might have caused Dr. Gardner to revise sane of the statements which he recorded at that time. In his interests and also because of the Laboratory, which must continue as a lasting memory in his honor,. I know you will agree with my alarm. I am surethat Dr. Lanza would concur. Therefore, Dr. Lynch. I would appreciate your comments and views so that our action concerning the host of studies, reports and publications which we contemplate might be prepared accordingly. . . '.. . .. Page 2 Kenneth ~. Lynch, M.D. August 1, 1947 We at the Laboratory would welcome you at any time should you find the opportunity to visit us. Sincerely yours, AJ":LB cC: Dr. An thony J. Lanza A;rthur J. Vorwald,. M.D. Director of Research '!he Edward L. Trudeau Foundation c ,. - .. d" ,& . ';-" , ~IETROPOLIT.A.&.~ LIFE INsUit~~cE COMP.ANY FREDERICK H. ECltER. ~oIt1w8OGrrJ lEROY A.l.INCOLN.~t ONE MADISON AVENVE. NEWORJC ..J.O; , ~ ' N . Y , i '. A..VTHONY J. LANz..... M.D .Assocu.:rz MimlCA.l. DDtII:C'1'OIl BZA,:rB ABD WZUAJUll Dr. Kenneth M. Lynch Dean, Medical College ot the State of South Carolina Charleston. 16, South Carolina .I. .~ x -X August 4, 1947 ... 'y6l 9 9nV . I ...-. .. ~'...,,\,-,c .'~ ......!..."...:,, .. ..". Dear Dr. Lynch: \ I am in receipt todaT ot a copy ot the letter Dr. Vorwald wrote 70U on August lat. I am not too clear a.bout the concern that Dr. Vorwald expressed. However, I note that a.t the end 0. his letter,. he hopes that 7oUmigh1; be- able to pay him. a visit. I am going up to Saranac tqSelt on August 16th. Would 70U consider making a trip to Sa.ranac at &nT time soon, poSSib17 we could meet there on. the 15th. Iou can tJ.:T trOllL lew Iork to Sa.rana.c in about an hour and a haU, wbich certainl,. takes the curse ott that part ot the trip. If y-ou could tind it possible- to come, we would be glad to take care ot all 70ur expenses and make reservations tor you. ; Please do nqt think that I am trying to urge y-ou to do anything tor wbich you have no inclination and it 70U reel that 70U do not ba.Te the time to make such a trip, or th&.t it is unnecessary, do not hesitate to saT so. I have to go to Washington on Thursday- so will telepaone y-our ottice Wednesday- afternoon to get y-our reaction to this letter. With best regards, I am, Sincere17 Tours, ,. ~'<",I oJ -e ~ !. J. Lanza, M. D. Associate Medical Director "" .-' , :~' .~ ... : Charleston, S. C., .4-ug. 7, 1947. TELEGRAl-I - straight me,ssage. Dr. A. J. Lanza, Metropolitan Lite Ins. Co., New York 10, N. Y. (1 Madison Avenue) ACCOUNT SCHEDULE IUPORTANT MATTERS UNABLE TO LEAVE AT TI1-tE BEQ,OESTED. FOLLOl1S. HERE LETTER (signed) I. lIt. Lynoh. KML:kbp. 11:55 A. lof. August 7, 1~47 Dr. A. J. Lanza, Associate Medical Direotor, Iofetrol)olltan Lite Ins. CompanT. New York 10, N. Y. Dear Doctor Lanza: c Following 1OU~ telephone call Wednesda7 morning~ I recelved 10ur letter.~t August 1 and I assume that 10u also received a letter trom me which was- then mailed. Because ot very pressing business here dur1ng that" time, I do not teel thRt I can make the trip to Saranac on or- about August 15. It there should remain a reason tor a conference the~e, 1t is poss1ble that I mi~~ make it somet1me in September, o~I might at least get to New York City tor a conterence there, if' that maT be desirable. Like 70U, r am not clear' as to the reasons fo~ the concern exprc~aed by Dr. Vorwald. However, t~m the copy at.m,r letter to him which I sent to you, you mar see that I think that the course to be followed (..... should be deo1ded by those on the ground. W1thout" any knowled~e or what 1a 1n Dr. VO~7ald's m1nd, I pt1l1 believe GardnerJs material 1s publishable AS it stands and tllat T)e~hnps revision b1 an70ne else m1ght not truly. represent him. On the other hAnd, 1:( Dr. Vorwald 1s to carry on the vork, 1t should. be dec1ded wbether'Dr. Gardner's ettorts mar be merged, w1th tull cred1t to h1m. r. . . o~er' these suggest10ns out or a . ooapera- til'e 1nterest, and I teel that" the deo1A10ns should be made by you and him and your colleagues w1t~out regard to sny" othex- cr)nl:i1derat10n ot my part1cipnt1on than that. Ino1dentally, r wish to otter Mr oongratula- t10ns and beRt w1sheR on your new conneot1ons whioh I have seen announced. S1ncerel1 ,-ours, Kenneth M. Lvnah. M. D.. THE SARANAC LABORATORY OF THE EDWARD L. TRUDEAU FOUNDAnON SARANAC LAK&. N.Y. August 8, 1947 Kenneth M. Lynch, M.D.. , Dean Medical College of the State of Soutn Carolina Charleston 16, S.C. Dear Doctor Lynch: I appreciate the expression ot your opinion as recorded in your letter ot August 4 apropos the work accomplished by Dorr. aGsbaerdsntoersidsu. ring his many years of research in the interest Al~ ot us recognize the high. degree ot relative urgency regarding the correlation ot our exper1.m.ental and clinical studies tor the purpose of a. report for the sponsoring industries and for publication. Every effort will be made toward an early accomplishment in that regard. I will appreciate your continued counsel and advice concerning it, so that in tina1 analysis ~e contr1bution 11'111 be a creditable and lasting record in the memor;r ot Dr. Gardner. c. Your letter ot July 30 and the manuscript which you enclosed have been forwarded to me by Dr. Lanza. He will be in Saranac Lake on Satur~YI August 16, and I will discuss the matter with him at that time. Please know, Dr. Lynch,. that the Laboratory would be honored should you collaborate in the tinal publication. T.b1s point will certainly be considered at the time ot discussion wi ~ Dr. Lanza. With sincere good wishes,. Cordially yours, ,. AJV:LB CC: Anthony J. IAnza, M.D. ~~~e-- Arthur J. Vorwald, M.D. Director ot Research The Edward L. Trudeau Foundation ,..FE~-13-95HoN17:18 . J F HUMPHREYSATTY FAX NO. 3043434186 P.05 " ~---r~vC 1. kIBS,TRC.Al:C1( ' ...c.~ -?-E:.".!i-e- l 2. ...:' -~--., .. _-' ... " --.:~' I. c.;. 6. S!,ec:tes SU5cept.ib:i.1:i:ty 5 c:: -' 8 Rate of. T:tssue P..e2.ction to Asbestos ~ibers 6 9. /o..sbestosis Boci.:!.ea 7 7 8 J2. Dusting Haterinl. 8 1.3. Dust ComPosition 8 14. Dust Concentration B l5. Reaction in .A.ni.tna1s 9 9 1.6. 1.7. Rate ar.d Type of Reaetion 9 :LB. ?ro&ression 19. Infection Coincident ~th Dus~ ~~ation 1.0 20. Inf'ecti.on after Dust. Inhal.a.t1.on II 21.. Asbentosis Bodies 12 12 22. rlabbits 12 23. 2.3 2h. .. FE8~ 13-95 MON' 17':18' J 'F HUMPHREYS ATTY FAX NO. 3043434186 P.06' , L , 20. Dust"ing l{atariaJ. 27-.., Dust ComposiLion 23. Dust Concp.ntratio~ 29 .. Size-frequency- or Dust. 30. Reaction ~n Animals 31_ Guinea Pigs )2 ~te and 'l'y-pe or Reaction 33. Procression 3h. Asbes"tosis Bodies 35. Rats 36. Rate and Type of Reaction 37. Ca.~s 38. Rate and Type of P..eaction 39. X-r~ Chanriss uO. Asbestosis Bodies hl. Rabbits u2. Rate and Type ot ReAction h3. Asbestosis Bodies, 1.16. Dusting Ua.terial , i!7. Dust Composition U.S .. Dust Concentration II 119. Size-f'requ.enC"'j" of Dust . : . _ - - -.... lu ~-'--IS 15 IS 15 15 1.5 17 l7 1.8 16 19 19 19 20 20 2(; 20 21 21 21 22 22 23 _ J F HUMPHREYS ATTY FAX NO. 3043434188' P. 07 __- - - - - - - -____. . . . . . . . .. '.l.'.'" . . . . . . . . . . .'"I.I1"1II. . . . . .. ~... (; ;: J' -~: '.i' 3 ~'"' -- so. 51. -". S2. 53. Sh. SSe 56. S7. ~g" 59. 60. 6~_ 62. 63 .. 64 .. 65. 66. 67 .. 65. 69. 70. 7l. 72. 73. Frogres~ion ~h Node Invol~e~ent Asbestosis Bodies Rat.s and llice Dust. Com:position Dust Concentration Size-frequency or Dust. Reaction in Animals Guinea Pigs Rate and Type 0 f Reaction Progression Iqmph Node Involvement. Asoostosis Bodies cats Rate and Type of Reaction X-ray C'ha,r...ges Rats Rate and Type of Rc;;a.et1on ._: .....-.-._-..... - -:a..sze -_.- .2.3 ..__ .. " L./ 23 2il 214 2h 25 26 26 26 26 27 27 ?7 27 28 29 29 30 31 J' r HUMPH~EYS ATTY FAX NO. 3043434186 P. 08 75 .. 70 ~ ::'l~ratr::'(;:-:2al ~l~~"::1;;~..-- a,":' ::-.;:.::-;~r-:'~ .t.. .~;.;. ._~ ."r r- -. - . . /' :,;:,;~v!I... ...:. :.: :t;~-;-:';:'It-::: ::::.::?~!~:r~~~~;' .:~~'.~ - , I \ ~ , ..... ~ Exp~j:':!i~=-':~s 7 ,"" *'" 80. 31 :.:' :.,,.. ::ntr;:l.peritone::;i 90. Suscept5.b.ility t.o 'l'llbe:-cul:ms I;li';')ction R 52 Ii : . - _ " _ _11 _".1.... __ _ .. - ....."';" )2 32 -"-~') J] .3L 35 .35 35 36 37 37 38 ]a 39 tio iL3 - 7l " ... ( ~. FEB-13-95 MONT7: 19 \ . J'F HUMPHREYS ATTY FAX NO. 3043434186 , _..... _ _ _ _ _w ..... ~._ _ _ _ .. _ _ ............. _ _ - - . -.. .. P.09 ,- - - - A.S3TRACT : I ;- "'vL"\.'--~': Asbestosis 1s Q pu~~onary dise e caused the inhalation of asbestos dust. In' anilr.a.ls It'is-characteriz' by eribronch.1ol..a.T'" ~bro5i~::-..sich-~ ! V' (/>~eems to b~Yh.fe res\ll'i I~J{ I~mhclc"h4ahn4ic"a" - thaI' th.an chemical, irritation of " )....,~.\ ./ I \. /I .' c the tissue b1,asbestos fibers. v....c:-t .. reaction; short fibers ~e rela ve the long ribera produce a typical c~ incrt~ The !llaD1entedstruct1:lI"6 of. the istic t1ssue response can produc i m -:: I V. u, I.e. ""'~ f).y.AAI mechanism of tationj, tJt..c.ltaracter- o)J ,./ by non-s1liceous ~tl as Sili~uV - " estos ~t ~paren~ ~ " ,\J not al~er . " b......~ ~ ,cvIi ~~ '\ ' : ~~~ ~ ntal tuberculosl.S in gt.lL~e~ plgS. The C f\ 1\ . e \ .prevent". further Ggre8:sion of the; e U> the reaction ~en n against. the .tissu expo tissu concomitant or aabestoslS and forms os tiber into the lung" ~ betlt!V ~ , " - ', 'S;- by the fiber and thus .. limit pro- ceaseS.. Alum:i.mnn does not exert a fibers as :it does ag FEB-13-95 MoN 17:19 J F HUMPHREYS ATTY FAX NO, 3043434186 P,lO . 2. --Introduct:icn ... ' ........-.... .....- ..--.:- tiOjl a!: asbestos dust. '!h~ na'i'.e ~b3Stos, J.:j;tera1~y" flunbu.~n.aOle~ n is i~O'~ t~t. of &. p.::..rtic-",loJ' J::i.:'lClla::.. b'..~t is a- t.erm applied to 8 mrnber ot c.ii.r~1:(;\nt. mnsrals .mose ci-:arac'l;.e"C'istic ..feature is a structure composed o.f lor'6~ paralle~, nroci.bl.e .f'"iber3. T'r.is structure i.s uniqU9 bacau.s9 the f5..oers .at'e capable of rSp<3ated ~!)ngltudina1. S11bdj:vj.sicm t.o 1.ll'.its of mo~ecular proporticnc. In le!'..gth the .fio'3L's -ora'!':!" from a. e.w micror.a to sU: or mo~e i"cr.es. SO!11S varieties are stiffer t.h~.n others b-.l.t many are suf.ficienU-.- flexible i::..) be :l~u.'"l into :-ra..T"l1. and woven en modified textila roachinery .3 - Asbes'tos l.iineral.s The asbestos n::in~a1.s are silicates of variabl.e composition and be~ong to the serpent.ine and th'3 amphibole groups. Listed bslO1f' are the more coumon va..r:iet:ie3. A.Tl~h()phyUit e (t4r, F'e) silicate Au!Cl3:i.te (llg, Fe: Al.) ~:ilicate Amphibo).e (Ca, 1':g.f Fe, Al, Na, K) si.]~ce.te 'I'remo~5_t6 (Ca. ~) silicate Actir..olite (C"l., rt.g, Fe) silica-to Crocid<J~ite (Na, Fe) silicte + Fe silicuv6 $erper~ti.tla GrouE. l.'.g silicate (hydroU3; -2- FEB-13-95 HON"i 7: 20 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 11 posi:tj.on t,o .... ch):"":3oti~,(;; ,;:,,:;.:.t -r:!.1i.ch e..~ts in Ir..'af:si-.re .[orm .:u;:;. i9 JI"..g.t;i.!i=E2....0~ __ .____ _ microscopic fibers r.l1.~!:O'lt the JX'...rallel ol~_ent4t.i.on !:hI>.ra.oi;.er:istic o chrysc- tile. The massive blv.e bleek serpentir:e, ~hich is :)!!I.ooth ;:;.nd soapy to 'the tOllch, is t.raversed by reir.s of fibl'OU!i Cl1':;:S<:>t.i1_8 7a.ryj..ng in mdth :from a barGly pe=-ceptible :t:i.."'1.e to six OJ,- !l1O;~(~ inches _ 'Ina fibera .."Un across t11G vein and not 'l.engtlnri.se 1'1.ith -chI:! formation. At.tention is direct.