Document bakEbgOYy3v2Bv5qkpp9ZwrmD

EXHIBIT IV .-*-h r^^ -w- v/* -**7^; V''"1.*.t)''? ~A * i W if W * 'x* * * 4 * V * ,' W W vW .*,it<v . 'w*?1C"*\rr' T ,'**.*"" " .. *r-~.*"-".-' r-t^ <crt'C^.CJ *4 J + t .\ `+ 1 >*)"-- ul K** * * *-rf 1 V / * A" * Mm 't -i'- - r V - k . W ^ . f i v V * .'m W* m V * W *:* ` # ll-lhlOD; Oo/'Jl'/co ** 0w,-*.../ .v i hrancapai Investigator; _ . y/.li.inn S* Smith, M.D. ,,k^lth Retearch Institute farr.*.crgn Drcninscn univtrsr mani son, N u * 0/940 1 c? v**--- n^ J i l r - . ^ C c r t f i ;o w * PV.. ,* arm O m V 4*A was to test 23 prepareti pr asbestos or other.minerals tor carcinogenicity ry mans of intrapleuraisl1 injections into hVat*msr-t--erts<. Each sample was tested in a group of 50 boasters. In addin . groups of untreated control hamsters were followed N^Nr ***<' W V>**CfeaMWOU*/ wVfca*-*w'* ciX^O) Q V"1Nrmm V#Nr*<OMm'\S . Ancillary experiments--and::observations arc describee* _ uii end of m s report ( All hamsters used for this work wera LVG:LhIi mal crtained^ as weanlings from Lakeview Hamster Colony., .fevfiold, H.Jv When the hamsters reached a body weig of ICO f 10 gns (about 2 months of age) each hamster be treated was given a single injection into the righ pleural cavity* Each- injection consisted of 0.5 ml of suspension of the selected material in C.5-3 ha Cl sol i**e v.or^ or</c.s, to rn.wxm.im P'ornoas or wpt**-ww* w WwWV~.4 ^Vwlu\.M C^. W*W<iiSw WA*W Opt CCi.'.wW 4..C1 ,060*::.v f ..w>-Vv i ' l,, w oc;::.r t l , . >- lor ana head. Groce observation' -.*1 ^ i 4^ ^ W W 'v* Vm, 4*h W V*. -*' ' rad. v v I J a U C U Thoracic menus were fixed in formalin as were oertinanc xes-.c ..'curd elsewhere. Microscopic eotrons wore cut and ..a l a n .*enato.*y*.*. c-,1'* o -v. por recording and retrieval, of data;, we designed and 'nsec a pun on card cor inc^viuUu* herrs^e.s a* ^^*rb;i ^V n,rv *i^3 ^ * 4> ' Pig' 1* Punch card -used to record findings on individual ' hamsters. ' ', 'ire necropsy, -the prosector entered identification . 0* C-4 4 OC% W 1 Vfc W-* **" N"< ' . - < y x. n >- ^ *. ** jkwi> v Ud A ^ >, C*r --s ^ Ai*ik Am *, v. V h, A J y l ^ O w b l-- Wi y acc .iCcw-^r Vw**# days on oroerirr.cnw ^# c'"i'`,^r^n C.->-n7 V . .d ' w of pleural uoaosicne. character c ,,y *,. i * * w w W '-- V W -.. _j.-vCeV-O-* or diffuse), P_~ . a or absence of dc2/'w, v***w---- .* pj.t*.guce, caraiac tj.* C .* ' other pathology. Gross rinding- dr. the thorax were w.iC. .<Vetched On diagrams shown in the center of the card. VT W- ^,c-'.-.thologic findings were subsequent entered in the spaces provided to the right of the double line with special reference to diagnosis of any tutors, to characteristics cf pleural adhesions, presence or 'absence of mineral particles, ferruginous bodies or - other pathology. Where additional descriptions of gross or macroscopic pathology were warranted, these were entered on a separate blank card. All animals in these experiments have been examined ml necroosy except for rare cannabaliaad individuels, . Histopathologic studies have now been made on tissues saved from all animals except for rare autolyzed individuals. 