Document aDmg01BwoOmKLq7NE1oV1YMQM

PLAINTIFF'S EXHIBIT 3A/M OCCVPATIOXAL CAXCER Of the Urixary Bladder in Dyestuffs Operatives axd of the Luxe. tx Asbestos Textile Workers axd Iron-Ore Mixers CEORGIAXA M. BONSER, M.D., J. S FAULDS, Mi)., a.vd M. J. STEWaRT, LL.D. University of Leeds and Cumberland Infirmary, Carlisle, England j The study of occupational cancer has proved to be a valuable method of 1 learning some aspects of the biology of cancer in its wider sense- This form of cancer is an unwitting experiment in mail, but until it can be reproduced in animals at will, doubt must always exist as to the exact nature of the carcinogen involved and of its mode of action. The time lag between the observation that cancer occurs in those engaged in certain occupations and the successful induction of the disease in animals may be very long. For example, Percival Pott'- de scribed cancer of the scrotum in chimney sweeps in 1773, but it was not until 1922 that Passey15 induced cancer of the skin of mice by means of an ether extract of soot. Similarly, in 1S95. Pehn15 described cancer of the bladder occurring in workers engaged in the manufacture of aniline dyes, but it was not until 1937 that Hueper and his co-workers10 were able to induce bladder cancer in dogs by means of ingestion of the dye intermediates. So far no attempt has succeeded in reproducing the lung cancers of the Schneeherg and Joachimstal miners (Kaerting and Hesse, 1$79;T Siki. 19301S), thuugh this disease has been known for cen turies. The induction of a few local sarcomas in rats following injection of cobalt metal (Heath, 1954') might be a stimulus to further experimental work. We are well advised to be ready to recognize new forms of hazard in any industrial process, but it is even more important to advise industry of the dangers that are likely to be inherent in the manufacture or use of suspected or proved carcinogens. This was certainly done when the uew planes tor effecting the catalytic cracking of oils were set up (Symposium on a Cancer Control PjOgiaui, 1351).51 As such a variety of occupational cancers is now recognized, thi.' presentation is confined to making a classification of the most important and to di>cus=ior. of those with which the authors are most familiar (Table 1). It seems hardly necessary to say that, before it can be claimed that any particular form of cancer has an industrial origin, it must be shown that the incidence Is significantly higher in exposed workmen than it is in the general population. This is not always easy, as morbidity statistics of cancer in most countries are nor available, hospital statistics being nuke failaciou^lv high. ?e<*imdiy, in site* where titer? is a high natural incidence, any occupational risk tends to he marked. ' Received for publication August ."U. 19->i; accepted. September 22. 195-t. Dr. Bonser is Reader in Cancer Research, University of Le*iis. un<! Morbid Annr<'fn;..t to St. James Hospital. Leeds: Dr Facies is Pathoioffi>t. CcniDeriand Rnyni inn.-mary, Carlisle; and Dr. Stewart is Emeritus Protessor oi Pathology. University of Leeds 126 Tf5" :x L.D. : or n i :n gen mac :;on .util -act ? in 037 by i in urt. eu;u!l .nv *he ; <jr ''-0 : roi ion of ij\* ,-Of lot F/o. UCCl'?AT!` >\\L C.