~c~ to the mineral. bruc:tte, }.(gO .fl~, .miell. is often .found :in the some .formati.ons with serpentine end. chry9ot.il.a and may be' tibrcus :in structure. It has no ootIlI!1ercial. value at. presa.'lt. because its fibers are not au:f.f'iciently flexible to be "GSed in textiles b"lrt. they are capable of' repeai:.ed lOr.gi-tudi.n.aJ. subdivi.sion. Unli.ke other asbestiform. rd.nsrals, brucite i.s not a. silicate and or "this ree.san it. has been a. val:nabl.e tool in. an experimental evaluation of the action of fibrous Piner-ala upon 1ung tissue. For many years $tu.di~3 have btm cC'-rri.ed on -by the Saranac Laborat.ory in an ilwestigation of the cause, nature and deve1op:Det1t of asbestosi.s. The }l1'"esent re- port is devoted to Ex:pGr:iment:a.1 As~stosis.. In:it. are described the a.n:i.;:na.1 ex- periInents wit.h ViiL-1.0US a.Tld i.ssued 1..ater~ ...:ill ," Idnds oi a.abe::;tos ba ccncern:::c. "IT"i.t~. du.st. dl.m-'~! J..:r..oc,her I'E.port, to be prspar<:id . ... .. AG03S1:.09:1..8 &rid. 'hi.i.:i. CCI\"'i::>4' 'vl1.0 i;!!:c...:....."".:. aspects of workers -;'iilo hav~ been exposed to aabeDto8 dust. in an industrial environmemt. -3- ,.. ." ... :: - : fEB-13-95MON l7:20 J F HUMPHREYS ATTY fAX NO. 3043434186 P.12 istic t.i.ssue changes "VJhic!'l are simiLU"' to t.he le.3ic:as of r'!"lJ.lllC'.n au~stosis. Si~(;e the life-span 0::: the aA'peri.mental 2r.:L-na1 is re~e:;:':l.vely ::;,':crt; i:t is not posZiiblEI 'e ~ to i.nhal.ed particulate ClZld .fibrous materi21:r it. ::..::. r:.C!ce~sf:ry t.o accel~l'9.te tl1e react:ion by employing higher concentra!.ions of cLlOt. tt~1.1 ..oul~ crCi.'1a'!'i:!.y 1>3 encountered in indust.ry. ?nile ~ondi"bions of' eX?osuz's ere thus ci:U)?erent l ~he information yielded by ex:periments Tlit.h animals is i..'lV.a1.'I.'l.~.blfl in furnishing a better undor5tanru.ng of the reaction of the h~ (,rgnnie;:r. 'to ir.haled asbP..sto5 dust. 5. ~riment.a.l. lfetihods For i.uvestigat.:ing the bio1ogical l""<~a.ction of the a1qlori.ca!l.tal animal to th9 various asbestos m.i.nsrala, t-wo types ox tecbn.i.que have baon employed, naJl1e~v7 t~.e inhalat1.on method and the injection method. In inhalation ekperirJents, groups ot ani.inals - up to 100 or more guinea l,'dgs and SOQIlt.:imes small.er mllDbers 0:( rabbits, cats, dogs, rats or mice - are kept. f'or ei.ght. hO\~6 a day in a cubical. dust room, eight feet in dimension, in which a. clot...d of ~bestos dust is mainta.i.ned. At illtervaJ..a du.r:ing the exper:iJnent., a few aniliiaJ a \1"e S3.cr1..r.i.ced and t.be t.issue ex:em1ned to determine the nature and extent of tru, dust r~tion. Son-e ani mal s the dust, either dq or 6uspt3nded :Ln nui.d:- is int.roduced into the animal by t..'1e intravenous, intraperitoneal. or intratracheal procedure: .'3Te used to determ:ine -enether or not. a particul.ar dust has a potential capacity to produce tissue reac~ion. -u- . . F HUMPHREYS ATTY FEB-13-95. MON 17:.21 J FAX NO. 3043434186 P. 13 ._____ ____.._ _ _ _ _............:.._ _ _-...."_..,... ....m_ _.~>'t""'M __ _"""_ _ _ _ _ _ _ _ _ _ _ _" "_ _" _ "_ _ __ ~ Iong-ta..-.;:! irmala:tio!l. ~,,?er:!.rr.ent.s .fUrnish i.a:.'orm.a.tion 'U.1'on much great r'eJi.- ance is placec.i when e::3ti:r.at,ing t.he degree to ~ch a dust might ~e baz2rdoU6 ;:0 industrial- Trorkers. 'fit.ether or not atmospbenc c!ust., even t.ho~ potential.:Y . d~erous, can be inhaled, pass the nat.ural. de!'ense barriers and .each tne !.1Ul- ... _;, ...i.=':::---... .__ ......_~_ -. DJOna.ry- tissue in quant:ttie.s . sufi'icient. to ca.use ~e can. be det.e!'J:l.ired o~ i::Jy' :L...". la.l.ati.on procedures. Inject.ion e:qle:riments are usef\1l. bec2.\\se i.:n them cor.tGl.ct bet1l'een the dust particles and tissues is asSU1."ed Bild. t.he potentis.l. ce.pa.cit:-r o.f the allBt t.o prod\.\ce rea.ction 1!at1 be est.irnated accurs.tely'. ~ben deaJ.ir..g 'tTit:~ fi- brous mil".eral.s like asbest,os, the L"'ltratracharu. met-hcd is valu9b1e since 1.t per- mit.s observing the effect of the fibers on pulmonary tisS"J.8. 6. Species Susceptibilit.y t1n1ike !'ree s:1l.1ca.7 asbestos does not exert. its specific Gi'fect in a:u organs of' al.l. Spec:i.es of' an.iJDU (Tabla 1). Injection of fine quortz into various orga.~ , ...... or 'the gu:1nea pi.g, rabbit., ra. cat., dog, chicl<en and even tadpole m.il prOdUC3 '" eill.cotic nodules. HC/ilreVer7 similar injeC1;ions Or ~ong or short fiber asbestcs .1"'- ,...." . r. oth";' -~. . ~, ~ ~ haVli: resu1ted in a fibrous reaction in the lung and, to a lesser exte&t., in 'the pe w4 rl_bu -I.. .. t. ., .."........ta.i.n~......... \-" r-".. 7. Peculiar Ch.a;racterist.ics o~ Asbestos 10 "'"~~. ~ ~..",~v. - - ~..... ... ~ to .....CJeeA,,,T-.# hperi.ence has demonst.ra1;ed that. TlDst of the -particulate t:latter inhaled into the 1.ungs ot man and ani.roal is 10 mi.crans or ~s in maxill!DT!\ diamater.. :Larger -particles a-pparently are excluded by tih.e protect.ive mechanism of' 'the upper respiratory t.ract. In the Ca:le or ,fibrous materials, hmrever, th1.s restriction does nC,l't applJr and fibers 1.00 and even 200 microns in 1..ength have been o11D.d.1.11 the terminal air spaces of hnm.an l.t.mgs_ In smal.l laboratory .n:ima,l.<; exposed to asbestos d'USt tha maximum lengt.h 01' fiber .fo'W"Q in t.he lung rar'Qly excsOOs 60 microns_ Not every kind ot f'ibrolls material. :i.E! inhaled with equaX readine56; for example ~ FEB-13-95 MON 17:21 J F HUMPHREYS ATTY FAX NO, 3043434186 p, 14 .'. through the nose, pha.ryn:~, t:-acr'<:;;::.i. a,::id brar.chi and :';E:lc0!TI re2ch t.he t.3i-~nal bronchioles and al.ve.~li. :1.1IInedi.a.tely distal. to bronchioles linc:::d by r,i~i3~,ed epithelium. Their ,mIl essen- actua.l.l.y .function in respl.r~tion 'th~ough lat.aral e.l-reol:! givea off a!l Fouches of the lining epithelium, or t~e decrease in diameter :"If' t~\g tutx~, or perhaps t.ha comb1nat~on or a11 three ~actors is responsible for loc~~ retention of the inhaled !1her. On:l.y af'tcr asbestosis is -r.all est.ablishe6 are app'.:.eoic.bl~ numbers of !i- bars carried into the more peripheral sir syaces. 8. Rate of 'ri.ssue Reacti.on to Asb6StOS Fib61'S The rate of tissue reaction to asbestos is much. more rapi.l thsn to an active dust l:ike qu.art~. Evi.dencee 0 r tissue response a~ AS soon as f"j.bara have lo~ecl in su.ff1.cien:t conc&"1tration 1n spaciiic sreas _ In]:"a t.a recel.....l.ng asbeat08 f.1bers by intratracheal. injection this ~vide:1ce is visibl~ :!S early as t",o 1Ieeks ai'terinjection; for quari.z dust the la.'!.ent period might t:.e t""o ~~i:w or more. The behav2OT'of the tissue ~action to inhaled oust ~fter the t~tion oi exposure is not the same in 13il.icosi~ as in s.sbestosis - ~n 5ilicosi:!t, the ji'OUDg nodules become lJlrger; in asbestosis, young 5C'.B.!' tiss-u.s of that may have f'~~'"IDSd,c~n- tracts and becomes IOOl"'e G.P,IlS\3 but the area of invo1.ve!Ilent C:ecrea..ses in siz. If' _ mcposure to asbesto9 dust is t.e;:-minat.ed eJ.'t;.m" ~ bri.ef' ~riod, 'i:.h~ ~ecently-:i:nhaled FEB-13-95- MON 17 :22 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 15 .' fibers in the lung may causl;r the fibrous t.i~~e ros?Qnse to con-::.:5.U'I.i.s Eor Q. short tiJ;'lE, until the fibers have been coated. This prcgreDsion is of" only n slight degree and of little significance. 9. AsbGS1;.osis Bodies ,'" "",. -~. --....~ -.--'.----- The pacu1iar structure knalm as the asbestosis body" or cUrious bod,y' is a specifio concom:tant of asbestosis. The typical. bcdy :if; a gclden-Y'el101t~ baaded or haustrated rod v.hich ma;y be eithsr si;raigbt. or~. 01.'t.sn one or both ends moe 'bulbous like a dumb-bell. The bodies vary considerably in length, and di- mensions up 'to 250 microns have been recorded.. It is beli.tlVed that asbestosis bodies 8l"e due to a. deposi.t o protgin and :iron pigment upon the suri'ace o inh.al.ed fibers. In guinea pigs they .fOI'Q aft.er about 60 days or contact 1d..th the tissue... They are abundant 5.n man and the guinea pig (see Table 1) but are IIlUch l.arger in the .f'armer. probably because the larger- sized sir tubes admit. fibers of greater dimension. In cats, rabbits and mice there is an atypical coating ot a t8'ff ot t.he :fibera after 12lUch l.onger residence :in 'the lungs. In rata and dogs no bodies couJ.d be di.sc~ered. Al.though the evidence is .Ci..ber/ \ > f t \ 1ncompl.ete, ~t appears that the tormat.i..on of the asbedtosi.s bodiY prevents damage t.o the t1..tJsw3 by i;he ~ ~ \.~A..,Le~'t<(i<.rv)c:r. c~ .,.., ... '- ~ '..uS.~ ...~'~ Y; . .r-..,---- '"x. tnINHAIATI"O'""N~EXP"E..R-.-D-O-O:-.tl'ST / 0 FO'UI" compreheo.si.V'9 :1nhsl.a.t.:ion exper1.r.mlt5 have been conduct,ed a.t the Saran.a.c Laboratory -nth 'VariOU5 .forms ,0 asbestos duet.. In each of t.hese im'est.1.ga:t.i.oIl5 JDOre than 1.60 animals ';IIII9Z'O used and the ~ents were carri.ed on orperiods ranging f'rom 2 to more t.b.an S yee..n;. The .f'onr k!.nds of a.sbsstos dust emp~oye.d are ident.ll1.ed as Iliog' G J:l.oat.:), shorl fi~ > 100 par cent ball-milled, ami long-fiber aabest.os dUBt. J' F HUMPHJ<l:.Y!:) ATTY ~AX NQ 3043434186 P.16 asbeat.os dust was begun in 1928.. ~.oi..'na.l.s inhaled the dust for periods Up t.o nearly" three y-ee.rs and some gd.naa pigs llved .for about. ,four 1e2:s A.L~er 'their f'. --. ....; ...... __.-....,. ___ ' _ _ _.:o_ :first" exposure to dust. J,. pral:imiDary roport giving oOs6r'Vatior.s after 29 months at: exposure appeered in the Fe~rua.ry, ~931 issue of THE JOmN.AL OF num- stRIA!. HIGIENE.* At tha.t time observations covered a period of only 2-1./4 years and the conclusions as to t.he ul't:i":Jate af"'fects 01: inhal.ed asbestos duat were proV'isional. Results at: the completed st.udy snarr that, most. of the concl.us1.ons drmrn in the prel..1minary report m:lra substantiated.. 1'1. contp1.etc revie;v of this experiment f'o11~. 12. The dusting material. TI38 a co:mnercial variet.y or asbestos d\lSt. lalo1m as Kj.ng IS f'loats end,..as c0mp08ed o short. f'i.bers and particles of' ---- ~~~~~ variable size. Corporation of' America. ed tXora the l'het:Cord, Quebec pla.n:t o the Asbest.os 13. The dust. composit..ion (Table 2) reveal.a that. "the aulOtmt. of fibrous cbryso- ti1.e '1'fSS onJ..y llc. per cent, a rat.her low va1ua. li.owever, there was su"- .fic:i.ent i"ibrous ma:t.er1.a1 t.o produce a cha.racteri.st.ic fibt-osis. J..h. The dust. cODcentrat.:ion at :first. was qui.te low and :for jJnpinger samp1.es taken soon af't.er the expo..riment. was 6UUOt.ed, t.he average light field count~ by the standard technique ~as only 6.0 mi~on particles per cubic root o~ air. An appreciAh1.e number o~ ,large pa.rt.ic1es <or .:ibers) a1.so '\'fere present, as ~TUDIES ON EXPERIMENTAL Plmm.IDCONIC5lS. VI. Inhalation of Asbestos Dust., Gardner, L.U., and Curmnings, D.E. J. Ind. Hy-g., 1J: '6~1, 97-llh, 1931. FEB-13-95 MON 17:23 J F HUMPHREYS ATTY FAX NO. 3043434186 P.17 After the inhalation eA:p9Timant had ben under ~_y for ahct;t. -:-;<'0 years, ..he speed of the rotating paddle in the dustin{; r..achine Tfas ii~c:,eG.sGci mld for the =-e!ilain- iDg 9 or 10 months of tha ex:perilfl..ant consj_derabl;r :1tore duot 1tas dis~9rsed into change were 53.7 million :for -cha U8"'..t<W. light.