1*11 tumors diagncsld as mesotheliomas have been confirmed m i c r o s c o p i c a l l y t u m o r s suggesting mesothelioma in the gross werf'in nimals where autolysis precluded tt."**. ~ histopathologic study. Tumors listed in -this report as mesothelioma resembled these illustrated and described r previous work with intrapleural injection Of otiie and am.osite into hamsters. (Smith, W "3m*."!'at.*^ T**ik il',>%Elsasser and D.D. Hubs rt. Tests .A. vJ .nogenicicy of Asbsstco; Annals. N 1* Acad Sci 132 (Art 1) *.450-433, 1955) ,, (Smith, VAH., L. Hiller, J. Churg , i 4k ' .ar.a 1 *3 * Sclikoff, Mesotheliomas in Hamsters Follcwincr s . cur.--L i-- * - . y V <.4 J* *. -, ' ..\ / '- ^ \ w* -0* tr U O U I F t W %.> v. * ,, C m, e */ - -- V , . * ^"" " , ^: b 4 A > ' - ' *. *1 1 * Ci ro summarized in Table 1. , , *wr W O * * lj* kW - * -- w . Tumors listed in Tabla 1 under -the heading "Mesothulicm. ura with few exceptions large nasses in the'pleural space. They compressed but rarely invaded the lungs. Mic4 W C#C/ C!.s*-*4. *^ They were composed of elongated or rounded cells that appeared malignant. Under a separate heading of "Lymphoid Tumors", Table 1 lists lymphomas, lymphosarcomas or reticulum cell sarcomas that were found in occasional animals of the various groups. These "Lymphoid Tumors* occurcd in mediastinal or mesenteric nodes, sometimes 4 vidth leukemic features. Injection site sarcomas, also listed separately in Table 1, were tumors found sub- cutaneousiv on the chest v/ail in -the area where intra pleural injection had been made. Mineral particles of the test samples were usually seen in microscopic * sections of injection site sarcomas. ** From yields of tumors designated as mesotheliomas in Table 1, information emerged on the following points; 1* The yield cf mesotheliomas in response to 3 dose ` levels of chrysotila (Groups 2,7,8}, 2 dose levels ot amosrus (Groups 9, 10) and 2 dose levels of crcc.ucoj.ite (Groups IS,19) is dose related, hence -ii*Ci i*' '*V.- . .. . r * f V in exioeow- -'--> ?r ,"'- v-i.- v ^ * * w ~ - crocidciiu ...ne o*/ ^v.w t* u*.'**.*~r^'^-*OvL.^; . jr.oi.it.; ^J L4. 'W - * - Closely comparable yields of mesotheliomas resulted from soft (Croup 1} an harsh (Group 2`, chrysotile fibers prepared fr6n Arizona ores, and from the sair.s soft fibers hcahec. to reduce tneir content of molecular water to the level of harsh fibers (Group 3), The tumors arose more rapidly'. in response to native harsh fibers (Table 2}. Studies of pleural adhesions revealed that harsh chrysotile induced thichet and denser scars than ora chrysotile Aiun^.a^n heat w-- eatrr.cnt o^ ;0_w chrysotile jjgkve no appreciable enhancement of carcinogenicity, it did enhance fibrogenicity (2) tested (25mg) ,3 *3 , fiber lengths 22 and 39 microns yielded 8, S` and 10 m.eessootthaelioma bearing animals (Groups 1,2,3). When fiber lengths of these chrysotiles were reduced to an extent where the large ma~oricy of fibers were less than . microns in length, fibrogen-wC uy was reduced end carcinogenicity vas ^limanatsd (Groups 4,5,3).  