Document a4xEkrZ6qVVXya9gmMj8jRVBY

The Saranac Laboratory FOR THE STUDY Of TUBERCULOSIS * Of TXt E7WAID L TBUDUU SOVNOaTiON Saaahac Dju, N.Y. February 24, 1943 I i J*c Vz, I ^ 1* **;.* r1/* 94; Xr. Vandiver Brown Johne-Kanville Corporation 22 East 40th Street New York, New York Dear Hr. Brown: ,, I have at laet succeeded In analyzing cost of our vcUSilnoufi experimental data end assessing the results?] I realize that this should have been oonpleted before thle, but the emergency has left oe short-handed. In the Laboratory and also necesalteted oy doing a good deal of extra traveling. I hope that the sponsors of our study of astestoels will be charitable and realize that the work, has far exceeded lte original scope. ` We have done over 40 different experlDents, many of then divided into several parts, which Involved exposure of animals for 1 to 3 years to various dusts. The business of preparing clcro- scopic sections and ohemlcally analyzing the tlseues on core than 600 enicalB has been a Job In Itself. Xy tine for studying sections and analyzing data has. been so United that we are behind our sched ule.' T have still not had tine to write a full report of thle work which will of neceseity be monographic. Bowever,. for the benefit of the contributors, I an submitting a table of oontents and an an notated outline to lndicato conclusion and the line of-argument-that will be developed. The latter itself occupies 15 pages, but I hope they will find it sufficiently lntereetlng to reed. I ehall work on the final manuscript aa I have opportunity. There sre a few experiments etill in progress which chculd be completed by the tine ve are ready for them, `he work on nethod6.of dust determination, I oonslder important enough to In clude in the study. The o.uestion of cancer susceptibility now seens core significant' than 1 had previoualy imagined. I believe I can obtain support for repeating It from the cancer research group. As It will take two or three years to oocplete such a etudy, I believe It would better be omitted from the present report. If it should become poeaible to cake thle 6tudy, 1 hope that I any count on sone of your Dembers to supply me with enough pure, long fibre asbestos for the purpose. Mr. Vandiver Brown February 24, 1943 fce Naturally, I shall velooDe any orltioien that you or my of the other oontrlbutora would care to offer. Should any of hen want to diaouBB detalla, 1- would bo pleaaed to oeet with then. ..ay I take this opportunity to thank all the eponaora throuh you for the eupport that ve have had. Binoerely youra. i J . :oWu a 1 Leroy U. Oarir.er, >!. D. director  v*ri OUTLINE or PROPOSED H0SP3RAPH OK ASBESTOS! B Saranac Laboratory Study under Orant frcn Aabeatoe Aae oclatlot? PART I HUMAN A3SE3T0SIS 1 Kucen Pathology - a etudy of 25 autopay oaeee, Illuatrated 2 X-ray Patterns In Aabeatoela, Illuatrated 0 Aah and Mineral Valuee in Human Aabeatoaie 4 Corapllcatlona of Aabeatoela (a) Susceptibility to infection .1 Tuberouloua 11 Kon-Tuberculoue 111 Cancer of.the lung 5 Disability, caueea and cocparlacn with silicosis 6 Diagnosis . (f) History cf adequate expcsure Cc) X-ray film pattern (c) Physical examination (c) Aabeatoela bodiee in eputum, their aignlflcanca (2) PART II Experimental Aabeetoele 1 Methods (a) Inhalation exposure to plant dusts. (b) InJeotlon into lunge through trachea of pure minerals, (o) Injection of pure olnerale into other organs. 