Document oD8xXDe9DbjyB48wmVVp7okEr

FILE NAME: Owens Illinois (OWILL) DATE: 1948 Oct 30 DOC#: OWILL042 DOCUMENT DESCRIPTION: Report by Saranac Lab - Regarding the Biological Activity of Kaylo Dust IST1UM REPORT RSSAfiSISa TSE BIOLOGICAL ACTITITT o r z j.u a tust to tho a v n s -m jH o is g la ss co m piei TOLEDO, OHIO TUE 3AHASAC LABORAICBI s i s m e LASE, 5V IOBE CCTOEZS JO , 194$ taittad tyr 'ihur J . , Yorvald, M* D0 E iroctor ' Wvard L . Trudeau foundation Lx. coopration v ith i P h ilip C. P ra tt, H. D. Thoana M. IXirfczn, H* X Anthony B. Delah&nt <f U d .T nrrftopicncg Gae year ago, on October 30, 1947, *a in te r !* report vua subedited, rearing tha prograee o f certain a a ica l experlueots v ith Laylo oxer a to ta l riod of. 30 nonthe. I t vn* necessary a t that tia e to recoamand further perineat* concerning cart In phases o f the problem The praae&t raport deals Ux. the f i n a l phases- o f the experiment than la prograss and vith the acrly :arrticxLa oada In tha new series o f experiments - Tha original experiment ha sov been coopla tad and tha conclusions dravn baaed upon tha results o f f u l l threat year 1 exposure to an atacaphorio pension o f le ylo dust* Proxioua experience has siiovn that this is tha ro-- rad period 0x 3r vhich exposures t o V aunt, o f doubtful biologic*! nctlTlty t fca continued. before f i n a l conclusions ara varrentod. This experiment, in V, ccn stitalas an example o f tha importune o f auch prolonged atudy fo r , as in to hcvn below,. tha findings at three- years- vara? strik in gly different from those .'vo and one-half years, and tha taatatlxe conclusion reached at that tine suet, nsv ifcared. thus, at tha tin* o f tha prexinus raport, tha exldsaca Indicated that 0 acted aa an in e rt duet, in ooraal rata and guinea pigs) resulting, only la. fo rsatica o f cliiap* o f dust c e lls , vithcuh. fib ro sis .. Severer, i t v i l l be 1 bole v th a t fa y lo la eapsbla, on prolonged in h a la tio n , o f producing asb e sto a is m lon gs o f gni^aa p ig s , and th a t i t should be handled In d u striA lly aa a haoos dust This report v i l l be* procanted in four sections aa follows* 1* f i n d obserrallons, dost inhalation- in normal guinea pigs B Discussion. C . Conclusions. D. Progress report on nev series c f axparinaata. ' fi n a l o b ^ ry ^ tlc n a , da*t inh?lotion In cora^I trulnea fLefarecco to tho Interim Report, o f October 30# 1947, v i l l reveal th at tvo uups o f normal guinea pigs vere placed la the dost room one group in Jfcr>7 1945 and td second in iuguot 1943 The animals vera exposed to alaospherio sponsions o f ICaylo dust fo r eight hours daily# fir - and one-half days a v e al rougbout the axperiaeut* The dust concentration, which varied somewhat from. tine lias# has averaged 16 a llllo n p a rtic le * par cable fo o t o f a ir over the entire jxaa o f the experiment to d ata. 1 b r ia f rev iav o f the observations described on page 4 o f tho previous r e rt w ill reveal that up to th ir ty month* tho reaction in guinea pigs v j s lim ited the accaoulation o f clumpa of aacropasges, ooot.xin.ing dust particles# in ups o f adjacent aix~ spaces. While occasional aultinuclet,t<d gir.nt c e llo were ixf there vat no undos p ro lifo ra tlo a o f tissue h is tio c y te s -,nd fib ro s is vaa f a t . 4 fe v unnistAlablo asbestesia bodies vers' id e n t ifie d . In general# the sau latioa o f c e lla o f the types described sto re end th e ir persistence is such, r a f u l l three year period, without the developueat o f fibrosis# has been cd to in d icate that the egent responsible fo r then is not capable o f producing re a la . each agents are now conoidared to be " b io lo g ic a lly in e r t ," since the - c e llu la r accumulation has a ct been shewn to e ffe c t pulmonary function or Uta&ce to disease Severer, o f nine /miauls sacrificed subsequent to th irty Booths in the pro 1 axperineot, a l l hare shown not only the ubore lesio