V <r. 4 4 :^r :\ A--, -- \ ,-v * */", %* V > . *i-* , ,' * -* O X* * vP O . ^ V - * * -- '*- ./ C- t-. v-r-*-A 'i viCl 0 ^ 0 ^L. tiC*O. 0 Cr* ** * * ^ ` * "u'' U ^ t-t-/,OMl^ *-- *-^ C/ **!S / <*u t ,, Gantt. Preparation of a^"* w Fibers for bay:;rinanta1 Us e. frmals Of 1! b head Sci j ^ 4***iJw rim J # ' 1965). Fibers w u s prepared were ground in a 17ig~L-2ug to produce 44 tha short fiber samples. The 'Wigflr-Eug process was monatorcg by pease nrcl occupy and stoppeci bc^o,t_ uestruetrcn cf che nstijcc of the mawe^-ic*.*.. These samples were furnished to Dr. CT# Loineveber at Johns-Kanvi1ie Research u Engineering Center for electron micrography. From-his photographs it was Jr-V*4 %* -- <&- C-* 4.O b C- U 4 4 U fiber sar.pl ly few fibers *i a c* <" **V ^ C t. t J O 04*Ui* w whereas the short fiber samples contained relatively few fibers mere than 5 microns in length. Dr. Leine- webor noted that the short fiber samples had not been reduced to amorphous Material but preserved the fibrous structure of ebrysotile. Further -discussion * Of length measurements is offered later in this report 4 Tests of long and short fiber anthophyliita t gave results consistent with an hypothesis that ,,eduction an fiber length reduced carcinogenicity/ - . * # ^ ^ `w ' - l y j * r u . --. C* V rfC * -* -- c. > *+. M. r W- -4 n . C w w ^ r s *- * *** *-! *- - C l > V*. i i fc L - i V. - L* - - o ** *-4 U W )*' rw W4 it* tnu IGmg -lovely long fi' anthophyilite incuced 3 mesotheliomas (Group 20, . short fiber anthcphyllite induced 1 mesothelioma 'Croup 21) ' The short fiber sample was prepared by grinding the'long fibers in a Wig-1-bug, the process being ^ stopped before the fibrous nature of the material was destroyed. .. ;5 At the 10 mg dose level, mesotheliomas resulted from a sample of jaicrccuartr with mean fiber length of 55# 7 microns' (Group 12),- but not^from* glass fibers_ with or without phenol" formal binder (Groups 16, 2V . , _, , I, , i M O t w n an -- t i n i - - - p . . i n m -- i i i r T "**'***'*'- T r* ^* * * ' 1 " * lfri 111 Kean fiber lengths of tnese two. samples were 24.9 arc ; crcns, respectively. . o *At our highest (25mg) dose level., mesotheliomas were induced in hamsters by distcmaceous earth and by calcined %' diatomaceous earth, but net by talc, nemailta or, except for a single case, by serpentine rock dust (Groups 15, ISA, 14, 13, 11). The- sample of talc contained a large amount of tremolits. * I Mesotheliomas were unauced by powdered nickel tested at a IGmg doge level, the-yield, of mesotheliomas in response to nickel was closely comparable to the yield % **. ' LU \ y C* *,fchfciV. " J>. 