2 Bpecies Susceptibility Kan, guinea pigs, rabDlte, cats, white mice and rats, doge. 3 Peculiar Characteristics of Aabestosls (a) Unusual localiraion of chryeotlle fibre In lungs. (b) Rate of resultant tissue reaction core rapid than to quartz. (c) Reaction to chryeotlle not progressive after exposure ceases; 'again the reverse of the situation In silicosis. (d) Asbestosls Bodies 1 Composition and methods of formation. 11 Occurence in different species. lii Formation doea not parallel developnent of fibroaia iv Oradu&l disappearance after exposure ceases.. * 4 Comparative Effects of Different Asbestlform minerals. ' (a) Canadian Chryeotlle. (b) Arizona Chryeotlle., low iron. (c) Crocldollte 1 Bolivian specimen, stiff and elastic. . 11 South Afrioan, soft and flexible. (d) Ar.thcphyllite ... (e) Amoeite. (f) Tremolite. 5 Effects of Control Minerals (e) Gracr.ulcr Serpentine, same ohemicel composition as chryeotlle. (b) Glaae Wool, a eynthetlc silicate fibre. (o) Bruolte, a fibrous magnesium hydroxide almost free of silica 6 Chemical Composition of AabeBtlforn minerals' In Relation to Irritation. (a) Nothing In composition correlated with relative lrrltatin capacity. (b) Preliminary acid treatment 1 Hydrochloric aold' 11 Carbonio uold r. ^. 4 (3) (c) Effeote of Alualnun 7 Physloal Properties In Relation to Irritation (a) Length of fibre (b) Ef-f-eot of Crushing (o) Heat-treatment 8 Nature and Significance of Aabeatoala Body (a) Fornatlon (b) Protective effect preventing further Irritation (o) Ultimate solubility in tissue 9 Theories of Aotlon of Aebestlforo Minerals (a) Chenical - reasons for considering Invalid (b) Mechanical - experlnental deaonstration of. 10 _Coapllcationo ' (a) Infection, tuberculosis and other varieties (b) Cancer of lung - experlnental data suggestive but not proven 11 Disability 12 Essential Features of Hazardous Exposure (a) Nature of duet - fibroua conponent and site factors (b) Atnoapheric Concentrations - probably lover than for .quartz _ . r /. *. 1 Inadequacy of standard lcplnger.sampling method * which does not oollect the dangerous fibres 11 Electrostatic preclpltatat'sacpling preferable but nethod oust be codified .. . (c)'Duration of Exposure 13 Recommendations for a New Standard of Safe Atnoapheric Con centrations of Asbestos Bust (a) The Quael-offlcial etandardof 4 to 5 cllllon perticlee per cu. ft. (b) Work upon better nethod of eenpllng (c) Necessity for comparison of resultB with X-ray findings in enployees 14 Prevention (a) Chenical neane not practical i (4) { 1 Acidosis necessary to dissolve fibre In lungs "worse-' than Asbestoels 11 Alunlnua Therapy Inapplicable 111 Chief reliance still upon dust prevention with apeolal eophaels upon the fibrous oocponente * ASBESTOSI5 *A--'-.'-L--'-C--T--E--D- -O---l'tT---L-J--U---E- IKDICA' 77VO RESULTS P/TT 1 - HUMAN ASEESTCSI5 1 Human Pathology enfl X-ray Patterns - Description Based upon 23 hunan autopsies 2 Ash p.r.l Mineral Values lr. Hunan Lunrg. 3 Complication of Asbeetoele (a) Susceptibility to Infeotlon 1 Tuberculous- High lncldanoe in English experience not duplicated In surveys of Anerlcan Plants. Available autopsy statistics deceiving because of. sel ection of saterlal. 