Document b58oD13eEaL044yDw235vkGgk

FILE NAME: Owens Illinois (OWILL) DATE: 1948 Nov 16 DOC#: OWILL058 DOCUMENT DESCRIPTION: Letter to OWILL from Saranac Labs with Attached Report - Regarding the Biological Activity of Kaylo Dust A Horeaber 16, 1943 . Hr* 8*- * Bovea-- Ovena-IllinoisGlass Coapeny Toledo 1, O h i o " * 1 - - ' ' ; / * ' . V " '; Doer Hr* Bovesi ' Enclosed you vill find three copies of a report on the results of animal experiments with E&ylo dust* As ia our custom, ve have easaarixed briefly material previously prcssuted, including our in terim report dated October 30, 1947, end have given detailed dis cussion only .of subsequent developments*. "When all experiments have been ccapleted, ve expect to prepare & final report vhich will inelude details of each phase so that all data vill be available in >ne place* However, the experlsent&l study of the effects of Inhaled Caylo dust cn normal uninfected aninsis is nov finished and conclusions xpreesed on that subject are final rather than tentative* . In the report issued one year ago, vhich describes the findings In animals that inhaled Xaylo duet fcr periods up to 30 nonths, the tallowing tentative conclusion was node* la consequence of the experimental studies vith .. guinea pigs to determine the biological activity of ... ir "Xaylo, it say be tentatively concluded that Eaylo alcne ~ fails to produce significant pulaonary d&aage when in- ... . .-i haled into the lung.* luring the 30 to 36 months period, however, definite indication of tissue action appeared in the lunys of enixals inhaling Kaylo dust and there-- "ore, I regret to say, cur tentative conclusion quoted above aast be al-- red. In all animals sacrificed after sere than 30 months of exposure to aylo dust unnistaxable evidence of asbeetosis has devslopod, showing that aylo on inhalation is capable of producing ashestasis and oust be regarded a a potentially-haaardous material* It should be noted that oince n3ither ilico?lo nor the diffuse puluonary flbroris enured by inhaled diatenaoeous arth vao observed, the quertz and diatcsacecua earth components of the dust pparently do not produce their typical lesions Ua order to present snore Infomaticn on the subject asbet06is, certain Videnco derived from pur experimental verk vith asbostoa dust has been dis-- useed* As these findings have not yet been rloaned for publication, I rouest that, while using them 03 required in formulating a safety program, on regerd them as confidential* Page 2. Mr. (J. E. Baves Ovens-illlnois Gig3a Company Bbvgr.bar 16 1943 The new 'sries of experiments with respect to the influena of Eaylo on tuberculous infection are veil under way and are pro gressing satisfactorily. It is, of course, toe early to expect si&iiflcsnt results on which to base even tentative conclusions* At this tine gay I review briefly the financial arrangant^^ for conducting the investigation with Eaylo? The research program, up to this year vas carried on under tt contract, Initiated In 1945, by which the expertisants vould be subsidised with a grant of $5,COO. per yaar. As pointed out in =17 letter cf March 3 1948, the contract terminated officially cn February 15 1948, but the investigation would be continued without charge until June because the original experiments vere started late* Since a check vos received which took care of the subsidy up to Koveuber 15, 1947, there la due on the old contract the suau of 1,250. for the final quarter of the contract (from Hoveaber 15, 1947 to February 15, 1948). Ve have delayed .sending an invoice for the final quarter until all work ccold be finished end a final report submitted. Following the tenaisaticn of the experiment in June, It has required several scathe ta do tba histological work, study the tissue sections, collate the data and prepare the report which acccspanies this letter. Ve are including in the report a brief review of the new experlcanis in which the effect of inhaled K&ylo dust on tuberculous in fection