'S*. c. i c* .i u * ^ ^1 level of crocnuonta. i.. lover or cnryscta-c v:he '-'id obtained wit yy 5o mesothe 1iorr.as nave scan found an the \i**w-ea-^a control groups. .. .' 9 Lyr.pr.oid rumors occurred in 14 cf the 23 treated groups t and l.* a o-- w*.a . u-. e oa i*cr.tcj. g ^ - * 1- These timers ware regarded, as spontaneous turners unrelated to treatment. . 10* 'Tumors of the adrenals ware common in both untreats ' A* 19 control groups and in treated groups. Hepatomas were found in 2 control and in 4 treated animals. Aaor.o- carcinoma of the intestine, was found in single animals in groups 2,5,, 13, 15, 15 and 18. '% **.v*/"***V*** i^ the left cardiac atrium were a common cause of death in hamsters in our experiments.. Such # occurred in .untreated control groups.- but in seme of the treated groups they vera f A ^?V*T^ V S7''> ~>f***i Li 4 * i U L U * w V i* V *4U **S^m W frequently, as shown in Tenia 2 cf addendum A (3) Computer programming and analyses or data from ^ for animals in grou*<p-ss.* r.hcra in rmable 1 has bee: Ccnr. --wcSW ir*** $ ^-r.*t oo ?e ;remev ' ; - - . 0 l i v l S * T .4 . a C 1 u. j - -- - W - ' -- ' ' < A # Ua r broder, cova 'W' I. 50 ^f X * / j* . XX W - - **- X / <- ------ 0 w-v --' ^^ X^ \ S *1 ,r v - - v i * * A i W*~4 * V* V ` , ^ j dead ir. period VI E S lost in period -W ... .*. W / -* or perioa-> '' - ^ iU -, *v" a -- ^^ W f . * ' 17i e s withdrawn in period ' * ^ 3 effective number rat risk in the period r L-* Qi probability of dyaag in the-period Pl probability of surviving in the period b survival rate 1 standard deviation :hese analyses, the group size used for tests in Aable 1 (50 hamsters per group) seems satisfactory for cau- narason of relative carcinogenicity of the tesued samples in uhe 100 cay periods. ' uu% Hay-ton's report on his statistical studies is attached as.Addendum A. 1 # In the preceding tent, fiber lengths cited for our samp 1 and 2 (Table 1) were determined by light microscopy using 40X objective and lCx ocular. These measurements were m T, /- the laboratory of' the Occupational'Eeal th 0<.a<.by Sw u o r New Jersey, at w ^ .uw Ot OUc -f- U a X. w C . '.rveu.^aa aamprs e^ s .y.n animals. Also an `cr.. sr * u < - U r v m wO 0 T JL V c* d -% 1 2 ^ O r. c* ', * ^ . n n i r A* -- '- C><. U - v . o f ' ? * tr. it w i. t* * w 1 w< w Va cW *-. o U -- v* ^w^ VW ,* * ..... # * * i*"N * f*. -s - 'I VT ri `~ xtn*uni.ny ra^~~aty in Cines.v ; u where 4OK objective, ,,.*; * ocular and phase contrast illumination were used. Recently, ; furnishes to Johns Kanvi11c Research a Manvilie .- id* J., whsre they vers stud .ve and a EM ocular by dark fiaid micros `linages being projected to a final magnification of 1C0X, photographed, then enlarged 2>iX for measurement of lengths and dimeters* Mean lengths reported under these latter conditions v:era considerably longer Maasurar.er.ts of samples . conditions are shewn in Table 3. arc measiirements made on these and u.'cr'cgr&phy at JM?ME*. . v^* -- t ; made at 20COM ana was V . i C . i ^ 4 i -A. C . ~ ^3 2*jX for no novo:aments. fibers extending beyond the EM field v.i;1'cre excluded from measurements, hence mean lengths reported in Table 3 for samples 1 and -2 are much smaller than mean lengths reported for these samples by optical microscopy,, 2a EM photographs, fibers less than 5 microns in length v:ore relatively scarce in samples .1 and'2, which were samples thc/c proved highly carcinogenic ir hamsters. *In samples 4,5 and 6 which proved non-carcinogcnic in hamsters, most fibers vote too short for meaningful measure- ft ns by optical methods* EX measurements cf sample 4 gave mean titer length cf 0.7-5 micron* 'EM photographs cf c a m as r 5 ana 3 each asout the same as sample 4, but have not yet bee .-.* o>'*'1r3 UJu.bti ' - i, \ . G UV-S i n HAUST;;u s al- ;:u u ;n :A R iu :u r \c i r: j i : c i 'l o u 5 U }i; ur: >i;o r i 'p o r qi.'OUp . u l a h i v e d a t a l o (50 d a y a e > :e c p t >.!.<: ce n o t.o d ) MAAM DOSS MBSGT11EI#-- SARCOMA LYM1MIOID REMARKS HIRER . LENGTH # 1 OKA UJJLCTIOH UUMOHS LITE m orons ^ -o*.-r--- --j. _ - ^-- J*- .^5*V-**.. 11rjV* . 1 s o u : CHIU. *'' -`T IL E 3 2 ,5 4 25 8 .2. . 1 4 2 haus n CHI SOTTLE S^u-U CHRYS, . (110 A G<1) 4 e*_.;.'V*. 4t.' C1i'.V' o r I LB `3 HARSH r : 'Tf : 33,05 * . 3 2 ,5 4 * 76 . % 1 (Up AjCCR ) 25 25 25 25 9, 10 0 0 < . #* . 3 '1 . '4 00 , 0. . 2 *a . ^a 700 d ay s ' . 700 d a y s ' ' . ' * > .. - . v i? UIU. s , (Ag g,1) 1 25 -'o x .) 1 / */ .o 700 d?.yo ' . \ 7 HA I'.SH CHRYSOTILS 3 3.85 * 10 4 ' 4 1 1 . r ;A.*.Ai 3 8.85 i.uHY. ./. u.r,-: ,) %\ ' , ' ^; "ni *7* 17 1 10 0 * 3 1. . . 2* 0 0 700 days .. '.0 .. -V' \fn 17 . 1 ' ' o 0 0 \4 AT (US [ ,iJ lJ I , ^. VUORIVCS) ' 25 v1 i - ' \- ' ' - 1,'* '3 5 ,7 * 5 3 .1 10 * A ar$ 0' 0 X4 . J o 700 days . 3- 3 V..a) j;;-<:;otUG!>. IN HAMSTERS AFTER IMTRAPLE URAL XMJKCTION 5) ham.*;toa:s per group (Cumulative ilata "to 050 days o^-ept where noted) ` ,nj> ;:o._ I'iKAN fiber LENGTH ;rf:'a'DCY13.t a l c , riA' a m a c e g u s ' DOS 25 25 \ IdA.A*'AACECUS ;;//;T:! (Calcined) 25 yj AS V?JT'll 24.9 'AAA 9A'"CAL UTV-'.'ER 10 ' *', 'o .V-.LA f 10 .- ;'A FACTS U* `C.,C.O. 10 C:AA A r'OACTE IJ.I.C.C. 1 .\AAi`A.;iALL ITE Long (UXCC)10 .. . :A':,XAE ShOAt (37)10 . . :Tie:AS 16,9 10 . . 1 .> . Sion3 - ,1 *.1J ' ilOAA MESOTHELTOMA --*--*&m*r+e* o SARCOMA JFIKCTXON S X a'JE 0` 32 4 ' '; 2 LYMPHOID REMARKS TUMORS 0 700 days 41 ' 2 ' . 1 ' * * 4 , 0 4 . 10 . 2 3 X o 9 0 0 . .4 5 0 V ` 4 5 *. 0 .1 4 *` 700 days 0 . ' . t 0` 2 o ; <s H . 9 0: 0 700 clays .0 ** ' 4 4 660 days (sn.cvi. ors are Ue^vj tol Xov.'cd to 100 days) .KS . p>4 y .VJjO O F Mil-SO'THK-L^OMA S ,, U A M S V * * A T S ' 3 ,MJi:CTWt'^ "" `::,J''" f'.vop ^ _ __ _t.^ - -t- .***''' *****' Sample ^ v,, -<tTM""**-*1-1'*** &Z (Karsh) 151 days 1/41 C2 ' (Soft) 0/44 *;M1 `.U Soit) 0/37 340 days 4/26 0/33 1/35 37?. days 4/21 1/30 450 days 7/16 1/20 500 550 days ^ days 600 days 7/13 ' 7/9 \ 4/11 . 4/9 8/5 7/3 650 dvi/V ` ,V k^.