Document 85DdLR1B7ak8V2rwqdJL2yMVm

FILE NAME: Owens Illinois Library (OWL) DATE: 1957 DOC#: OWL046 DOCUMENT DESCRIPTION: Article from the Archives of Industrial Health Pulmonary Tumors in Mice Exposed to Asbestos Dust * : ^ PU B L IS H E R S AMERICAN MEDICAL ASSOCIATION CHICAGO 10, IL L . I '>ur.,;u, ..... t * vVv Vou:::,,.i`.e Conce:::r.. `Mr.:p<phere .. Ohio. July * c >;r.oke vi:m Instita:, Pulmonary Tumors in Mice Exposed to Asbestos Dust CINNCTH M. LYN CH, M.O.j FORDS A. M ciVfR, M.O., a g JA M fS R. CA IN , M .IX, C lw riM tM , S. C >;".cc the first case of carcinoma of the Experimental Study \ "C associated with aslwstos was cited hv :.ch and Smith in 1935,1 there have been . rous reports in the literature of sim- Animals.--Mice were selected for this work be cause the use of inbred strains would eliminate some of tlie uncertainties inhereitt in the use of :>es. Authors rev owing the literature ,,-':r;bc an incidence of carcinoma of the latirf associated with asbestosis ranging from :.u : to individual reports, usually dealing with relatively small numbers of other animals. Furthermore, the published report of X'ordnutnu and Sorge, which' has !>cen pre viously mentioned," and unpublished data left by Or. I . U. Gardner,'* of Saranac Laboratories, at his death suggested that mice might be suitable test animals. Dr. Gardner mentioned that, of 22 ' sses. describe an incidence ranging from mice inhaling short liber asbestos for not more 7'r to 50#.*" In an editorial in 1953, than 12 months, J (14%) developed lung tumors. Kueper 7 stated that 127 cases, of asbestosis Fmioftnyth-osndeevmeilcoepeedxpluonsgedtutmo oortshienr 2d%us.ts Infobrot1h0-o12f ' arenoma of the lung were on record and these studies the number of animals used was | described the occurrence of 114 cases of small, and the strains employed were not men | puiaionary carcinoma in 738 autopsies of tioned or apparently varied. asbestosis cases collected from the literature In the study to be described, it was decided to l .15'. use the Ft generation offspring of Strain A male mice1* and Strain C female mice.11 It was frit [ Experimental work has not kept pace with that this hybrid strain would possess the genetic the accumulation of clinical data. An in* purity of the parent stock but would be hardier creased incidence of pulmonary tumors has been recorded in mice following the subcutaneous injection,* intratracheal in* iec.ion.* intravenous injection,1" and inhala and hence more suitable for long-term studies. Strain A breeding stock was obtained from J. J. Bittner, of the University of Minnesota, and Strain C female breeding stock was obtained from Lloyd W. Law, of the National Cancer Institute tion il of a variety of substances, but only As soon as the Roscoe B. Jackson Memorial ooe published statement has been found Laboratories had recovered from the disastrous ! suggesting the induction of tumors in ex- fthiraet osfou1r9c4e7, all breeding stock was obtained from | perimental animals by die inhalation of AC Ft animals from the breeding colony were | asbestos.13 tlivided into approximately equal gn>tt|is, and at ! The purpose of the investigation to be the age of 2 months one-ltalf were plural in the I dncriiiv! in this report was to correlate, if cwaegrees mexapinotsaeidnedto aassbaestcoosntdroulst.groTuhpe. oMthaelre haanldf ! possible. the effect of asbestos on the lungs female mice were kept in separate cages to avoid of ex{>erinicntal animals with the suggested breeding in both the control and the dustrd groups. arriiiogvtiicity for human subjects. Of the hundreds of mice bred for this work; a great many succumbed to cannibalism, intercur- Lrrriu-l for putiHra X'ov. 19, I95A. rent infection, .or oilier accidents, hut 776 mice ; v ..;fw.cMi <' i'atholosy, Mnliral College of were subjected to portmortem examination. Of (\.rr.iiita. tilts number the largest groups were the control 75.1 u< rk hr iccti supported by a research and test animals Mttdied at 19 and 24 months of i-r.