11- Hon-Tuberoulous- The sane reason probably applies ehould be checked, by analysis of ab senteeism among asbestos workers. ill Cancer of Lung Ditto, but there are now on record ID caoes of. lung cancer In asbestos workers. Compared to the total number of autopsies on aebeBtoBlo, thlo Incidence Is exceaslvi Ko such frequency has been discovered In silicosis other fores of pneunoconlo- ele exoept^tbe Schr.eeberg nine's of radio-, active ores. The evidence is suggestive but not conclusive that aebeetoeis nay precipitate the development of oancer in susceptible, individuals. ^ Slspblli Clir.lcal experience canifected by les6 suggests striking that X-ray truly disabling aebestosls Is chang es than a corresponding degree of silicosis fiuch disability i r. asbestOBle is due to disease within slli-ccsie, the assoc lur.ga iatec and not to sec or.iary heart dlseaee. As pulmonary infe ctlon Increases the amount eA'* severity of the duet fibrosie with r esultant accentuation of disability.' There study of pulnonory is urgent need for a careful physiological function In asbestos is of varying severity, Undoubtedly, there are many dlagnosable cases with no significant A 1^ability. 5 DlernosiE depends upon three factors. (a) History of adequate exposure, usually 6 to E years, some ' ' tines longer, at work, where both the concentration and character of the asbestos" dust are hetardous. < *":r '* 2-: (b) Evidence of disease *.in a characteristic X-ray pattern. y?H^ ' V lc) A physical jxaoinstlon which reveala certain characteristic, signs and coy reveal evidences of dieabllity if present. (d) Asbestosis bodies in the aputun are oonflraatory when the previous.factors are* all positive. However, the bodies cay be absent,'particularly 1:. the absence of bronchitis infection. .'*; Asbestos'** bodies unsupported by other evidence do not cake.;, a diagnosis. `Oocaolonal oneo heve been found in about 15 autopsy specineno of portions with no known exposure and no fibrosis, probably'of ;non-ocoupotional origin. . ^ * : t PAR?. II Experlrsentwl Asbestosle I .Methods r . r.; (a) Inhalet ion Exposures .to Plant 'Duajt Specifio Sibroeia;Lr\*:- lungs, but no ohangee elsewhere.? * ** .. % " -. o/V* I ' (b) Infections of - Suspension's of Pure Minerals into 7r&ohea':'A*v* Sinilar results. j . .. ' :.. *.:.** - (c) Infection of Suspensions of Pure Mineral into other organs Fibres dissolved; no aBbestoels bodies; . tissue resetion'con- .in any organ of-apy: epeolee -of,anlcal.-;~It onuses fibrosltronlyi the lunrB of can and thoee of*a yeV'-Qf.-the epeolee-tested. Soecie s Fibrosis Kan 4+ Guinea Pip 2+ babbit + *\ * . 1 >.*' * i * ' i 0 Asbestos BodiesSoecles'-`Fibrosis Asbestos-Bod -Y*1' y ,`-,T *" _ -.s, 4 v/- .- ,1a:.- -p... ; ,>*-,,-. -v v^its House '0 -- Vhito Hat - Q >' -* -1- ?. 't 0 (<~-f - verr wtvrlrel w sbestoe bodiesV' - 0 '' - - :. *'y rO\*n\* Ill Peculiar Chnrsoteristlca Of Aebeeton 1 r\ (0) Locn*l*lz otlon'of fibrous* minerals >in^i\inc 'froc*that of granulnr dust portiolee.');-T* . . . *'. *.s . 'x:--jt'...... .v - . .Le v i-.A-:. ; --3-- I Fibree like ohrysotlle having a oertaln decree of flexibility and elasticity aoruaulate within the finest air tubre; granular duet la oarried further on and la vldely aoattered through the ` terminal air apaoea. (b) Rate.of tleeua reootlon to aebeetoa la nuoh nore rapid thon to an active duet like quartz. Evidences of formation appear ae eoon as aufflolent oonoentratlon of flbree has looallzed 'In epeolflo areas; vlth quartz, there le a latent period of nontha. (c) Reaction to aabeatoa does not progress on oeaeatlon of expceure. Young acar tlseue that may have forced, oor.traote and becocee core dense but the area of lnvolvesent decreases In. size. In sllicoeis, the .young nodules becoae larger after exposure oeaseB. (d) Asbeetosle Bodies are a speolflc