Document qaXdNE25kZOdBqYnLarmoY0QG

Defc- Brinco -- UH (25) Icmuel Turner r. information end return to l-,r. W. W. F. Shepherd Kiii No. 2831 T7S/AM. TAN No.' 2579 -.........7' - f i r < f' W.'C Kf".-. ' 3. Huehlock, Eaq., taaobay & 2attiaon Co'/, /' Ambler, Pa. r ~r, :-i z:,: 7 5th May 1943. Dear lr-. Muehleck', ` J* Br. Leroy U. Gardner*s Asbestos Dust Experiments Thank you very much for yonr letter-1 Kfcftf Be. 2831 or Maroh 8th enclosing photostat eopy of Dr. Gardner's letter of* Jebruary 24th to Mr. Vandiver Brown, and also a copy of the "Outline of the Proposed Monograph on Aabeatoais". I will arrange'for these doodmenta to be 'studled by those of our officials who are beat Inforaed on the subject.of. aabeatoala and will let you hare our oonmonta as aoon ^ 'they 'are available." / `SZ c. Tours fait \ Uitunvl ##'! (Bl'iuket License Ho. i>-1^99) Keashey & Mattisox Compaxy AMULSa.PZNMSn.VAKL* " Deft. Brinco -- HH <2i) March 8, 1943. KA.'J No. SSIl W. W. F. Shepherd, Ksq., Turner & Newell Ltd., Spotland, Rochdale. Deer Ur. Shepherd: 4^ Subject: Dr. Leroy V. Gardner's Asbestos Dust Broerlaenta. Further to this subject, Z now hare pleasure in handing you herewith photostat copy of Dr. Gardner's letter of February 24, 1943 to Ur. Vandiver Brown, and also copy of the "Outline of Proposed Nonograph on Asbestosis." I hare found this outline to be extremely interest ing. It brings out a nuaber of Important new develop ments, but no feel that reference to the question of cancer susceptibility should be omitted from the report since it is inconclusive. C I would appreciate receiving any core.-ants which you r.ay bar9 to rnho concerning the enclosed outline, anddso will forward you the final report as soon as received.* ^-"Tours sincerely, \ *. a ^ --f" x em: ci Kncl. TSASBSI 4c MA.TTIS01J COIiPAItf First Follow Second Follow / \- s The Saranac Laboratory FOR THE STUDY OF TUBERCULOSIS ' Of THI E7WAID L TIUDIAU fOUKDAHOH Sakahac Lau, N.Y. February 24, 1943 -- 1; v. L Hr. Vandiver Erown Johns-Kanville Corporation 22 East 40th Street New York, New York Dear Mr. Brown: ,, I have at last succeeded In analyzing most of our valSainoua experlnental data end assessing the results/) I realize t'RaT'thls should have been oompleted before this, but the emergency has left os short-handedl In the Laboratory and also necessitated ny doing a good deal of extra traveling. I hope that the sponsors of our study of asbestosls will be oharltable and realize that the work has far exceeded Its original scope. We have done over 40 different experlnente, nany of then divided Into several parts, which Involved exposure of animals for 1 to 3 years to various dusts. The business of preparing nlcroscoplc sections and chemically analyzing the tissues on more than 800 animals 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 this work which will of necessity be nonographic. However, for the benefit of the contributors, I an eubnlttlng a table of oontents and an an notated outline to Indicate conclusions and the line of argument that will be developed. The latter Itself occupies 15 pages, but I hope they will find It sufficiently Interesting to read. 2 shall work on the final manuscript as I have opportunity. There ere a few experlnente still In progress which should be conpleted by the tine ve are ready for then. *he work on methods.of dust determination, I oonslder lnportant enough to in clude In the study. The question of cancer susceptibility now seens nore significant than I had previously Imagined. 