\N<~EP. rr TABLE 1 L:>t of s.hjs Sc3sTANrf5 C.U'-INO Can> zk, I X 0 V i <tr C'''|.,i;sNF.D, aXui Site of Cancer SuC'tiace Tndu{ry * j Site oi Cisfi: | Proof Lrscn. Minerals , | Arsenic ' Sheepdip manufacture and usage ! Skin, lung i Doubtful 0 Chromium (ore) ' Electroplating, tunning, Respiratory, Doubtful dyeing j usually lung 0 Nickel SilicaAsbestos . Iron -hematite) Chemical manufacturers : Respiratort* Scone blasting 1 Lung , Miners and users i Lung Miners ' Lung Doubtful Doubtful aa. 0 0 0 0 Beryllium : Fluorescent lamps : Lung, bones 0 -r Unknown Oils Lubricating Petroleum ; Pitchblende miners ; : Mule spinners 1 Hefners ' Lung i Skin Skin `0 -r + Pitches Soot Tar nays Actinic ` Chimnev sweeps : Road workers i ; Farmers, sailors Roentgen Scientific personnel Luminous paint <ra- Dial painters cium' ' Skin Skin 1 Skin, exposed sites . Skin, exposed sites Skin, exposed sites *r _ j. -f Organic chemicals D'*e intermediates Chemical manufacturers, 31adcer and users A very signihaant fart ha.11 been observed by many workers and ha.? been emphasized bv Her.nuwav flOoO).11 The "amount'' or incidence of cancer Ln any give*', population does nor vary greatly; as resards either .-ex or rare, but the proportions of the different "forms-'' or sites of cancer may vary greatly. For example, there is a high rate of carcinoma in organs peculiar ro the female, in contrast with the high rares in lung and stomach in the maie. b:na:iariy, primary arcinoma of the liver is high in the Javanese in Sumatra, hut insignificant in European populations. "There appears to be a general law that when in a ir.ven population the incidence of cancer Ln one particular organ ir markedly increased compared with another population, there is then, a compensating decrease in rhe i l\ J i! `K .r : til 2>.J "I a* -? cl =53 =-3 '>5 ^1' 1 12S honser rr .il. ToL 55 incidence of cancer in a number of the other organs" (Cramer, 193G)/' A con stant watch must be kept on "amounts" of cancer if proportions are being altered by industrial forms of the disease. OCCUPATIONAL CANCER IN THE DYESTUFFS INDUSTRY Why should 1 in 10 or even more of men engaged in the manufacture and usage of certain dye intermediates (aromatic amines) develop tumors of the bladder? These workers are exposed by inhalation, ingestion and absorption of these compounds through the skin and yet the tumors are located in the bladder. This striking observation has fired the imagination of many workers and we think we are justified in stating that we are beginning to understand the reasons. . The knowledge thus gained has altered our conception of the range and mode of -r action of chemical carcinogens in an interesting way An extremely good survey of tumors of the urinary bladder in workmen en gaged in the manufacture and use of certain dyestuff intermediates in the < British chemical industry has recently been published by Case and his associates4 ;j (Table 2). They have shown that although there is a small spontaneous incidence - of bladder tumors in the general population (2.H times greater in males than in - femaies and rare under 55 years of age) the risk is 30 times greater in chemicai workers and the age of onset is on an average 15 years earlier. Manufacturers. - users and purifiers are affected in descending order of severity, the noxious sub stances beins 2-:iaph:hy:amine, ber.ridme and possibly auramine and magenta, There is no evidence that, aniline is incriminated. As the induction period is constant at 15 to 20 years, the age at onset of the disease is dependent upon the age at entry of a man into the industry. This is linked with the fact that :t is the length and not the severity of exposure that matters, individual susceptibility beins a marked feature. There is no special tendency for industrial tumors to oe TABLE 2 Occterencz or 3l-a2DITr Tutors !> Manvtacturcrs and Users or Dvrsrcrr I.NTEKMEDtATES i'CaSE Z7 aZ.*) Poouiation a: Risk -- --622 Mea expected deaths in coruparubie general Doouiution Actual deaths ir. industry Actual cases in industryRisx in industrv Chemical exposure Age o: onset Induction period Degree of malignancy Surriva! alter diagnosis Exposure Irv.uv'.citai \i'Cet>t ;i'il:ty * or 252 30 tiw.es thnt of genera; Benzidine 3eta-nr.phthyianr.ine Alona-nuuh: hytaruioe 15 years earlier than d 15-20 years Contsarside to tumors ooouiatmr, 20 per cent survived 10 Length not sever;a A mark--.: .'vatur? ot un pcruAafi* ;c i :ub:H-'wr. . n cau?e IU<IV }wr ft' of the fn rii t riii-ii r.'