Document R3NadyvK2VBJMgBbkYXyZKg8

Tmi Saaakac Lasoratory FOR TH1 STUDY OF TUmCULOSIS . or TNI BWAtt U T1U0IAU raUNOATION February 24, 1943 Xr. Vandiver Brown Johns-Xanville Corporation 22 East 40th Street New York, New York ' , ' . Dear Mr. Brown: , Z have at laet aucceeded In analyzing cost of our 7a2&lnoua experlaental data and assessing the reeulte. I realize tEat this should have been eompleted before this, but the emergency has left ae short-handed In the Laboratory and also necessitated ay doing a good deal of extra traveling. I hope that the sponsors of our study of asbeatoels will be charitable and realize that the work has far exceeded Its original scope. Vfe have done over 40 different experlaente, nany of then divided Into several parts, which Involved exposure of anlaale for 1 to 3 years to various dusts. The business of preparing alcrosccple sections and ohenlcally analyzing ths tissues on nore than SOO anlaals has been a Job in Itself. Hy tlae for studying sections ar.d analyzing data has been so Halted that we are behind our sched ule. T hov still not had tlas to write a full report of this work which will of necessity be aonographlo. However, for the benefit of the contributors, I as subnlttlns a table of contents and an an notated outline to Indicate conclusions and the line of argument that will be developed. The latter Itself ocoupies 15 pages, but I hope they will find It sufficiently interesting to resd. Z shall work on the final nanuscrlpt as Z have opportunity. There are a few-experlaente still In progress which should be eoapleted b7 the tlse we are ready for then. *he work on nethods.of dust dstermination, Z consider Important enough to In clude In the study. The question of oanoer susceptibility now eeeos core significant than Z had previously lsuglned. Z believe Z can obtain support for repeating it froa the oanoer research group. As It will take two or throe years to ooaplete such a study, Z believe it would better be oaitted froa the present report. Zf It should become possible to cake this study, 1 hope that Z any count on sons of your aeabers to supply as with enough pure, long fibre asbestos for the purpose. *? L-'lCs -tri 060 06 00091 Mr. Vandiver Brown -2- February 24 1943 Naturally. I shall weloone any criticism that you or ar.7 of the other contributors would care to offer. Should any of then want to dieouee details. X-would be pleased to. meet with then. May I tales thie opportunity to thank all the sponsors through you fe the support that ve have had. ' Sincerely yours, L'J5: -3H Leroy U. Gardner, M. C. Director <s_ pH 060 06 00092 OUTLINE OT PROPOSED MONOOflAPH OfJ A3BZ3TQ3I3 ' 3a.ran.ae Laboratory Studj under 2H40i lSS Atfrtltail Association PART i HUMAH A3BE3T03I3 1 Human Pathology - a study of 25 autopay oases, Zlluatratad 2 X-ra7 Patterna In Aabestoais, Zlluatratad 3 Aah and Mineral Values In Hunan Aabeatoala 4 Complications of Aabeatoala ' (a) Susceptibility to lnfeetlon . 1 Tuberculoua 11 Non-Tuberculoua 111 Cancer of the lung . 5 Disability, causes and cooperIson with silicosis 5 Diagnosis (a) History of adequate exposure (o) X-ray flla pattern (c) Physical exa'ninatlon (d) Aabastoala bodies In sputua, their significance 060 06 000D3 (2) ?A3? 21 Experimental ktutaili Z Method* (a) Inhalation expoaur* to plant duata. (b) Injection into lung* through trachea of pur* oinerale (o) Injection of pur* mineral* Into other organ*. 