1 believe I can obtain support for repeating It fron the cancer research group. As It will take two or three years to oonplete such a study, I believe It would better be omitted from the present report. If It should become possible to make this study, I hope that I any count on sone of your members to supply me with enough pure, long fibre asbestos for the purpose. \ mm Mr. Vandiver Brown -2- rebruary 24, 1943 Naturally, I shall veloone any criticism that you or any of the other contributors would care to offer. Should any of then want to dlaouas details, I-would bo pleased to meet with them. May I take this opportunity to thank all the sponsors through you for the support that we have had. Slnosrely yours, ^4 LUG:-3H Leroy U. Gardner, M. D. Director OUTLINE OF PROPOSED MONOORAPH ON ASBESTQ3IS Saranac Laboratory Study under Orant fron Asbestos Association ( PART I HUMAN AS3E3T0SIS 1 Human Pathology - a study of 25 autopsy oases. Illustrated 2 X-ray Patterns In Asbestosls, Illustrated 3 Ash and Mineral Values In Human Asbestosls 4 Complications of Asbestosls (a) Susceptibility to Infection 1 Tuberouloua 11 Non-Tuberculous 111 Cancer of the lung 5 Disability, causes and comparison with silicosis 6 Diagnosis . (a) History of adequate exposure ('oj X-ray film pattern (c) Physical examination (a) Aabestoels bodies in sputum, their significance -L- Dr . (2) PART II Experimental Asbestosls 1 Methods (a) Inhalation exposure to plant dusts. (b) Injeotlon into lungs through trachea of pure minerals, (o) Injection of.pure minerals Into other organs. 2 Bpecles Susceptibility Man, guinea pigs, rabolts, oats, white mice and rate, dogs. 3 Peculiar Characteristics of Asbestosls (a) Unusual locallzalon of chrysotlle fibre In lungs. (b) Rate of resultant tissue reaction more rapid than to ouart z. (c) Reaction to chrysotlle 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. Ill Formation does not parallel development of fibrosis lv Gradual disappearance after exposure ceases. 4 Comparative Effects of Different Asbestlform minerals. (a) Canadian Chrysotlle. (b) Arizona Chrysotlle, low Iron. (c) Crooldollte 1 Bolivian specimen, stiff and elastic. 11 South Afrloan, soft ar.d flexible. (d) Anthophylllte (e) Amosite. (f) Tremolite. 5 Effects of Control Minerals (a) Orannulsr Serpentine, same ohemlcal composition as chrysotlle. (b) Glass Wool, a synthetic silicate fibre. (o) Bruolte, a fibrous magnesium hydroxide almost free of silica 6 Chemical Composition of Asbestlform minerals In Relation to Irritation. (a) Nothing In composition correlated with relative lrrltatl capacity. (b) Preliminary acid treatment 1 Hydrochloric add' 11 Carbonlo add ? f Xt " K 4 (3) (c) Zffeots of Aluminum 7 Phyaioal Properties In Halation to Irritation (a) Langth of fibre (b) Effeot of Crushing (o) Heat treatment 8 Nature and Significance of Aabeetoala Body (a) Formation (b) Protective effeot preventing further Irritation (o) Ultlaate solubility In tissue 9 Theories of Action of Asbsstlforo Minerals (a) Chenlcal - reasons for considering Invalid (b) Mechanical - experimental demonstration of. 10 Complications - (a) Infection, tuberculosis and other varieties (b) Cancer of lung - experimental data suggestive but not proven 11 Disability 12 Essential Features of Hazardous Exposure (a) Nature of dust - fibrous component and size factors (b) Atmospheric Concentrations - probably lower than for quartz 1 Inadequacy of standard implnger sampling method which does not oollect the dangerous fibres r. 11 Eleotrostatic preclpltatarsampllng preferable but ^7 method must be modified (c)Duration of Exposure 13 Recommendations for a New Standard of Safe Atmospheric Con. centratlone of Asbestos Dust (a) The Quasl-offlclal standard-of 4 to 5 million particles per cu. ft. (b) Work upon better method of sampling (c) Necessity for comparison of results with X-ray findings in employees 14 Prevention (a) Chemical means not practical .3j ' .