-*irw54> _*J'>t/'>=. '. i a/i ` ' * 1/27 4/17 5/lS 8/4 ' 10/1 . .. * . having mesotheliomas. C m m h H v i number of hamsters /-OV -^.tor: Number of surviving bamstere. Pleural atfnsslouc. but =0 tern**, Ml survivors at o/<j<O> u..a, y,,3 wWoc ir oC k-i ll e d o.n Ifc^t A a Y - " Fos: s a v a b a ^ . i - . . * . * s. <2 oJ: Selected .:J * 1 l.< ('?or .M'i'i'-m.eit'i'-M'd.i; oJ: other eanplos' see Table 1) r.abiA- OPTICAL HIC ROSCO)?Y EBBCCftOM ilCKOS COPY .. ib_er lend Te M*a...nn fibe-r lengJth nu.cirons' ~ * Huerons 30 rB y* < ' ' 32,54 52.5 6.0 30 B 30.35 0 63.5 c 5.3 0.75 hav-x--** o 12 c 56.7 7.38 ** S~e.plo nos, '-jro a5 those in 1 TC v j ri>*w js,.,."? **-- u*-f- a 4* Bab As 4GX objectiva, OX ocular (phase contrast) Lab B: 40X " 1CX (dark field) Lab.Cs 12X ;1 5X , o uiplo 4 i/ero tco ttiX1 `oc noasa:.:e-ent by ooti. ^` ... Tu O- <-*.4m ^ W* j v:u are indebted to Drj* - mes ieir.ev or, *11 c^ * a ^ .4. w + * * 1 * w* / Dailey ana Com srovn*,, . Dsimaes oi ofu ci^.v... . oil 'wiirys lie orspare a -- laboratory from Arizona- or-s were sent. to DDrr.. CCrraaal~lva~y/ iirn. 1-9a- `for analysis of trace elegants by atomic absorption spectra- aeotv. The following report woo received trot him on toes- saitples, v;hich ware the "long .finer** samples tnat proved highly carcinogenic in our intrapleural tests m nans (Groups 1 and 2). .- * ' Sample >"<?. #r. * ^Oh ' Material Hieroerram Ni Chrysotile .(harsh) N.D. elernent/ errn samela > Co 4*--n 'h.D,,. it*y1*># 420 * WW* Chrysotale {soit/ 9.D . *>v iimJ1 ms..J**V#. * Prom these results, it can be seen that no detectable craiunts of nickelt chromium or cocaat were found .... f t sanaics as xngeccacL into hems tors Subsequently, Dr. Cralley's group developed a micrcsiev method for separating "longer than 10 micron" (-rlCyl and aZess than 10 micron (-10u) fractions of asbestos and etna certain trace elements m higaar ccncentr c.^.ion in "in.~ - fractions. In .359, we r ^ viubmitcec. our samples to D r - They were 4 m -- -- O ntory and n<; 3 <i <-i-U *nv . CX r* <60 *riOp <so. * V - .r- M V .> uLj*# -10u <50 *A1SJ>.`1 157 27i <10: .. -j k 'o 230 3i0 < 9 4>yJ> WA. 46 w-A 710 1800 185 118 - './ .J C. ; *=1*^ 2.1 iOl< means not derec a& ^WnCOc^e '47*rem the VU* * it is seen that detectable amounts of chromium and nickel ware not found in the s-lCu fractions bun were found in the I'*M W * fractions. The -10ji fractions constituted 6 to 76 by weight or the sanles. Thesenfractionations were nrace or. our ftlor.g" (2-39 rean fiber length) samples that preved y carcinogenic in hamsters. If'trac >^ .-n ** ^ ^lass than 10 micron11 fractions were important in carcincger.esi then high carcinogenicity would have been expected in our "short" (1-5 micron) preparations of these ores, but such was not the case, our short preparations proving essentially U'* non-carcinogenic. . * _ The following, studies were not part of the aims stated ror this project in our original proposal but were carric out as ancillary work: ' ' . a. xn a previous project, we had carreea out ZtX..,UmmUI-wAO^ U.