*'.:. NV C-474. in to the Public Health Service, age. The observatitsis in these groups will lie i'-*! address (Or. Mclver), University of emphasised in the discussion which follows. School of Medicine, Madison; t Dr. In order to study larger animals with a tracheo St. Joseph'* Hospital. AIInn.a. bronchial tree more comparable to that found in I 2117 It t Ti%***>*. . ; .V 4 ./ 1/. .//>'( I l l V I S Oh I . X D C S T h 'l . t l . ///:.//./;; Fig. 1.--Dustin;; parntus for mice: i .( i. mouse cage; (If), lor aslwstos; (C.J, ir;per tubing svitli mitr;holes directin'.: c: pressed air toward and (/V), pulley u sd rotate L-sliaped u in paddles. man. dos lave also lieen subjected to dusting; with a.-lwsto*. Tlte results of this study will form the lasts oi anotlter report. Methods and Materials.--Test animals were kept in wire cages on racks in an especially con structed rnom. Usually 10 o r fewer animals were piaevti in each cage. In tlte early stages of tlte work a ingle metal bin, with a paddle wheel near the huttom. was tootled with asbestos to provide a cloud of dust for the entire room. la te r a trough tilled with asbestos was run behind each, row of cages (Fig. 1), die asbestos was stirred by a series of small rotating metal agitators, and dust waj blown toward the cages by multiple fine streams (,f compressed air. Most of tlte test animals were dusted in this manner (cause heavier concentrations could be obtained. Tlte a>lstos used in this work was generously supplied, as was much of tlte information concertting its composition, by the manufacturers. This material is referred to commercially as As bestos Floats 7-TF-2. It is described as a "very fine- float with little fibrous content*' but was selected because o f its simibirity to "King Floats," used in other asbestos sttidies,'* and be cause no material with a greater fibrous content in the 10a-100a length was available. Kenneth \V. Smith, M.D.. provided tlse information that Voi' of Asbestos Floats 7-TF-2 passes a 200-mesh wet screen. This large proportion of the dust appears f'i'-i- 2.- -A-lcstos Flouts ' ' *1' 2. Photograph ilnuvi t|,;,, j^rtion of the material which failol to pas* dirnush a 200-mesh w-t -iTcvn. x 100. 2i in -A . iK Y Tf.'.'/o/- ..rl;. irreg'jlar ; - :::c rix k. Chrytot : material in that ; .--iiig the 2fKi-:.-:e*l i<.m|iO!.ition of . . .McO-iSiO.-' H / h war -upplic-i by - --r:t Itigh and low* 1.--C h m k A . Ckrys-'-tile Nt.-o it ,0 K-rt . ts-ts `i Ui p' rent. !i >r counts were 'lone : r extended periols foot of air were tn - ring to time of d: . **. but it was possible : rratinns of 150.000 v ;-er culuc toot :hro --"vrtt. Dusting ctjuip 1 2 hours daily fo r : .-.ere collected in v by means of a s o n :' .-*Ale-*ize determinat c l in water from mi : articles and fibers - . I 18% to 21% oi : .r of air collected it : -.at to tlte Iaborato ' at the Georgia I . i the following less titan 3p. 15.5' -v - 2%. and greater t Rest . .tr.il Animals.--. wa starred In i 't m ice. at:d :h e -- m im als was oh- 'Ttl'.-rcSt. Itt .ien rt " a in ta in e d \>.*icit> : " - t o f the atxitnai * **r 24 m .`t::hs i "* " ;y w as in :lu* ' i. ap p a ren tly . fro ::iy w as at.-.* mp ....... - r m o n th s w ith " .a* o rig in ally pi * " live out a full . 11. / rv r.v ;.-'/. /*/.* Kfc. i . - l >.>:: ;* :"U*c iV.iic: */*'. r .*<>; 1 : ?r win*] 'i-- iire-.-rijs- i-**'. ; .lir :v;.r : `V ;'v.ilt*y manner lecnuse : v. . 'laired. is work u ai i:. i ;!:e imoncntici . by the rr>njim':;i - :o o ntnerctally ' i' <i*crihed a> a '< ri.-.u eor.iettt" Li: similarity to "Kb. .(Ir,t u<!:cs. '* ' . -re::er fibrous atadnhlc. Kent!