is being studied* Tour purchase orda*AS-170 authorizing this experiment at $5,000. for cne 70->r la dated February 3, 1948, but owing to 6 shortage of animals and other unavoidable delays the actual experi-- aental work did not get under way until May* Hence ve have concluded that financial support for this new pregrw* should be dated frea May 1, 1948. For reasons outlined in ay latter of March 3, I suggested a tvoyeer contract at $7,000. per year. lour letter of March 31 acknowledged this but failed to confirm the extra amount of $2,000. involved. Severthelescp ve have proceeded at tho old rate and are endeavoring to absorb the increased cost from our Foundation reserve* In a few days oar accounting departaont will forward a statement of the payments new due in support of the rosearch program, as follows* Original experiment, began February 15, 1945, at rate of $5,000. annually For final quarter (liove.ibor 15, 1947 to February 15, 1948) $1,250* Key exporlaopt, begun Kay 1, 1948, at rate of $5,0C0* annually For first quartor (May 1 , 1948 to August 1, 1948) aa j $1,250 5, * K. Bowes tnB--Illinois Class Coasanr Koveaber 16. 1948 I realise that our finding regarding Kaylo are less favorable in anticipated Severer, since K&yl i* capable of producing ae~ ttosia, it is better to discover it now in eniaals rather than later industrial workers Thus the coapeny, being forewarned, will be a better position to institute adequate control nessuree for cafe rding exposed enployses and protecting it3 ova intersstc* Sincerely yours, iLB . (3) Hr. Dayton Arthur / Vcrvald, MD* Director 1STHUI4 SLZPORT RSCAETIHa T22 BIOLOGICAL AC7ITI7T Of SAILO OJST to tho (TtfOS-ILLINOIS GLASS CCMPOT TOLEDO| OHIO *T THE 3AEAS1C UJBORAICRX SA5/JUC LAXI, SSV TOES CCTOEZS 0, 1943 tadttad lyt 'Vjut J. 7orv*ld, M. D.-, Slroctor ' Idvard L. Trudaau Found* tloa la cooperation vithi rb lllp C. Pratt, H. D, Tboraa M. Curtin , H* Xathccr B. Delahcnt t-' :.t iaraoRiCTica Cne year ago, on October 30, 1947, an interia report vt3 submitted, vering the progreea of eertcla aniaal experiments with Laylo over . total rlod of 30 Booths. It vos necessary- at that H a s to recosrsaad furthar Tarloent* concerning certain phases of the probing. The present report deals th. the final phases of the experiment then in progress and with the aerly crvatlcas asde in the oev series of experiments. * The original experiment ha# nov been ecaplsted and the conclusions dravn > bcsed open the results of s full three years' exposure to an atacephorio pension of JCeylo dust. Previous experience haa shevn that this is the rered period evsr voich exposures t o V dust, of doubtful biological aotiTlfcy t be continued before final eoucluslona are varTantod. This experiment, in V, ccsLstltntee an example of the importance of such prolonged study for, as is to hnvn below, the findings at three years vere strikingly different frost those .'uo and one-half years and the tentative conclusion reached at that tine sust. nov llered. Thus, at the tiss of the previous report, the evidence indicated that o acted ae an inert dust in noraal rets and. guinea pigsj resulting only in . foraatica of eluapa of dust- cells, without fibrosis. However, it vill be a balov that &47I0 is eapeble, on prolonged inhalation, of producing ssbestoels xe longs of guinea pigs, and that it should be handled IndustriAlly as a haous dust. This report vill be preeented in four sections as follnva* 1 final observations, duat Inhalation in aorsal guinea pigs. B. Discussion. C. Ccaeluaicna. D. Progress report on nev series of exparixaata. * final f>b-er-r*>tlcns. du*t lnhlntlnn In coras .ruinen -.'ly. Reference to the latera Report of October 20, 1917, will reresi that tvo pups of aaraal guinea pigs ver pieced la the dost roer.: cae group la febm7 1913 end the second la lugust 1913* The anisla vera exposed to etaospheric apensione of Itaylo duet for eight hours daily, fire- end cne-half days week roughout the experlaent* The dust coneantration, which