2 Specie* Suaceptibillty Man, guinea pig*, rabbit*, cat*, white alee and rata dog*. - 3 Peculiar Characterietlo* of Aabea.toala ' (a) Unuaual locelltalon of chryaotil* fibre in lung*. (b) Hate of reaultant tiaeu* reaotlon oore rapid than to ouartz. * (e) Reaction to chryaotil* not progreeaiv* after expoeure eeaeee; again the reverie of the aituation in elllcoale (d) Aebeatoel* Bodie* 1 Compoaltlon and method* of formation, li Oeeurenc* in different apecle*. ill Poraatlon doe* not parallel development of flbroel iv Gradual dlaappearanea after expoeure eeaeee. 4 Comparative Effect* of Different Aabeetlforo mineral*. ' (a) Canadian Chryaotil*. (b) Arizona Chryeotlle, low iron. Co) Croeldolita 1 Bolivian apeolmen, atlff and elaetie. il South African, aoft ar.d flexible. (d) Anthophylllt* (e) Amoalte. . (f) Tremollt*. . 5 Effect* of Control Mineral* . . (a) Grannular Serpentine, aaoe ohemioal eonpoeitlon a* . chryaotile. . (b) Ola** Vool, a aynthetic allieat* fibre. (o) Bruelte, a flbrou* magnaalua hydroxide almoat free of alllea . 6 Chemical Compoaltlon of Aabeatlform mineral* in Relation to Irritation. (a) Hothing in compoaltlon correlated with relative lrrltat: capacity. ' (b) Preliminary acid treatment ' 1 Hydrochloric aoid li Carbonic acid ` t At-U'-i 060 06 00034 (3) (e) Effect* of Alualnua 7 Phyaioal Proparti** in Halation to Irritation (a) Length of fibre (b) Sffeot of Cruahing (o) Heat traatnant 8 Natura and Signifieano* of Aabeatoala Body (a) Formation (b) Protactlv* affaot preventing further irritation (o) Ultimate aolubility in tiaaua 9 Thaoriaa of Action of Aabeatlfors Mineral* (a) Chemical - reaaona for conaidaring invalid (b) Keohaniaal - experimental demonatration of. ' 10 Complication* - (a) Infeotlon, tuberculoaia and other varlatlaa (b) Canear of lung - experimental data auggeatlv* but not proven 11 Dlaablllty 12 Eaaentlal Feature* of Raxardoua Expoaur* (a) Nature of duat - fibroua component and ala* factor* (b) Atmoepharic Concentration* - probably lover than for quartt . i Inadequacy of atandard lmplngar aaapling method ' which doe* not eollaot th* dangeroua fibre* li Eleotroetatlo precipitatafaampling preferable but if . method muat b* modified (e)'Duration of Expoaur* 13 Recommendation* for a New Standard of Safe Atmoapherle Con . centralion* of Aabeatoa Duet . (a) Th* Quael-offlolal atandard of 4 to S million particle* per eu. ft. (b) Vork upon batter method of eampllng ., (a) Keeeaalty for eompariaon of reeulta with X-ray finding* in employee* 14 Prevention (a) Chemical mean* not practical ? - wh- 080 06 00095 (4) I 1 Ael&oala neooaaary to Alaaolvo fibre In lunge voraa than Aebeatoela - . 11 Aluninua Therapy Inapplicable 111 Chief reliance etlll upon Auet prevention with apeolal ecphaala upon the flbroua componenta 1X 1.(3 - tsS 080 08 00096 -I- asbestosis - a.t:ctQ outuse ikdicatiwo results . PART I - HPMAH A3BS3T03I8 1 Human Pathology and X-ray Patterns - Desorlptlon Saaad upon 23 huaan autopsies 2 Ash iCi Mineral Valuta lQ Huaan Lungs. 3 Complication pjj Asbestoels (a) Susceptibility to Infection 1 Tuberculoue- High inaidanoa In English experience not duplicated In surveys of American Plant*. Available autopay statistic! deceiving becauae of eelectlon of oaterlal. 11 Non-Tuberoulous- The aaoe reaaon probably appllea ahould be checked, by analyala of ab- aentealaa aaong aabaatoa worker*. Ill Cancer of lung ' Ditto, but thar* are now on record 10 caaea of. lung cancer In aabaatoa worker*. Compared to the total nucber of autopiiea on aabeatoala, thla Incidence la axceaalve Ko auch frequency haa been dlacovered m alllccala gr other forma of pneumoeonioala except^ the Sohnaaberg min*'* of radio active orea. Th* evidence la suggestive but not oonclualv* that aabeatoala may precipitate the development of cancer In aueoeptlblt Individual*. 