.'iti. f-Mir ; Mi-: :::iv :: C -Ir.v.vt! -yt.-vr i m- r~ r r. ~ u ;;; cr > cud : the on of icier. d we be of n eni me .cnee an in u-ers. .'UO- an *a. od Ls n the -, ?: d - i to r> rrr ;CiOn :r.c>rai urns r-h.lQ-J-5 OCCU NATION AL 'ANCItl i'20 more or ."-s malignant than, spontaneous one?. Tins is a killing disease, ouiv '20 per ;,ent of ail cases having survived more than 10 years from the first recognition the disease. - In 103*>. certain alterations m plant ami technic were made and these have reduced the nsk just significantly, but another 243 cases (over and above the 202 traced cases m a population of 4622 men) may be expected among 3ritish workers engaged in the manufacture of chemicals during the next few years. In 1945 and 1950, more drastic piaat alterations were made and we can expect these to bear fruit in about 1965. Meanwhile, we need to be ever vigilant in recognizing as occupational tumors any that may occur in ocher industries in which the dyeatun intermediates are in use. Case aud Kosker (1954)5 have recently demonstrated an occupational bladder-tumor risk in the rubber industry in England and Wales. Attention was drawn to this by the finding of a high incidence of biadder tumors in the hospital records of a County Borough which is an important center of the runner industry. It is probable that the risk was introduced into the industry in 192S, when a certain antioxidant" began to be used. The latter was known to have caused bladder rumors among the men in the chemical industry who manufactured it, and it contained about 2.5 per cent of free naphthyiamine, both alpha and beta isomers. The treatment of the rubber "mix" containing the antioxidant volatilized quantities of naphthylamines. It needed a most laborious and careful search of records of many kinds to establish this risk on a sound statistical basis and it is satisfactory to report that thejnamtfacturers of the antioxidant im mediately ceased its manufacture and the users discontinued its use and de stroyed old stocks. Of great interest to the experimental worker is the search for the reasons for fhe localization of the tumors in. the urinary tract, or perhaps the wider concep tion of localization along the routes of excretion would be preferable. If 2- T.aphthyiamine is administered by feeding to dogs, ai! the animals will eventually develop tumors of the bladder, though the number and location will vary in individuals (Hueper and WoLr'e, 1937;:o Bonser and her co-workers, 1D511). If 2-na?h.thyiamine is fed to mice, hepatomas or benign choiangiomas will occur. I: fed to rat-.- or rabbits, occasional benign p.opiilomas of the bladder will be seen. If benzidine is fed to dogs, bladder tumors occur after many years (Spitz, per sonal communication), but- if injected into rats, hepatomas and acoustic gland tumors wiii be found (Spitz, Maguigan and Dooriner, 1950)m if injected into mice, hepatomas or.iy will occur fBonser aud her associates, unpublished obser vation) (Table 31. Such localization of tumors suggests that 3 important factors must be at work: (a.) species variations in biologic response; fb) excretion of the original chemicai or its metabolites along a specific pathway; ana (c) concentra tion of these substances in certain sites. A study1 of the metabolism of 2-naphthyiamine in various species showed that a conversion of the amine to 2-amino-l-naphthoi conjugates occurred and that the capacity to form tumors was roughly proportional to the concentration of these substances in the urine. In the dog, the ratio of urinary to serum content of *JS^&gg0%s?' 130 BOX*Lit ST AL Vol. 25 TABLE 3 Rt.spo.vse or Specie* to Apiixm-thation of Dyesti:vr Intermediate* 1 Chemical Tumor * Man Dog Cat Ferret Mouse Rat Rabbit 2-XaphthviamlDe : Benzidine 2-Xapbthylamioe : Benzidine 2-Xaphthyiamioe i Benzidine 2`Xaphtbylamine Benzidine . 