concoaaltant of this fore of pneucoconlOBle. They are due to a deposit of protein and Iron upon the surface of Inhaled fibres. In guinea pig they fore after about 60 days of contact with the tissue. They are-ebund ant. ,ln nan and guinea plge, (See paragraph 2 above) but ouch larger In the forner probably becauee the larger elzed air tube adnlt larger fibres. In cats,- rabblte and sice, there le an atypical coating of a few of the fibres after nuoh longer resi dence In the lungs; In rate and dogs no bodies could be dis covered. Froa paragraph 2 It la apparent that their occurence' does -not parollel development of floroeie. In lung injection experiment, the bodiee have developed an*1l after fibrosis all e.crr.r.ced. The number of bodies seems to decrease . several years after exposure desses. V Compere me Effects (a) r. Different AebeetoeH Kln'erglc *' - highly irritating. (b) Arlrora ^hrveotlle (low In iron) equally Irritating end pro duces Just.-as- cany aabestceie bodies ae the Canadian product with over 11 tines as nuch Iron. (c) Crocldolite - The South African blue a6b?etoe la known to cause a6betoeis. Only a Halted supply of this material In pure fora wee available, nost of it was used'earlier In the work in non-productive experlnente. For the later critical Injection testa Into the lunge, a Bolivian variety was substituted be cause of its high purity. Its fibres were much atralghter, stlffer and nore elastic than the cottony South African variety. Perhana because of these peculiarities. It has not given reactions comparable to ohryaotile. It produced aebeatods bodies but did not localize In the ternlnal air tube6 nor cause any flbro6la. Teata now being repented with a typlcol South African crocldollte with physlc/.l characteristics simulating chryootlle. > t , (d) Ar.thophylllte -<-atiff, -straight fibrea - atyplonl aebeetoale ' bodios force slowly but no localization or ribroalo in lunga. (e) Acoslte - Ditto. (f) Ar, phi bole - Ditto. (f) Trenollte - Ditto but vory few aebeatoala bodies bring oontlnued. O; be.ervation' V Control Mineral . .u- (a) Grwnulqr Serpentine of ease chenioal oonpoaltlon ae ohryootlle ' ia inert causing no fibroala in lunga or other organa, ut V* attracts iron fron the lungs but of oourae, no bodies* develop. (b) Ola eg Vool(a aynthetio ellicate) fibrea are not inhalebio fron air-borns auapenaions, apparently becauae of their stiffness (the dlaneter ia not responsible aa soce ueed were leae than V* 1 nlcron thich) On injeotion into the lunge, they do not v localize in the air .tubes but are widely scattered. They, oauae no fibroola. After 3 or 4 conths in oontaot with lung fluid, a few glass fibrea tahe up iron but reaain acootb. They nover shew the swollen ends and lateral projections of the true V > asbeatosis bodies. te of interest because it la a fibrous cineral praotlcally free of 6illca (o.9^). Cryetallographioally the arrangement of ltai$ g and OK groups in each unit oell la ainilar to that in chrya otil.e. The Bacple ueed also contained about 16.* iron, pro- . bably fron oontaainajing cagnetlte. The fibrea are stiff end neecl e lihe. Observicns not yet oonpleted but after 2 contha in th e lungs, typipal asbeetosia bodlee develop but there la ae yet n o fibroala. `he fibre are scattered through the lung instead of fce ing. localized inside the terminal air tubes and tissue react ion'.occura around, instead of within the tubes. 