4 Disability Clinical experience suggest* that truly disabling aabeatoala la oanlfeated by laaa atrlklng X-ray change* than a corresponding degree of alliooala. Such dlaablllty In aabeatoala la due to disease within the lunga and not to secondary heart disease. A* in allleoals, associated pulmonary Infection Increases the amount severity of the dust fibrosis with resultant accentuation of disability. There ia urgent need for a oaraful physiological study of pulmonary funotion In aabeatoala of varying severity. Undoubtedly, there are many diagnosabla oases with no a.lgnifloant disability. . ' 3 Diagnosis depends upon three factors. (si History of adequate exposure, usually 6 to 8 years, aometines longer, at work where both th* concentration and character of the aabaatos* dust are hatardoua. D l* W 060 06 00097 To) Evidence of disease tin a characteristic X-ray pattern. - rc i- Co) A physical exanlnstlon which reveals certain characteristic slgna and cay reveal evidences of disability if present.. (d) Aebestosis bodies in~the sputun are conflrnatory when the--' previous factors are* all positive. Hovavtr, the bodies *-Yi- nay be absent,'particularly i:. the absence of bronchitis 'X- infection. ; ' Asbestos-bodies unsupported by other evidence do not oaks a diagnosis. Occasional ones have been found in about 19 autopsy speoiaens of/persons with no known exposure and no fibrosis, probably'of |,non-ocoupational origin. . .. . Methods ** * ' '*' ........ PA2I II; Eamerlasntal Asbestosls . .. '/.I...' (a) Inhalation Ebxtpoosures to Planntt'DDuuasJi .-.SSppeec1c1ific fibrosis.in% lungs, but no changes elsewhere. (b) Injections of - 3uspenslbris of Pure .Minerals into Trachea *'fh: Slallar results. *T. ' ' ' (c) Injection oi Suspenslohs jjx ?ur,a'Mineral*into' other organs" * Fibres dissolved; no asbestosls bodies; tissue reaetloncon- faisnbeedstotos pr_h>rywgmsoooyfto.*hs>uianaann;ds.iu.dbhnJisc.oa..tps.su. lation. /.Co. n..pare'the. .* V . . * .r .' . II Soeclea ausceotlbllltXyX , *. *** v' Unlike free silica,'asbestoe\does not/prdduise its specific effect in any organ of any speoies.bf.anloal.-.YZt-oauaea fibrosis'ohlyl the lungs' of aan and those of-'a.-fswpf-rthe apsoiea teated/v.^-yi, Soecles Fibrosis Asbestos' Wdiss A^^TMapsolssrpinWsis AsbestosriBa<i i a a 4 Suinea ?lg 2+ 3* ' - - . h.'t'v White Mouse 0 -____ ?.abbit *^ ttl Z very .-.11 atypical asbestaa'bodies^ _ __ III Peculiar Charaotsrlstldl rflf Asbsstosla , v.i, i (a) I^oslitstion"bf ^lbMUs^ainsla%n of granular duat partiolsaTsfcj^ ,t y> Q ~a< i - mm pa differs Jfronthat 060 06 00098 1 Fibres lilte ohryaotlle haring a oertain degree of flexibility and elasticity accuaulate within the finest air tubee; granular duet la carried further on and la widely aoattered through the terainal air apaeea. _ (b) Hate of tiaaue reaotlon to aabeatoe la auch aore rapid than to aa active duat like quarti. Evidences of foraatlon appear aa aoon aa auffloient ooncentratlon of flbraa haa localized 'In apeoiflo areaa; with quartz, there la a latent period of aontha. (e) Reaction to aabeetoa doea not progreaa on oeaaatlon of expoeure. Xoung acar tiaaue that say haTe formed, contracta and becoaea aore denae but the area of Involvement decreaaes in. alze. In alllcoaia, the-young nodulea become larger after expoaure oeasea. (1) ,, Asbeatoaia Bodlea are a apaclflo eonoomaltant of thia fora of pneuaoconloaie. They are due to a deposit of protein and iron upon the aurfaoe of Inhaled flbrea. in guinea pigs they fora after about 60 