* **'V - * S (4) 1 Acidosis neoessary to dissolve fibre In lungs-*orDe than Asbestosls 11 Alunlnua Therapy Inapplicable 111 Chief reliance etill upon duet prevention vltb epeolal eophasls upon the fibrous components ' 5 1 ".ti?. -I- assestosis - anucted outline indicating results PITT I - HIT1.AN A3EE3TCSI3 1 Huaan Pathology and X-ray Patterns - Description Based upon 23 human autopsies 2 Ash and Mineral Values lr. Hunan Lungs. 3 Complication of Asbestoele (a) Susceptibility to Infeotlon i Tuberculous- High incidence in English experience not duplicated in surveys of American Plante. Available autopsy statistics deceiving because of sel ection of naterlal. 11 Non-Tuberoulousu The ease reason probably applies should be cheoked. by analysis of abeenteelen anong asbestos workers. ill Cancer of Lung Ditto, but there are now on record 10 cases of. lung cancer in asbestos workers. Compared to the total number of autopsies on aebestoslo, this lnoidence is excessiveNo such frequency has been discovered in silicosis ,^r other forms of pneumoconlosls exoept^the Sohneeberg mine's of radio active oree. The evidence is `suggestive but not conclusive that aebestosis nay precipitate the development of oancer in susceptible individuals. 4 Disability Cllr.ibal experience suggests that truly disabling aebestosis la manifested by less striking X-ray changes than a corresponding degree of allloosle. Such disability in asbestosle la due to disease within the lungs and not to secondary heart disease. As In silicosis, associated pulmonary infection increases the anount W severity of the dust fibrosis with resultant accentuation of disability. There is urgent need for a' careful physiological study of pulmonary function in asbeetoels of varying severity. Undoubtedly, there are many dlagnoBable oases with no significant disability. 5 Dlernosie depends upon three factors. (a) History of adequate exposure, usually 6 to 6 years, some times longer, at work where both the concentration and character of the "asbestos" dust are hatardoue. D ' k t' (-') ~~ ---- v*-~- (o) Evidence of disease'in a characteristic X-ray pattern. (c) A physical jxaninatlon which reveals certain characteristics Blgns and nay reveal evidences of disability if present..- . (d) Asbestosia bodieo in the eputun are oonflrnatory when the . . previous factors are-all positive. However, the bodies nay be absent,' particularly 1:. the abser.se of bronchitis ' infection. Asbeetoeobodies unsupported by other evidence do not nake.; . a diagnosis. Occasional ones have been found in about 15 autopsy specineno of persons with no known exposure and r.o fibrosis, probably of:non-ocoupatlonal origin. ****t***e**MH*Mt*t*t***M* / i- ' PART II Experimental Asbestosia I . Methods : -v (a) Inhalation Expoauree .to Plant DusJ Specifio flbroais .in'*'. . lungs, but no ohangee elsewhere. ..... / '- (b) Injections of- Suspensions of Pure Minerals into Traohea>' Sloilar results. j.:' (c) Injection of Suspensions of Pure'Mineral into other organs - . Fibres dissolved; no asbestosls bodies; tissue reactlon^csn- flned to phygoeytosla and encapsulation. Conpare" the ''-l'-.;' asbestos carets of huoan. subjects .-.UI'- v: v -.vr'r II S-ace^lbmtj 1.V'-.V;U:k+.cI',. ''.'-S;'*.- Unlike frse silica,.asbestos';does not;produoe its speolflo affects in any organ of-any: speolea -of anlnal.M''It:onuses flbrosle'only in ___*___________ - _ m______ __ - ^ ' _______ . a _ - *___ Species Kan 4+ Guinea Pig 2+ . - ~.c. -A-- Babbit + 4* v'.