2-Xapbthylanune Benzidine 2-Xaphrhylamine Benzidine 2-N'apbtbvlamine Benzidine Bladder carcinoma 1 : Bladder carcinoma i : Xot known ! i Not knowQ j Hepatoma I . 2- ' Bladder papilloma Hepatoma, acoustic carcinoma, intestinal . carciooma Bladder papilloma N'ot known glaad - metabolites was. approdmately '200:1. In addition, the dog was found to have a high level of urinary sulfatase. which would aid in the liberation of free 2amino-l-naphthol from the conjugate?. A consideration of these factor? has Ird to the hypothesis that- aromatic amines and a?.o-eompounds produce their carcinogenic effects at distant sites along the routes of excretion because they undergo metabolic changes in the animal body, which, coupled with certain favorable local factors, determines their site or action tClnyson, 1053).i OCCTTATIOXAL C.\XCZ?. OF THl LIWG Two aspects only will be considered: its occurrence in (i) asbestos te.\ie workers: and (2) hematite miners. The series of cases presented here are, as yet, unpublished. Tor published series the reader is referrw[ to Hueperb thorough -- surrey (1952)* Lo which he cites 60 cases of cancer associated with asbesrosis, 33 of which were reported in Britain. Hneper also refers to S cases with coexistence of siderosis and cancer of the lung. 1. Cancer of the Luna in Afontos Tertilc Workers In 192S. or a little earlier, one of the present authors <"MJS) began to collect information and material from the workers in 2 factories, and it will be remem bered that he was euriy in the field in describing the j>eculiar bodies and the sisr.aficaace of their occurrence, especially ir. chimps, in the sputum (Stewart. 192$::: Stewart and Hnddow. 1929:;;` Stewart. Tartersall and Haddow, 1932?0). Stewart's ^erie? consists of postmortem materia: from SO persons who had worked in the 2 factories, and were thus likely to inhale asbestos fibers. In S persons no punnouarv isbestosis could be demon.-imred. though small numbers of bodies were usually present. The effective number for consideration is thus 72, 4u muie= fib. 19J~> INCIDENCE "- " _ \'unii>er of Iucideuce o \verasre acAverage aie Average pe Total Prior to '. In cases t * (>ne m* Figtirer was availab am! 2B fer oncer art pnr-ent in higher inc ii.-forp riie **u!u>i>. T! ex;* isur ;!>!> "T-fijSlN in the dye I'liiiirr. It "infer riia A fair a. T.ikiiri; in applied rr mahmiant ai'-tory u: Ufi-try fo i` In >! iiMn; Tv..,' ;:sf t:u- :o '`\r wr-n wvr rt V ; in; . ;. f-j:.----- -^5 --! I * ^'| I --'V-r^,- -- sw^l -e -:^^---'Y-7^--rN,i- ^i 9i ~ * :iaad nave a free 2hna led a *h r 'ertuin :-:-x:ue 25 yet. .or-ugh o-s. 33 listener ^ouect `.-.r.emud the 'ewart, o^or" worked was :io bodies males fi`>. '.Oo-:, OCCUPATIONS !. CANCUK 131 TABha 4 !n'*:o.\ce oy Ca.\c;.k :.n Asseoto- Tcnt:l *1 yRKr.S a T I'oST'.foR Til JoXAMTNaTION U.v U6fSC0IS \AuT!cCumb*ieWrs-ist.sd 1: j Us; Cascef AabSl"i> CPAjinrsr,eiioes:ntnsetnuidl Number of cases investigated postmortem (72 Invidence of iung cancer (per cent) Averuze age at death Average aze at starting work Average period of exposure -Wears) Total Prior to 1931 In cases entering alter 1931 Nt r 22 IS 54 .'21; f 31<21; 23(21; 14{19) ; 5i.2) m f ! il F 12* 3 ; 12- 2 ] 26.1 S.7 47(12) 56 f11) 2S(12) : 27(10) , iso2) : 25 (TO) 14171 i 12(10) 7 (3.' .M F 13 . * One man had osbestoeis, tuberculosis and ur.g cancer. was available. and 26 females. In Table 4 the data in regard to the as'ociarion