daye of oontaot with the tiaaue. They are abund ant in ann and guinea plga, (See paragraph 2 above) but auch larger in the foraer probably beoauaa the larger aized air tubes adalt larger flbrea. In cata,- rabblta and alee, there is an atypical coating of a few of the flbrea after auch longer reeldence In the lunga; In rata and doga no bodies could be dis covered. From paragraph 2 it la apparent that their occurence does not parallel developaent of fibrosis. In lung Injection experiaenti, the bodlea have jstf developed nntH After fibrosis Ve-'Uall advanced. The number of bodiaa aeeaa tu decrease several years after exposure ceaaea. Cor-tarstive Sffeota of Different Aabestoela Hlnerale * * (a) Canadian ^hrvsotlle - highly Irritating. . (b) Arizona chrvsotlle (low in Iron) equally Irritating and pro duces Juat. as many aabaatosls bodiaa aa tha Canadian product with ovar 11 tinea aa auoh Iron. - (c) Croeldollte - Tha South Afrlean blue asbestos la known to cause aabestoela. Only a Halted supply of this aaterlal In purt fora was available, nost of It was used earlier In the vork in non-productive experlaente. Tor tha later critloal injection teeta into tha lunga, a Bolivian variety was aubetltute<d be cause of its high purity. Ita flbrea wars auoh atralghter, stlffer and nora elastic than tha cottony South Afrlean variety. Perhaps baoause of these peculiarities, It haa not given rssetiona oomperebl# to ohryaotlle. It produced aabestoela bodies but did not loeallz# In tha terainal air tubee nor cause any flbroala. Tests now being repeated with a typical South African ereeldolite with physical characteristics aliqulating ehrysotile. ' - - L- tz G) 060 06 00099 -4 .- (4) Anthoohylllte - itiff, straight fibres - atypical asbestosls ' bodies forma slowly but no localisation or fibrosis In lungs.'* (e) Amoeltq - Ditto. .. . y. y . (f) Aaahlbol? - Ditto. . . . . *'*V * (?) Treaollts - Ditto but vary few asbestosls bodies" Observation being oontlnusd. r s * f; Y Control Mineral , (a) Sranular Serpentina of saas oheoloal composition as ohrysotlle la Inert causing no fibrosis In lungs or other organs. -It attracts Iron froo the lungs but' of oourse, no `bodies1 develop (b) glass Wool(a synthetic silicate) fibres are not lahalable from . tlr-boms suspensions, apparently beoause of thslr atlffneaa ' (the diameter is not responsible as some used were less than 1 micron thick) On Injeotlon Into the lungs, they do not ycvp localise In the air.tubes but are widely soattered. They osiuse no fibrosis. After 3 or 4 oonths In oontaot with lung fluid, ' a few glass fibres take up iron but remain smooth. They never show the swollen ends and lateral projections of the true asbestosls bodies. .- ; -- . (c) Sruclte of interest beoause It Is a fibrous mineral praotlcally free of silica (o.9/f). Crystallographloally the arrangement of its Me and OH groups In saeh unit oell is similar to that in ehrysotlle. The sample used also oontalned about 16J5 Iron, pro bably from contanlnajlng magnetite. The fibres are stiff and needle like. Observilona not yet oompleted but after 2 oonths ir. the lungs, typipal asbestosls bodlss develop but there is as yet no fibrosis. *`he fibre are soattered through the lung mates of being, localited Inside the terminal air tubes and tissue reactlon'.oecurs around. Instead of within the tubes. v* Chernies! Composition Xu Halation Irritation (s) Nothing in the following eheaioal compositions can be cor related with variations In oapaolty to provoke tissue reaction. (See Table Hext Page) i - (# w oO > >* >*'. . - . 