*'" : i:i"TMai<*n tli;: 2 .1:. a 200-rre- v.n or the dust : ' **** : ( I.MOX. u<!)- T C U O h 'S I X M U H H X I'O S H P TO . IS H H S T n s IX S T he mostly irregular pieces of inert granular :<rpciine rock. (,'hrysolile asltcstns is the ini- rtant material in licit portion of the substance r.ut passing tin* 2fH)-mosli screen ( hig. 2). Tlie .'.cmicil composition of Canadian chrysolite asrrstos. 3MgO*2$iO>*2l r,0, is represented iti Table ; which was Mipidicd hy tlie producers. Tlie 'lata apresent high and low limits expressed in per.vntage. Tarlk l.--Chemical Analysis of Canadian ChrtsotUe Asbestos M)t MsO It-.O WO Kckj. At .O CaO m:- JOjt- li-t.t ..jii I3A>0 1-3 e.2U IMM rite Amiri's in each Unimi rrpnweiu Ills:.1! uimI low tlmlts n i tw ii in per erne. Dust counts were 'lone on numerous occasions, inti for extended periods 500,000,000 particles per cibic foot of air were maintained. Counts varied according to time of day, humidity, and other factors, bin it was possible to maintain atmospheric omcentrations of 150,000,000 to 500.000,000 partides per cubic foot tlirouglHHtt most of the ex periment. Dusting equipment was operated for S to 12 hours iaily for 5 (Lays each week. Sam ple. were collected iu water within the mouse ruge* by means of a stamiarri midget impinger. Fartide-siate determinations on samples of air collected in water from mouse cages in 1950 sltowed that particles and libers 10p. in size and over formed 13% to 21% of the total. In 1952 a sample of air collccteii in 99% isopropyl alcohol util H-nt to the laboratory of Dr. J. M. Daila Valle at the C<orgia Institute of Technology showed die following distriliution of particle ?!2cS: less than 3* 15.5%; V IO * 34.0%; 10*20u. 2f>.2%, and greater than 20*, 24.3%. Results iT. Control , f u m ia k.--At the time that this " work was started little was known about AC l*t mice, anti the biologic behavior o f the**; animals was observed w ith consider able diu-rest. In general, the control colony utainiaincil without undue difficulty, i tm-t of the animals survived until killed I`J iir 24 m ouths of age. T he greatest mortality was in the male group and rc'uiad. apparently, from lighting, but some ikiiculty was also encountered during tlie 'raavr months with infeetious diseases. 1 m , originally planned to kthiIi :uitr-.b to live out a full life span. but exam - ,-t .11. inatioit. e|K:eialIy microscopically, of animals which were found dead roved very unsatisfactory, and eventually only killed animals were considered in the statis tical studies. T he microscopic ap[H:arattce o f the lungs o f control animals is shown in F ig u re 3. Alveolar septa are delicate: alveoli arc well expanded, anti macrophages, when present, are small and eosinophilic. O ne o r two small collections of Ivtnphoid tissue arc fre quently present, and mtlaimnatorv changes are found but are uncommon. Large foamy macrophages are occasionally found in areas of inflammation. Tn Table 2 the occurrence o f pulm onary tum ors in control mice killed a t 19 m onths of age is recorded. O nly those tumors con firmed histologically a re included. Tt should be pointed o ut th at on rare Kcasions a nodule regarded as a tum or grossly proved to le inflam m atory on microscopic exam ina tion. O n the other hand, tumors w ere occasionally found on microscopic examina tion which had not been detected grossly. For practical purposes the results on gross aw l microscopic exam ination in the control group were the same. It is interesting to note that there seems to be a significant difference between the number of male and female control mice Fig. J.--f.img of control mouse at 19 mouths-- Mouse AM <female!. Photograph hows a portion of the wall mi' a bronchiole and related alveoli. Alveolar walls are delicate, and there is a rela tive .iliM'iice "f iutra-alvrolar miuToplir.ue. X 425. r. * -1 b * S < rv 4 i* * . 