-f'r;* Whita Rat -0 * -';o`ch> - - `J-fl + - very wcftll atypical asbestos ItpdieaLli:---- Dog -r*tm__J>-------------- :' 0 r'.: .' r, - iv- III Peculiar Characteerriisticss of Asbeatonlg 'v'.': * . .. _ -``.ji #1. ` ` ml naval n'1?l-in:pft-Kd'' iffer V*. ** .* *fv * *-- fa) 5* 1 Fibres like ohrysotlle having a oertaln degree of flexibility and elasticity accumulate within the finest air tubes; granular duet Is oarried further on and Is widely soattered through the terminal air spaoes. (b) Rate of tissue reaotlon to asbeetos la muoh nore rapid than to an active dust like quartz. Evidences of formation appear as soon as sufficient oonoentratlon of fibres has localized 'In speolflo areas; with quartz, there la a latent period of months. (c) Reaction to asbestos does not progress on oeesatlon of expos ure. loung scar tissue that may have formed, oontraots and becomes core dense but the area of Involvement decreases In size. In silicosis, the -young nodules become larger after exposure oeases. (d) Asbestosis Bodies are a specific concommltant of this form of pneumoconiosis. They are due to a deposit of protein and Iron upon the surface of inhaled fibres. In guinea pigs they form after about 60 days of oontaot with the tissue. They ere abund ant In man and guinea pigs, (See paragraph 2 above) but much larger In the former probably because the larger sized air tubes admit larger fibres. In cats,- rabbits and mloe, there Is an atypical coating of a few of the fibres after muoh longer resi dence in the lungs; In rate and dogs no bodies could be dis covered. From paragraph 2 It is apparent that their occurence does net parallel development of floroels. In lung Injection , experlnenti, the bodies have rt developed snfft after fibrosis $"flh advr.r.ced. The number of bodies seems to decrease >- several years after exposure oeases. V Comparative Effeots stl Different Asbestosis Minerals *' (a) Canadian Chrvaotlle - highly irritating. (b) Arizona ^hrveotlle (low In Iron) equally Irritating and pro duces Just.-as many asbestosis bodies as the Canadian product with over 11 times as much iron. (c) Crocldollte - The South African blue asbestos Is known to cause - -asbestosis. Only a United supply of this material In pure form was available, most of It was used earlier In the vork in non-productive experiments. For the later critical Injection teets Into the lunge, a Bolivian variety wae substituted be____cause of its-high purity. Its flbrea were much etralghter, atlffer and more elastic than the cottony South African variety. ...Rerhana because of these-peculiarities, It has not given reactions comparable to ohrysotlle. It produced asbestosis _____ _bc.dlea.but did-not localize In the -ternlnal air tubes nor cause any fibrosis. Tests now being repented with a typical South African crocldollte with physical characteristics simulating chrysotlle. j j j I lI v- bb L3) . i -r. y * -4 (d) Ar.thoohvlllte - stiff, straight fibres - atypical aebeetoBla . bodies forms slowly but no localization or fibrosis in lungs. (e) Amoeltc - Ditto. -V, (f) Ar.ohlbole - Ditto. :' (g> Trenollte - Ditto but vory fov aebestoelo bodies - Observation' being oontlnued. '.. * *; . : v Control Mineral *" . ` . * r* , (a) Granular 3ernentlne of eame ohemloal composition as ohryootile * la Inert causing no fibrosis In lungs or other organs. Ct V> - attraote iron from the lungs but of oourse, no abodlesa develop. (b) Olaee Wool(a synthetic silicate) fibres are not lnhalable from air-borne suspensions, apparently beoause of their stiffness (the diameter Is not responsible as some used were less than V' 1 nlcron thick) On lnjeotlon Into the lunge, they do not v localize in the air.tubes but are widely scattered. They oause no fibrosis. After 3 or 