060 06 00100 ? -> o. o Chrye- Crocid__ - 37.435 - M.995 2.335 l.gT* . 0 4.295 Antbo-'^^'iaoalt* ' Ml* . . - 'tw-- 37.435 - "3 ' 0.315 4.055 Q Vi- 33.835 33:045^ 36.205 -O.'gdd*^ * 3.065 ^ 7.215' -5.7A4 >15.0 o *4 0 0 0-355... 1.025 0.055 0.795 39.775 _12.255 0.29 6.92 0.235 0.445 29:345 0.32 11095 2.015 ' 6.295 0;33 1:695 0.365 - 0.465 '* o.W ' 23'.295 -^20.'625".83.995 ^ ^ 0.40 *6.78 *" 3>vbTR?$ \^0 0.00 .. 0.37 0.13 o'. 10 OX.F'^O.n ' 0.16 aas 4105 * 4.30 0.02 0.82 0.68 0.32 0.34 0.53 >105 14.92 (b) 2.35 2.42 . 1^' -3.39 --2.70 --26.66 " , i?T * *' V'wVSTvKx -;:.v ''.r`5 a* Acid treataent of ehrysotlle' flbrea'isVs#; ... 1 On# hour la dilute or oonoentratednCL does not altarrap^" pearance of fibre but after auob treataent it rapidly'die-: solves and disappears on injeotlng Into living tissues.vyb 11 Treataent with COg bubbled through water or lung juice .rlv suspensions of chryeotlle fibres eauaes partial solution ' with liberation of sllloa and nagnesla. . y i.' y.; y ' (c) Colloidal allualna does not neutralise the 'effects of asbestoi as It doss quarts. On lnjeotlng ohryeotlle suspended In alualnun hydrate solution, fibrosis and asbestos bodies dev elop at the usual rats. It reaalns to dsaonstrats whether th< . fibres*beooas ooated with a layer of alualnun aonohydrats as has been proved In tha oass of quarts. they have, the coat does not sffsot their capacity to Irritate tissue. . VII Physical Properties delation Sfl Irritation al Idi&S HUM y (a) Length fibre ' ' 'y Short ehrysotlle fibres under 3 alorona are practically Inerti 20 to SO aloron fibres oauss typloal fibrosis. 1 '; The effects of longer ones could not be tested for technical reasons. .. '` -wV' (b) Crushing ooapletaly destroys the fibrous structure of ' ehrysotlle. With loss of atruoture, sll^oapaolty to irritate disappears. - V!Xlo- 060 06 00101 Heat - At .Ignition tenp*ratur*e7vat#r,*iajdriv*n*ofJibuti, fibrowatruoture .it prsservsd.>^ffibres beccM\>'xtrnely-brit^'t;r. ' 'The physical ohange alters typical looalliatlon'wlthin the^t^.^' lunge, no fibreele develop* ,-r#actloolinlt#d to'phyagooytoele'^ No aebaatoals bodies 'formed.^^v-^ij^t^^i-j^...-,-;- - . viii Nasaa asa .w . :';& ,t ,, r;VI^4#fy-TCli (a) Bodies probably result froa depoaitionrpf-lron'jand organio - natter on a slowly :diaeolvingiflbre.ofJaifb#atoa.'.pSTh* souroe of ths iron is nore.llkely .toj'* *" alneral itself a '' mineral* of low. (b) The effeot of aabeatoaia'body^jrofpatioh^iajaaauaad'to be pro-*f; tectire although .'it "has not:bee'n">poaftlbleJtojIlsolate a large enough quantity of.theea 'struotureslin'iuhaltered';fora for w. ;rrt . purposes of teat. " The saoothiiqunded-endsJSreaented by the bodies would not be mechanicallypirrltatiag;?f^fl#i.>t;V'\-r-'.` ' ,V. >: -' , -c- (c) If they were capable of caualng-lrrltation.^the -fibrosis in the lungs should progress after exposure'oeases^which it does not.' - '. -v (d) The gradual disappearance of ^bodies (and^fibree) .long after \ - exposufAr'Jfeinta.to ultlaate solubility inrtlesue fluids. ;* --............. -*` - (e) *he bodies are probably a fortuitous ooneonsltant rather than* . a cause of fibrosis. '. . . . IX Theories & Iprjtg^ ASi2B iX Aabeatlfora Minerals - (a) Chenleal these experinents do' not eonfira the theory that asbestoeis is merely a fora of silicosis resulting froa free silica liberated in the solution of a eilioate molecule. If this were true asbestos .like cuartx^phould cause fibrosis in any organ of any spools! for the experiments have shown that injected asbestos dissolves in these looatlona. However, it Coes not. e-.ua* such reaction