^ VV"kmotors given repea or W*nAv*.X wyOr-O^W4-***- with and withour. % ^^^ {*Cl\t r' r -- *<**-^ W w' 1 6-  #' ' 0 <*-*- O -- f-t'*.W>"* fccJV*`Vz4*-v-'t; v** vh -ft.* -,iTs-*-v1 m o s e an.-....aas we .v/.rCft A'* W**'-- CVft.ft.ft.-.a of -he prCwiftiz W h rJsAv-*fW>rr*V.*<-A'W'"-*f't{-"*A -***''4. ;;-. aatached publication ( 4 h. Hesters given a cicyla intratracheal injccuica of ohrysotile were sacrificed at intervals for examination of lungs by electron micrography with results described . . c 2 >, i e ) ( 7 ) . 4A . Cr For ..f.c)SAcrr.othcrsT*3ev*tif: trials, a fast-grov/ing n.eso* ' thaliota induced by ehryaotilo ,and a slcwggrcv?ir*g r.es ' .thelicr.a induced by eroeidolite have been established and are being carried in serial transfer in new loses - (hamsters). ' i* j a. Dc*aan:ot? cell car ciner.as and adcnocarcincr.se were intoned iron rouse pulmonary tissue exposed to chrysccil { 8 }. For chemotherapeutic trials, 2 lines of these * walmonary seruanous ceil carcinomas- ar.d one line of * pulmonary adenocarcinoma have#been established and are being carried in serial transfer in new hosts .(BlLl/c mice)4 . '' biSF OF FF3U1TS *fti*M& ftVT.A* W*. ftVfti*A^ MMW ?Wift1-ft--ft-^MMCt*-Aft " ftAt^"%*0WftftVbft1 VfGtS4 JAftWftft*ftf ft-S rN /'ft N '-VS o ^* r V -_4__-- <ft - nj. - ju. 4 1 b M `t O U C ^ ^ f . *- \.`V /" ~ - ", H ** ; .* ' i v u ' *' "1 t y - ''i.. -> -, -j "* y *-- - c* J - -* /Af<t*"- y * v- 4** U * 44 ^ ft* * W ftA <--- A >w4 -- *W W 4^ fthi W. v-ft 4ft* C- A X a 1 ft# W ft C 4ft ft 4 A. V *^*J G ^ft ^' J. u 'A* ci , ftv 'i * r- ^ vft ^ ft- *n a ft ^ /*> " vi ,*. v * ^ r* \ ~ Z : /-N *~* *- , - t f r A ^ - ' "* SOVftft.* *' * A - -*-.-ft-_ ^ ft" -- -ft i. V. *.ft- ft -- ft- w. 4. A. ^ w* Sm ft*'ftZ * ft Sr' ft'^fftftt-WW VVy -- J `ww U'/ -ft**- '-- * ft-ft'^ <*4ft ^- ftft* -- ^ i-ftj -ft -> ftift Vft'^ ^ V Ju r ftC\,*"w 4jto1 w ft^P* f 0 ftft Uft..Uft vftft- s -ft-ftw w ^ G ftft.tftft w Vft*ft-.4`^K Vft*ft* Vz Wv O Orr J.' *4b'ckel *o*owd'er and rbcroqu`arc:: fibers, VtUM -^action of trenailta tele.. T~>i;.ta or glass fibers. Ser- v\ >r~m %. pontine rock dust- (antigeritr., induced only a single case of mesothelioma. '' 2* Native harsh chrysotile induced tumors more rapidly than soft chrysotile. Heat treatment of soft chrysotile increased fibre-gen icity bun not carcinogenicity. 1 hith reduction in dose,, there was reduction in. fibrogenic .and carcinogenic response to chrysotile, arosite and croci- dolite. Hence, hazards associated with exposures to asbestos should be controllable by measures to reduce.amounts of ex -%.r^wc*w*l;"*t*(WC*i# * * *` * * , <U At the lowest dose level tested (Irr.gj, no tumors arose an response to chrysotile or emosite, but tumors were found in response to crocidolite. '' . * a V7ith each of 3 samples of chrysotile, treatment to reduce liber length reduced fibrogenic responses and eliminated car cinogenic