Document Qk15vKNqqbezavQ9pL9zkK0r4

FILE NAME: Asbestos Mining (ASMI) DATE: 1952 May7 DOC#: ASMI023 DOCUMENT DESCRIPTION: First Interim Report to the Quebec Asbestos Mining Assoc. RE Asbestosis and Pulmonary Cancer from Saranac Lab F ir e t J-fitori's Deport iw,ta w-- AWSTOSIS AS) TdJ-V'COSStY GA'iCFP. o o Clv.cisc A stetes F ining Aecec.iatiora The Saroncc- F rtcra'jory o The Trr.de. rv. Foundation Sarc-no.c Lrhc f Few Ter!" ra v 7, IS 5?. S"ubj.ttd o'*: ,,t*\i\ c .*v a .itf , Arthur J , Yor u til , Lr,D D ir e c to r , TIio Sarar.: and The 'Trudeau F e r r ia ti, or. suwauv 1st - ining /.ssoc, Report - 5-7-52 ASBESTOSIS AMD RUIA'OL'ARY CAV.CFR I!!?RODUCTIOi: An experim ent has boon in p ro g ress a t The Saranac L aboratory fo r some 14 monthc in an attem pt to a s c e rta in th e in flu e n c e of in h aled a sb e sto s dust upon th e in cid en ce c f pulmonary tu n e rs in n ic e . The purpose of th io study i s to obtain oxporincntal d ata fo r 'c o rre la tio n w ith exporr.onco p e rta in in g ' to pulmonary cancer in in d u s tr ia l vrorlcers exposed o c cu p a tio n ally to tho inhalation of asbestos dust. Two s t r a in s o f n ic e , one su sc o p tib lo and th e o th er r c c i s t e n t to the de/elopmonc pulmonary tum ors, have been exposed to the asbestos d u st; compai ab le num.cc;*3 o f c o n tro l anii.ialG o f each u tr a in hams boon IcoDt in normal a i r b u t under c o n d itio n s c f housing and d i e t id e n tic a l vrith th o se o f tho oxporim ontal a n im als. Tho onporimont haa been designed t o re v e a l a p o ssib le e a r lie r onsot of tumors in the exposed animals than in the co n tro l gi ouo as v e l l ns to clc'.orninc th e t o t a l in cid en ce of tumors o c c u rrin g ovor the e n tire period of tho experiment, I ^ y QQ s :orc- t h a t th e evidence obtained re v e a ls no tendency tcv.ard3 a^i o a rla o r onset of tumors among exposed n~imal3 in com narison w ith j^ o n tro l anim als. n e v e rth e le s s , th e re doos appear t o bo a tre n d tovnard a preauor incidence of tumors in tho exposed o rim ls then in the co n tro l animals I t is im portant to note, however, th a t s t a ti s t i c a l an aly sis o f th o data o b tain ed up to the prooer.t allows t h a t tho d iffe re n c e s botvecn tho o x p o ri- r x n t a l and tho c o n tro l anim als a re no g re a te r than might bo expected t o occur by chanco alcno* Tho oxperimont i s no t completed and i t i s co n sid ered lilco ly t h a t , i f th o r a tio s o f tu n e r ir.cidence a t th o next p erio d when anim als w -st .Report; 3-7*-52 aro 3:?.llsd a rc su rd la r to theca fo r tho li- x c n th in te r v a l, th e tror.c vni io new notod ra y f i n a l l y bo chora to t o s t a t i s t i c a l l y s ig n if ic a n t becaus 0* oho l a r g e r oocc.2. muiLor o f an Serialo o b se rv ed . XI. yjlTSP lALS ' A" H 2 ^ 2 5 jj5 i2 :S l! Tho f]ast v.eod in tills oxper-L-uevc v.uc rec eiv e d on January 5, 1951, from th e John ton Company Aebostos K lees o f M tfto d , Quebec, ar.d v:as given th o Saranac L aboratory mrabor KD..135, Xray c i f f r a c t i o n a n a ly s is re v e a le d t h a t th o m a te ria l ccr.w fcainu c v nriouy of n in u ra la , o f v h ich th e s e rp e n tin e group c o u r t e d to 1 PGr c e n t, Tnougn t:;c p a r t i c u l a te ndnernl s e rp e n tin e and tho fib ro u s m in eral cr-ryscrx.'