1 Chenlcel Csoooeitlon In Relation to Irritation (a) Nothing in the following chesical compositions can be cor related with variations in capacity to provohe tissue reaction. (See Table Next-Page) t  <; 0 .7 0, c0 L}0> 37.43* 2.35* 0 0.36* 54.99* 16.27* 4.29* ~ 1.02* *7.^ ^ MB.'23* ... 53:04* - - '56.20* 0.90* - 0.51* "0 * 0.25* A! 06* .33,63* _ 1.09* * '3.08* *' ` '** 1 0 -* - l.'eo* ' '? ,2\?> 6.7P* ' 9.36*" *. , r .a. >, 0.56* 0.46* 0 0.05* ^0 38.77* 0 0.29 vO o.oe jsdlOS 4.30 ' >105 14,92 (b) 0.79* 0.44* 2.01* 12,22*_ * 4.45* 0.40* ' r~`; _ 12,25* 29,64* 6.29* 23.29* 20.62* 63.99* -1*: * .* - 6,92 0.52 _ Oj 33 0.40 .6,76 . 0.91 ' * 0.57 -0.02 2.56 0.15 0,62 2.42 0.10 0,65 1.61 0.12. ' ' 0.99 0,32 - 0.34 3.59 ***' 2.78 >- cv *. i.-' 'JL16 ` ' J *'* . * 0.53 *V;'r`v * '* *_ ^. . 20.66 ' - ... . Acid treatnent .of ohryeotile fibres y:'f : .. ..................... ... , yj, 1 One hour In dilute or oonoentrated'BCL does not altar/ap^T pearanoe of fibre but after euoh treatnont it rapidly' dle- aolve8 and disappears on injecting into living tissues; il Trea.toent with CO/> bubbled through water or lung Juice *-U '"suspensions of chryeotile fibrea oauees partial solution : ' with liberation of silica and nag ne*.* *s.ia. * ; *. * \i' *' (c) Colloidal allurina does not neutralize the'effeots of aebestoe as it does quartz. On injecting ohryeotile euepended in alucir.ur: hydrate solution, fiirceie ar.d arteetcE tcdiee der- eiop at the usual rate. It recalne to deccnstrate whether the fibree* beoone ooated vith a layer of alu.pl nu^ conohydrate ae hae been proved in the case of quartz. `f they have, the ooat. does not affeot their capacity to irritate tieeue. , 9 VII . Physical Properties In Relation ---- *0 Irritation o1 f Lunr Tissue ^ ), * ' 1. ( (a) Lenrth of Pjbrg ' . ,* . Short ohryaotlle flbreiunder 3 nlorone are practically inert.' 20 to 50 nloron fibrea cauee typical fibrosis. . The effects of longer ones could not be tested for technioal ;;- reasons. ~ ' (b) Cruehinr oonpletely deetroye the fibrous structure of . chryeotile. Vith loee of structure, ell, oapaclty to irritate diaappeare. VIII ------ fibre*fltruo-turo ie proeerved.'y Flbroe beooco' extrcnely brittle.: * i`The physical ohange alt ere typiool localization'within thottVri:* lunge, no fibroe*e develops,:reaotionlinlted to pbjagooytoolV?' Ko aabestoels bodies ' forced. .iV''-:- V-V.'CV I ' Koture end ii "S ,r`* ^ # * *# AebestoMe Boflien . .. *; t --- - : *.: irrT' (a) Bodice, probably result'fron dopoeitionTof lron-and organic natter on a olowly dioeol^lng-fibre .of .'aobeatooU:\The eouroe . of the iron io nore lltol7 to/be .tho lung tiooue .than the . nir.eral iteelf as tho coating .1.0 *rJuot`ae-heavy'on-fibrous - ninerala of lc* iron oontont..-'ttfl'!upon. thooe 'high, in iron. .`.'v' (b) .The effeot of nabeetooie'bodylforaatlon'ie oaounod to be pro-`j tective although it hae nofbeen :poosiblo :to. ieolato a large *.:y enough quantity of. theee otruoturee-in.unalterod-fora for . *.yt*:` purposee of test.- Ths ocooth-rounded-ends*preaontod-by the ' bodies would not 'be neohanloally.irritating*: 'r'*'- 1 * . *. 4-VV .-.