of osbestoda and cancer are given. Cancer arising primarily in pleurae, lungs or bronchi was present in. 26.1 per cent of males and S.7 per cent of females. This significantly higher incidence in males may be accounted for by the fact that 7 women died brfwre the cancer age. 4 .fotlc'vlr.g parturition or abortion and 3 from tuber culosis. There was no significant difference in average age at death, average period of exposure or average age of starring work between male6-' with uncomplicated arbesto-is and those with the complication of lung cancer. This is Interesting, as in the dyestuff industry death was accelerated by the supervention of bladder cancer. It was noted that the degree of fibrosis was rather less in the lungs with cancer than in those without. Tuberculosis significantly lowered the age at. death. A fair assessment of the period n; s>\-nosnr > dimcuir in such a varies of ^as&a. Taking into account the known fact that after a carcinogen has ceased to be applied to a tissue a latent period is repaired before the development of the malignant change, it ueoiuea to use the period from the first entry :nro the factory until death as the peri<xi of exposure. This disregards abseuces irom the fu'-tory for any reason. It also presupposes that once the fibers have gained acres- to the iur.g the carcinogenic process is set in motion, becoming tally developed at the end of the latent period. Two interesting features deserve mention. The morbid anatomy and histology of the 13 lung cancers of which full notes were available was ums.-uaily varied. Four were large tumors situated near the lung hiium. dis.-eminn.ting in char acteristic fashion and of adenocarcinom.ut.ous or oat-cell type. Seven were situated in the periphery of the lung, usually near the base, 3 disseminating by hlood and lymph streams and the other 4 remaminu confined to the lung substance. Six of thoc were adenocarcinomatotis or of oat-cell type. 1 being spindle ceil and po-'-iblv a rhabdomyosarcoma. Small peripheral cancer5 were described by Raeburn and Spencer * l ?!.>.>i14 as the likely precursors ot the large hiiar mas.-es 1' *` 1... i ; i .s '' i ' 1: , ;-v i : . *' ;* - ; < 5 :a; =H; - : i :-3 !i# IS. 51 if i! S: (* LI `-a 4 r<^. ?o usually seen at postmortem examination. The peripheral cancers in this series may, therefore, represent a stage prior to hilar involvement. Two tumors were pleural in distribution, 1 disseminating and 1 not. Both were adenocarcinomas, the former having spindle-cell areas. Attention must also be drawn to the 4 peritoneal cancers, I in a male and 3 in females. This is a very high number in such a small series of cases. All these tumors were anaplastic carcinomas, the primary site not being found in any organ. The possibility of an origin from the sequestrated bronchial epithelium present in the diaphragmatic areas of hyaloserositis Is suggested, but without any clear proof. No adequate comparable postmortem material from persons working under factory conditions and not exposed to asbestos dust is available with which to compare the incidence of lung cancer in asbestos workers. The incidence here cued is very high and by comparison with the incidence in iron-ore miners must be highly significant. The occurrence of occupational lung cancer in the exposed female is noteworthy. In connection with this particular form of industrial hazard, it must be em phasized that since the introduction of regulations for the control of asbestos dust in 1031. the amount nf exposure of the workers to dust ha* been enormously reduced and we shall therefore expect to see a disappearance of those severe degrees of pulmonary fibrosis rha: have been described heretofore and possibly a disappearance of associated cancer. All the present cases that had asbestosis and cancer had been exposed prior to 1931. 