0 a . m . a . . t/\`< m r i . s n i i x n r s T K i A i . h e a l t h T aim.k 2.--. IC Ti Hybrid Mice: Controle ot \ incten Months Sfx No. KeiiiaU*..... . . . . . Maw .................. m Total MIit with Turnare. No. iwr Cam 32 a 4S 4T Miv win Mm's Tuni*f., X. |HT Cant a a w as M ira -.viih M iiltiplt T iimnre. So. par C 4 IS 12 Tlw minore li.mil art* imlnwiMiry uii<-nma*. Only tiimor* etmrtritiwl an ninnv>|p rvim fnntion are rwtmlt!. hearing pulmonary tumors at 19 mouths of nodes, o r hepatomegaly. Mood counts were age. Males developed pulmonary tumors not done. Tour animals, all females, devel in approximately 47% and females in 28% . oped extrapulmotinry tumors, one of the However, in a smaller group of mice 20 breast, two of the ovary, anti one of the months and older this ratio was reversed, skin. O ther breast tumors were seen, but and, of 43 female controls, 29 developed the affected mice did not survive to he killed pulmonary tumors (6 7 % ). O f 41 male at 19 months. ; controls in this age group. 24 dcvelo|>ed T est A nim als.-- The microscopic appear- -s pulmonary tumors (58% ). ance of the lung of a mouse dusted fo r 17 ^ The nature of the pulmonary tumors ob served in AC Ki mice lias been a m atter of considerable interest in this study, and we have not felt warranted in referring to the neoplasms observed as carcinomas. The tumors are basically papillary adenomas, although sonic arc very compact and in some Adds do not reveal a papillary appear ance. Tum ors may be surrounded by small neoplastic masses which we have described as " satellite nodules" ; their margins may be sharp or ill-defined, they may extend into the Iunten of bronchioles, and they may show very few o r many mitotic figures, but we have never found evidence of metastasis. This absence of metastasis is true of all age groups examined, but the largest num Fig. 4.--Lung of test mouse at 19 month?-- Mouse II-43 <female). Photograph shows some what congested and thickened alveolar walls. Large "dusty" macrophages are prominent; X 425. bers of mice, as mentioned previously, were in the 19- and the 24-month categories. Some of the tumors do present a relatively malignant histologic appearance, but in 25 consecutive control mice bearing 31 pulmo nary tumors, which were studied in great Fig. 5.--Lungs of a control animal (Mouse 8-3$) mid of a test mouse ( Mouse C-26). Both animal? were kilted at 19 month of age. lit both specimens tlte hearts are attached and partially hidden by the lungs. The test liuig; are larger and heavier and present a mottled gray pleura! surface. detail, not a single one was classified as malignant, even on a histologic basis. O ther findings of interest in the control animals at 19 months include! an abnor 'S'vdT' At - W - ) mality of the reticuloendothelial system AS in 7% . This entity is characterized by ... i i :^ splenic enlargement in most cases and also in some by excessive lymphoid accumula tio n s in th e lungs, markedly enlarged lymph B - 3 3 B--2 5 Jin Vol. I?, March. 1<>X l `l 'I.MO.\'AiY months and k I- illustrated ilu.-ted animal than normal were thicken* deal more nun an d contained material, ``du; f brown mat >.ere found i untrol, but within tnacroi lusted animal i Fig. 6.