-field ll1C'"thc.d, and 1.6 ll'.illiorl for particles larger than 10 microns. 15'. Reaction in AniIr...al.c; to Inhal.ed "K:ing fS FloCl.tsl: II.SDCSt.o:'3 Dusl;.. Results or the i.nvestigation~ brie.f1y su.-rm:l2ri:bEd i...1'l Table 3, 'on01'l that 1nhal.a.- tion o King's :f1oat3 asbestos dust produced ~ typical. peribronchiolor fibrosis in ~ea pigs but not. in rabbits or rats. 16. ~ea Pigs. Seven groups or gu:1.nea. pigs -were used. IiI tlu"ee groups "the et'.fect o a. continuous a...?td o.f Sll 1ntaTTup"ted dust expoSlll"e was a"tudied; in ttrnot.her groups the Tal.a:tionsh.1p bet'..-ee>l in.f."ect.ion and dust exposure lm.S investigated. The rsmai.ning t.wo groups were i.niect.ion controls. 17. Rate and Type of' React.ion.. Ou:1.nea p:igs i.nha.ling t.h.iB dust. f'or peri.ods up to 33 mont.hs dt:1V'e10ped a characteristic fibrosis occorring in conical. patchea about. the respira.tory bronch:ioles. During rd~ t.his exposure the periphe:ra:l alveoli 1II'3re not 1i.nro~ved. 'I'he -particulat.e elecen~~ "in the dust ""I'n:3r9 transported 'to the l;ymphatic syste.'n ~ere t.hay caused no 9igni- f'ica.nt. reaction; t.he fibrous e1.ements remained rixed at. the sit.e of' original loca1.i.zation and were seldom detected in t.he ly-mpho:i..d t:issU9. Plelh-isy and fi- brosis in the septa "Were observed only when 1n:f'ec'/iion cOlilplica"tsd the process. After exposure of approx::i.ma:teIi a. year ~ a srea.ll. azr.ount of cclluJ.ar reaction _ had been produced abou.t n--my respirat.ory bronchioles. As more d1l.9t wag 1.nha1.ed, it continued to acc:.lllU_late in the same locatioll and l.s:::-e::- st.a.gss of -t.he aisease FEB-13~95 MON 17:23 J F HUMPHREYS ATTY FAX NO. 3043434186 P.18 ilp;arent~y~ J,jhe inhaled i.i~e:;s ~""e!'e caught. in tna p:'(!k't-li:<~ UV:9oli .t.h.ll.~ arc gi.Y<m off from the J...::::teral nalls 0:' t~e :r:espira~or~r ~ronchiolas. Th~e tlla:;, ltore pl1<lgOcyt.ized and lll.'lIny o:f t.hem "l1er3 carr:ied into t,~1.~ "..;J.l by- l'iLi.gratory cell.s, :.:Oiionuclear leucoc,iteis- attractCKi ;;:0 the &rea causecl an c#jpr~i"a.bi~-=traCf..:Ol:'inE;- ..,1 the brcnchial wall. After 1.6 I!!.onth..~ B. delicate fibrosis made ito aJ.1J:-a~ar..ce. The process evolved GO gradu.al.l.y t,h,..'\t ::Jitotic division of i'!.brobl.u;ts ,;ould rarel.y be discovered} ne-ra.rthelGOs, the number of fine intcsrc3l1.cl.ar coll<:!genc;.u:; fibers (fibrosis) st.eadi.1y increased. i~s tbis fibrosi.s contracted." i~. partiall.y closed the alveoli, 3l'ld 'With this atel.ectaai.8 the ll.11ing epitheJj.um assumed its eznoryonic C1lboi.d~ .form. The result lm.S the adanoma.-J.j..ke appearencE! t.hat nillis described in guinea pigs inhaling s~11con carbide. The longer ~osurvs resulted only in more thicke~ ot the ~ or the a::1.r spaces, "L:I.rgely due to sn 1.n- crea:se i.1"l tho amount of fibrosis. Tne fibrous t.issue always remained celln1ar and never showed the hyal1nizat~on characteristic o s~licosis. ~8 Progression. The reaction prexiuoed in exposed gu:i.neapigs did :Liot pro- gress S;igtti.fi.cantl;y dur:i.Dg a sttbsequent peri.od. o~. 31 , i -::aont.hs "'l"I"hen the smmaJs lived in a normaJ. atmosphere. Between 8 and II mont.hs aft.er exposure c-eased, the cellu1.a.r reaction had been oompl.etely replaced by th:Ln stranC..s ot: .fibro'\l!l t.i.asue. Obser'1"ed still ~oDger, the scar "tissue decreased in o.:rnow:tt bt1.t. in the last animal sacrificed, 37 months after discontioniog dust exposure, SODle f'ibros1.s was stUl. nsib-le .... 19. Irlfection coi.m::ident nth 1)ust..::lnhalation. Of' the group of 40 guinea pi.gl3 i:n:fect,ed l\'ith att.er~ ua.t.t:Xl v1,A1;>,.,rcl-", 'ba.c.i.ll:'- (R~ ",t:.r-~i.n:' 3l diead" or "ll""ere oa.cr:1.ficed before tm> yearn (If cust. ~posare and ware report~d in tho paper by Gardner ,",ToC CUllIlU.ings mentioned FEB-13-95 MON 17:24 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 19 1 61l1ts -r.ere as i'011mrs: 10 reyealed serna evidence or spread 01" tbe tuberculous process; :L."l 6 of' these it \'rcU'I conIined to tha lungs and in t,he other h the aOOo:l"inal viscera also ..~. re i:;:IVolved. USUE.ll..~ A slight local. extension of t.he tuberculous ir..fection-hoci oecmred b:;.t &ubSGquei:rt. heali<ng h.ed-:res\E:tled"'in-~"" crosis of both t.h~ pu.l..n::mary l.sions and the secondary l.esj.ons in other organs. The hes.l.Qd pulmonary lesions sho?fP,d more fibrosis than is characteristic 01" either ~u.bercuJ.osis or o.s~st.osi:; alone. The 9 anima's. 1ihich were still ali.ve after t'WO years of duot exposure T:ere sacrl..1.ced at. int.erv-aJ..a during t.he .ro2.1ow.i.ng yearA In h of them the pr1llla.ry- foci of :infect.ion hB.d healed w.i..th fibrosj.5 and even cal.oi.fication and there lf3.S no evidence of progression. In the other S iohe tuberculous foci. ah0170d evidence o.r haring previOU8~ spread locally: in h of them it had healed, by the tiJne of aut.opsy, nth e:xces51~ fibrosis; in the other animal t.here was a. generalized chronic t.uberc:u1ous pneumonia in one J.obe and isolAted primary tubarc1es5 "IIhich were still active bllt had not spread, in the other l.obes. Evidence o;f extension or the infection ~ .firat seen after 7 months o.f dust inhal..e.tioo; during the next 20 1Ilonths more thaD. hal.! of' t.he ani.mals sh01fed an actively spreading t.uberculosis and in 3 of.' t.hem small cavi.ties had daYel.oped. During t.he 1.ast. 8 mont.hs no arrima.13 exhibited any- evidence o active infect.ion a1..though in haJ..f' or t.h2m the healed f.ibrous scars 0.1' previ.ous extensions were 00- nous. Sixty per cant of the guinea p:4!s with spreading pulmonary tuberculosis showed tubercul.osis o.i the spleen and liver. 20. Infection Srl:mposed .Upt>n an Ilstabllshed Labeotosis. Twel.va guinea e pigs!J &1'ter inb.a:I..L.-,g aobestos dust i:or nearly 26 month3 JI ~re i.nOQ-t.e<1 wi.t.h t.ubercle bacilli snd then removed to norU13.l. air. 'I'he subpleur<U. t.uberc~es in the dusted animals ~ere -11- FEB-13-95 110N 17:24 J F HUMPHREYS ATTY FAX NO. 3043434186 P.20 found in the dept~~ of the l~~ about :oci o~ asbestosis. The ~esct~o~ ~o infaction shOYled only slight local ext,.en.,ion abo~"~ the origir.al sit01ll i.:l. t.he ~ungs one a.ni.ma.l. Casea~ioif"11aS fOlIna i.n ~jllbcrcl~:; 1-1/2 "'\'" months _t -=;:-.-._y ?ld b\.'-t by- '"-'-7-':'- 5-1/2 2l~ Asbestosis Bodies. Modera.te nu~bGrs c.f c.sbestosis l::"~-c.:I.GS occurred i:1. and more dist.1.nctly segmented in later IDor..~s. 22. Rabbitos. Rabbit.s EIl...'"Posed t 0 t~e aobestoa dust or p<'.rl':Ids 119 to 19 JJlOnt~ developed a. l..aw-grade i'oreign-body tY.!le of reaction but no i'1.brosis. Al.though their lungs contained partic~l.at.e clements of tl-ts dust, .fibers ~e DOt present, indica.ting that the upper rasp:irat.oT'Y IlIBch..~islll o.f. t.he rabb1:~ is adequate to excl.ude fibrous f'Ot"e1.gn bodiGs. 'I'r.c rabbIts, ai"t,er inhaling dust for 6 and 1.8 l11Onths, llved in normal. air .for :i!lDre that:. tuo year8. .\t autopsy ~ither an.1mal. showed tm:1" evi.dence o cell~ reac'Ii:ion or fibrosis :'-n 'the tenll:1.nal. bronchio1.es nor -were t.here .atJY" asnest.ovis bodies. 23. Rate. All the ..mite rats had acquiT"eel a.ll in.f'ec~iCJn~ result.ir.tg in the ApparentlY, DO much heCIV"".f lDllCUS obstructed their bror..chi that .er~.,. fe-eo fibers co1l1.d have ent.eroo their ~ungs. :in a re:tr of the rat,:j:> an occasional a..soe6tosis body ....as discovered but. there was no fibrosi5. -12- 11:25 . .FEB-13-95MON .... tt e .' .. t C , 1 '1 J F HUMPHREYS ATTY - .... ,,1 '... FAX NO. 3043434186 , P.21 ized \lUdEll' three headings. A.E.t::fect of the inhaled dust -:>n normaJ. an1 :re1 s. ~ t,.. Ths Kil"..g t S !"lcats _~ ...,----'1 ..-... ,----..:.- G.ust. ca.used a charac- teris"i:.ic peribronchiolar t'ibrosi.s in guinea. pigs but. not. in rabbits Or rs:ts. 'l"nG , fibrosis did ~"ot progress after t.he dust Di:pcsure 'P.SB discont.inued and the guinea pi{;s tra."'lsfer:r'ed t.o normal. air. B. Ei".f'ect o the i.nhsJ.ed dust. on tubercul.osis in guinaa pigs. ~ guinea pigs in- .feet-ad 'With , at.tetru.a.ted tubercl.e i.:ac:Uli and then placed in the dust room~ the resu~ts 'Were mc>TS variable t.han is ~ in an experimsnt 0:1' t.his type. A ~ ani.mal.s sho1lfed no Sign o~ Fogression; in roost. o~ the= there 'UaS evidenee of tem- poraI7 progression :nth subsequent healing; in one animal there was continuous progression to death. In contrast, 1ifhen guinea pigs, af'ter being infect.ed, are exposed to quartz inst.ead of asbestos dust, the infectious prOCEiSS continues to progress and eventU2.lly" causes the death of the animals. On t.he other hand, ex- posure or 1n1:ect.ed anir.lals to a harml.ess dtzst. l.fi.-e cal.ci.te or gypsum does not lead to anY progression of the in!'ection. Outnea p~s 1n.f'ected 'With attenuat.ed t-llberC1e bacilli ro~1.o;tiDg the ter:ni.nati.on or abO'n two ya8.rs t exp031~e to asbestos dust. did not. develop prognmsi.ve disease. The onl.:y' modificatd.on of the lll'ection ~ in its localization, s. re;r baci.lli. being ret.a..incd in the fibrous termtnaJ.. bronchiol.es and .fortling , tubercles there in addition to the usual. .foci beneath t.he pleura. In vimr of' 'this variJlbill~y~ the unusu.aJ. natura of the rl:lBpOIlBe and the hi.gh propoTt.:ion of de.at.h..q from int~~cu:rrent pnelloonia. {t is felt that de.f':i.nite concl'U- a.,.ot',.f.C>hI-::' :::d.ons ~..s to t-he influ.ence of Uli 5" ~st on the course 01" t.tlooT<.:ulous infection are not justified. /i' \ .... <. "'..:; ' : , " FEB-13-95 MONt7:25 J F HUMPHREYS ATTY FAX NO. 3043434186 P.22 ,ck~' ~.~ c. . of ~~~~~~~~~~~~~~~~~~~~i~n~~/ ~led~~a~~-~-~. J. ection co~c3~i t'SUg~ .-~ dust t.o produ .fi.brous _ . . !~ *?:y{t\AIaA~~ - ( lesion'mU)' contact the :;:.rea f du..<ft react. on. di:. <, .. ... -.......~- / - I.rUftt:ie px~~en~ wi.Jh~~~~J'et<~~at~8 ~~ n ... .. Since hazardous dusts ~ika quartz are mos~ e~ecti~e in producing x~brosis ..men the particles .u-e 3 microns .and lass in sue, an :iDhalat1.on ex:per.in:ant was carried on to determine ..mcther this condi.t.i.on ~,s t...'1'"tle al.80 or 2.Sbestos dust. It was thonght that by using a short-fiber &sbes'~os dust. consisting almost. entirely o~ f'ibers and particl..es smalJ.cr than 3 mcrons an accelerat.ed tissue response might be initu:ted and an advanced reaction obt.a1.ned ill a ahort time. The prerlous i.nhal.at1.on exper:i1:lent. 1dt..h King IS .n.oa.ts asbestos, 1I'hich cont.a1ned ibers i'r0l:l 1 mm.. to 1 micron or less :in leng'th as '1:9ll as a grea:t deal. oE part:1culat.e matter and. '1Ifbi.ch produced a t;ypiC2l peribronchiolar .fibrosis in exposed gu:i.nea. pigs, servOO. as a bClS:1.S or compar:ison. 26. 'l'hs dusting material. for this e::cperiment 'Ir8B :fonGU"ded .t'rODl tbe 1ia.nrl..l.J.e ple..nt of' t.he Johns~e Corporat.1.on. It...-as tbe remains o nbers col.1.ect.ed in dust. b:tna after a ca.t"d.:i..ng operation and screened t.o pass 200 mesh. Since t.he material as received contained _lZIaXIy"' ~ong fibers, i.t, was grou:od in a steel ball. mi.ll to reduce practica.lly 811 the pa.t"t1cl.ee to :3 microns. or 1..e.ss in size. 