Varied soaevhnt froa tine tins, has averaged li ailLiea particles per cable foot of air oror the entire are of the experiaont to date. 1 brief review of the observations described on page 1 of the prevloas rari will reveal that up to thirty souths the reaction in guinea pigs vas United the accaaulation of clunpa of nacrophages, containing dust particles. La ups of adjacwat air spaces. Vhila occasional aultinucleated gL->nt cells ver n, there vas no undue prolifaration of tissue histiocytes *.cd fibrosis was cat. few unmistakable asbestosis bodies vere identified. In general, the anulation of cells cf the types described above end their persistence as such r a full three year period, without the developneat of fibrosis, has been zi to indicate that the agent responsible for them is not capable of producing reals. unfa. agents are now considered to be *biolcgicalIy inert,* since the . cellular accumulation has net been shown to affect pulmonary function or 1tanca to disease. However, of nine aninals sacrificed subsequent to thirty nonthe in the pro-- i. experiment, all hire chown not only the above lesions but also hero developed * fibrosis of e type characteristic of tho response cf guinea pigs to asbestos. ! li t rathar diffuse type of fibrosis which fora chiefly about the snail air known as bronchioles, from which the air spaces, or alveoli, of the lung , The -appended p h o ie * ie r i;r* p h * aserv th e njtt*r- * f th l a lo a o Vias 41>d. Tixia condition is identic! vith astmtosls ae con b* seen by- censoring - 2- .;}J^ eh Tir* 2 vlth figura 3. li; lesiona la th tracheobronchial lyapb cedo9 shovad no chang between Lrtj acatha ad tar* yearsChsaliil t.raxl7 Bis of th* lungs of guinoiv pigs that had inhnld laylo dust r periods np to 36 oath yielded the data given ia Table 1. It viil he notd .t as th period of txponur* fcca.*a< langur too ash value gradually iocrs*G*d, '1eating on accuarolation of ainernl natter In the lungs. Thar* vac a pro need, increase in tha silica conpoaent up to about 3$ nentha and then a slight i t m s *. The reason for this ccoditicn, uaieh has been cbw n w l la experiments a other dusts, is not entirsly clanr. Since cnl7 tvo enlmla vere aftnlysed acch asposura parted, individur.1 values were cecaaionally out of line but fanenl treed v*.a elerl/ Indicated, i l ClecusaIon. The final cfciicrmtiene in thie experiment with Zaylo inhclotloa in nom a i ** pigs, reported bora and illustrated in the figures, prove th--.t Eaylo ia -bl* of producing the characteristic reaction, ashestosi*. It is evident, afore, that a. considerable portico of the asbestos coapoaont In f.ylo rantina snged during the tsenufr.cturing process or, If it la changed, that tho altered het a*latalns its capacity to cauti* flbroole. Vhi.l th* Iasione up?' to 30 hs shoved no flfcroaie, certain epects of thei v*r compatible with a prelin* T toga in the develo*rent of asbeetonis^ Thee* aspects vere naslced by the 1 type of reaction to the sstarials other than asbeatca in the dust. Th* *t*ri*tio early stags of th reaction to asbestos la the predilection cf th* r to lecaiis in th* luren and vail of th* snail olr ducts, fcasva *a teminai 'hlolas. This ia la contrast to particulate aatarials, which locali** chiafly 3jjiii V W X the actual mlr spaces, or alveoli. In the presflnt erpcrijwnt the graiteafc fSTtioa of the inhaled dust, being particulate, lodged in tho alveoli and masked tbe peribronchiolar depoeittoo of ague of the fibrous component. la retroopect, it ic possible to discern that there- is acre evidence of dust ceil activity in the region of the bronchiole than is characteristic of the reaction to an inert jarticulato dust. Little significance was attached to this at the tins of the jxeTioae report because thorn vas no evidence cf tho devolocaent of fibrosis*. Cio differenco between the early reection to Kaylo and that to aobeetoo y be interpreted ee e aodifiention cf tho lesions 1/ the particulate components *.f layio. *Hodification* of