-/ * (c) If they were oapablo of causing-irritation,vtho-flbroela in the lunge should progress after exposure.oeaeea^which it doee not. . " ' ``.'r-'......... . / < ;? * ** ' * * (d) The gradual dleappearnnoe of .bodies (and'flbrea) long after ` - expoaur^'pbinte. to ultlcate aolubility in; tiaeue flulda. ^ . * *i. T (e) ^he bodies are probably a fortuitous oonoocaitant rather than" a cause of flbroale. IX Theories of Irritsr.t Action of Aebeetifore Minerals (a) Cherlcnl Theee experinente do not ccnfirs the theory that aebesto?i6 le pereiy a fora of silicosis.resulting fron free silica libereted in the solution of a ellloate noleoule. If this were true asbestosyllke cuarti^phculd onuee fibroeie In f--ry -o--r-g--a--n- cr tny Bteciec for the exp-riner.ts have ehevr. that injected asbestos diesolvee in these locations. Eovever, it ices not. c-use such reaction in any location but the lunge of * species. (t) Mechanic si Irritation Ve ure proposing the theory of nechanicsl irritation which le nanifeeted only in the lungs because thle organ is the only one whose nornal physiological functions Involve a high degree of nobility. Experinente designed to prove the necessity for notion in this tissue have failed for technical reasons. For thle theory to he applicableIt le neceeeary that the flbree be concentrated in the Tlr[e ternlnal air tubes. It hae be^n shown that only ohrysotlle of the aebeetlforn nineralJ thue fcVjfiaa the proper physical oharaoterlatioa.to insure such localization. It la also essential that the fibre shall peralet long enough before it dissolves in the;lunga of apeclee like nice, rote,'* doge. It apparently dloooivea eo rapidly that It exerto no irritation. Dinllorly rapid solution nay explain in or.rt w tV.<' Ii>cV of f* -->r.i n in f'rrf,r.(> o *., r^~ "'ir-t. 7- The fibres Duet be long enough bo that they oannot be conpleteiy surrounded by phagocytic oells vhlch' would prevent contaot of these round, broken'ends with the delloate cells supporting the air tubes Observation has denonetrated thnt these conditions arc reaXlsied in guinea pige treated with long fibre chrysotile and fibrooie results Vith the other asbestiforo ninerals that havo been tested, eons or all of the prerequisite vers lacking and no fibrosis developed. (c) If the irritation were chenlcal, fine serpentine which hae the etr.e* chenlcal oonpoeitlon as chrycotlla should have also cauee fibrosis. The crushed chrysotile ehoudl have been nore active than Intact fibres, becauao of the greoter ourfnoe nreno op posed to body fluids. On the asoucptlon that ohryeotile, like "ouarti, beconee coated with a very thin layer of alunlnee on treatnent with oolloidal aluninun hydroxide, oapaclty .to cause flbroals should be destroyed if the eotlon were chenlcal but such 15 not the oase. (c) 2 * 4he heavy coating resulting fron asoeetoels body fornation ap parently does stop tlseue reaction but here the effecte are probably nechanloal for reasons cited. (e) Heat sufficient to alter chealoal structure d eetroye power tc Irritate but it also alters essential phyeioal chorecterlet that affect localization of the fibres in the lunge. X Ccnollcntlon6 (a) suscentlblllty to Infection m Bttih i Tuberculous,- Asbeetos behaves like noet other nlneral/4in this respect and not like ouarti which specifically, lncreaf native susceptibility to the tubercle bacillus. -This in- ; feotlon nay spread for a tine but then heal6. The reeultar fibrosis accentuates that oaueed by the nineral fibres 11 Hon-Tuberculcus - of no greater frequency then in animals inhaling duets of other kinds. Occasional epidenlce of pneumonia occur in our duet roone, but these are due to nethode of housing rather than to duBt; they free also occu: .in unexposed animals. Ill'*- Cancer of Lunrp No experlnente vere^deslgned to elucidate this point but certain evidence suggeete that aebeetosla nay actually favor developnent of tunors in euaceptlble epeciee. 