'When used al.one in a cst.a.ndard dust.ing mach.:1.De, this inel:r-ground asbest.os or tended to pack in the hoppeT and i t became necessary to mix ona VO~WIIB the un- ground ma.ter:iaJ. l'fit.h three vol.umes of the ground to generat.e a. sa:tii.sfactary dllSt c1.oud. The addition o~ the Sln.Bll quan:tity or unground i:!Sbestos ..as 1JIl'ortunate or ~e it con'nsed the ..... int..erpre1lat..1cn o reS'uJ.:t..~_ Probably the uri.nor amount. reaction tha.t developed 'Wd.9 due to the :tong fibers 1.n the tJrixt.urc alt.hough i:.be - , ii. i FEB-13-95 MON 17:26 J F HUMPHREYS ATTY FAX NO. 3043434186 P.23 data of' this experi.mant do not pro~e t.he poj.TIt. - "Z7. The composition of' the short..-.f1.ber G.sbestos &5 !"eceivad is disclosed. by - the chem1.cd s.ild petrographic analyses given in Table h_ Ss:np1es ta.kel'l ~ore 8;l'l<l af't.er ~~ng jielded. eblJut the sa.u:e values "~~ li:lo'?J.;r~:M itJ.ti.~..g that there ~as no con~ation from the mill or los3 OL ~etsI' cc.ntent. 28. The dust conoentration varied somEnihat ci\,rln6 the ~rimant and light ield counts for atmosp~ic samples collected inside the ~ cages with the impinger apparat.us ranged from 83 mill.:1on to 1.82 m:i1llo::J... The average of counts 198.S 130 tJtiDion :Cor the rtrst. year of the exper.1mgnt" ~3h u::Ullon for the secocd year a:rxi llto ndllion for t.he t.hird Y'ear~ 29. Si~e-i're:t uenCf MeS3Ul"ements of a.:ir-i'loated dU&t trom inside the cages at a magn1f"icat:ion oE :l3GOX revealed a great prapondel-ance oi fine par- ticles (TabJ.e 5). Nearly 90 per cent of t.he part.1cles sean were sma.ll.er t.han 3 microns. JO. Reacti.on:in Animals to Ichal.ed Short-Fiber Asbestos Dust. Four species of an1.mal.s - guineA pigs, "Rh1.t.e rat.s~ cats and rabbits - _ere used in this experiment. The reeu1ts of' the dust e:xposure, w'oic..'" are sumrnari.2:ed in Tabla 6, -.:t11 be considered ~re in det.a:il. below. 31. Gu:inea. Pi~s. Eighty guinea pigs -.rere original l]" pJ.aced in "the dust 'rOom \ but 21 of tham'1rere later e11lDina.ted i"rOl!l the experi.msnt. and ld..l.led because 0: enl.a.rgEid lymph nodes. Of" the other 59 aruN\)s" h6 remained in the dust room until they were sacrificed or died from natural. cs:USes and 13~ atter being mcposed 'to dust .for 20 months, .ere t.ransi"at"red to a norr:!al. atmosphere. 32. Rate and Type of Reaction. The type of tissl.'le rea.ct~on to the iDhaJ...ed FEB'"""13-95 MON 17:26 J F HUMPHREYS ATTY FAX NO. 3043434186 P.24 oately the 8aliJ3 but. t~le ext,em. of involv8Ill9nt ;ri~~h the short-fiber dust was 0.1 'rea.ction, which gGnera.l.l.y"" ::'aqu:L-:-ed miCJ;"05C()P:l.C ~na.ti:on. di-....dete'ct;ron;wera produced in th ~u)~Ga pigs. Until exposures had continued lor appro~'eLY one Jeer, t.hera ?as littl.e tendency :I:t'Jl" ciusi:.-contail1ing p!t.:!.goc~~.e:o:; to collect into clumps. By 16 montbs phagocyt.es had beg-un to collect about 'eM W"dlls of a (ffl of t.he respiretory bronchiol.es with a little proliferation or infil~ation of ~noDUClear cells in these l'fa.1ls. There were also soma IlI1l1.tir..ucleatGCi. calls but they -were al.?laY3 of the inert .foreign-bociy tyPe. At 20 to 2).1 nonths t.he cellular clumps were sometj.:;qes qnite marked and sometiJncs ch~es in the epithelium resulted in the adenoma.-l:1.ke or "ade11OI:latoid" appearance previously described in Section 17. In !:lOst. or the subsequent members of ths3eries, the reaction romained co1.llllar in type. In a feP1, hO"Pie!Ver, fibrous el.Em'..onts do.ud.na:t~d the picture. Ll'1 the latter case~ the collagen ...as 1&1-3 in color and t.enuous ld t.h no hesv"7 swollan hy111inizat.ion. As in the ra.ts described beJ.mf, t.he alveolar mUJ.s ~t be made up o.f a. ~ of' co1.l.agen 8Upporti.ng a la;:rer of epitheliUI:l., but. wi:th no contained capillaries. In t.he tracheobronch:i.al. lymph. nodes the react:1.on "1ie.S more pronounced in t.his experiment than in the previous one "1dth King1e i1.cats asbestos, probably because o.f the transportat.ion of an excess 0:[ .fine pc:1L-t1cl&'5 t,o the nodes in a.ni.roa1.s inhaling short-.fiber asbestos. The reactiOtl 1fas esscanti.a.11y an increase in reticu1um, rathar than a fibrosis, -;dt.h preserva"tion of' the ori&illal. ce1.1s bet.eeo t.ha thickened reticular .fibers. Diffl,U; chron.ic plettri5Y;z;-ithout evidence 01' pulmonary i.n!'ect.ion 1rnS present in a ew: animals. -1.6- FEB-13-95 MOH 17:27 J F HUMPHREYS ATTY FAX HO. 3043434186 P.25 .. 33. Progrsssicn. In tIle 13-3/4 1::::mt.hs .follonng t.bG ces::n-!:.:i.on of 20 n;cIlths I eT..::x>sure to (l.ust, progr&~s:ion of disaasc. T"~S I::ot deiinit~ly demonstrated but. neither could i.t be o..b50~uteJ.y disproved, OiId.ng t~ the variabil'ity o :the respo1l3e in different 6.:limal.s.. At ths end of the dust exposure of 20 months t."IrO pigs wergre.s.d as + and one as 2~. Alllong t.h.e~ l~ re;ro.;ed ~~;;om-c.i~i'~t. the findings were variable: in 2 th.e reaction "l(as :t:; in L. it lTa:.,' -(..; i.;1, 3 it "Ras 3+; 1n 3 it vas L.+; and 1n one anilnal it. was 5"". It. is quite possible that those with the JlX>st marked changes had alre.ad.y developad more reaction than the remainder by the tiloo ~3ure ceased. Since tho more severe reactions occurred sporadiea.l.J.s e.JXl bore no rel.ati.onship to the J.engt.h of t1me a1'ter cessatiml of exp0sure the d1f'i'erences l1'ere attributed to va:r:iai:i:ion in iDd.1v:1.cllUU 3USceptibility_ Th:1s view received support :!'rom tha c.hem1.eaJ.. anal.yses (Table 7) ~ \':hich often revealed co:Dparabl.e 8lI'!Ount.s o ash and sill~ in l.ungs nth wideI.:r dU'terent. amounts or tissue ohange. For ~l..e, the ash and si.lica values were quit.e simjlar or three anjmpls 1n dust 20 mont.hs and then in normal air l.3-J/h months, yet t.he t,j...8- sue reactrion tor one 2llima1 was h...; fer another" ~; and ror the t.hird, onl.y .. 34 .Asbestoeia Bodies. The torma.t:i.on or asbestosis bcd1QS l'U a.t first 97:- tremely' lim1.ted. A.f't.er- S J:iOl1thsl exposure only a very rare short body could be .round~ ~ inside of cells. Around the f'1nest intracellular pa:rt.i.cles t.here -were yellow deposit.s h.a'll"1l:lg the Sa:De color &oS the asbestosis body. Exposure of one year had permitted an accumulat.ion or nany longer fibers about 'Which the asbestosis-body coat.ing devel.oped. IIDst. o these were st.ill short enough to be part~ or entire1y wi.th:in phagocytic cells. By the 20th JDOnth and thereat'ter, 'they -.rere comparat.1vely oumerous a1though 6till. rare 1n cOmparison wi th the :finciings :in the ICing t S fioa:ts exper1men't. -----..........---.:------------------------------- _ FE8-13-95 MON 17:27 J FHUMPHREYS ATTY FAX NO. 3043434186 P.26 ............._.................... -'" _.":-..........:-....._............ ........,......;"..-........ - !:icings dl.tt'1;og the 1'irst 20 m;T."lth.s "fi6l"C ~.de biJnoni:i~ ~!).d for the remainder of' ~: .....:::-.=---.., . ~-' ..... -.:- 36. PAte ar.rl Type or Reac-i:.j.oD. 'r.'1e dust cells l.U1:i:.il. 5 months t79re ldd~ 3cai:.t.ered sl:".ci e:d.eted in .1"oci only sporad:i.- ca.l..ly. Reaction'1t'aS limit.ed to occ~sicnc~ sllght thickenings of the septa about. amall a.ccumula1;ions oJ: du.st, ce1.ls _ In a :f'ew rats at 10 1Mnt.he~ there vas a. sugf,est1on of GOr~ fibrosis but tho ob.a.nge was gO alight. t.hat it would probably be ~ Ol7'el"looksd nt-bout the clump or dust. cells t.o s.ttre.C'c. attention to the. area. On13- 10 an'mals 'Were eXposed .from. ~2 to 32 n:ontbs.. In each or t.hem the lungs ah01lOO minute ps.t.che:s of 'Well-defined fibrosis distributed like t.hat. ot: astx:!st.osis but without aabe8tosia bodies. The lesions, v:l.si.ble only a.t a magn1 f'i.ca.t.:1.on o 1$0 dialOOters or more, consl.2ted of patches s.1.or.g alveolar duct.s in \fuieh the 1Ta.l.l..s \ ot: the air SpaCes 'Were ve:r'1' t.hick, due to snolla:l collagen .f"ramework. Connective t.issue and Foot-Bielschowski. ail.ver prepara.tions re1"ealad complete loss o capillary bed Jocci11y. Out.si.da the collagen"l'1a.S a thin l.s;,y'ar of epithelial. oalls. '1'bis did not l:'68embl.e the lIadenamat.oid" oha.tlga characteristic o guiDes. pig ~ bes'toS18. ~ro pleurisy was presont. Near the lesions 'the air spaces wera iil.l.ed crl.th -phag~B contairling gre,y to yellow particulate dust. and a. rare long n.aJr..ed asbestos fiber_ Csrsf'ul saarch i"a:1.led to ~eal ev~n a auggestion of an asbsstosis boQy. The tra.cheobronc~ nodes 3b.ot'led. compact focal. coJ.l.ect10ns or DOno- I cyt.1e cells at 12 months .and, at. 20 months, ~ome di.,r.fusG thickening o the reticulmn. In a feTt rats t.here 1m5 de:f1ni.te !,ibrosis along the margj.n8 o the nodQ ADd artending into the m.ed.innt.i1"M .!U'~'J...ruo t.igs~~. CnmparM 'I'ri. th the rsspe..."ga ~A) active dusts l1lce quartz and cher~ the r~act1on ~o short-fiber asbestos ~as nagllgible. FEB-13-95 MON 17:28 J F HUMPHREYS ATTY FAX NO. 3043434186 P.27 val.ues .fOr rat$ i.nhaJ..i.~g other c.U!>ts" ~e. concen-c.r~"t,:tcn of: at.r:9apheric particles t,o, '3!1i.ch thg a.r...:im9.1..s were exposed tv8S app:"orl,mate1.,. t11.:.'" t;:i1Qe for ssbest.os and qu.a......:t.z; !'or tl''. ~:urtz :T.iJ..-tUi~~; 'it ~v..':i' D.OOUt. t-r-j.Cg .a:c l-.if;!'l' ~or--crlcrt~ .five t.iIr.es as idgn. It l'.'".ill be not.;)Q. that i-.::,~ prcent.....:.;..lS ~t:)r a.abestoG ore 10\"!'eJ:' r::dx:ture, in which a.tt:lOspheric a?,glll't,:inal:.ion tamed to redu.ce the .!!r.IOWlt. or dust in.llsJ.ed. It :m1.ght. be :inferred that the to'taJ. qt.ta.nti"'vy of asbeet,os dust 1nhs.1ed was l.ow or ths:t i t had been el.im:!.natd !rO'11. or diseo1~d ;dth:in the l.U!'..gs. In t.he present state of our knOl'flcc1ge e\",s,j,uat,ion of.' t'b.ss~ h.,~tl1e$eS is not. poss:ible.. 37... Cats. T\!:ent.y cats 1mra usoo in th~,s llihaJ.a:t:1.oiJ. experiment 'With the short-fiber asbestos. Eighteen iileI'e l::ept in th~ dust. room lmt.il death, the ex:poaure period ranging '1'C!:l one month to nea.rq h-.1/2 years, and two, attar a dust. expOB1lre of' 31-1/2 months, were r61loved to norm~~ a.ir~ One o t.hese "n3S sacr:l..f'1ced S tnOn:ths, and the other 2h. toOnths, l.ater, 38. !late end t m of P...eaot1on. The reaction was essentially that. t.o an inert dust, even af't.er nore than h years or expo- r:rnre. Tho tiS5U9 response in t.his species was ~ntined t,:) microscopic foci of' fibrosis in 'the ~ o groups of sub-pl.eural. al:vsoll, rathe-,- th311 in t.he peribronchioJ..ar. ereas. In onll animal t,h~ change ~:a..s ext.'5Ill'J~va enough to be "I1i.atIal:U:ad on gross inspection of the ,.section. 'J7 X:i%r Ch~s. Only in t.he a.n:iJl..aL m t,h the longest. exposure di.d the X-rq r3~reil1. de~tel.,v ah!lOrmal. shadouo. After 29-J!h _ ~nt.h6 t.he picture -.,:;a..~ ,nega:tive; after 45 l!lonttJ3 a faint. mot-t,ling coul.d 'be dewct.sd ------_...._---._ FEB-13~95 MON 17:28 ~. .. J F HUMPHREYS ATTY FAX NO. ..---.----.:.~----"-"---- 3043434186 P.28 !.zJ.~ P.2.bb:its. Eight rabbit~ ':1Jere ax:posed to dust. for perio:il~ c:::::t.G~!.i~S i"rot!l on~ to u;,ora tt.an !iv3 y-Qat'3. Thl!! l~t ellii~'s.l 1':'8.S I'61l'.O"e::ri :fl-cn the cust room and lo.f.'t in Dar!lUll air 6 months bGIore bai~ sacri.ficGci.. U2... Rate and T:r:pe of R.e.a.ction. There was never enougb fibrosis. to be de- t.ected grossly' and the!'e ~6 j,10 ohronic adhesive pleur:1.sy.. l.ticroscop:ic evidenca or cl.