.c y ie ld .trie s?jt.c d if in a c tio n p a tte rn ., p etro g ra p h ic oxouinc. tier cheered t h a t th e re was c o n sid era b ly noro c h iy c o tilo than se rp en tin e p re s e n t in th e m t o r l r l , huch of tiro c h ry s o tilo occurred in th ic k unopened biurd ie s , bus a t r,as estim ated t h a t a t l e a s t 25 p e r c e n t o f th e c h ry s o tilo r;ao p re s e n t a s i ia i v ic u o l f i b e r s or p a r t i a l l y opened b u n d les. Ocher consonants, l a r g e ly p r.rti.c u la te , in clu d ed a for? p e r c e n t o f m ag n etite, chrom ite, b ru c ito , tc.lo, and q u a rts, and tra c e s o f rrlccellanoouo m inerals,, Tho q u a rts c o n te n t vmc about 1 to 2 p e r c e n t. Of th e p a r tic u la te m a te ria l ftt lo a a t 35 p e r c e n t c f th e p a r t i c l e s v.-orc le n s thou 0 nicro n e in s is o . S tu d ies o f 3ar.plco o f ati.ioephc-rie d u st talon, fror. tho rnircai exposure ro a a re v e a le d , v>itb re upset t o th e le n g th c f th o c h r y s o tile f ib e r s , t h a t tho fib e rs oecur.-od in the follow ing d is trib u tio n of sise e ; F ibT9e rs rt tr u l e s s v,hn.n G r.icrcn a fre.n 5 to 10 rt " 10 to 20 tt " 1 0 to 50 it w 0 to 100 n in length it n u rt t: v R 1! 32,3 % 35*3 20 v7 - 8.3 2,7 2-- S9U3 % B* roctnnls; The m ice 'isc.T in t h i s ex p erim en t ~;orc o b ta in e d frc is th o Javhscrt !':;.-.orjal uiv.0T & tcry a t Kar H a r te r , L'uine, ?}a.t lisiboratoxy c a r r i e s coj.05.ictj o f two d i f f e r e n t s t r e i i 's o f id e e , i d e n t i f i e d ac S trf.in A and Stra.-.:i C. cu scepfcibis t o pulm onary tim ers,.. S tr a in A, ur.c!cr th e u s u a l pro* tico c f . c i e r r i r g "ho o b s e rv a tio n f o r tum or u n t i l th s n ic e accro ach p e r e s iitt Strc.i.i. . , x.oi'jT eaiidher o ira u rn ta n s e e , has an incidence o f .cr.o tumors o f '.bout 00 coi' s c n t4 S.Lr.co in- th e p re s e n t experim ent i t van proposed to ctudy uhc i c i l u .r e a of d u st a::rcBij:.*o upon th e over-:'.?.! in cid en ce c i tumor. S tra in A vrss cons:.- uiiuv.'..ua...-f.e f o r e h ia n v o e tig a tic n beoGuss any in c re a se incidonco cbov: bh:: no real r a te o f 95 nor cent would be d i f f i c u l t to a o cer- t a i n t S tr a in C v tr sc-Lcccec... th e r e f o r e , because i t had ci lo v er i ccic cr.ce which v ac th o f a c t th e '; th o ia o ic e n c o o f raau:eny c e r e in o v a ,in S ta r i n C. which n i d i t i u t r r f - re n i t h in ti-rp re ta u io r o f tho gulxonory lo s ic r.s , was lew , Of th e cerera..1 r-.'-iilahl i s tr a in s o f n ic e r o d a ta n t to tho development o f pul:r.cr.!'.5.'y tu n e r: t i l s S t r a in C 57 b la d e was eh:-con encauso n ic e o f t h i s e trr.in were r c a c il;, e r a :lia b le i n r u f f ia iv v it numberr. to n o r n it o b ta in in g a colony o f en ago a o ta x r a t i o o im parable to t h a t o f t h s S tr a in C colony* n?.. l^ iic c s A*. /jLmo X.'.ia ari.:.t;x ji; Tha nuchaic: d e v ita d ;vt Tho :`hxar,.?.c Jh ib o rato ry sor.o f i f tc.cn year's r.;p f o r th e disscadinntion o f a s b e s to s d u s t ii,,to n h s a i r f e r u u p c rim e n ta l pur.