1 In guinea pige, rabblte, rats, oats and doga lung tucor are rare. 2 When these species were eubjeoted to 2 to 3 years In halation of asbestos duet, the incidence of lung tunor was not lnoreaeed. -8- 3 Soce etraina of white aloe do develop tunora without apparent o&uee. j 4 Such a'etrolh of white nice vae unintentionally uacd in three inhalation experinenta with aabeetoa. 5 Of 11 nice inhaling lonr fibre aebeetoa for 15 to 24 nontl B developed nnlignant tunora in their lunge and 6 of then had tunorn in other organa. The lnoldppoe rate l.jL< Ip excessive. e Of 22 nice inhaling ehort fibre oobeatoe for not longor ti 12 nontha only 0 doveloped lung tunora. Rate 1 3.65 7 Aa oontrole. we have only the experience with aloe in othe duet experinenta. * or ehort periods. there were 51 nice expoeed to 4 other kinds of du6t for 10 to 12 nontha. Incidence of lung tunc 1.95. . For lcnr perl ode. there were 142 nice exposed to 4 differs kinds of dust, lnoluding pure quartz, 23 to 31 nontha. Fo all thla group of nice the averare incidenco of lung turor vbb 13.85: the higheet rate (255) *aa In a subgroup expoee to flint dust. Thus the incidence of lung cancer in the lonr fibre aabeatOB nloe vae over 16 tinea the average for nloe Inhaling other duate for coaporable periods andover 3 tinee the naxlnun for any other'grou Rice exposed to the praotloally inert ehort fibre aabeatoe ehowed fewer lung tunora although 7 tinea nore than those In ehort expoeu. to other duote. ^'hese obE.-.-vfctlona are suggestive but not conclusive evidence of a cancer etinulating action by aabeetoa duet. .They are open to several orlticiBC6. The strain of nice ves not the aane in the ssttsice experirer.t as in nany of the others cited; apparently the fcrner were unusually euooeptible. Kot enough eninal6 uurvived in the dust for longer th_n the 15 nonthe apparently neceeeary to produce nany-tunora. Ihere were no unexpoeed oontrols of the eane etreln and ege and no dicilar controls expoeed to other duete. It le hoped that this expcrinent can be repeated under properly controlled conditions to determine whether aabeetoa actually favore cancer.pf the lung. XI Disability Cannot be deternined in enlnals. ^he accidental deaths were froo the eane causes net with in all our duet inhalation experi nenta. XII 1 vhe hszrds increases with the proportion of. intact fihree in the duet. Granular material and crushed fibre are inert diluents. S"V:*.; .1^ 11 '^he Ion? fibres cust be thin enough (1-3 Microns), end 6hort enough (under SO Microns?) to be Inhaled. ill Very short fibres (under Z Microns) are practically inert. (b) Atmospheric Concentration Still under study. Apparently this factor is lover than in the case of duets composed c- granular ninerale but oethode of estimation are misleading. . . .V I The average standard Publio "ealth Servioe lmplnger count in the long fibre asbestos dust roo3*wae AO nllllon particles per cu. ft. of air. *his`concentration"caused flbroBle visible to the naked eye in 20 to 24 ninths. For conpariscn the average inplnger oounte in an experinent with pure quartz was 120 nilllon particles par cu. ft.'and flbroels developed at about the eane rate. *. ' > ; v . II However, icplnger oounte are deceptive becauee by thle method of sampling very few fibree, which are the significant elements in the duet are oolleoted.'