in any loeatlon but the lunge of *e specie*. . : - . . (b) Mechanical Irritation ;. ` We are proposing the theory of aeohaalcal irritation which la nanifested only in the lungs beoauae this organ is the only one whose norsal physiological functions involve a high degree of nobility. Experinents designed to prove the necessity for notion in this tissue have failed for tsohnioal reasons. ... For this theory to be applioeble,-it lsneoeesary that'the fibres be concentrated in the fbfo terainal^air. tubes. It has been.shown that only ohryaotlla of .tha aabeatlfora ninersl* thus fd5ri*a the proper phyeioal oharaoteriatioe^to lnaur# such loealliation. It la alao essential thaV'jeh#,fibrt shall psrelst long enough before it dissolves in tha "lung* of apeolee libs nice, rata,*dogs. It apparently'dissolves;ao rapidly that it exert* no Irritation. Similarly, rapidjbolution nay explain luagg.in part, the lach of flb*r--o--a--i-a--in` orga' najSthar.than tha .' .1L; - Kb If' t. <o) 060 06 00102 -7- The fibres must be long enough so that they cannot be eoapletfly surrounded by phagocytic cells which' would prevent contact of these round, broken'ends with the delicate cells supporting the air tubes Observation has demonstrated that these conditions ars realized in guinea pigs treated with long fibre chrysotlle and fibrosis results with the other asbestlforn alnerala that have bean tasted, soae or all of the prerequisite vers lacking and no fibrosis developed. (e) If the Irritation were chenleal, fine serpentina which has the sane' ohealcal ooaposltlon as chryootlle should hava also eause< fibrosis. The crushed chrysotlle shoudl have bean nora active than Intact fibres, because of the greater aurfaoe areas ex posed to body fluids. On the assumption that ohrysotlle, like cuartz, baooaes coated with a vary thin layer of alualncb on treataant with colloidal aluslnua hydroxide, capacity .to cause fibrosis should be destroyed If the action wars ohealcal but such lj not the case. . (d) "he heavy coating resulting froa asoestosls body foraatlon ap parently does stop tissue reaction but here the affects are probably aechanlcal'for reasons cited. (e) H-at sufflolent to altar ohealcal structure d estroys power to Irritate but It also altera essential phyeloal characterise that affect' localization of the fibres In the lungs. X Coaollcatlans (a) Susceptibility $0 Infeotlon '^ 1 .tuberculous - Asbestoa behaves like aost other amoral/.In this respect and not like ouartz which specifically Increase native sueceptlblllty to the tubercle bacillus, "his in feotlon aay spread for a tlae but then.heals. The resultant flbrools accentuates that caused by the mineral fibre. 11 Non-Tuberculous - of no greater frequency than in anlaals Inhaling duets of other kinds. Occasional epldeaics of pneuaonla occur in our dust rooas, but these are due to methods of housing rather than to dust; they also occur In unsxposed anlaals. Ill ' Cancer of lungs Mo experlaents were,designed to sluoldate this point but oertaln evldsnes suggests that asbestoels aay actually favor development of tuaors In susoeptible epeolee. 1 Zn guinea pigs, rabbits,- rats, oats and dogs lung tuaors ars rare. 2 When these speoles were subjeoted to 2 to S years In halation of asbestos dust, the inoldenoe of lung tunor was not lnoreased. \..-v , St ( (uCj C"1) 060 06 "0103 a 3 Soma (trains of white mioa do develop tumors without apparent causa. y 4 3ush a strain of whits mios was unintentionally used in three inhalation experiments with asbestos. 