4 aonths 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 aebeatosis bodies. (c) Bruclte of interest beoause it is a fibrous mineral praotlcally free of silica io.9%). Cryetallographieally the arrangement of its and OH groups in eaoh unit oell is similar to that in chrysotlle. The sample used also oontalned about 16, iron, pro bably from contaminating magnetite. The fibres are stiff and needle like. Observ&ions not yet oompleted but after 2 months In the lungs, typlpal asbeetosls bodies develop but there is as yet oft fibrosis. Ahe fibre are sosttered through the lung insteal of bilug. localized inside the terminal air tubes and tissue reaction'.occura around, instead of within the tubes. VI Chenlcpi Composition lrj Relation to Irritation (e) Nothing In the following chemical compositions can be cor related with variations In capacity to provoke tissue reaction. (See Table Next Page) S-Io - Ic l? (_i) St_2a p<_o__ c*._o__ Chr78- Crooid- otlle ollte 37.43< 54.99* 3.35* 16.27* _0___________ *.29-< o-ag.< 1.02* 0.05S 0.79* .... - -"'rj -- 1 mJ&2i '46.23* 63104* -36.20* 0.90* JLJSlt.l ' 4.06* ' - ''5.085 r ^7.21*' Q ? ' 33.85* 6 -P.as* -&>25*___ 1.09* 2.0l l.'eo* ' o.3P* o.4$.3 12.22* >- 4.45* 0,40* T'" "' *3_g__ 38.77* 12.25* 29.34* 8.29* 23.20*20 .'S2*'-63.99* K^. 0 Kj.0 0 .39 0,,08 6.92 0.57 .0.52 0.13 0.33 0.10 0.40 0.12 6.78 : 0.99 0.91 ' ^ o,i6 w'- Loas4105# 4,.30 ` >105 14,,92 (b) 0.02 0.62 0.66 0,32 / 0.34 __ 0.53 `1 g.58 2.42 3.59' 'v.?tza- 26.66 ';;:^-**X:* r .. * ; -4^-- t;A^** - .', .' -- " .i .,*r Acid treatnent .of ohryeotlle fibre* i-.*.,*: . 1 One hour In dilute or oonoentrated HCL does not altarfap--" pearanoe of fibre but after suoh treatnent It rapidly' diesolves and disappears on lnjeotlng into living tissues; . 11 Treatnent vlth COg bubbled through water or lung Juice \K suepenelons of ohryeotlle fibres causes partial solution with liberation of eilioa and magnesia. .V (c) Colloidal allunina does not neutralize the`effeots of aebeetce as It does quartz. Op Injecting ohryeotlle suspended In aluslr.un hydrate solution, fibrosis and asbestos belies dev elop at the usual rate. It renelns to deconstrate whether tbs fibres*beoone ooated with a layer of alunlnun nonohydrate as ' has been proved In the case of quartz. If they have, the ocat does not affeot their capacity to Irritate tissue. VII Physical Properties In Relation to Irritation of Lung Tissue (a) Length of Fibre Short ohryeotlle fibres under 3 olorone are praotically inert. 20 to 30 nioron fibres cause typical fibrosis. The effects of longer ones could not bs tested for technical reasons. (b) Crushing oonpletely destroys the fibrous structure of 1 chrysotlle. Vlth lose of structure, all. oapacity to irritate disappears. \ VIII </ f 1 branstructurn ie preserved.*'* ribres become' extremely brittle.!\ i~The physical a banco alters tjrploal localization' within tboV/r":'" lungs, no flbroOsB* a develops, :reaotion'limited. to phyogooytbBia?' - No asbestoala bodies formed. <'.' -f-' rfvIiv;< \ f ' J >; V/'-i, 4 , '* Nature ar.il Birnlfloanog of AsbqBtosls Bpdlefl ' . .. r - . la) Bodies, probably result Iron deposition^? iron'.and organic natter on a slowly dissolving`fibre .ofIas'bestoaU;;Tbe source, of. the Iron lo nors Utol7 to;be tho lung tlsous than'the mineral Itself ae tho coating 1.0 `Just 'as-heavy 'on fibrous minerals of lctf. iron oontont. ae !upon. those 'high .in Iron. `; ; '*0.*'^ i*; v** P*. ^" 00 The effeot of asbeetoeic' body\fornation`ie"aeounod to be pro-j tective although It has not-been.poeslbloito leolato a large enough quantity of these structures;ln.unaltered'fora for . purposes of test. The smooth'rounded-ende'.presented.by tho - bodies would not be meohanioally 1lrritatlagi''f-ts'-ji*<.