-ronoe i s b e in g m ec ir. th e cu rro : i i s t r a y , Tli;- nathr.d c o n s is ts c-scaut:ixll.;y o f ns sheah.c a l a g i t a t i o n ' -3- Quebec ij b c e t o s Lning A ssoc. 1 st Interim Report 5-7-52 o f the asbestos dust by a ro ta tin g peddle in a largo hopper f ille d n ith a sb esto s d u st t o approxim ately th e IcvelT oF t h F a x l e o f th e peddle The edges of the paddle are equipped u ith s t i f f u irc brushes to break up the em ail b a l l s o f a sb o sto s u k ich te n d to f o r a . The d u stin g mechanism io .leapt i n o p e ra tio n in s id e uho 8 -fo o t c u b ic a l d u st ro o a fo r 8 hours a day, 5 1/2 days per v;cek. Animals liv e continuously in the room, vhich i s v e n tila te d Yrlth fresh .cl.cciL Jd ilT ;h cn t h d u c t d isse m in a to r i s not in opera - - hi ' ^ tic n 0 _ Atm ospheric samples aro c o lle c te d i n th e room a t re g u la r in te r v a ls TTith a G rccnburg-S nith m idget in p in g c r and d u st counts cade by th e l i g h t f i e l d te c h n ic tilth a n ie r o p r o je c to r . The d u st cqr--t-c_b^re avoraged 817 m iJJion p rrtic lo s per cnbic_oot of a ir . In general, th e fib e rs have ' r e p r e s o n te d ^ b o u t^ d per cent o f th e to ta T c c u n t, o r *53,8 n illio n T " O f th e t o t a l number o f f i b e r s , about 11 p e r cen t a re lo n g er t h an 20 m icrons. I t YiiH be re c a lle d t h a t , in regard to th e production o f a s b e s to s is , th e flo o rs g re a te r th a n 20 m orons in len g th axa of th e g re a te s t im portance 0 ^ ^hc s t a r t of th e experiment 2c0 ra.co r a r e placed in th e d u st room: 130 of th ese r a r e S tra in C n ic e , and 130 vrere S u rain C57 b la c k m ice. Of each s t r a i n 30 mere males and 100 v?ero fem ales, This sex r a tio ran d ic ta te d by space requirem ents, since male nice ten d t o f i g h t and must be k ep t i n sm all groups, m hile many fcsaalas may s a f e ly be placed i n a. d i g I s cage. The t o t a l number o f c o n tro l n ic e mas 3ii0, Trite a cccz dastraouv.icn s im ila r t o t h a t o f th e exposed groups<, In order to f o llo n the development o f turners and to observe any p0o3ible e a r l i e r onse-o o i tum ors among th e exposed n ic o , expcrim ontal anim als and c o n tro l ci\mmalx uc-re k i ll e d a t re g u la r in te r v a ls a f t e r th e o Quo'd2c < Jozies llin in g Aoncc, 1 st Xntlu/m Report 5- 7 -5 2 beginning o f th e eerposuro t o n o t. The in te r v a ls chosen were 2, 5 , 6, 10, nnd ll* months; th e nex t i n t e r v a l h as been s e t f o r 16 months. At each p e rio d 35 iceporixentol and 3l*, c o n tro l anim als v e rs k i l l e d ; o f each group o f 35 an im als, 17 were S tr a in C and 17 were S tr a in C>7 b la c k . Ln each c a s o , the* 17 anim als in clu d ed h males and 3.3 fem el.es. IV* P-ESUIffS The o b se rv atio n s made a t each o f th e p e rio d s when anim als rrcro k i ll e d tr o p resented in tab?* 1. I t w i l l bo noted t h a t the t o t a l number o f anim als examined in each o f th e d if f e r e n t groups v a rie s s lig h tly . This v a ria tio n 3 th e r e s u l t of a few spontaneous d e a th s i n each group. Tho oboarvr.tiono made in such eases have been in c o rp o ra te d in th e d a ta f o r th e next p e rio d . I n many in sta n c e s anim als dying spontaneously have boon eaten by t h e i r cagoiTVtttes. I t has boon nscesoary to d is c a rd th e s e anim als com pletely from th e record of experimental