~eola.r .,..all. thickening 1fa3 fLrst dci;ected after ;.bout. 3 years ot: expoSt".Te and 1\39 seen :in all. 1ve a:uimaJ.a eT..emined t'herea:f't.er. In ona animal that di~ o.C' pa.ral.ysia a..f'ter nearly:roul." years. of exposure the reaction was ~D;3iV'O no\:gh to be rlsib~o on gross ir.spect.:!.an of tis.sue aections.. '!he possibility ()f puJ.lIlOnary :inf'ect.ion ill this ani.mal. could not be excluded. Hcme'Vllr~ iil another an:ima.1 dy:1ng t~ -yeAT'6 latGr tl1~ focal. !i.bI"osis ~ not nearly' as obv:i..ous or as advanced.. AJ.-eas o involvemnt, .mi.ch ~e largely v:isuaJ.ized because of' phagocytic reaction 'Wit.hin thg atr spaces, tended. micro5COpical.l,y "to become -more fibrous ldt.h the p&83age of tine but t.here mu;: never much enc:roachIDent upon the lumen of air spaces an6 t.he architectUl"e of the ~ -.ras presEr~ed. ,. h3. Asbe:st.osis Bodiea_ Asbestos bodies '1I'are not dt'Jt.gctd in rabb:i:\.;s tha.:t died em-1y l.n the ex:perizlant. but tiGrs 56SIl in all an.ir-Als th.e.t bad boen E:Y.pOsed to the dust for more than thrG2 Y2ar3. ~r. ~>~. - FEB-13-95 MON 17:29 J F HUMPHREYS ATTY FAX NO. 3043434186 P.29 ._-- tion to aso.e::;t,(,G -rna::-e ci'.ecc..ccl in cri~.n .:!I.tl &eoel.erateC:. or accentuated. rGISp<msa .... ... I .......-~ ....._. __....... _ This EOq)Ori:ment, in ~hicll tho reaction ~ alcw6r and lest; e~n~be t~1a:.l 7;:i\~h i~il1g JS nO~-"G8:!J i.ndi~at&s tha:t 't110 reaction ~ is not. priIa&rily ohelic<l3.. In V nature. or t.he four SPOCiS3 wq:>ODed in th.i.s experiment only the F;Uinea f..~ G~d ra.t. roacted o;dtb cha't'a<rtaM.G-t,ic -pecl.bronchiolar f.ibrosis. The ca-t. react~ w:i.th atypical. SUb-pJE:2I"aJ. fillrosis ~"1d :in the rabbit the fibroe;..s wb.i.ch occ.urred could not. be posit1veq attr1.buted "to t.h~ dust becsu3e of a strong possibility at: pal.J.uonar:y 1nfection. X'-'_._t~~A\aA'-~N- ~.0 .~t-i . - ~Wf!j:lf ~-:!J!flt.twilh ~ Pr= CentBa.l.f'=lt1.l\ed Asl{e:fr,01 Dust.. In the .inhalation ~t, 'ldtb short-f'ibsr asbestos dust. a small quant:1.ty o ungromJtl. asbestos TcIS ~ 11i.th grotmd mate:r.1al. in oreer to produce .. SUitable dust cloud. 'i.'han evidence o EL dust react1.on appeared in the guinea pigs during the experiment., :it was not. cl.ec...r "Ghet.her this -.as a. tissua response to t.lls SiA1Bll. number or long fibers :in t..he '\lllg:round aabest..o8 01" "fe.s a delayed effect of 'the Ia.o.ra abundant, fine dust. Consequent,~J another jnbaJ at1.on axperiment W""~ .stsrtea. in "Yh.1.ch no unground ID.ater:UU wall UBed. ,. l46. 7he <i:ust!ns me:t.er:1"..l uaa the ground short-f'iber asbC)St,OB used in the ~ous inhal.a.tion En:peri.mcnt but no unground mat.er-ial. 1tdS nr.."."ted witb it.. To obt.ain a sui".fic1cnt 8ll!Ount o:t a.tmospheric dust;, the design of the d'USt~ _ apparatus was changed to an opsn t.ype o:f hoppgr QIl.d 1"resh dust. was added daUoy~ FEB-13"""95 MON 17:29 J F HUMPHREYS ATTY FAX NO. 3043434186 .. (.._._........'...n .............#,',u.......__,_......-.-;. ....... rt' tz w' C' s'i 'f 'hin .. or ~ ..bC.t . P. 30 doiin*...i'jcj;WdiiW'fSiW% '*,~ I ... il'aS IT.c:.chine "ml.5 rzcODv,;0:r.t.:;~ ~;'0 its c!':';:inal ciasi~n. To r.7.'eYent. np"~lingll or th~ ... ~ ...... _ ..... _ 9 - ... - - ... - . s:J..da eur.face oJ: the hopp-?'!" and t.o tr.e rot,atj.?!~ -pad8:: _ S'lJ:'....s c..-. ...'?.r~emt=nt ;;ave ph.er:f.c dust liberated i'!.-Cl7:0 iji1e ball-r:lilJ.ed proeuct in -tote d\:sting ma.chine is given i.n Table 10. 1'hes:? va.lues ::;'1'<I: cn.'Jed '"'pan Fst.rographic study and X~ay dU'i"ra.ction analy!>is. 'thg at/!:l'~::p!1or-:S.c .s31iIple .'aG collected 1'T.ith an electrosta:tic precipitator after wire br:lshen hed been inst.alled in t.he dusting machine. Previous to Uris ~ the ci1rysoti.le. content. of the air-suspendsc material was uru:ioubtedly less 'than t.he 15 r..er cent. vz.lue i;iven :"n 'I'able 10. !n an interim report" it was stat.ad tha.t. the air-born.~ dust contained about 5 per cent of chr:rsotile be.fore thQ wire brU3ne9 ..lere 1.'.S2ri. c:.nd 'Up t.C' 8 per cent. a..:rt..enrards, bl.lt. these val:ues were probably l<m. C::uant5.tative estilllates on ball-p.ti..lle6. asbestos dust may be oomEmhat inaccurate beca.use it. io difficult to deterru.i.ne bOlT much o a c.ust saQple is .fibro~f3 cl1r:n3oti.le a.nO. h<m much is non-fibrous o<3r.~nti.:."Je. LB. The dust concen~'ation fo!' i',iH~ f!.rst 7 months of t.he experiD'lEmt lIaS about 1.00 mi1J..ion particles per cubic foot. 01 a.ir. J..f'ter the wire brushes had. been inBtalJ.ed, tpe dust. CO\;D.ts 1mre a. li'!:.t1.e higho!" and the overall average for the 'irst year ~ 106 I:!IIT!..ion. The aver~e of counts for t.he second yea.. T.aS 16) r.rl.ll.ion and for the thL-d ~ar lhS :'!lillian. FEB-13-95 MON 17:30 J F HUMPHREYS ATTY FAX NO. 3043434186 P.31 r.;L~".=~:; "",-r'r"'-"'sncv .;...;.J...;.....i...J'-' .... v~.... "~..l' - ~.",<o f3 coll.act.ed in Table l i . Two samples ,/ere taken, one bd'ore tb-a ...~. irc b!".lshGe 'P."el"G instaJ.led and one after.. It "Will be notci t.~~.t. af'l;er the wire o:r1;,snss ~ra in 'u::e a in-to the air. 5'0. Reacti,on in A.n.i.m&l.s to Inhal.sd 100 Per Cent Ball:,-l.i'ill6d Asbestos Dust. Guinea pigs, rat::? and mice 'Fere u:;eci in the i,-UHIJ..s.tioc Gxperimant with the 100 per cent bail.-m:illed asbestos dust... The results arc sUJIml!:lrized in Ta.ble 12. 51.. Guinea PJ.gs. The experiment lIaS started with 3.00 guit'.ea. pigs. As the dust exposure proceedadJO there were 39 accidental. deaths, 32 o pneumonia. in an epidemic. ll.i'ter 28 months 01: dust:ing the 16 survi.ving guinea pigs were traD5.rerred to normal. air. 52. ~te and Type o Reaction.. For the .first. year or ~sure practically the onl.y react.ion to the dust 'Was the preBence ot auttered phagocyt.es acd an occasional minute asbestosis bod;r. At 16 and 20 months no gross response was rtsib1.e on the "tissue section but. m1.croscopically peribronchiol.&r f'oei. of l.nf'lamma.t.ory cel.la could be seen. At 24 mont.hs t.here wss sUll no cha.nge large enough. to be seen'ldth a hand lens although talcroscopic eatanO.nation %"eV'eal.ed cellular accumul.ations about termina'l bronchioles and many mare asbestosis bodies ~ chie.fly within celJ.s. Q"emlcal analyses of t.he lungs (Tabla 13) reveal. that l.n Bpite of the lindted tissue reaction consi.derable dust. r.a:i: been ret.ained in t.he lung ...,.., FEB-13-95 MON 17:30 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 32 r _ _ _ ~_ _ _ _ _ _ _ _ "-"";_ _ _ _ _ _ _ _ _''''' _ _'_ _ _ _ _ _ _ _ _ _- - - -_ _ _ _- - - - - - - - - - - . (2& liv:mths) ~.nd th\3n li.-.ri.ne in norTi1oS~ air for 2 mcnth::; reve.al..ed t.he changes described above and al:!:o very. sJ.ight per:Lbronchi.olar .fibro- sis. ._- 3 After i3 raonths in normal. ai:r the .findings ,.-ere siIrllar but at 12 !Uoni:.hs. ..I ' ..................... ..._ - - - .. ...... o-'u a:rd:ms1s sho",-ed g;..-ossly-visible characte:t:'istic peribronc}ri.olar fib:;"03is nth adenomatoid change. 54. LY3?h Bode InvolveI:lent. The traoheobronch:ial. nodes were essentially n ..~g9.tive until exposure ned ooen c::mtinusd for more than a year and a half. Animals sac:-ificcd a:t 12 tl!onths and 16 months revealed a r~ minu~ collsctions of phagocytea containing particles but practica1ly no fibers large 6."1ough to be recognized as such. Arts!" 20 months of exposure many lDOnocyt,es filled with yellow granul.es l8'er8 present. At. 30 months there had been a slight :increase in reticulum but no fibrosis. No .further changes occurred in the nodes. Asbestosis bodies were not seen in the nodes of ~ or the guinea. pigs. 55. Asbestosis Bodies. M:iJ:mte asbestosis bodies 'Were obse.rred aD early as .3 DIDr1ths af't.er exposure began, but they did not beCOll1e numerous until 1.6 months had el.a.psed. The bodies were shox-t and practicall.,v all. were j.ntracellular, although a.t 20 months some were l.ong e~h to project. beyond the cell borders. It is important to note that in the l.a:ter months o exposure there was a 6is- tinct increase in the number ,of l..ong fibers ~ to 70 microns ~ l.engt,1:V in the llL'lgS and that .a..:f'ter exposure ceased characteristtc lortg asbestosis bodies v.~re seen. 56. White Rats and },tice. In this wq>er.iJll~mt. }~O rat.s ...-ere e.'qX'sed :or perlod::5 up to 20 months End 20 mice for periods up to :12 -_._ FEB-13-95 MON ...- - _.....- - _.... 17:31 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 33 was l.imii:.ed to '!?h.el.goc:',rt.osis o.f inhaled pa!'tlcles by 'l'f"ldeJ..:,,--ecattel:.ed dust cells 1'ih.ich ret:lained free :in a:ir spaces or we:-e tra.n.9J'O..t~ to the tracheobronchial. lymph nodos. No asbestosis bodies ~ere found in t.he rats btlt in the ;:nice there 'm3re a. very- f e'f'I sU'..alJ. non-haust.rete::l forms wi.thin P~lagocytes In 21 mouse lungs sectioned there were 3 i.."'lst,allces o pulmonary adenoma. (l.h%). The ~;i8sue !-eactioru3 cbservad in this ex:perimsnt 'W8l"'e much leS3 e:;ctensi.vG and B~awer in davelop;nent thD.1l in the yrev10us invest1ptio':'l with short.-.fiber asbestos. Since presumably there'l!'ere f81'ler fibers longer than 3 microns in the material. us9d in this experin:.ent~ the reoults tend t.o con.fi.rlD the 1nterpretation ,C made in Section hL. 0: t.he short-fiber eY.periment t.hat. t.he react.ion 2 *Q" is not ~ pr1lna:ri1y cltemicaJ.. in nature~ The finding of long asbestosis bodies in animals in..'1.aling the ball-milled material. 1s an example oJ: t.he e.ifficru.l.t.y O.1~ completely e1i.::ninating long fibers from an asbestos preparation. In regard to progression of reaction af'ter removal. i"rom dust, 1th.i.ch was ob- serYed in t.his experiment but not. in the ot.hers J t.he f'o1.1.01fi..ng interpr-etat1.on is o.fered: \';hen the T438-ction is "Il'ell-developed a.t. t.he termi.nation 01" exposure~ the cont.ract.ion of the .fibrous tisSl:e would obscure an.y p05s1'b~e progression. In this experiment, however, si.nce only the earliest stage or reaction 'WaS present at the ,. time of removal .from dust, ita subsequent. progre!ls ":faS apparent. It. should be noted that the degree of progression 1fa6 so slight that it can have llt.t1e, if' any, practical. significance. FEB-13-95 MON, 17:31 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 34 7- --- uK'Eto --T~(t:..(No V~ A. -~/}nh.:"laticn Bx";:{ll"i.m~t ~'\. lj;. A.!'ter ani::1J3.1.s :1..n."12.lir~ asbestos dust .for more thBIl a year had ailad to develop significant reaction, ~he bypoth~sis that asbestosis is pro- duced by the mechanical irritat.ion of long fibers 1fc'1S given added support ..I ' _ _..... - - . . '.'-.... -. ___ __ -', Since the K;'lng' s floats asbestos used :in th~ iil-st. inha:lation sxperilllent had a rather low conten~ of fibrous ~u-Jsotjl3 and contained consicerable serpentine and other impurit.ies, it; was decided to c~nduct a DGli inh.alati.Oll experiIEnt. 