3 Of 11 mice inhaling long fibre asbestos for 19 to 24 months 8 developed malignant tumors in their lungs and 8 of than had tumors in other organa. T^g incidence rate id 6 Of 22 mice inhaling short fibre asbestos for not longer the 12 months only 3 devsloped lung tumors. Rate 13.6< 7 As oontrols, we have only the experience with mice in other dust experiments. - For short periods, there were 91 mice exposed to 4 other k1i.n9d5s. o f dust for 10 to 12 months. Znoidsnos of lung tumor for long periods, there were 143 mice exposed to 4 differen kinds of dust, including pure quarts, 23 to 31 months. For all this group of-nice the average incidence of lung tumor was 13.85: the highest rate (2357 was in a subgroup exposed to flint dust. . Thus the incidence of lung cancer in the long fibre asbestos sice a over 16 times the average for mice inhaling other dusts for comparable periods and over 3 times the maximum for any other'grcup. Mice exposed to the praotloally inert short fibre asbestos showed fewer lung tumors although 7 times more than those in short exposure to other dusts. . `hese observations are suggestive but not conclusive evidence of a cancer stimulating aotlon by asbestos dust. They are open to several criticisms. The strain of mice was not the same in the asbestos experiment as in many of the others cited; apparently the former were unusually susceptible. Rot enough animals survived in the dust for longer th#n the 19 months apparently necessary to produce many-tumors, Ahere were no unexposed controls of the same strain and age end no dialler oontrols exposed to other dusts. It is hoped that this experiment can be repeated under properly controlled conditions to detsrmine whather asbestos actually favors cancer.pf the lung. XI Disability Cannot be determined in animals. T^* accidental deaths were from the same causes met with in all our dust Inhalation experi ments. A.J-te -(s'*'(59........... 060 06 00104 f f. XII Essential Factors s Hatardoua &mm (a) Mature si Du>t 1 A'he hatrda Increase* with the proportion of intact fibres -*};' in the dust. Granular materia!1 and crushed fibre are inert diluents. V f , . *v* li 'The long fibres must be thin enough (1-3 Microns) and short enough (under SO.Xlorons?) to be Inhaled. ill Very short flbreii (under 3 Kiorons) are practically inert. (b) Atnosoherlc Concentration Still under study. Apparently this factor is lower than in'the case of dusts coooosed of granular minerals but methods of estimation are misleading. -V. . *. I ?he average standard ?ublld 3ealth'Servioe isplnger count in the long fibre asbestos"dust room was .40 million particles per eu. ft. of air. '.^hli'.conesntratldn'caused fibrosis visible to the na&ed eye in' 20 to 24mlntha. For comparison the average implnger.counts !.ln an experiment with purs ouartt was 120 million particles per-cui' ft.*and fibrosis developed at about the same'rate. . - .. ...... . II However, implnger oounts are deceptivebecause by this - method of sampling very fey.fibres,?which are the significant elements in the dust are oolleoted.lH'-r'*/- - .v*. ill Sampling with an eleotrostatio preoipitator is a much more efficient means of collecting. .fibres ..from sir-borne sus pensions. Samples from our .'long fibre asbestos room shoved that the dust in the air contained 32.SJJ of fibres few of which had been eolleoted or counted in the implnger sample. ?hs latter sampled largely the inert granular parti cles . .. . >. > lv As ordinarily employed preoipitator samples are weighed and the results expressed in mg. per oublo foot of air. There ie no means of converting such values into numbers of partiolaa particularly when these vary in site, shape and "spaolflo gravity. " ;vv-vi " v Simultaneous sampling with preoipitator and standard inplngsr yielded the respective values of 0.68 mg and 80 mil lion partloles per oublo foot of air. " n ^^ vi `heoretleally the best index of hatard would be either the number or weight of fibrous elements in the dust. 060 06 00105 (c) Duration of Exposure . . 