observations, I t w ill bo notes, th a t w ith in S tra in C th e re is a higher percentage o f tumors among animal ri c l o s e d to a sb e s to s d u st th an among th e c o n tro ls., Tlie sano s i t u a t i o n i s tr u e w ith in th e S tr a in C5? b la c k . O bviously, th e same c o n d itio n aa t r u e a ls o o f the o v e r f a l l f ig u r e s combining both s t r a i n s . TliO oiiyiifi.cance ox. a3.1 those p ercen tag e in cid en ce fig u re s has b ztxi te s te d s t a t i s t i c a l l y by m an s o f th e rell**r ccogiiiaod form ula: S*5 , ~ \i PI ,Q1 ^ nx ~ v P2` Q2 u7~ where S .E t K1 c Standard Grvor o f d iffe re n c e in in c id e n c e between tvro groups - T o ta l number o f anim als in th e group . . u le t' I Jjrim . Report 5-7-52 - Per cen t o f anim als w ith tumor in e. s p e c if ic -youp o f anim als Q i 2 .B M n n w ith o u t tumor in th e same s p e c if ic group (Thu9x Qi s* lOO-p^) C orresponding symbols f"c r m o fchor group of cixuualo J I t "vrill be re c a lle d th a t i f ;m observed d iffe re n c e in percentage in cid e n c e botv.'oon trio youps i s g re a te r th a n tw ice th e stan d ard e rr o r o f t h a t d ifferen c e ^ tn e ch.fj.ci encc m y bo considered to be s ig n ific a n t and duo to fa c to rs o th e r th an chance. I f th e observed d ifferen c e i s le s s than tvnlco th o stan d ard e r r o r , i t i s v e ry l i k e l y due sim ply to chonco. I n ts.blo 2 tho observed d iffe re n c e in th e incidence of pulmonary tumor and th e c r i t i c a l v alu e c f tvri.ee th e sta n d a rd error, o f d iffe re n c e a re compared f o r th e various groups. I t t r i l l be nctod by comparing tho values th a t none o f th e o b se rv atio n s made to d a te a re s t a t i s t i c a l l y s i g n i f ic a n t . An example o f th e method of calc.ule.cicn follow s J ' " - - C a lc u la tio n of stan d ard e r r o r o f d iffe re n c e between over`- a l l in c id e n c e of tumors in th e control animals and in trie experim ental mice from d a ta in table 1: Incidence of tumors: Experimental animals 9.5# Control animals 5.5 Number o f anim als observed: Experim ental anim als 179 C ontrol animals 131 S.E. | 9 .5 X 90. s"^ 5 -5 X & .5 s \ |l *.80 * 2.8? = 67 N 175 * 3j61 2.77 2 X S .E . tr. O Q1sut.ebLssr--U'jvrsimbesRtoespolrint i0n--g'7^A52ssoc, Thus a d iff e r e n c e up t o 0 .0 p e r cen t i s l i k e l y to occur by chance. The observed d ifferen c e o f h per cent (9.0 - 0 .0 = h.O) nay th e re fo re have occurred sin p ly by chance d is trib u tio n o f aniroals and is not s ta tis tic a lly s ig n ific a n t. ' . v . core if,in? It'-K ill be apparent iro n a review of ta b le 1 th a t th e experiment is ncm i n i t s no3t im p o rtan t phene* The in c id e n c e o f pulnonary tumors ha3 begun to ric e fo r animals h ille d a t the lU-nonth period, both fo r th e c o n tro l aruna l s a n d f o r th e anim als exposed to a sb e sto s d u s t. The increased incidence i s noro pronounced fo r th e group exposed to d u st, but th e r is e has occurred a t a b o u t th e same tin e i n b o th groups. The d iffe re n c e s between th o two groups, however, as has boon n o ted , a re n o t s t a t i s t i c a l l y s i g n i f i cant * Tho im pression i s g ained from an in s p e c tio n o f ta b le 1 t h a t th e la rg e numbers o f anim als