'With a purer fort:! of chrysotile' wtli.ch would be r-icher ir.. long fibers. $9. The dustip.g material. emrlloyad i:l this ilTlQSt1gation was obtained f'rom. the Manville plant o the Jol".n3~vil1.e Corporation. Samples ot Be- veraJ.. variet.ies ot asbestos dust "I'fere .first submitted to the Saranac Laboratory e .tor- eX'ami nat..1on and one ldnd, identified as Lot D, which ~ 1.0\'1 in magnetite and. chrollli.t.e and had Q fibrous content. est.:iJna~ed t.o be about. 7$ per cent, lIaS sele<:t.ed as most. suitab~e. St.eel mre brushes lVGrg f'astenod to the inside surrace of" the hopper and to the rota;ting paddle :in order to open up the bundles of' aabestos and liberate tilOrefibers :into the atmosphere. 60. The CO!Ip?sition ot tl't..9 long-.f1ber asbestos used in this exper.:l.msnt :Ls . I iDdica:ted by the chemi.caJ. and petrographic analyses gi.ven l.n T~le 14. \ .1 It appears that. ttds mater:i..al ..as a. much pc.rer form of asbesto.:; than tho shortiiber dust. used in other ex:per:iJnonts. This is borne out by col!lp8rl.ng t.he approx- ims:te a.nalyses of the l.ong-fiber and short-fiber idust in Table lS.. 6~. The dust concerrtr"ation as reveal.ed by imp:i.nger samples taken inside the animal. cages .-as much l.ower t.han the concentration for the experilllents '7ti.t.h short-fiber or ba,l.l.-nd.lled dust.. For the first. year of the experiment with long-fiber asbestos the average of the light. field countsl"aS 32 million; .for ---_ FEB-13-95 ......._. .. _ MON - ' .......... _-_ 17:32 ",. _.. ..... - - - - . - F J ....~...... , .. H-.U... M. PHREYS ATTY rAX NO. 3043434186 P. 35 ~tion o.i:aclos&l that. mBtlY !'.tne partic~e::J less tM"a ona T,r).CX'O:1 in size s..c':)o.mpa:1iec. -.. t:L"!l9S lart::er than '" ... ;--;. the light field - counts. .,. ..... we~e collected ~ith the electrostatic praciyitat~r. ~t niL~ ba no~cd th~t tr~~c was far more :fibrous mat.erial. in the long-fiber C;U5~. 63. Reaction i.n Ani....al.s to !nha1ed lo!'..g-Fiber Asbestos Dust. Guinea pigs, cats, rats and m:3..c:e were amp~oy~ :L, the inhaJ.e.tion exper.irne:Jt "\\"1.th long-.f'iber asbestos. Resu..1.ts of the experiment, summarized in Table 17, are described in greater detail below.. \ 64. Guinea Pigs. The experiment was s"tsrtad 'Wi.th 100 ~nea pigs _ A.:t'te:- exposure had been carried on rot.'" a year., 6. severe epidemic of pneumonia arose in the dust room and abOllt. one-third o the animal s died Ol' "1IeN kil.led. To replace them, 38 more guinea pigs were added to the :n.trviving group in the. dust ro<T.il_ 6S. Rate ~ l';yp\! of Reaction.. Histo::togicaJ. examina:tion revea1.d grossly visible lesi.onn :L, tbe lungs aft-at" 8 mont.h!! , o exposure to dust, cons1.st.ing of cellular infiltrat.ion Bbaut t.he te:rminal. bronchio1.es. At 1.2 months, the:e were adenoJIIs:toid crumges in the air spaces a."'ld by t.he l.6th month a. dei'inite i"ibrosia was present in t.hese areas in balI the ani.ma.1..s _ The f'i.bro1.l.9 leSion could be ueen JlIa.CToscopiCaD..y at 2Q montr..s. From. this time on the react.ion increased in- ex:tent and in the amo\wt of" collagen and FEB-13-95 MON 17:32 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 36 p - ::10 tendollC".! 'cc .ru.-;~; even in &ni."':12.1s El.jX)sed 1:or the ~ pez-iod (3 :r~ars). Alt!1ou;;h _the irrt::-a-pulmonarj reactior: zo:oat1m9S reached troh.....e pl~\lr~ there i'fe..!3 no _! ..J _____.-., ....._ ... _ _ _. _ :!.nvolvcme!1.t of t,hat mcmbr~ne. No etlI?hyse:na TI~ visible at ~ JX>int.. Some thickenim; 01' the larger bronchl. l'dth a. chronic inI'...2i~tory infiltration was re- veal~, out. it p!"ob:1bly was no ~ore tha.""l 1'i'ould be produced by' a silni:i.a=' exposure to a..",\v dust. For the f.":i..."""St ~ month$ the phagocytes consisted of Jr.-onocytes or very snalJ. giant cells i :tater, gia..""lt ce1.1 formatloi\ was more prominent. A.ft;.er 16 m:mths the giant ceLls '!reI'! large, filled with ye:;:lowish-1:rmrn pigrnani; a.'"ld somet.imes vacuolated.. .A..T} occasional animal shar.e<i an ,\dmixturs of' polytnorpho- nuclear leukocytes and, in guinea pigs exposed for a. cO::J..,id6rablo 'PGri':Xi, eosincphiles. '!'he reaction 1'!S8 at first entiral;y ce1::"uJ.ar 'l)ut by ~6 m:mths 1.- arous tissue f:;rn:.ation ..as de:Cinil:.e. 11~er, it never atta.. !len a staze of byal.inization ~!:esti'l!'e of silicosis. ll. mO<1erat;.e indiv:i.dual variat.ion occurred &long the exposed aJ..il:la.l.3, both in the rate o developing lesions and in the stage o devol.opment &tt~ned at the end of expo~e. ~ses or the ~t!1lgS (Table 18) dif'lolosed that alt.hough the tissue.. response was much greater in these guinea pigs than in those ~sed to eitber shot~-iber or ball-milled 2..5oestos, the amount '.:Jf nrineraJ. matter :.i.l:l the 1.1ll'Ig ash lmS 1.. C:~. 66.. Frogression:. In ginnea pigs exposed to the dust for 20 months and t1.':l removed to noinal air, there ':las a mat"!-'.ed tendency for cellular infl.aImnatory reaction to clear. This affect, accompanied by contract.ion of the fibrous tissue, Z'e~mlt.ed in a diminishi..ng sizG of the Iocal lesions. HOlle FEB-13-95 MON 17:33 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 37 d 'i ' 20-m0oth eApos-:n-e period 01' t.hose in aniulal::i T:hich rc!..aine<l in '.:.he O\1St rCiom ;e"";;-;isible--- for more tha."1. 20 l1\cnth.s. Fourteen -;nonths after." GUS':; ~y.ral5uJ:"e cessed: the foci in !our o the six rernG.inir.ae guinea pigs 'Y'!'ere,, 80 sma!.,]. t.h~:~L tilY=' a!l1y lti.t.h a hand lens. Reaction in t~e grcup e..~pos:ed fer 27 months ~.r~ ~~ha;,1 traT'..sierred to a nOrJilal. raentioned ahcn-e. P.mmver!) small .foci 'Were always visible on gross inspection of' sections o all guinea :pigs of tha 27-month series bui.:. in no instance ~ there evidence of extension or the reaction. 67. !fmph Node Invol.vement. Reaction in the tracheobronchial ~ nodes wa.s .first vi.si.ble at. tbe th.:ird month o ex- posure. h.t t.he 8th month patcnes of cellu1.ar connective tissue begen 1.0 appear in the medul.l.a and by the 14th month most. or the node had been replaced by ce)llllar eOl".nect.ive tissue. This picture, wbicb resembled 'that iA early silicosis, p!rB1sted t.o the end o;f t.he exper1Jnent. Some aninm1s, as a. variant., sh01led heavy sheets of diffuse monOCyt.93 and J..arge aetna giant cell3 but thare was never 8.D: necrosis or bTcUi.ne forrea.tion.~ The spindls-sha.ped new cell..s were yellmdsh in co].or from fine I'igment granul.es tha.t stained for iron. No fibers . or asbestosis bodies lleI"e seen. ~~~ V"'"" 68. AS0e3t.osis Bodiese Although a.sbe~tosis bodies 1'F9re SeEm",a.&, early as one month after exposure cegtm, they were rare and. hard to find. At. S months rr..ore were v:i.sible, ohiefiy coiled ins1de giant. cells, and at 8 mont.h5 many- bodies were free 1n cotulect.:i..ve 1:.:issue - They- became f'airly' a.bundant as ~:n\l\~ exposure ~gze~eed altbough ~ some later Eniw4 ls the asbestosis bodies ~ere on~ r.lOderately n'UlllOrous. FEB-13-85 MON 17:33 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 38 ~.!.,.u~ .....,..c..:.: , ;-.,,.; an,"..-l lL.\-.A..",. mant hs, !"espeC ti:va1y, ano. 1fer~ J..l!IIIled.1a t f)17 sacrificed.. Tv.-;:, other eate, after be1.ng exposed to d"t.L5t for 18 months, lived in a norm.al atr.:.osphere ..tbr an add:i tional. 24 months. -r..... ....:. ____~ ......... ___",_ 70. Rate A.l'ld 'I)pe or Reaction. Expo:rure for JJ.. months""WaS sufficient to produce cellular ec~umulations of phagocytes al-f);JX'..::i terr:1.i1'll..l "b!'ollchioles and peripheral a..-terioles toget.her "lli th compact col- lsctions of siIo.:i.1Ar cells :i.n t.he t.rachGobronchiaJ. :ymph nodes. At -that tim:: there ware no typical asbestosi.s bod:ies, but smooth pointed jellO\'f fibers were ~een verj rarely. i'l'ith cont,iuu-ad OrpoS".ll"e, up to il2 mont.~s, reaction in the l.ocations noted progressed to the formation of cellular connective tissue which made well-defined sheaths about the respiratory bronchio1es and arterioles, narked lymphoid hyper- _ plasia and l3'mPhoid inf'il.tration of bronchiolar YIalls. The bronchi.o1ar spit.h- elium r.as l.mr and !l.a:tt.ened, givi.ng the tubes a smoot.h contour. Typj,cal. asbesto- sis bodies "Were not. f'ormsd although there was an occasional. yellow, smooth, pointed .fiber. No pleurisy m present.. The reaction "WaS simi.la.r in locat1on to that in the 8Uinea pigs, but fibrosis "1IIaS lIIUch 5lmrer in devel.opment. and had not reached the same degree of maturity. ' (l.. !--tt.a.y IJhangea. Roentgenograms oJ: t.bree cats were made after exposure periods of 25", 33 and 11.2 months, but tissue changes were not dense enou.J;h to be See!l en an X--rgy .film_ 72. Ra:tB. A1.thaueh 20 rats were plAced in the dust room, many died from pneumoni.a and were n?t su:1.t.able for study. r"ive animals, of 1I'hic:h one was exposed ror ~9 months C'Jld ::ou=" for 25 months ~ ware free .from pu.1monary infection and offar a bruds for conclusions. ;;:ifi~' FEB-13-95 / ~--""",.,,,,-.,,.,,,-,,, 1 MON '17: 34 J F HUMPHREYS ATTY FAX NO. 3043434186 P.39 $~C"6~ a well-r~ked peribronchiolar fibrosis. In the 19-month ani.rn.a.l, r-e.e..ction 7TaS jl.l..~t b~imri.ng. Asbestosis- bodies were practically absent at both 19 &."1d 2S w:c;}ths aJ.t.h~~gh tT10 small 8!!looth bodies ~e i"0Und in the 19-month"a."lil'i\Z1 e.;ft<::r c:. lO:1~ see~,ch. Thus,..,t.hesa,.!luimalp .~:2..!!:ed fibrosis without asbestosie: bodies. 74. ).!ice. Oat oi 20 'Yful.te :ill.C9 1!3~d in th:i.s e;ocperiment, II lived a. year or more in dust Cii.d o.i~. or "t1are }d]J.ed without sh()'W'i-.ng a.'l appre- ciable degree of p~onary inection. 75. Rate and T:rpe ot Reactio~. Ree.ot.ion 1'Ia5 limited to phagocytosis by mononuclear cells. vsual.J.3r these were lfide- ly' seattered t.hrougb the air spaces; a l.i.nd.ted nmmer ....ere grouped about the tar- I minal. bronchioles producing some thickeni.ng of' their walls. There WlJ3 no eug- I \ I .. ,'- - - - ~! of' t.ne expe' " was that. 9 t of: the :'" --_.-._---- Numerous asbestosis bodies WGre observed in ani.mal.s kilJ.ed late in the e:q>e:ri- ment. asbestosis bodies without 1'1l:Iros1.S. 76. s,1ll:IJ'!Jal'Y and Intp:pret.ation. or The pw:-pose of this experiment "f1aS to eval.'W\te the importance ~ong ,. !'ibers in the t:i.ssue response to inhal.ed. asbeat:)o.. The res:.D.ts indicate strongly t.hat 10ng tibet-s are chieflY' rel?por..sibla for ~he rGaction. Thl!9, in guinea pigs reaction de"Yel.oped earlier and became more ext>e:u;ivl3 t.han in previous experiDJents. in spite of a smaller concentration or atroospher~c dust and a l~r ~neral con- tent in the lnngs. t'd:- Furthermore, 0). ty-p1cal. peribronchiolar fibrosis was JU"Oducad {~. 'if ,'.i- :'L FEB-13-95 MON 17:34 J F HUMPHREYS ATTY FAX NO. 3043434186 P.40 '\.... -"-~;""fto~~,_. \'. . ~. . ' I in cat.:; al.though in a previous expe:::-iment!with shor.t-:fiber dust it did not develop in this specios. The cause oJ: the cell't'l.a.r fibrosis f in the lymph nodes of the guinea pigs is not clear. It dip not occur in other inhalat~on experiments with asbestos. ;- ' - .......,:.. r .__ ._. 4 ~n:vIl. tJluA ., '{ ~Bcc...~,c-.(-~--. Zlo/RI~N \E :( XP~ ' \ .4-"_'. __';'_ In order to determine to what extent the various r.1brous minerals possess - the capacity to produce tissue damage" l2IDD9ro'U.S inject1.on experiments 'Were per.formed. In these exper1.m9nts guinea. pigs and rabbits .ere used and. the mineral dust ..as injected by the -intratracheal, int.raperi.tonea1. and intravenous tech- niques.. For t.he purpose of simpli.icat1.on the f'indings in each series of test,s ha.",e been condensed and. reported in t.ables~ to 1Ih1.ch reference will be made later .. 