2. Cancer of th* Lung in Iron-Ore Miners Or.s of the authors f.TSF) has had a unique opportunity to -study this disease (Stewart and Farads, 1934).13 Ke has personally conducted postmortem exami nations on 192 Cumberland hematite miners during the last 20 years and in addition has performed postmortem examinations on 2373 Cumberland males above the age of 20 years, unseiected in regard to cancer or lung disease. The dif ference In incidence of lung cancer in these 2 groups is statistically signinciini (Table o). The age of onset is not significantly delayed, most of the miners having entered the mines under the age of 30 years. Ail the miners' lungs contained much silica and iron at death, but there was no significant difference in the content of either mineral in the iur.gs with and without cancer. There was. however, an interesting difference in the degree of fibrosis 'Table 61 and this has greeter significance when a similar occurrence in relation to asbestosis is remembered. All the tumors were classified as oat-cell or squamous cancers. Ta3LL 5 Ca.nccs or t.hz Long in Iron-Ore Miners Norr.ber Lon; Ciccers Iron ore Timers mvp- year-, * <i > 2^ Isciiss ; 5. $; 1 Sc- -- S' JiroriL- Fi:>r- Xo fir Fla Th it is ~ -riicir aunt v. hid: ::: i ion thus.'! ox:: mi d:r- !:: cnturt .\,., 2-5 his series ;ors were cinemas, and 3 io Ail these i :n any .ithellum without ig unaer vhich to ace here ere must exposed -t-r - be emtcs dustrmousiy ? severe )ssib:y a osis d / \ i 'i ;j *4 disease exa miand in i males The dirrincaat having <1 much uent of ver, an greater red- -All 1 ;-'cdeoce r. i I * ii. 'cb. .'5 -'-5 OCCUPATIONAL cancz.t 123 . TABLE 5 Mintxai. Content, Dcfunox of Occupation* and I'cmiosAav Fixaosts is Ison-Ore Miners Number in Group Av enie Kp 1 AlTfSM Du nuon o OtruSANoa (Ver; Averist ?ff. craii;? .Micerai i ConieLcuca* Dry Siun 1j *ire D*vr { Fiords is 3roachiaj carcinoma Fibrosis alone Fibrosis and tuberculosis .No abrosis and ao tuberculosis 15 59 75 25 61 32 (11) 60 34 (20) 57 2S (48) 62 ' 25 (10) l.n 1.15 1.14 0.59 5.3 " 6.3 5.4 4.04 -r _j_ J-O. -r-r 0 Figures io pareatheaes represent the number of eases in which the information was available. -: The common factor in these 2 types of occupational lung cancer is silica, and it is suggested that this may be the carcinogenic agent. The presence of silica (as silicic acid) causes pulmonary nbrosis, which precedes the initiation of the malig nant process. The nbrosis is usually of lesser degree, however, in those lungs in which cancer supervenes. On published evidence the case for an etiolcgic re lationship between nodular silicosis per se and lung cancer is much less strong -than in silicosis -na-aociated with sideTosis and in asbestosis. Hueper (1952)* examined the literature very thoroughly and came to the conclusion that "the available evidence supporting a causal relation between silicosis and cancer of the lung is unimpressive." It seems possible, therefore, that tiie fibrous nature of ashertos or the presence of hematite dust may exert a modifying effect on the chemical action of the silica or on the fibrotic process itself, Further study of the nature of the carcinogenic process in pneumoconioses is thus obviously needed. SUVMA3Y The value to the cancer problem as a whole of the study of occup?*ionalcancer in the held and by experiment, together with the rime lag between -these 2 aspects, is discussed. -A short consideration of the total amount of cancer in any population follows, and a classification of the types of recognized occupa tional cancer. More detailed consideration of industrial bladder and lung cancer follows, hi regard to the former, the extent of the hazard, the nature of the chemicals involved and their metabolism in various species are discussed. In regal'd to the latter, the occurrence of lung cancer in. a group of 72 male and female asbestos textile workers and in 192 hematite miners in Cumberland, England, is de.