n s but also hero developed * fib ro sis of a type ch a ra cte ris tic of tho response c f guinea pigs to asbestos, s is a rather d iffu se type o f fib r o jia which forms c h ie fly about the email a ir known as bronchioles, from which the a ir spaces, or a lv e o li, o f the lung a, The appended photoad erographs aaov the nature o f the le sica s being d ia d. This condition i s id e n tica l with astro basis as can be seen by. comparing - 2- 2 v l t h f ig u r e 3. Xha la o io n a l a the tr a c h e o b ro n ch ia l lyap h nodes nhovid no change between !x ty scntha and th ree y e a r s . G is s iiiL unalyoia o f the lungs o f guinea pigs th a t hrd iahnled la y lo dust r p e rio d s up to 36 oath s y ie ld e d the l& ta g iv a n in. Table 1. I t v i l l be not*d .t so th e period o f exposure bectcin lon gor tho ash Tdlue g ra d u ally incr-seeed, d e n tin g jus e c c u x u la tio n o f n in e r n l a a t t o r l a th e lu n g s . Them v a c a p ro seed in c r e a s e l a th e s i l i c a aoapanent up to about 30 nentho and than a s l i g h t Tfttee. The raaoca fo r t h is co n d itio n , uhieh has been cbsarvrd i a experiaen ts a o th er d u sts, i s not e n tir s ly c la * r . Since only tvo anlu.il vers analysed etch; exposure period, in d iT id u rl values were o cca sio n a lly out o f lin o but io n & r a l tre e d v*-.s e l e r l y in d ic a te d * tlrcussion. The f i n a l cbserrntieni in th i* xperlxent vitti Zayla nhclntlon in nom ai a* p ig s , reyertad bove ad lllu s t r s t e d l a th fig u r a i, prove thr.i Eaylo is .ble ot producine th cheraotariatic rsse tio n , a u b a a to iii. I t ls eTldant, a fo r * , that jl consideri bla portico o f th asbestos coapoaont in Ef.ylo rao-ains -aaged during th acnufr.cturlng proci o r , i f i t i s changad, thut tho nltered '3ct aeinteina it a capacita to cause fib r o c i* . Vhila th lesiona up> to 30 ha ihoved so fib re ai s , carta,in apeets o f th* vere r a p a titi! v lth a p r illa -- 7 toga in th deveiopaent o f asbeotonis. Tbeee aopectc vere aaslced b7 th t type o f renction to th n a ta ri*la othor Uu>n sabe atea in ths dust. The ceteristi ta ri/ atags of th renctioa to asbesto la th p ro d ila ctlca o f th r* to lo c a li* in th lussa and v e l i o f th e s a li n ir duets, fcaavn e tero ln al h io la e . Tfcla la in cen trasi to p articu la te a r t e r i a l i , vilieh lo c a li ! c h ia fly t i I . i, ;r & i > H the a ctu al a ir h jr w s , or e lr c o H . Ia the present ex;riJiout the greatest portion o f the inhaled dust, being p a rtic u la te , lodjjsd in tho a lv e o li and a*akd the peribronchiolar deposition o f coua o f the fibrous component. I a retrosp ect, i t ii possible to discern th at there- i s sort evidence of dust c e i l a c tiv ity i s the region o f the bronchioles than i s cb n ra cte ria tic o f the reaction to an inert particulate d u st. L it t le sig n ifica n ce vas attached to th is a t the tin e of the previous report because there vas no evidence o f tho davelocaent o f fib r o s is * The d ifferencoa between tha e a rly racctio n to Kaylo end that to asbestoa ay be interpreted a a a o d ific e tio a c f tho leaien s V/ the particulate coapouente \t la y io . ''ik xiif le ctio n * o f s ilic o s is ia v e il recognised when laaiar.3 o f that iiaasc develop following inhalation o f i nixed dust containing quarta together ith natarLtda o f an in e rt nature, such as iron oxide* "r I t is. o f Laportance to note that vlxile the peribronchiolar rsacticn s ch arred in c ris.l n.ate Ky.ylo as capable o f producing aabestoaia, they exclude the i l t i l i t 7 th a t i t asjr cause s i l i c o s i s , sin ce , ever a f u l l three year period, are ia in no k n iaal an/ fooua o f hyalino oodulnr fib ro a is ch arcatariotio o f : reaction to quarts 7urthensore, i t ay be added that the a sisa la ahov no lio c o o f the type o f d iffu ee fib ro a ia which ha boen observed in th is laborrj to follow inhalation