78. ~t.s Usj,ng Intrat.ra-cheaL Tectmique. Since the asbestos mi.neral.s do not canse a typical. advanced fibrosis in extra-pulmonar;r ti.ssue, the intratraeheLl technique is the per.ferred. way ot introducing fibrous dust into the experimental. ani me) In t.h1a met.hod t.he dust. suspension :is injeeted by means ot a special. needl.e or cathet.er deep uto the trachea, t'rom 'Whicb it. ..t'l.orru into the ~W1gs. 79.. C~i8on o Flbrou5 and iron-Fibrous Dusts. To demonstra.te that the ability 01" asb~Sto6 to produce 1brosis resides in i:t.s fibrous charact.er, the series of injection experi- ments reported :in Table 19 1fere per1-ortned.. The test.s '1\'ere made 'l'ith unheated _ long-fIher cl1ry3ot,Ue and vith cb.r;rsotile that- n..aa 'been ign:1t.ed W de;:Jt.t"O;Y' :its -32- FEB-13-95 MON 17:35 J F HUMPHREYS ATTY FAX NO. 3043434186 P.41 .finc!:!.~s l:evsals t.~k:l". onlr tte <;Inheated lo~-.ri.ber ch;::Tl.";cTo:.:'-10 prc:.c:,:ced .rtbi:'=s;'~ ... -4:-~ .._ ' . __ ~ .... t.o CQ:.!lS3 3erio'!.:.S tismlS tianaze. Ignj c.ion proci.uced impo.rtp..l'l't ch6ng6s i.:. ~~'3 c::u.'y:::01:.1J.9 tibera, EIlriOllg them 1:ai.ng 103& of ';fata!"", G...'"l eltE:rat.:1.on frv:1 H fli:l:::ible "t.:) 80.. ~i.Bon -ot.-'~aIriOU5 LCliu;-Fiber Dwrlis. Son:ae very' i.nter~et,in iir~dings a:rlS clist:J.o:::e6. 'r:5y' t.he results cf the EIq:lerir:u:mt.s inc~uded 5.r, Tabla 20. Firs1;, alJ. tb0 l.on:;-.i~ibe:;.. ascost,os m..-i..nera.1..:s tested. ldth t.he except.:ton of Mthophy11i1;e~ produced a t:yp5.cal fibrosis. It. is _ not. entirely" c~ea.r -nby anthophyl.l.:..te behaved differently i!.~ the ot.her asbest.os minerals. ihrort.unately, ~ o.f 8 a..'"lil;Ja1.s died oi: pn9uruonia nthin t.he fhst t'7>O "'Reeks of the e:x:per:i..r.Ient. an': the rerna.ining ar.dIilB] S ~ sacrificed at l~ 8 m:d 12 months; t.hus observati.ons TTarG not. made at t.he opticum periods of 2 ~nd h month6.. Second7 with "the ::uinera.l. brucite, "ldrl.ch iJ! not a s:i1i.c."?te cut in 2. .fibrous i"oI'ln o magnesi1D11 hydroxida t a characteristic fibrosis like that of t.he s.sbest08 mineral.s 'Was obtained. Since the bI"'..tcite used coutained o!ily 0.90 r.er ce...""lt silica (as an impur1.ty), it :is ob""i.aus "tha.t a ei!.i.coous coIllp()nant is not an Gssen'tial .factor in t.he develop;nlnt e,f asbe3'tosie. 1'hird, no fibrosis , ra*Ill),~ed. .from t.he injection of gl333 wool. :fibers, eV"en though glass WOO~ resemblen c.sbesi;.;)s in SOJ13G l1a7'S. There are .fundsmeutaJ. dif.r~r- ences, hO'\'t"eVer. .a. gJ..sss 'Woo:!. fiber :; microns ill diaset.er iB B. solid rod. anci, in short. ~engths, i.e ah-1y ri.gid, -w'oi~e An &.5bestos fiber 01 the ~aI!l.e dlsmeter is a _ bundle of' extreII!Bly fine i'i.lunent-.Q .,r."li.ch impa.rt to 'the :fibar a high deE;1""ee of: fJ.ex- F.. FEB-13-95 MON 17:35 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 42 ., ! : I j .~ l&:- ; :""!.. II ,.: . I~~ ,. , t Ie! ... ! i . 1JDpOrtant factors gCN'ern1ng the ca.:pacity of a mineral to produce pclbronc)iiolBr fibrosis. 81. Comparison of J.cttg-Fiber and Short-Fiber Du.sts. With quartz dust it has -'. the sma.ll.er the particles, the more intense is the tissue reaction, and that there is little reaction to particles larg;er than J nrl.CroIlS in diameter. In the case ot asbestos, h~erJ the rever;3e is true and apparently only long fibers have arq specific effect. 1bis is conf~ by the data or Table 2lJ in which a series ot tests with fibrous minerals is reported.. \ihen the injected dust consisted of fibers 20 to 50 mcrons long, all the JDi.nerals tested (except anthoph;rlllte, as noted in Section 80) produced a fibrosis,; 1Iben the material11aS prepared by first. gri mi Dg the fibrous dust. until the length of fibers 1I8S reduced to 20 microns am less (or, in some cases, 3 microns and less), none of the injected iIiJ.n9ra1 dusts cm1sed fibrosis. 82. ~nt8 Uldng Intravenous Techuiqt!e. The aper1Jaents, described in Table 22, in lddch the intravenous method or injection was employed, shO'Jt that the' asbestos minerals are tar d1!erent trom ~z :m their action on tiBsue 4 It has been repeatedly' demonstra.ted. that iIItra- venoms injection of quartz particles 3 microns and.l$Ss in diameter will cause a ~"'"'"'~ I ~- typical tissue reaction with the devel.opllBIlt or .fibrotD In ext.rap1.1lDxlary sites, h .o4"\C sUch as the liver and spleen. Asbestos minerals, lxnteve.r, on intravenous injoction gener~ produoe 0D;ly an inert typ3 of reaction, as is revealed by the results given in the table. The reason for the early- deaths in the experl.ment with ebryso- tile particles is not clear; it may have been caused by silicic acid llberatOO. by the finel.v-erolL~ mineral. FEB-13-95 MON 17:36 J F HUMPHREYS ATTY FAX NO. 3043434186 _ _ _ - - - - - P. 43 . . . . . . . ._ _ _ _ _ _ _ _ _ _- -_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ tr _ ill 8). ~Dts Us;1ng Intraperitoneal Technique. Thea results of' :1.njectioo 8Xper::i..ment,s wi th the intrapar1tonee.1. technique ere givun in Teb1e 23. It w.tll be nOted that. the lo~.t'iber dusts producai a t1broUB ~t,ion -.rhil.e dUS:B _~~mp:>Sed of ~ticlea 3 mie-rons andIt....lass ...in. .___!.....-i.J.!ye cenued only ...._ ..... _ .. _ an 1xIert t.ype of" response.. These expur1.men,ts ind:1cate al.so t.hat the t:1hros.ia initiated by t.he irr1.t.a:t.lon of asbeet.os t:l.bers 1s not restricted t.o ths 1ungs, \ lUl was ronner~ 8.98l:UDed, but can be p,r-oducsd in the peritoneum 83 wolle .. ' ( .:.... Nll.. ,.' ,. .~ ----',I--. ---- A IIUmber of" add1;t:1cmaJ. experiments ....-e conductGd t.o throw UIOre l:i.gb.t on specific praaes or the ubestosis prooblea. 85. Protagt.i.ve Action ot AlmdmmI. ~. Intratracheal inject1.on or a swrpeaaion ~ long-.ti.ber ehrysotlle to _h:1dl ,?o1lo1dal. .sll1m1mm hJIdrdx1.de had been adde.d reveal.ed that t.he add1.t:1on of t.he aluminum compcnmd did DOt prwent .the tissue 1rr.1.ta.t.1on pt"Oducad by- cbr,yeot.1.l.e. ~ / It anyt,h1.z:Ig" the acute intlaaIatolT reapoase to the 1.J3Jected .fibrous Jld.neral. $l.8 acc:elerated. One lIDQ't.ll iL:rter -the a . t ~'1.oD o~ the dust. smsper1S1on t.he brcnch.1ol.1t18 1138 beeozn1 ng !1hrons ~ 86. Formation at Asbesto~ Bodies. 'l'he iron in the eoat.fne of t.he asbest.oa:1.e boCb" appears to be d.nTed .from. blood or t1.ssue elements 8Ild not, as has been suggested, !'rom the tII:1.neral. !1.ber. 'Following aubcutaneollS injection or t-wo Jct.ms o c:hr,ysot.1l.e 1nt.o t.he groj.n o e'lUMA f'1.gs - one ldnd con1;ej ni Dt; 2 per' ceit:t. aad toha othar 0.2 par cent. "2<>)- . ~ the aube6tosis bod1.es -..ere equally nUJDerous at, both s:l.tes o.r illject:Lon ...~ 1''''''1-' . ~''-'v-l ()~~-I.r. "\ ~.'{." ~ FEB-13-95 MON 17:36 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 44 An attempt t.o pt"Oduce asbestosis boct1ea in guinea pigs by 1mplant.e.tion or three silk bags conta.i..n1ng fibrous ch:rysotil.e 1It8S ururuccessttl. ~ One b~ planted BUbcutaneoUSly' i.n the abdominal 'I'nlll disapPearedJ ~t.he other t-wo bags, placed m the peritoneal. cav:1.ty, produced a little f'oreign bod,y reacti.on but no asbestosis bOdies iD a. year. '" .... ...1 ~:-':---'1 .. ~... '. - - " ' - Intratracheal 1njeot~n into guinea' pigs oE asbestosis bodies recovered 1"ro:n human 1U'llg t1..ssue i'ailed to produce the typical tissue reaction to &.,bestos .f'1bers. The injected UJ&teri.al. was obtained by digesting with .sodium bypochl.orite sol.ut.ion lung tissue z-emr:wed at ant.op6;y .trom. an asbestos 'Worker. The asbestoai.8 bodies could be seen :in the guinea pigs or at least a year a.f't.e:t:' injection. 1h.is exper1.ment "hcnr.s that the asbestosis body bas a rather reaist.8.nt coating ?lM.ch 1:1' not destro;ted by mcdara:te bypochlor:1.te trea~ and may be mainta:1..ned. in rtTO -Lar a ;rear or l.onger. .e Two J:o'potbeses have been propoeed to axplJd.n the t.:Lssue irr1:tat1.on and reac- t.1on CWU& 14 b.r asbestos.t.1bera: the cbelrd.cal aDd the mec:"'uJica'. In tbe cb8m.i.ca.'l theory ..td.eh is bG.sed. upon ezpe:rience with qua:ro1iB, i:t is 88SUID9d that. the as- bestos m:inereJ.8 dissolve in the body tbdda a.nd. tbato in this process their bases are le.acbed .tnra,y to ]save ~ca in a .form capable ot irr1:tati.ng tissues. Accord- , ing t.o t.1ds b7P0tbes18, asbestosis ~aJ.d. bo ~ an ind:1.rect s.1.11cosia. ScsveraJ. . ~acts make t.be chemical. t.heory UIlte:Dable I (J.) 1ntrat.racb~ 1nject1.oDB oE bru- cite fi.bar8~ which had a B1.lica content or only 0.90 :per cent, ca.u.secl a 'typical. !'ibroeis l.ike t.hat produced by the-aabeat.oa m:i..Deral.sJ (2) .t.t-eo-cdll.ca.particles increase in potency as 'the parti.r-l.e a1se becomas :Less, but asbestos fibers ahorter than about 1.0 to 20 microns &'"8 relati.vely 1.nnocuou.s; (3) aluminum ':I":' ... > "_ -, FEB-13-95 MON 17:37 J F HUMPHREYS ATTY FAX NO. 3043434186 P.45 ,,---_. , hydraxide neutralizes the 1rritatinc eff=.C"i;, of Qil2I'tZ but not of asbestos; (1.1) serpentine has the same chemic~~ CO!&!p,)sition as lo~-.fiber c!!I'"J8otile but it does not produce the sa:ne k:iJ:ld. !)f tis!ru.::! reecticn; (5') there is a tide range in the chemical cOiiq;-osit.ion of the !!line!.~als l':hich do cause asbestosis (see .t'...... __: . ....;=.=-~ ......_... -_.:- Tn viaif at-this evidence it SGE!.iilS more likoly that e.sbestosiB is CCUlsed by an ~ua1. mechanical. ilTitaticn .n:-om lone asbest.os tiber::; i'robabloy this irritation~1related to t.he pacl111az" filamented structure of the fiber and the associated nexiMlity, which ure possessed 01' no other 10reign body. For example, ignition of chr)rsotlle fibers changed their structura and made them inert 1Fh1le the 8al!le fibers, before being hea.ted, ~ produ.c) fibrosis (see Table 19). Further support for the thaury of Jtiechanical irrit.ation ia that asbestosis occurs in an orga.n of high Iilobility - the lung - and that a fibrOt18 reaction can be produced by injection of asbestos fibers into the peritonel1lll, 1Ibere there is also a degree o.r mbility, bu.t not in other extrapul!nona.ry organs .. The experimental investigation with asbestos m:iD!rals \'18.S C'.oncerned primar1ly 'With the e!'.f'ect of the d.ust on nor.naJ.. tissue but some attention was gl~en to other phaaes, suoh as BUSceptlbility to inf'sction and occurt'snce of m.l.ignanc;y. 89.. Ini"eet1on. Tha. only ~1'"imAnt. i.n 'Wbi.ch t.he effect. ot i.nh.a1ed .aebest.os d.ust. o~ a pul.- monary infection 1'aS studied -nas the. first inhala~ion experiment ~ carried on 1rith UfingJs fl.oats" dust. It is, perhaps, unfortunate that infection 8tudiee "'ffere not made :in the other i..-malation experiments also. . ...... ,.LYe. I ..' FEB-13~95 MON 17: 37 to,"' - '{W'Tr'iMb" S" tt' , n J F HUMPHREYS P' En ' , -ATTY FAX ,NO. 3043434186 P.46 , 90.. Su.~ceptibility to TubereuloU3 Infection. The development of a tuber- - CulOUB process~i.nit1ated at the begirming of exposure to asbestos dtU3t, and also o an inf'ection superimposed Section.s upon an established asbestosis J '?I'a8 rle~cri!led in 19 and 20,_Qf this re- -.::.