--Asb >2 i female), vngulfed by a \eals the tyj v 2000. a-l>esto bod very short 1 i-bestos bodi ung of aln 10 to 20 bodi n one mien ;td was glot a rc itraigl lies parti: ,cn`phages i-. usually T :x :u:::V'Ci U*t .i.' Vii. T<>u!m:hor*. [vr <'. :.! : / 'Ulltf 'CP' :nic*s, *ievt-i cue ..f :ln ' *nc of till Te (a n . !ui: c ) h e k ille d ''"P'-C appearInftti for 17 IV n:or.:i:-- -!:0\VS -*,- !' colar wail. "ir.enr. X 2; "e. In c ! (-< - 'ut; l;-rier Vf M R f t - i* i-26 '!:rrh. /'/ rn .M O X A R Y I T MORS IX Mil. li hXroSI-.P TO .is n iis r o s POST months ami killed at the age of 19 month. is illustrated in Figure 4. The lungs of dusted animals appeared grayer and larger than normal (Fig. 5). Alveolar walls were thickened; macrophages were a great deal more numerous and were usually foamy aud contained a great deal of tiny granular material, "dust." Coarse granular particles of brown material, probably blood pigment, were found in. test animals as well as in controls, but larger gulden brown particles within macrophages were found only in the dusted animals. These were thought to lie bodies, was also frequently observed in mice. Bodies more than 20/x in length were frequently seen, and the longest recorded length was 40,u. The great majority were shorter than 20/>.. H ilar nodes were not noticeably enlarged and apparently were not involved by.any specific process related to asbestos. Pulmonary fibrosis did not occur, and squamous metaplasia of brouchial epi thelium was ..not found. Inflammatory changes and bronchiectasis were commoner than in the control animals. The occurrence of pulmonary tumors in dusted mice killed at 19 months of age is shown in Table 3. Only those tumors con firmed histologically are included. The microscopic appearance of these tu mors was in no significant way different from those described in the control animals. Asbestos bodies were rarely encountered within the substance of the neoplasm. Fig. 6.--Asbestos body in mouse Isay--Mouse 320 (female). Each asbestos body is incompletely engulfed by a large macrophage, r.d each re veals die typical "stacked com" appearance; X 2000. asbestos bodies about small chunks and very short fibers of asbestos. Elongated asbestos bodies (Fig. 6) were found in the lungs of almost every dusted mouse, and 10 to 20 Inxlics were not iufrcqucnrly found in one microscopic section. At times one end was globular, but more frequently they were straight o r curving golden brown bodies partially engulfed by large "-lusty ' macrophage*. The "stacked -coin appear ance. usually described in human asbestos Comment Studies referred to previously dealing with human cases of asbestosis strongly suggest tin t there is an increased incidence of associated carcinoma of the lung. It is important to bear in mind, however, that there are no very large groups uf cases, ami one is beset with the problem of derid ing whether the cases reported arc weighted in favor of a high incidence of carcinoma by .election. O n the oilier hand, no con sistently high incidence of pulmonary carci noma has appeared in reports of cases of silicosis. In tact, the incidence of pulmo nary carcinoma in silicosis seems to be relatively low. ami one w rite rlT suggests the possibility that silicosis may protect the patient--from the likelihood of carcinoma of the lung. T.mm.k t:i Hybrid Mi:e: 7V.ri MUc at X itu lra i Months She Kern 1_____ Mai.. . . Siunbrr ia (il T*.nl M l Timor. No. t*r t>nt a w Xk a T in dim. lisinl an* pulmMmry :i*ii-n**iliu-. ' n:!y uut:- f.xncU .7 .11. Mil- with invi Timi*. No. P*f O u t * ! ft 19 IM Min* with Multiplo Tumor, Yn. per Cent r it 1 a .| mi itiu-ri...-*.>ic xuiuiiuiiiiin in- n iu n ln l. ill I a . .1/. a . A K U U f H s n r t x n c s 7 K i . i t . i i r x i / r x .Ik* references which dcseriU* animal .idles arc hot regarded as acceptable evi truer for the cxi>erimentul production of asltc.