-<-nbed. REFERENCES 1. Bonder, G. M.f ClaYSOX. D. B., and Jcu., J. TV.; An .experimental inquiry into the - of industrial bladder cancer. Lancet. 2; 1951. - R.\.ser, G. M.f Clatsox, D. B.,Jim., J. W., and Pyxah, L. X.: The carcinogenic properties of 2'amino-l-.naphtlioi hydrochloride and its parent amine 2-uaphihvl- amine. Brit. J. Cancer, 6: 412-424, 1952. . i i Si 1 Vi : J t' 1 i . X !! ;; > . .'-i 134 BONSER LT AL. Vol 25 3. Cass, 31. A. M., and Hosier, M. E.: Tumour of t he urinary bladder as an occupational disease in the rubber industrv in Englaod aod Wales. Brit. J. Prevent, ii Soc. Med., 8: 30-30, 1934. * 4. Cass, R. A. M., Hoskxr, M. E., McDonald, D. B., and Pearson, J. T.: Tumours of the urinary bladder in workmen engaged in the manufacture and use of certain dyestuff intermediates in the British chemical industry. Part I. The role of aniline, benzidine, alpha-naphthvlaniine and beta-naphthvlamine. Brit. J. Indust. Med., 11: 75-104, 1954. '. 5. Clatson, D. B.: A working hypothesis for the mode of carcinogenesis of aromatic amines. Brit. J. Cancer, 7: 460--471, 1953. 6. Cramer, W.: The importance of statistical investigations in the campaign against eameer. Report of the 2nd Internal. Congress against Cancer, 1: 443--459, 1936. 7. Haerting, t. H., and Hesse, W.: Der Lungenkrebs, die Bergkrankheit in den SchDee- berger Gruben. Vrtljschr. f. gerichtl. Med., 30 : 296-309 : 31: 102-334 ; 333-337, 1$79. S. Heath, J. C-: Cobalt as a carcinogen. Nature, 173: S22, 1954. - 9. Herper, W. C.: Occupational and environmental pulmonary cancer w-it h special reference to pneumoconiosis. Proceedings of the 7th Saranac Symposium of Pneu moconiosis, 1952, in preas. 10. Huxfer, W. C., and Wolfe, H. D.: Experimental productioo of aniline tumors in_dogs. Am. J. Path.. 13: 656-673. 1937. * 11. Exnnawat, E. L.: The data relating to cancer in the publications of the General Registrar's Office. Brit. J. Cancer, 4: 355-172, 3950. " -" 12. Passet, R. D.: Experimental soot cancer. Brit. Med. J., 2: 39-540. 1922. . 13. Pott, P.: Chimrgieai Observations Relative to the Cataract, the Polypus of the Nose, the Cancer of the Scrotum, the Different Kinds of Ruptures, and tne Mortincation of the Toes and Feet. London: T. J. Carnegie, Hower, Clark and Pollirts, 1775, p. 5". 14. lUacKt, C., AND Spencer, K.; A studv of the ortgiti and devetopmetr: of kmc cancer. _ Thorax, 8: 1-10, 1953. ' _' 15. Rehn. L.: `Blasengeschwillste bei Fuchsin-Arbeitcrn. Arch. f. klin. Chir., 50: x 3S95- _ . 16. SXEL, H.: Cber der Lungenkrebs der Bergleute in Joachimstal (Tschechowiowhkei}. Zischr. f. Krebsforsch., 32: 609-613, 1930. 17. Stewart, M. J.: Diagnosis of pulmonarv xsheetosia at necropsv. Brit. Med. J., 2: 509, 192S. *' IS. Stewart, M. J., and Favlds. J. S.: The pulmonarv fibrosis of haematite miners. J. Path. 6: Bact., 39: 233-253, 1934. ' 19. Stewart, M. J.. and Haddow, A. C.: Demonstration of the peculiar bodies cf pul monary asoestosis ("asoestosis bodies") in material obtained by lung puncture and in the sputum. J. Path. J: Bact., 32: 372. 1929. '' 20. Stewart, M. J.. Tattersall, X.. and Kaddow. A. C.: On the occurrence of clump? of asbestosis bodies in the sputum of asbeeto* workers. J. Path. k 3act.. 35: 737 741, 1932. ' 21. Symposium on a Cancer Control Program for .Wh.Boiling Catalyticnily Cracked Oils. Arch. Indust. Hvg. L Occup. Med.. 4: '297, 3951. 22. Sktz, S., MaGTIGax. TV, H., and Dobri.ver, K.: The carcinogenic action of benzidine. Cancer, 3: 7S9-504, 1950.