c f diatosacecus earth duet* . In regard to hydrated Ic a lc iu a a ilie c t o , a najor-constituent o f S s y lo , i t any bo said that v h ile re i s no pointed evidence as to i t s a fre e t on pulnonm-y tiaeue,' there ia such -nee to ahov that a variety o f s ilic a baa, including son ferns of calciu a U a to s, are b io lo g ic a lly in e r t . I t aoaaa l i l e l y that tas ccloiun s ilic a t e U ylo should ccafora with th is previous experience.. ' Thus, the p o s s ib ility erpxeaeod by Doctor Gardner in M s early conaideration his problen, that L*rl* a ig a t produce Wo pnausoccnioaes, ssbestoai.t end 3 iIie o a ia> tie resultant safety ha&ards, has teen adequately 3to ile d , and concern over la t t e r condition con be 11.o i sued. Further consideration au<?t be siren to ^ct-oria, however. ' lb * laboratory hsa recen tly ccdplatcd a la rg * amount o f work v ith asbeatcfl, ch baa been retorted to ce rtain other supporting companies, but not as yet Llihed. The follow ing d iscussion o f the problera i s dravn la rg e ly frcn that and va would request th a t these ccauents be considered co n fid e n tia l. I t sit th a t the follow ing inform ation nay be o f aid to the C v e n e -lllln o ia health rtaen t in foraalatlng a a a fc tj progrua, vhich certainly is necessary in rtev i he results o f th is Eaylo experiment* ia b e a to sia , both in nam end c n ln a ls , i s a chronic, alovly developing p e ri- ch iolo r fi b r o s is , vhich in la t e stages extends from the o rig in a l s it e o f illa t io n into the surrounding a lv e o li. E: hronchlolar lo ca lisa tio n is eppar- T due to the fibrous nature o f th* m ineral. Experimental studies indicate the c h ie f sod* o f action is by taechcnical ir r it a t io n c f tissue by the fib o ro . itruetur* o f these fib e r s , and the c a p a b ility o f reposted longitud inal d iv i-- to x cle e u la r stra n d s,is important in the aechnaism o f actio n , since the fib e rs c f la s s vool are not capable o f producing the fib r o s is . Cboaic-tl in is of l i t t l e or no importance in causing reactio n , since ch ryeatile reo-- i particulate by cu tting and separation does not in it ia t e fib r o s is . Certain investigationo hare indicated that a seeaingly n egligib le proportion trous asbestos i s s u ffic ie n t to produce the ch a ra cte ristic renotioa. Thus, 'halation arperiaoat vas carried out v lth to ll-a d lla d asbestos in vhich an *?t vns so.da to elim inate n i l fib e rs froa tho m aterial. I t vas found to be aible to brsok up e l l o f the fib e rs and about one per con.t o f the a ir bus-- 1 dust consisted o f fib e r s . The c h a ra cte ris tic peribronchiolar fib ro s is oped in the erpccad a a in a li a fte r fo rty ecatha. Thus, i t that Tory - 5- aril aunbers o f fib e rs are cnpsbl o f producing s3b3ato:ifl, although tho d*Tl- rJ*at c f tha lesions la delayed. Tha present experiment with la y lo la also na aaple of th is fa c t. Tha important natter o f pTOgreeeion o f reaction a fte r exposure to asbestos t so s has been oxtsaaiTsly in re stig n tsd . Tha results indicate that ia con sist to s i li c o s i s , vhere progression continues fo r 900a tins, there ia no sig td - .ua\ dagTea of progression la extant o f tho lesio ns* Rather, tha sire o f the t I leas decreases la asboatosifl duo to the tendency o f the fibrous tissue to I strict a fte r tha sttsulua to i t s production i s reaored. Tha ir r it a t io n o f tissu e sa asbestos fib e r ia apparently arrested v ith in a fav aontho a fte r i t eaters long by the foraation of the eabeatosis body* (a coating o f tho fib e r by iro n- :x*iaing a a te r ia l) , with tha re su lt that the existing fibrous tissue contracts. >'htr thia contraction exerts a b e n e ficia l or deleterious e ffe c t cn lung funo-- n Ls acw under in v e stig a tio n . Safortunatoly, the otudlea with ocbestoa hare not as yet coaplotely c la r ifie d 'r'rr-*y~~*nr* i problem