^s':4'/ " (c) If they were oapablo of causing-Irritation,<the fibrosis in tbs lunrs should progress after exposure.'oeases.which it does not. (d) The gradual disappearance of.bodies (and'fibree) long after M` exrosuttf'Jfoints . to ultimate solubility in* tissue fluids. * - r. ? (e) The bodies are probably a fortuitous oonoonaltant rather than"" a cause of fibrosis. IX Theories of Irritant Action of Aebestlfora Minerals (a) Chemical These experiments do not oonfiro the theory thst asbestosis is merely a form of silicosis resulting from free silica liberated in the solution of a silicate molecule. If this were true asbestos,like ouartz,phould cause fibrosis In any organ cf any species for the experiments have ehovr. that injected asbestos dissolves In these locations. However, it does not. c-.use such reaction In any location but the lungs of eiHe species. (b) Mechanical Irritation Ve are proposing the theory of mechanical Irritation which Is manifested only In the lunge because this organ Is the only one whose normal physiological functions Involve a high degree of mobility. Experiments designed to prove the necessity for motion In this tissue have failed for technical reaeons. Tor this theory to be applicable,it is necessary that the fXixbdrje*csd bDec cofncoennwt*rafltwecQd. in tmhe* f+ltfe tvermQiinnaAli asir tvuuboepsb.* Iati has beerv.shown that only ohrysotlle of the aebestlform mineraall! thus fax nas the proper physical characteristics.to insure sluch localization. It la also essential that the fibre ehall pp ersist long enough before it dissolves In the .lunge of spades like nice, rate,+dogs. It apparently dissolves so rapidly that It exerts no Irritation. Similarly rapid.solution may explain In part, the lack of fibrosis In organs other than the lungs. \ f > bL-'Ck) A .. -7- The fibres oust be long enough so that they oannot be conple'tely . surrounded by phagocytic cells which' would prevent contaot or these round, broken'ends with the delloate cells supporting the air tuhee. Observation has deoonetroted that theoe conditions aro realized In guinea pigs treated with long fibre chrysotlle and flbroole results. With the other aebestlforn minerals that havo been tested, some or all of the prerequisite were lacking ana no fibrosis developed. (c) If the Irritation were chemical, fine serpentine which has the same" chemical composition as chrycotlle should have also caused fibrosis. The crushed chrysotlle ehoudl have been nore active than intact fibres, because of the greater surface areas ex~ posed to body fluids. On the assumption that ohrysotlle, like ouartz, becomes coated with a very thin layer of alunlr.ee on treatment with oolloldal alunlnun hydroxide, capacity to cause fibrosis should be destroyed If the aotlon were chemical but such lj not the case. ... (d) Ahe heavy coating resulting from asoeetosis body formation ap parently does stop tissue reaction but here the effects are probably nechanloal for reasons cited. (e) Keat eufflolent to alter chenloal structure d estroys power to Irritate but It also alters essontlal phyeloal characterleti that affect localization of the fibres In the lunge. X Complications (a) ausceotibllltv to Infection asib 1 Tuberculous - Asbeetoe behaves like most other mineral/. In this respect and not like ouartz which specifically Increase native susceptibility to the tubercle bacillus. -This ln- feotlon nay spread for a tine but then heals. The resultant fibrosis accentuates that caused by the nineral fibre. 