1 Fibrosis visible to the naked eye after 13 contha exposure lr.creaaea In extent In subsequent ia,nonths. ' . `--i 11 The span of life of our nost susceptible..laboratory aniaal, the guinea pig has prevented continuing exposure longer thar. . three years* .In this period only>the cooperatively aarly stage* of asbestosls have:beenproduoed.: With the know- " ledge that we have gained, it ;is probable that more extenaiv disease could have been produced with a purer long fibre chryeotile. The-long livedjipeolea, -like.cats, dogs are un- . fortunately not susceptible.* ... "! V;.'' ' Hi For these reasons X-ray changes have, been nininal and we were not able to fulfill one of the objeotlvee of this pro . .^xin Recsmendatlon for a New Standard pf. Safe 4'taospherlc Concentration AX s' a'sn'sit' . ~ " ' **......... : >. , (a) While there ia no official standard, .the'tentative one of 4 or S nililon particles per cubio foot'of'alr is frequently quoted. > . -- (t) This ie probably unreliable beecaut se ilat ;.ia Jba-ee.id upon soapllng. with a standard lsplnger which.we havecshown doee not collect amt ot the fibres that are;the' source^ofj^pfxard (c) We now think that a standard ahould be'bleed upon sanples collected with an electrostatic precipitator.if it Is feasible to deterslne readily the relative proportion of.fibres In such arterial. *' * ''&&` ,*.4 . . U) Work la still In progress upon the latter-point'. (e) XIV Preventi The experlnents have failed to*'develop 'a^r^^^^oel dhealcal v ' neons cf neutralising the aatlbnvofflbrouifosbestos.V- ' a) To alter the hunan>>llung so that it;VouldTpiJsblvevasbeito* fibres rapidly like a rat would neo,eaal^jiteyipw>>ab\y) . creating an aeldoals which would. bejAbreeithan'-.the `effects of. the fibrosis. Vlf <* ? te -- Co (o (j* O) w&-. * \4.aA. }. #0 S !.* . * ' 1 - .V: : *060 06 00106 vu - 2, W3' (Id) Apparently alualnua;'.which la;>o effeotiTa'-aainatrae~jliioa, hae little lnflUehoe^upon' flbroua otryaotllarflWffl&igfe^5^ (c) However, It would be.:o:great.iJheortJLoal'<lntareet^to itreataS6l . V hfeawlaotaioenea. wWiteharreea-tlsrvdlj'napnoea'5jp.OB'aebtato.el*^pyialunlhun'?in^^ reaulta E lation of 1 -V s `? l .l' . .'T. i' ( XUj - k (c c' 0 060 06 00107 060 06 00108 IBi'iafttt uicaaat *v* --a*/??/ ICeasuey & Matoson- Company nnnKii niiWiwMww^m>^i#i AMfliiR. Pmmvuu Uareb 3, 1943. r>:i No. aaii W. V. ?. Shepherd, Ksq., Turner * Hawaii Ltd., Scotland, Roebdals. Dear Ur. Shephard: A; Subject: Dr. Leroy V. Gardner's Asbestos Past Bxperlasnt*. Further te this subject, I new hare pleasure la banding you herewith photostat copy of Dr. Gardner's lattar of February 2L, 190 to Xr. 7*ndlr*r Brown, and also copy of tba 'Outline of Propoaad Xonognph on Asbestosls." I bar* found tbla outllna to ba ortrasely latere*tlag. It bring* out a auabar of Important anr drrelopnents, but ea faal that rafaranea to tba question of cancer susceptibility should ba oaltted froa tba report sines It la laconclusiT*. I would appraelata racalrlag any comoata wbieb you any bar* to ask* concerning tbs enclosed outline, and also will forward you tba final report as soon as raeslTOd.* ea:ek Sad. First follow Second follow / 1 060 06 0010?