o f i t s e ffe c t on associated tuberculous in fe ctio n . I t appears that iU 1..ay exert a s lig h tly acre narked adverse influence ca tha in fectio n than i pure asbestos. Tha difference nay v e il be due to the presence o f the *t1 1 < utXtU.o**f quart in JLsylo or perhaps to other incidental fa c to rs. tte studies aov under vay ia to c la r ify th is problea. One purpose jkncluslons. i. *' la y lo , because o f I t s content o f an appreciable (mount o f fibrous e h r y c c tiia , la capable o f producing nshe ato o ls and should be ...h an d led os a haxardous in d u s tr ia l d u st. 1 fa y lo dees a o t produce s i l i c o s i s in ani ma l a . *imwSjNiwCAWti*1* w. 3 Zafio does not produce the d iffu se c e llu la r fib ro sis o f the lungs now recognised as resu ltin g froa i nha latic a o f di ato naceous earth. Progress Sccort on new series e f experimenta, Hie three phase o f the experiment, as outlined in the report o f October j o , H7 and in a le t t e r dated March 3, 19li3, are sov under vny, Vhlle l i t t l e o f Ifldficanee ha developed thus fa r , a review of the work; is presented hero, ^rsss and re s u lts to data o f these experiments are given below under the 'lie of each phase, (1) The e ffe c t o f Kaylo inhala felon on tuberculous infectio n In itia te d a t the onset of dust exposure. Thirty experimental animals were infected with the attontuated train (R^) c f tubercle b acillu s used in this type o f experixent and vere j placed in ths dust room the next day. Thirty-three control sanala were > ? infoctod a t the suae time and kept in ncraal a i r , Cf the experimental ;* animals, s ix are now dead, two haring been sacrificed at two oca ths, tvo h at four aoaths tad two having d ied , . Cae death occurred at fiv e vekgj' due to iatancurrent pneumonia. t * .the other vas so recent that sections have not yet been prepared, i *r fi . Ci animal t i l l a d a t tvo months showed lesiona comparable with * V,those in the co n tro ls, both grossly and m icroscopically. The snioals * J t llled. at four Bcntha have not been studied m icroscopically, but on gross * examination the lesions appear sim ilar in the two groups, *1 I (2) The e ffe c t o f Ltiylo inhalation on regressing tuberculous la sio a s la ? %t- guia pig a* In this phase o f the experiment, tvenfcy-fTe guinea piga ver y.{i Infected, od grou?e o f them vera kept in normal s ir for two, four and six *onlha before beiug placed la the dust roox. At the pros at tic to* f i r s t fevo groups have been placed l a the dost rooaj the third la to go l a on SeceAber 15, 1913, Calx tvo anJLsftla c f tho f i r s t roup hat been s a c r ific e d as j t , a ft e r tvo auotixa in the d u st. Microacopio observations have not been atde, but la the 2** the lesion vers coapsrabla v ith thoee in control crdxh.1** . (3) The e f f e c t o f eecuxalated Exylo in the lungs on a subsequent tubrculcus in fe c tio n . Thirty norxal guinea vorts placed la the duet rooa on nay 12, 1913, and ca August 12, 1918 vs A infocted v lth tho attenuated tubercle b id H i . rise oniasls vers sacrificed t this tine for c'.icaiesl analysis to e stab lish tha nsount o f dust inhaled Control enluel* vers in fected on Vthe f-juse d a te. nJLatls vers sa c rifice d recen tly, tvo nontbs a fte r In fe c tio n . >. Grossly, th leaicne in the experimental and control e n issls vero comparable, - /j |tu t rgaia aiorcscop ic observations ham not been aade. ij ` . r> ;.*iths re su lts to date in th is experiment are o f l i t t l e s ig n ific a n c e , since the v . '* ia a ehreale one end any changes due to the inh alation o f dust o f any nature * . ^ buna to be S la v . However, i t can be said that the esperinent is progressing * C! ^ s a tis fa c to r ily , and that v e n tlcip et none o f tho ecap lieeticn s which t n U r ` ft ^ eith the interpretation o f the previous experiaent in regard to the e ffe c t Vr ;,^ flo on experiment* 1 tu b e rcu lo sis.