11 Mon-Tuberculous - of no greater frequency then in animals inhaling dusts of other kinds. Occasional spldenlce of pneumonia occur In our dust roons, but these are due to nethods of housing rather than to dust; they **f aleo occur in unexpoeed Animals. ill'*- Cancer of Lunro No experiments vere,dealgned to elucidate this point but certain evidence suggests that aebestosis nay actually favor development of tumors in susceptible species. 1 In guinea pigs, rabbits,- rats, oats and dogB lung tumors are rare. 2 When these speoleB vers subjected to 2 to 3 years In halation of asbestos d-uet, the incidence of lung tumor was not inoreased. \ (ilo- bb-CT) S.'W -8- 3 Some strains of whits nice do develop tumors without apparent oause. j 4 Such a strain of white nice was unintentionally used in three Inhalation experiments with asbestos. 5 Of 11 nice Inhaling long fibre asbestos for 15 to 24 months 8 developed nallgnant tunors In their -lungs and 6 of then . had tunoro In other organa. The inoldonce rate !* Al excessive. e Of 22 nloe Inhaling short fibre asbestos for not longer thar 12 nontha only 3 developed lung tunors. Rate 13.6* 7 As oontrola, we have only the experience with nloe In other dust experlnents. For short periods. there were 51 nice exposed to 4 oth$r hinds of dust for 10 to 12 months. Inoldenos of lung tumor 1.9*. For lonr periods. there were 143 mice exposed to 4 different kinds of dust, including pure quart*, 23 to 31 months. For all this group of mice the average incidence of lung tumor was 13.8*: the highest rate (25*) was in a subgroup exposed to flint dust. Thus the Incidence of lung canoer In the long fibre asbestos mloe wo8 over 15 times the average for nloe Inhaling other dusts for comparable periods and over 3 times the maximum for any other'group. Mice exposed to the praotloally Inert short fibre asbestos shoved fewer lung tumors although 7 times more than those in short exposure to other duots. ^'hese observations are suggestive but not ooncluslve evidence of a cancer stimulating aotlon by asbestos dust. They axe open to several orltlcisms. The strain of mice was not the same In the asbestos experiment as In cany of the others olted; apparently the forassf. were unusually suooeptlble. Not enough animals survived In the d&ikt for longer thgn the 15 months apparently necessary to produce many-tumors. Ahere were no unexposed oontrola of the same strain and age and no dimllar controls exposed to other dusts. It Is hoped that thla experiment can be repeated under properly controlled conditions to determine whether asbestos actually favers cancer.pf the lung. XI Disability Cannot be determined in animals, ^he accidental deaths were from the sane causes met with In all our duet inhalation experi ments. A.3.1- -(a >'(?) \ XII Essential Jji (a) Nature 1 *he hairda Increases with the proportion of.intact flbree In the duet. Granular material and oruahed fibre are Inert diluents. * 11 -The long fibres must be thin enough (1-3 Hicrone) and short u enough (under 30 Microns?) to be inhaled. Ill Very short fibres (under 3 Microns) are practically Inert. (b) Atno8Pherlc Concentration Still under study. Apparently this factor is lower than In the case of dusta oonpoeed of granular minerals but methods of estimation axe misleading. ; ' . V I The average standard Publio health Servloe lmplnger count in the long fibre asbestos dust room'was 40 million particles per cu. ft. of air. *his'concentration-caused fibrosis visible to the naked eye In 20 to 24 ninths. For comparison the average lmplnger oounts in an experiment with pure quartz was 120 million particles per cu. ft.'and fibrosis developed at about the same rate. *; II However, lmplnger oounts are deceptive because by this method of sampling very few fibres, which are the