responses. Electron microscopy revealed that tie treated samples were fibrous in nature and had not been re duced to-amorphous material, ihcse findings afford informa tion pertinent to design of risks and to monitoring of dusts for industrial hygiene purposes. lb l?ol'/rvir.ylit'vridin-l>c.::iie- v..aa not inhibit fibrosis inused by asbestos injected intrap lourally into heritors . V. After intratracheal injection of chrysotile into ^;rns t-rs electron micrography revealed phagocytosis of asbestos fibers -- ------------ ---------- - -- -- LWO022G v L * r r . u c r o p h r c e s . . V* N* ;c ov eoitheb'iai ca~.~ v - ' - a o ^ o o . . . . 3. l b 0 1 * 3 t S i d ops X. O * *-1 a O -- 2 r / c r * .i m * . a c . . e ^ c lr r y m o t i l e i n t o h a m s t e r s S ^fA.* incidence of lung tutors was ereeutor than after banco u; pyrene alone* 5. After exposure .of fetal rouse lung tissue to cnrysotilo `r ? tissue tren.o'olaXit tcchmouc? ctucncus cell carc-t.aG.ias 'and ucenccarcinotns resulted. * 10 o For chsoothe repout!c nrlain, tv?o lines of transplantable aiesotheliorr.as were established in serial transfer in h.nr.jrare, two lino.? of pulmonary sepanmoas cell c a r c m o m s and one ir.c - of pultonary adenocarcinoma were established m serial 4 u.v^.m or .-ii tiu^u . H . . statistical traatnsat cf responser. of h a t e r s -co iatraj>lr.v!r?J. injection cf tar.tsd s:i.ncstls is dascrisr.i. 12 o * Additional manuscripts are in preparation rcr puolicnuior. 5C*-,G Ge as *' --,' . - -*S' ')*('< c*---.r,fcV* <> * *S> A . S.- * `A -- \ . . _ * * 4.4 V V % '* W v * V r f * * W V A f / ^3A/o1 Vs n r\ i. - m . , U * tm * A , K >4-- ' - Mf +~1 killer, ' T1*r V<* t* 4- *'* a. O tos V ^ ^ v. rv * - - Vw M ... V "p ^ j . b tier.. '> / Dre sden, Ga~.. --n Dem h.S. Bado1let and Baaollet, M.E., Physical Properties and Technical As pi c a n o n s or /to--v"n --^ rr *- r> ckJ *'^*v- h z""*--v*-f\ ^ r r, \ *n*1 11' "i S*wOTi i*kVafc . Xi *a^ wtf C* JLr . 2:432-427.;, April 19Gi `T^^*V->v*-w O^ 2*w? h> ** a^-ru--av*> aann dd bTlmn. E. Smith, Increased o n Ur*-C.-.-^-.U-1J.;4-N./-Pv , >w.. b a s eass i. n I a m t o r s Trcaned with Asbestos and Talc la J Path 55:31a, 1555. Ge Smith, Kn.E. , L. yiliar and J, Churg. Asa Experimental y.odel for Stray of Co-earesnegonesis in ahc Pc-spiremery Tract. Atonic Energy Commission Symposium. Series, in press. . 5* Suzuki. Y. , J. Churg and In. E. Smith. Development of . Asbestos Bodies in Euparinar.tsl globestoois. Amer J Path 52:20a, 19G3 *` . '. 5 Suzuki, Y., J . Churg and hi. E. Smith, Phagocytosis Asbestos. Laboratory Investigation 13:335, 1535. *? Susuki, Y. . J. Churg and Km. E. Smith, Behavior of .. Alveolar Epithelial Cells in Experimental Asbestos is II Internaticn Cenf. on Biel. Effects of Asbestos, .'Dresden, German Democratic Republic, 1953, in press. Smith, V7n. E. .and E. Yazdi, Induction of Carcinomas from Rouse Lung Transplanted with Asbestos. Arr.ar Assoc Cancer Bcsoazcu? J.G; S4, 15 55. . .