silicosis is veil recognised when lesions of that ijeaso develop following inhalation of e nixed dust containing quarts together ith materials of an inert nature, such as lrcn oxide* ^ It is of importance to note that vhile the perilreachicier reactions cb:prtd intrir.lc.ate Kaylo as capable of producing esbestonis, they exclude the uitilit7 tost it nay cause silicosis, since, over e full three year parted, are is in no irJ.ua! soy focua of hyaline nodulnr fibroaia charcotariotio of ; reaction to quarts* Turthersore, it nuy be added that the enisals nhow no ftnee of the type of diffuse fibrosis which ha been observed in this laber ry to follow inhalation cf diatonicecus earth dust* . In regard to hydrated x-- calcium silicate, a major constituent of Xaylo, it any bo said that vhile re is no pointed evidence as to its effect on pulaonry tissue,' there is nuch l*nce to show that a variety of silicates, including fonas cf calcium teatea, ere biolr-flcaliy inert. It boohs likely that tne celoiun allioaV 'aylo should conform with this previous ipcrisncc. Biua, the possibility erpreseod by Sector Gardner In hla early consideration hi* {rroblra, that Xeylc night produce tvo pneuaeccnioaes, ssbestoais end slUcojia> th* resultant safety haserds, has be*n adequately studied, and concern ever latter condition cum be difaiased. further consider*, ticn <auet be given to ostosis, hcvever. H e laboratory has recently completed a large amount of vorJc vith asbestos, eh has beta re^rtod to certain other supporting companies, but not es jet Liahed. The following discussion of the problsu is Jravn largely frcai that and va vculd roguest that these ccaments be considered confidential. It elt that the relieving information nay be of aid to the Cvene-lllinoia health jrtaent in formulating a safety program, vhich certainly is necessary in riev he results of this Ecylo experiment. labestosis, bcih in son end aainala, Is a chronic, sloviy developing peri- chiolar fibrosis, vhich in late stages extends from the original site of illation into the surrounding alveoli. The bronchiolar Iccnlisaticn is appar- 7 duo to ths fibrous nature of the ainertil. Experimental studies indicate the chief node of action is by taechtnicsl irritation cf tissue by tbs flbors. Structure of these fibers, and the capability of repeated longitudinal dlvl-- to xclecular strands,is iaport&nt in the oechaalsa of action, since the ! fibers of glass vool are not capable of producing the fibrosis. Chemical u; is ef little or no importance In causing reaction, since ohryeotiie ren-- i particulnte by cutting and separation does not initiate fibrosis. Certain investigations hnV9 indicated that a seemingly negligible proportion fcroua sabestos is sufficient to produce the characteristic renotioa. Thus, 'halation experiaoot van carried out vith bull-ailled asbestos in vhich vas sade to eliminate nil fibers froa tho material. It vas found to be sible to break up all of the fibers and about one per cent of the air us-- d duet consisted of fibers. The chamcteriatic peribronchiolar flbresis ped in expoced anlasls after forty ecaths. Thus, it appears that very - 5- y&rrrr f - w f w a **m w *? 'r xil numbers of fibers ere cnpabla of producing a3boeto:ifl, although the deTeipant cf the lesicna la dolayed. The present experiaont with loylo la also na s&apla of this fact. The important natter of progression of reaotion after exposure to asbestos .it ceasss has been extensively investigated. the results indicate that la con sist to silieoeis, vhcre progression continues for sons tins, there is ao signi.ua\ degree of progression la extant of tho lesions. Rather, the sire ef the fleas decreases la asbaatoaia due to the tendency of the fibrous tissue to alrtet after the ctlsulua to its production is reaovud. The irritation of tissue *3 asbestos fiber ia apparently arreeted vithin a fsv aonth's after it enters i long by the foraation of the steatosis body* (a coating of tho fiber by ironraining