ld.13.cd o a rly i n t h e experim ent aro w eighting th e f i n a l lag u rco and douracoing from th e magirLtude of the- in cid en c e o f tum or. I t must, be noued t h a t t li i s stu d y has-been an e x p erim en tal one and t h a t i t h as been nocc3sary to make o b se rv a tio n s by k i l l i n g a n in a l3 f o r stu d y a t r e g u la r i n t e r v a l s . I t appears t h a t by means o f a r a t h e r involved s t a tis t! - * c c l procedure the disproportionate weighting o f the values by the data of th e e a rly observations can be elim inated. This procedure w ill be carried o u t a f t e r f i n a l o b serv atio n s hsvo boon made, sin ce i t i s too lab o rio u s an u n d e rta k in g to bo perform ed a t th o p re s e n t sta g e when th e v alu e s obtained would be only o f academic in te r e s t. 7- i > Qucbc ^ iSbcctoo Joining Assoc. 1 s t I n te r in Report 5-7~$2 I t may be rioted in passing th a t i f th e o v e r -a ll in cid en ce o f tumor anons t h e l ^ e d only slig h tly g rea ter-1 1 per cent rather than per cent--the d ifference between the incidence fo r the exposed group and for the con trol group would have been s t a t i s t i c a l l y sig n ific a n t. VIo Stn/IARY e:rp0rir"ent concernin- th0 In flu en ce o f inhaled asb estos dust upon the incidence o f pimonary tunors in mice has been in progress fo r lh months. Analysis o f the r e su lts o f t h is experiment reveals that thus fab (after tho animals have been exposed to asbestos dust for lh months), the dust has not exerted an in flu en ce o f a degree s u f f ic ie n t to cause s t a t i s t i c a l l y s ig n ific a n t a lte r a tio n s in the incid en ce o f pulmonary tumors. The fin a l phases o f tills experiment w ill be o f great importance, sin ce at the most rocont period when animals wore k ille d fo r study th e incid en ce of tumors had increased and the incrca.se seems to be more pronounced among the animals exposed to asb estos dust than among tho non-exposed c o n tro l animals AJVtje TabiJ5 X l s t l-.Jcrria Report 5-7->2 . Occurrenco or PuILreonary Tirare In Mice Imposed to isbostos Dust sad in T.'dco Mot Exposed to Bust Strain of aie3 Strain C (Tuiftcr s u s c e p tib le s tr a in o r mice) Period of oboorv-ation months 2 16 . 10 Hi Number exrcoir.c-d 1 Incidence o f tumor : Number o f mico w ith tumor in the group . exposed to asbestos dust Mal Female 0 0 0 1 0 1* 0 I 1 7 12 22 72 9k 12 a 9k a 12.3;; limber of nice with tu o o r i n th e c o n tro "1 group not coreos od tc di^rt Halo Fenato 0 1 0 0 1 0 0 1 0 1* . 7 20 72 92 7 A 92 = 7.6 S tr a in C57 Black 2 (Tumor n o a -s u sc sp tib lo h s tra in of mica) 6 10 lit Number cccaoinsd: Incidence of tuner: 0 0 0 0 0 0 0 1 2 2 "5 19 65 35 S' 8,5 $.9f> 0 0 0 A 0 0 0 ?. 0 1 3 . 20 69 89 3 v 89 i; 3.1ft . Incidence o f tmr.oi i n both groups: 17 7 179 - 9 .% 10 f 131 r 5 .5 i Malignant V! Qucbc' y:.r>bcs bos *-xnin j.scoc. 1 s t Ii\-c.`c r in P.cnort 5-7~s2 . Table 2 W_irercr.ee in Incidence o f Pulx-onary Tuners in I/lce Fxocssd to iicbcotos Duyt and i n Itice Hot Exposed to Dust The v a lu e s fo r a l l -roupc ( t o t a l in c id e n c e ) a re based upon o b se rv atio n s fo r - th e asbestos an d 'th o c o n tro l groups and a lso fo r groups exposed to tno o th e r d u cts---iron oxide and quarta*in an o th er ex p erin o n t.