-tnsis carcinoma of the lung. Nordmann ,s reports a number of instances and tyies of epithelial change hut found only two pulmonary tumors in 10 mice living to the "cancer age" of 240 days. The number, therefore, is very small, and no suitable control animals are mentioned. G ardner,s apparently regarded his observations as merely suggestive. The work was done in a >tudy of pneumoconiosis, ami the inci dence of naturally occurring pulmonary tumors was not established for the test animals or for the controls. The animals used in this study, mice, are probably poorly suited for the purpose. The tracheobronchial tree is of small diameter, and the nasopharyngeal Altering apparatus is probably highly efficient. Mice readily form asbestos bodies, but pulmonary fibrosis is not produced. The latter change could be a feature essential to the anticipated epi thelial alterations. At least, in studies nmv in progress in which dogs arc used, pul monary fibrosis is produced and there is a profound associated squamous metaplasia of hvonchial epithelium. It is quite possible that future work should be planned about the use of primates. The incidence of newly developing asbestosis in man is fortunately very low at this time, and so the primate best suited for future studies seems to be the monkey. Asbestos Floats 7-TF-2 is a difficult.ma terial with which to work in a climate with high humidity because of its hygroscopic nature. By the use of heat lamps, however, it was possible to keep the storage bin reasonably dry, and all dust counts were certainly tar above those in which human .1,'botosis develops. Even the low counts or 150.000.(XX) particles |n.r cubic foot are. 15 times greater than levels at which human asbestosis is thought to bo a danger. Particle length is a factor in human nshestosis. The quantities of asliestos ma terial of various lengths reaching the lungs il 1 of test mice an- not known, it i known, however, that a sufficient quantity of fibrous material readied the mouse lungs to produo: asbestos bodies in great numbers and tin: the same material is capable of producing fibrosis in dogs. Tf the ability to produce asbestosis. therefore, were associated wkh carcinogenicity, then Asbcstor Floats 7-TF- 2 should he capable of producing pulmonary i tumors. . \ Tf the anticipated life span of a healthy mouse is considered to be 30 months,7 then 1l the exposure of our animals for periods of 17 and 22 months should correspond to very adequate periods of human exposure. As was mentioned earlier, animals wemr* ex|>oscd to the dust at 2 mouths of age. and f, the larger groups were killed at 19 and 24 - months, respectively. ; > The results summarized in Table 4 show that there is no striking difference between the total number of control and test animals bearing lung tumors, the figures being ap proximately 46% fo r dusted animals and 56% for control animals a t 19 months. > There are 7 possibilities in 100 that this ) .. difference might he due to chance. This | difference i< not. statistically significant.* Thcrv was a considerable occurrence of multiple lung tumors in both the dusted and the control groups. Table 4 shows that this incidence is 189* and 8% for the two - groups, respectively. U sing the same formu la. there are only 0.51 chances in 100 that the difference is a chance difference. This variation is statistically significant. A possi ble interpretation of this observation is that, f given a group of animals with a sitnilar tendency to develop pulmonary tumors, this *Tn evaluating the recorded statistics, the stand ard error is computed on the basis of the follow- j inar 'iormui*: . ' --. ' X'TflMl/.Yil/.Y*) | where *=tot:d ifrreiuavie invurrenee 4 = 1 --A -Yt=uitmbvr in first sample .Vsnumber in second sample The probability of occurrence of the stated results on the lords chance is computed from the num- licr o t stan d ard e rro rs w ith P e a rl's table. I'ii/. 15. \fiti\h . I"57 IMOXAKY TtJ. Gmup N 7 il t o u t e d .... t-. T Ml C o n tro l.... Tills Table 3Uinieoruts udency is accent i-liestos dust, and ecotnc evident, i -it* the widely he : wnt for the etTcc i susceptible host. ,vn. the more imt t host susceptibi Xo appreciable histologic charact mors in the dustt In the absence of hr term carcinc -uch neoplasms cificallv, the pre formations in tht ^sufficient evtde the occurrence o .tens. The torn for multiple toe - a result ot c least resistance, noted regardless logic appearance regularity of tur f "infiltration.' he cytologic w nancy. Enlarge ered not infreq pulmonary tunic S utniric \ ' ' i 'i mice \ iv res containi 'r various lew The larges: ' U-i.