~ ...1 t ......Il_...-----,. ..... , __ " . - _ . . : - . . . port;. It rill be noted that asbestos, wheD classified accordiilg to the eff'ect of a dust on tuberculous infection, would be placed belo~ an active dust like quartz but above inert dusts, suc."l as calcite and g7P3UJil. In enicals infected rlth at"iercua.ted tubercle bacilli, quartz will cause the infectious process to ' progress until the anlmal. dies of tuberculosis. Inert dusts nil have no effect on the infection and the lesions lYill usua.lly hBaJ. and the disease disappear. t..s~stos dust is in a differallt category_ V:,nen the fibrous dust. was being in- haled during the evolution 0.( thtt infection. there was a spreading of the tuberculous process for a time but usua.lly the stimnlus tar continued proliferat.ion of the tuoercle bacilli was not sust.a1noo, the pl"Ogt'eOsion MIS arrested and bea.ling fol101l"Bd. In guinea pigs infected lIit.h atteuuat.ed tubercle bacilli following t.he completion of nearly .three yaars of exposure to asbest.os dust, progressive disease did not develop. Th90~ IOOdif'icatiOll or the intect:ion was one of l.oc.alhation, a rerr bacilli being retained in the fibro1lS tem1nal bronchioles and forming tubercles there in addition to the usual foci benealth the pleura. Such tubercles healed in a few months &nd there 1raB notb1ng to suggest ;my- infiuence on the I cO'\lr8e of the dise.a.se. 9L SllBceptibilit:r..to Non-1'ubercu1oua Infection. There was no pointed experiment concerniDg the effect of inhaled asbestos dust on non-tuberculous infection. Intercurrent pneu- e llDnia among aniuaJ s exposoo to asbestos dust. -.ra.s rather coumm, the frequency in guinea pigs exposed jn the four :inhal..stion erperimen:ts ranging froJ\ l6 to .3S' pa!" FEB-13-95 MON 17:38' J F HUMPHREYS ATTY FAX NO. 3043434186 P. 47 r " dust on non-tuoo:-C1J.lC-:lS iT-faction. ~~G;.rerthele3s,_ since auch epi.der:ri.cs are not uncom:non in inhalaticn exper-1.u:antz ',nth other dusts and even in the colony of ..... '. __ normal Gniroals, i t i~ i"slt. that, the inhal.at.io~l or asbestos dU3t docs not as:::ert ~==.:...... ~,." a .: .. .t,.. ..! I -" . "-'. sio-ni.1'icant effe!:t on. the susceptibilj.t1 to ..non-t,werculous Jl1Jlm:lllary 1r.teotion. , CJ. c..~ ~ ].t:.~ LA - "1'" ,~ specific eT.'p_el'"-ir~lG("r\'t \w'~as' c'nd'lCyecl 'C;. .erm.ne to d ,.:.I~ .('____ eo ...m...::.e:-'Lh.e.r~Vth'/e",i\hch:.a.l-ati~on c; " \\ of v,"',J) l '(-;P,- l',oc.4_ ~ " . , asbestos fa..!~x:s._the c.evelopment ~ . ' ,,r , of neopla:Jtic...d1 ~j!3e, but "I ce.\...v.. atn observations on . posed moni\graph on asbestosis 1943.... In ii he called atten- tion to the ~ incidence r 1 ~ .fnl-..all.ng l.c::!g-fiber asbestos. \ In his e.xper:1.Dlen'hal not.9s hcnr: e sse lesions as adenomas. \ There 'is an :lJnporl \ \ made clear. A cancer i , and cancer fihich sbould be or neo~s-'m, capa';)le r l!>Cal in' 'aaion and de- ~ struction of t.is5't1e, Wt ich CR."l distrib6te cells through he l.;rmphat lcs or blood ted. foci, .trO;m' which new tumors of diaseznination is , ma.l.i.:.anant grOfti;h, 0 as / meJfastasis and any tumor 1Ihich . 'ilhicb cancer is one 1;y-pe. An adenoma, 0 the 0 .her hand, :is \ ' , a so-called. benign or ,no~1\"gnant tu:nor (neopl.as:n) which may capable of local asion bu\mich does not metastasize. ", In order to el..arify the!! ~ct nature of tbe36 lesions the pat i.al. is being carefully exatlined~, Since it 1.s :fe1.t. dedirable to ~ ha';, ho ~n~it of Doctor Vonval.df s judgme.t:rt" a \ ren.ew of the data on t.~ suhjec~", is b i.ng post- poned until af't,er his ret';Jrn from pe. Rather than delay the ent....-e r further discU3Ul.On will ba raservGo fo a supple:oont to 00 issued lat 1-. \ FEB-13-95 ;MON17: 38 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 48 'wu -'- convenient to state tuo c:mclusiolls/deri' :.... f!'~m t~e j.II'Iestibation a:;.~, ''''hen nece8I3ar")-~ IoJ.lw ach. one nth a br': r re:l1.~ of ~::.he evic::r..c~. ,-, .... ..' . ""'::':""::....-1 .- ' .. _"-'': ... c.., A. V<..ri011S forms oi asb'3stos,hibers produce a peribronchiCllar fibrosis of.' the lttngs of gui~lea p.:i..gs, rats" cats and rabbits bU'ii not. of mice anu. ~ii;tlreS Eoth ir.hc;.la:tior. lL...""<i injection e.."tpt':'rilDents prmride ~::.p.L... F'I~jlpor~ 5 and 6 ehotr t.he re<:,ctiCln ....... .. , to tno di,fferent k of asbestos mineral. ~ "'4~..,...,..- B. The mode of act.i0nE:gClIIj;a!P'5'~~~ 1f;eehtm~61 ruther l:,l1an che!!lical in :.la.tura The evidence is give LXXXVII. Figures l; 2, 3, 4 or.d '!he fibrous fiJ..a..l'len'i.:-:-,J struct.ure of nsbest s~?eea4 pla:f au essential part in t,h~ :L..-rit.ating a.ction, ince the solid fibers of glass lmol do not c. .. ' D. produce fibrosis ee I"i:;ure B). .. I L.:'" ( ~",.,.--, Short. asbes'tos fibere do not produce fibrosis. - '5(."'"~~.........o. The (Mil 1 elen is " plied in thg e~idence Entio~e~ i~ para- graph B above. are ;~tir. ru..3::lts l'lhich f".lI'"ther eupvort tr.is ficdin~ 'l'Jpical fibrosis CBn be produced by ~:.n atmospheric suspen5ic:l at: asbestos dust cant ." ~ or:l)" an e:n.remel-y :small prcporHor:. of long fibers. In the inhalatic e:cperi:nent wlth 100 psr cent ba11-ci.~led. , , _ .... (......1 J.' ., FEB~1~-95 ~110N 17: 39 . J F HUMPHREYS ATTY FAX NO, 3043434186 p, 49 ---.. -... ~--......... --...... -..... . -" .n.. t.. _1c..)..\, : ::-j.c:T'On::;: ?s is ::;'horm i:1 TClblc 11. In clntrns~ the 1ccr-&.- "trlichc;;0. ~.~:.:~ct.io!l expe;:i;;u:mt Tii.~~h finC) aab:3stcs dust con..,.. : t2..i.,.'~.!1:; ~::. -_ - ..-..... .. ( ~q.et:-> '-i'-tl.'I,'l", -::." Ini1als.ttQn o~ t.he /0. " ~~. N ~'\ L.'LtJ ~I? of e:Cl;erjli:e~1'::'~l,tubGrculC'lsis i.n '.. inC2a pigsJi"""'" ~t..a:- f' evidence or. 1'ihich it is baseci :~oe3 not conform with cur ence -:'0 ''!-,lble 3 nil 3hetr that v:hen ~afer..... cO:.!lcicient -;:tt.h oraser:, o.t dust, F.n..'"}:'Osure "there I 9 tarrlporarf progressior. of the c5.isca:3e ~1.th ~mbsequmlt healin J men i!.d"ect.ion mlS tuberculo',lS disease'r.as not ~>ppre L'l cent!".s.st) it haS be~n observ~~ in experiment~ containing ~~z that if there is a slight regression of the tubercu- losu ",hen infection a.nd dust. 6 effect is ~Te ElaTked (inst.cad a less .. as ~ith asbestos} ...t.en infectlon is inttiatec a.ftlS~ a. p rioc1 of dust exp~:mr6. This conc:_'.lsion concerni:1g the e feet of in..'1caed a.gbesto~ dust. on tll',:)e:rct.::!.osis seel!lS J'Usti t1.-.r9 tes't (i;:lfcct.io':1 initided a. ~ecaUBe in the ~ore ser~i- u period or dustei:posvTe) tuhercul~(:.:; infc:.ction. li:n;:B't"sr, ince t:le i'indi.ng~ in thE  FEB:"13-95 MON 11:39 . J F HUMPHREYS ATTY FAX NO. 3043434186 P.so \ \ \ Binca t.h~ du..'3;-.5.nf: r.:at.eri.::.l US3Cj3_1l -:'~F~ :~i:~;le E:xr~~rii;l~nt d8d--,L..-.....ng':l.:'tI1 ;',n.~.f.:lCi..;:.;.O~'. J e d ' COrti-.,a. ~il ~n..~~i_::;' -. ] ~. r!-l.i.cn,:;"~8 .,r S'UlC-."1:" ~:lO't:..i.\' of r;~~.t.L\../~ t.:..:.:i:~t.:.::,;,~;: :;.... :".~ .~:~._.;...c. ;.:.....:.~~.:~ ~: ....~~, :.:.. furt:"er iiIlJe:;tig&tion of side:i.'"6d t) ? _ The oI'!!l3.~io~ o f . iGS ~~e:.iS ~e!Jl"esen~ a coat.i~r of ~ bi~ t '1)~- {I,}. OJ,':;'" .. c.!:... ~I CIt.. ~\\~"t the fibers ~~s in 10 5 c.r tl:re ;-:').ll:!.ty~to -;:ro:luce f:5.'broflis. Intratracheal i..'"ljection r asbC:3tOSj.S b:)di~s f:r.il-:ld te. ?J,.'OC.uce the typical tis asbestos dus7. soon a! er axpos~ tarmi:"12.t.s !iL.':i.]' be due to the formation of asbestcsi3 hcdia::o ...---- .. \.Sf:;. ',' I. . I / FEB-13-9S- 'MON 17: 17 . J F HUMPHREYS ATTY FAX NO. 3043434186 P. 02 ...... PLAINTIFF'S EXHIBIT 4170.1 AFFIDAVIT WASHINGTON DISTRICT OF COLUMBIA ) ) SSe ) BEFORE ME, the undersigned Notary public, ._- _-,,:;- . .-I--..-~ '---' .. personally came and appeared MICHAEL RHODE, a person of the full age of majority, being of sound mind and body, who, after being first duly sworn by me, did depose and say: I, MICHAEL RHODE, am an employee of the Armed Forces Institute of Pathology, Washington, D.C. I am custodian of the original archives of Dr. Arthur J. Vorwald. Pages 1 through .:L L. attached hereto are true, correct and authentic copies of documents from Dr. Arthur vorwald's archives. The pages a ttache.d are Revised version of ASBESTOSIS Ex.,perimental Studies_ by The Saranac Laboratory. Report to. the Johns-Manville Corporation. dated January 31. 1949 Dr. Vorwald was the Director of the Saranac Laboratory of the Trudeau Institute. Upon his death, Dr. Vorwald's archives were donated to the Armed Forces Institute of pathology by his widow. I Dr. Vorwald's archives are in such condition as to raise no suspicion concerning their authenticity; they were received by the Armed Forces Institute of Pathology flOom Dr. Vorwald's widow after RHOD& AYFlDAVIT ~ Pac" 1 "f :z J F HUMPHREYS ATTY FAX NO. 3043434186 P.03 Dr. Vorwald's death; they are presently on file as authorized by - law in the National Museum of Health & Medicine, Armed Forces Institute of Pathology, Building 54, Walter Reed Army Medical cer:~.er, Washington, ..D.. C. 20306:-6000; and the arch-iYes halTa:-heen"~~ existence for 20 (twenty) or more years. SWORN TO AND SUBSCRIBED before me, the unders igned Notary PUblic, on this the _-L7~:It=~-_ day of April, 1992. My comm~s;:;i:p:.-ExPires: 2-/~- ~ , NOTARY PUBLIC -;:::<. __ . printed Name: ~I (<- Iii/. VVLLL. (ji,." $. ,. RHODE Al'FJDAVIT - 'P1l&" 2 of 2 ... . .~----------.--. .. .' MzTR~t.rr..Ur Ltrz llfstiRA>fcz CoKPAXY c . . N.u.c. JIIn:In;ra."",~- to,,.,y, .... ...,.."..l. ~M.A . . -. . . .. . . . . )' - .'& D - - &z -o ,,,.1 _ to. t:W I..J'1,ar Z. YCIA9.l.4 'I-.i4UGa an....r.z.....u....w.......~ , t II...olorrr tc ~..rt. 'rMab SAt~ lit' tar II r. J"OIU' ln1.er eL ood.a.z'oI:1 that & tM U \b. I!!I&.... jut ~ .... t.Uc b&a ::..- o.a..l.:i..-d ~ ae:::- a~u... 1.D Icz~ tor~l:rtr U. 1.0 cU.01UJ. 't.I:l.e .... ~ d ~t1o: 1Jl 1M ~ IOi31 Qu.~ &lX1 i.o ~ '-be po.tl Ucm tat.. It. ~ .. ~ or 1.~ ...... JI06&1bl.e t.o MTW ... or two M.l.pt'\&.l ~~ U" ooc:::u:a I'OpoM. aT" 1)- "'. t.o J r, eeat.......... ,..;n... % We u;a tn. !D I ~ ~ tor \A1a ctU:a~ t lIII'\ .c 11M .s.__ t:l.- 1.1 h&l.l.T ... ~. wi .1. W1\b '"" ~ &ad lien ~ ror ~ ....l s cf..e7 ....I'QD. a.1Aoe~ ,...,.., o -_ _....... --- -_.-- .... ,,; PLAINTIfF'S r EXHIBIT I 48 33. r -, PLAINTIFF'S EXHIBIT ML-l.\t 3:!> ~~~CoMPAXY Oint ~ . _ .... J:!:Jv":t>a . . KY. ........-..,.,.... ;. .. _.11 CC......,PI_I _ t: - ..... t ~ a ,M-r 20, 1.941 I .. .,.:...... ...."'r . t Pr.( . .~ ,. . ~. 'lI ~.~,~ '!M ~ 1.&bon.1m'7' a...r...-.a Wb. ]I ow %~ ~?' .u~ ~ 1a 1m4ar ecmt.z'oJ. &Dd. t.baA w:1.ll ~ ao .. ..~v ~or ". too ~~ ce t.o I&ca t : n & l . _ U. 23"t.b. " ,. , .'.~ \, 1MIYe U" r_.wll4 AI' "ft" A, 41..~..ta UH , l'uIa" u~t.A' l.Io.n.W.1I171.a, n...... ,t... t.M JIIl"-l.',ee er '1M "port .. ,....,t~ .,&1, ...t ...bl' Sa \M IClG.l'Ml .t Wutr1.al .. aN4su1 Ut ae , "l. '" . . ."ojriaw Sa.... DI'. &. 6. , . : , '- ''';. . . " ' " . .~ Y., 'nJ, r-re . / " '.. ~14M4~ , y..uYG'~ ~ ... IiIaeJoaI. " A'to..., . laid. . ~. Pl."'" , w ee AL.. .c.. BaH '. '. J. P. 1oodu4 .. " .... . . :._ a' ,. '.- " " < -... . .- .,..... . .. ... . : .. ::- ," ;:...'\ ~ ' :. ~ ": . . " :' ,';' '..