significant elenents In the duet are collected.vvi: 111 Sampling with an electroetatio preolpitator le a much more efficient means of collecting fibres from elr-borne sus pensions. Samples from our long fibre aobestoo room showed that the dust In the air contained 32.5? of fibres few of which had been collected or counted In the lmplnger sample. ?he latter sampled largely the Inert granular parti -Clea. ' lv As ordinarily employed precipitator samples are weighed and the results expressed In mg. per cubic foot of air. There Is no mesne of converting such values Into numbers of particles particularly when these vary in size, ehape and "specific gravity. 11-- v Simultaneous sampling with preolpitator and standard implnger yielded the respective values of 0.65 mg and 60 mil lion particles per oubio foot of air. vl *heoretloally the beet Index of hazard would be either the number or weight of fibrous elements In the dust. "Slip- (j>(a (_0 i r-- -10- \ * I.' . (c) Duration of Exuoaure v .. , V: * ' 1* * , ;< . V- ` ' --*' yr 1 fibrosis vlLlble to the naked eye after 13 months exposure, Increases In extent In subsequent 13,months. % '4r*' 11 The span of life of our most susceptible laboratory animal,' the guinea pig has prevented continuing lfexpSJre longer than three years. In this period only the comparatively early stage? of asbestosls have.been-produced.* With the know ledge that we have gained, It lo probable that more extenelv. disease could hf ve been produced with a purer long fibre chrysotlle. The long lived epeoles, like cats, dogB are ur.- fortunately not susceptible-. . v. Z&'r ill For these reasons X-ray changes have been nlnlnal and ve were not able to fulfill one of the objectives of this pror ;; ! gram. ... ...... > . g>;XIII Recommendation for? Hew Standard of Safe'Atmospherlo Concentration -of.A isbestoo1 ~busXt. *....** ,* .* a . . ; .i- t : Pi,%:`^..:.'(a) While there la n1IUo oV if1fibcilafll sB twafnilluduaArUd,0 tvhUwe'tentat*ive von* ev vo*f KvvV "* . ' 4 or million particles per cubic foot of air Is frequently ' ouoted. 4 ' S ' i:%'r ' ' '. ' F;/*(b) This Is probably unreliable because It.-la1 based upon sampling . with a standard lnplnger which we havefshown doea not collect E neat'of the fibres that are the source of.hpzard. b'.- (c) We now think that a standard should bebaeed upon samples collected with an electrostatlo precipitator If It Is feasible to determine readily the relative proportion of.fibres lr. such material. ;? .-V - ; .' : (J) Work Is still In progress upon the latter-point. J- . '.'V . V.'` . (e) To'4** of-value the'new etandard vould.'hayeY-toTbe correlated .* with the-'X-rpy findings-uponsfaployeeb.^exposed.'.to .different concentrations of-dust. V; XIV Freventlcn of Asbeetcslo''*! ~------------------ "--s- .% -Mi 7 `. The experiments have failed .to*"develop .anyTjjractical chemical ' ' ' means of neutralizing the actlou'of fibrous-asbestos.-. (a) To alter the :hunan*lung bo that it vouldi'dlsaolveyasbestoe fibres rapidly like a rat would necessitate- creating an acidosis whloh would be;,worse ,than the effects of the flbrosle. 't- /. :. KV'xf'' -..' *. - . ,^*V-> t> '--l >' \ >' yf .*rt,h y t-Iofa 0) `C. . / -W ^ L . (b)'\ Apparently alunlnun,*which to, *0 tffeotlvo' tgalnr^; I . r hae.llttla infldendo 'upon fibrous otrjBotile.':'<5^C^> *' '**' * **lL*-^i 1 * y* * *./v* . -.' *,-v.-JV * > ' vnS->>'- (o)\ However, It wpVTd-great?theortloal^interest't ;.*' lev oaaeB with rooiVdjapn9ea`,jiron aabeatoelo;.by'alur V.y* /... Vi**vV * ' ` ? '. :"v' -* -t :!' V-. - - ; -i/''.*'/.*S "** * ** * .V* y ' *'**'i* * , -*J1. * <v? ">; ,, , .* ' * V... * u. - i/A.: w ^ ? ^ Lo - (d C ' 0 * "/ i