-ted of 12! .'o r exposure compared . M: Vi A!.  s\ A* ....... - ' " V . . -* " r ;?* - . *..'. /'*. '" *1*4r*/;>',. '-V- v:r:.- :*. . I i i i - r '- i ~*'(f ir ih A ' i r n Ir t i i b- T ' i i ' . i i i -1 :--r *., V' * .. V .vV ' :* ^ t r A. At A. ARC!urns Ol- I X I H 'ST RI AL I I H A I . W University Hospitals. 130(1 University Ave., Madison 6. Wis. (Dr. Alclvcr) REFERENCES 1. Lynch. IC. At., and Smith, W. A .: Pulmonary A.-.l>cstosi$: Carcinoma. o( Lung in A.sIkuU*Silicosis, Am. .1. Cancer 24:56-64 (May) 1933. 2. Wcdlcr, H. \V.: AsbcsUwc utnl f.uu$;cnlcrcl>'1 Deutsche metL Wchnsrlir. 69:575 (Aug, 6) 1943; abstracted. Bull. Hyg. 19:362 (May) 1944. 3. Alerewethcr, E. R. A .: Atutnnl Report of the Chic: Inspector of Factories, London, Hi Majesty's Siatkuiery Otiice, 1947. 4. Wvers, II.: Asbeslnsis, Postgrad. M. J. 25:631-638 (Dec) 1949. 3. Lynch, K. 'ii, and Cannon. \V. M.: Asbes tos*: Analysis of 40 Necropsied Cases, Dts. Chest 14:274-889 (Nov.-Dee.) 1948. 6. Homburger, F.: Co-incidencc of Primary Carcinoma of Lungs and Pulmonary* Asbestosis: Analysis of Literature and Report of 3 Cases, Am. J. Path. 19:797-807 (Sept.) 1943. 7. Huepcr, VV. C : Silicosis. Asijestosis, and Cancer ot the Lung, Ant. .1. Gin. Path. 25:1388390 (Dec) 1955. 8. Shimkin, M. B., and Letter, J . : Induced Julmottary Tumors in Mice: Role of Chronic natation in Production of Pulmonary Tumors in 'train A Mice, J. N at Cancer Inst 1:241-254 O ct) 1940. 9. Shimkin. M. IV: reduction of Limr Tumors in Mice by Iiitrntraclieal Administration of Carcirntgcuic Hydrocarbons, Am. J. Canrer * 35:538-542 (April) 1939. 10. Shimkin, M. IV. and Lorenz, F..: Fartor; Influencing Induction of Pulmonary Tumors j Strain A Mice by Carcinogenic Hydrocarbon}. J. Nat. Cancer Inst. 2:490-510 (April) 1942. 11.. Camplielt. T. A.: Lung Tumours in Mice ` awl Man. Brit. M. J. 1:179-183 (Feb. 13) 1943. 12. Xorrimatm. M.. and Sorge. A.: Ltuieenkrebs .S durch Aslieststaub im Tierversuch, Ztsrhr. Krebs- forsch. 51:16K-I82, 1941. ^ 13. flardncr, L. U.: Unpttblislied data. '%' 14 Bittner, /. J . : Mammary Tumors in Alice in Relation to Nursing. Am. J. Cancer 30:330-538 (July) 1937. 15. Andervont, It. B.: Susceptibility of Alice ; to Spontaneous. Induced, and Transplantable Tumors: Comparative Study of 8 Strain., Pub. Health Rep. 53:1647-1665 (Sept 16) 10. 16 Gardner. L. U., and Cummings. D. E.: Snalies on E.\|*rimental Pneumonofcontoris: In halation of Asbestos Dust: Its Effect upon Pri mary Tuberculous Infection, J. Indust. Hyg 13:65-81 (.Feb.); 97 (March) 1931. 171 Sprlein, S .: Schtzt die Silikose vor Lungenkrebs? Zcmrnlhl. ailg. Patii. 89:197-200 (O ct 30) 1952. '* Dust Exposure incinerators W'LUAM H. M tCO N N H L. V Introduc* The widespread use , -.arch purposes has c u in disposing of rac rials for many institu* - fuse which may coma: experimental anima embryos, paper use* I used planchet*. The - municipal incinemt.-r *ractive method for -tes. During* the inc:: .ior portion of the rad he waste is discharge - volatile o r particular-.::!>ustion gases o r is iterator with the as: -.ited on the inter: nvrator and the sta turning of radio: w ith norm al tr. ,-< v o f dilution may reduce radioactivity i waste procedures u --t of such iuciiii. provide a >:u:e <li'pal. 1 o u co m b u stii-:. !:i*>is topes in ins* * ha*. indicated - >p-- lws or- Sr* :*(>* l111 retuatr. -h is a (>otentiai from the inc: o|lection and ' t:*I to person::. . . ' 'I :-.*r t*uWic:;::.'r.l Sviioot >C l'-.:: Iiysietie.