.?v*7; * ill Sampling with an electrootatio preolpltator ie a nuch nore efficient Beans of collecting fibres froa air-borne sus pensions. Samples from our long fibre aobestoo toob ahoved that the dust in the air oontcined 32.5^ of fibres few of'which had been oolleoted or counted in the lmpinger ssmpie. The latter sampled largely the inert gTanular parti- oles. . ... * lv Aa ordinarily employed precipitator saDples are weighed and the results expressed in eg. per cubic foot of air. There 1b no neans of converting such values into numbers of ^pcrtlcleB particularly when these vary in Bite, ehape and 's, pecific gravity. . .. V' * . *. ?* v Slcultaneoue aanplinE with preolpltator and standard implnger yielded the respective values of 0.65 eg and 60 Dilllon partlolea per oublo foot of air. r. * vl *heoretloally the best index of hazard would be either the number or weight of fibroue elements in the dust. T 1^* -10l: . (c) Dorati or. of Excoaure 1.. . r*. ;:v 1 fibrosis, visible to the naked eje after 13 nonthe rxposure Increases In extent In subsequent lS.nontha. ?I*'"iY. v v.y-.vf'. *fe;v **'W 4a*-- ` tr.;-I* 11 The span of life of our noet auaoeptlble laboratory enlnal.,*' the guinea pl has prevented continuing Exposure longer tht three years. In thio period only the comparatively early ... stage*1 of asbeatosls have.been-produced.* With the know ledge that ve have gained, it- lo- probable that nore exteneivi disease could h/ve been produced with a purer long fibre chryeotile. The long lived species,-like cats, doge are un- fortunotely not susceptible--. v' .-ill For these roasons X-ray changes have been clnlnal andvt were not able to fulfill one of the objeotives of this pro- rn ... . /-* * * - *>*X3II Hecor-ier.detlon for 'a New Standard of Safe Atcoephf rl.Q Concent rat! or. " . * .. .: ' --o-f-.A s' be sto' p b usi t . ? .v k .* /*, *, " *1% / I* '-" 4 (a) Whi^lev t*h^ewr4 ec Iisr nIIVo oU4f1fJi^cw JikaCtAl sB tandarUd,) tvhmwe'tvetnntativ1eh o^ n'ew of % Lt * r.-t '.V....i.-............4o...u..o.o..r.t.e...5c......n....l..l..l.i..on particles per cubic foot of . vf..*. _ air Is f'requently .1 * *. rj. M. * r; , , (t) This is probe'oly unreliable because it -is'baeed upon sampling with a standard inplnger which we hevefshown does riot collect [>;: ..... ncaf of the fibres that are the source of%.hpz&rd. fc:-.*' tc) We novi think that a standard should be baeed upon earaples collected with an electrostatic precipitator if lt la feasible to determine readily the relative proportion of.fibres ir. auch trterial . :? `.. ,, .4- * *.< V- .* (J) Vcr'/. 1c still in progress upon the latter-point. J` . ' - ''y;." .w.* .* (e) To be of-value'the* new standard vould.;hbye .MoVbe correlated with thev0C-rry findings- uponjecployeeb.'-exposed ;.to jdlfferent '' concentrations of duat. v' XIV rever.tlcn of Asbeetcslo'-' '. ?*: ^ ' `1 ->*' * --------------- --------------------- _ --? -\p The expericento hove failed .to'develop .any^.practical 'cheolcal ` means of neutralising the action'of fibrous'asbestos.*' * *v *. f . " ,1 ,% ,, ' (s) *o alter the huaan'lun `so that lt vouid'ldlsaolveyacbestos fibres rapidly like a rat would necescltate: (yrobe.br-r) creating an acidosis whloh would be.v**orae ,than the effects of the flbrosle. -V 'V'V'xT* . . / * -f.* *> ` * `'.'Vi ' ''$ ' Kr*.' ?-'t r- *> f&r- - * Ct.'-: 5? . v *r;x. - *Ajr- tSfk:r*- 1' Chief rellanoe-mu6t etlll.\be booed *vpon*:ppntroiv6f ' lr and, In vlev:of-jrthooe'>,oxperlpentB'(r,*partlcjilfirlj fibroui ' ' ..... - * ;.v'. y*-, y-.v i-. . . * ,, * # * /. . * . ' r- Jy- -- <: . ,,. -V/- ' .-.V: -.it- ... .. S: .r