saUrial), with the result that the existing fibrous tissue contracts, .'r this contraction exerts a beneficial or deleterious effect cn lung fonon is cow tmdar lavastig*ticn. Snfortunataly, the studies with ocboatoa hare not as yet coaplately clarified d% s problem of its effect cn associated tuberculous infection. It appears that ?U say exert a slightly more narked adverse influence ea the infection then I. * 3 per asbestos. The dlffor&nce any veil be due to the presence of the snail out of ciuartx in Kaylo or perhaps to other lnoidental factors. One purpose the studies now under way is to clarify this problea. jkcclaslons. / '' t* *Isylo, beenuso of its content of an appreciable amount of fibrous *" eiay&otlie, ia capable of producing esbsetoaia and should be ... handled es a ha tortious industrial dust. W 1 laylo dees not produce el11cosIs in animals. t I * Jn a! i ?,e rev I1 l~ ; .i** r i k \ I 3 laylo does not produce the diffuse cellular fibrosis of tho lungs new recognised as resultlag froa inhalation of diatonaeeous earth. % Progre.i P.ccort on new scries cf exrerisenta. Hie three phase of the experiment, as outlined iu tho report of October 30, :i7 and in a letter dated March 3 1913# are nov under vr.y. 'While little of Ifldficance has developed thus far# a review of the work is presented hero, ^reea and reruits to data of these experiments re given below under tho tie of each phase. (l) The effect of Kaylo inhalation on tuberculous infection initiated at the caeet of dust expoeuro. Thirty experimental animals were infected with the ettontuated train (Rt.) cf tubercle bacillus used in this type of experiment and were ; placed in the dust room the next day. Thirty-three control animals were > { infacted at the arjaa time and kept in ncraal air. Cf the experimental y * ~ aniaala# six are nov dead# two having been sacrificed at two months# tvo at four souths and tvo having died. . Cue death occurred at five veekj^ due to iatarcurrent paeuacnie. t ' h ^the other was so recent that sections have not yet been prepared. 1,., ft . The animal killed at two months shewed lesions comparable with l-.those in the controls# both grossly and rlcroacopically. The snloals * -.tilled at feur nentha have not been studied aicroscopicslly# but on gross 1 ' examination the lesions appear similar in the tvo grdups. *% *1 0* > U) ^ # The effeot of Cnylo inhalation on regressing tuberculous laaiens in guinea pigs. In thia phase of the experiment, tventy-fl7 guinea pigs were infected, and groups of then vers kept in noraal sir for tvo# four and six xccths before beiug placed la the dust room. At the project tis the first fcvo roups taro b*ea placed 1a the dost rooa; the third is to go la on S*cAbr 15, 19i3, Only tvo fenlsftln of the first roup has been sacrificed as jet, after tvo sooths in the dust. Microacopio obserrations hAve net been atde, but in the gross, the lesions vera comparable with thoee in control anirnla. , (3) The effeet cf aecunulated L<ylo in th lung cn e subse^uont tuberculcus iafecticn, Thirty nomai guise* pigs voro placcd in th* dust rooa on Hay 12, 19X2 and cn August 12, 19X8 vai* iafocted viti tho Attenuated tuberei* bacilli. Tiro cniaals vere sacrificed t this tire for cheaical onalysi* to estabUsh th nsount of du.it Ichaled. Control animi lt vero lnfeoted on i `vthe rasa date. Xninela ver sacrificavi recentlj, tvo aontha after infeetion. ;^Grcsaly, th* lealene la th# xperiatanUl and control miss la vero conper-tMe, |but rgcla aiorcacopie obeerratiooi barn not beea aad*. . i l ` ; >t> ;.iTh* resulta to date in this xperiment are of little significane, alno* th* **in la s chrcoie one end any changes due te the inhalation of dust of enj nature *S [`tesnm to be Slav, However, it eoa bo said that the experiment la progressing C ^.satisfactorily, and that ve anticipate none of tho ccaplieeticna which inter- 5"^ rlth the interpretation of the previous experiaeut ta regard to the effect ..Win on experimental tuberculosis. vK :? .<>. y