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ftnefrcAJ Toowo7=CWa//c/c T'/fTHococ'i 3i OCCITATION.U. CANCER 31 Or the Urinary Blaoder ix DrxsTum Operatives and or the Luxe rx Asbestos Textile Workers and Iron-Ore Miners CEOUCLOvA M. BONSER, M.D., J. S. FAUtDS, MJ>.. and M. J. STEWART, LL.D. 1 30 VnirtnUf if Lttdt a*d CumitHiad Infirmary, Cerlitlt, Enflnad ' . ..*w The study of occupational cancer has proved to be a valuable method of. rm learning some aspects of the biology of cancer in its wider sense. This form of cancer is an unwitting experiment in man, but until it can be reproduced in animats 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 tbs scrotum in chimney sweeps in 1775, but it was not until *? 1022 that Paa$ey" induced cancer of the skin of mice by means ofanother extract 8of soot. Similarly, in 1S95, Reha" described cancer of the bladder occurring in %workers engaged in the manufacture of aniliue dyes, but it was not until 1937 that Hueper and his eo-workera" 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 hug cancers of the Schneeberg and Joachimstal miners' (Haerting and Hesse, 1S~9,J Sild, 1930"), though 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, i ` 'We are well advised to be ready to recognize new forms of hazard in any industrial procees, but it is even more important to advise industry of the ' dangers that are likely to be inherent in tbe manufacture or use of suspected or proved carcinogens. This was certainly done when the new plants for effecting "1 the catalytic cracking of oils were set up (Symposium on a Cancer Control .Program, 1051).**" ' As such a variety of occupational cancers is now recognized, this presentation is confined to making a classification of the most important and to discussion of those with which the authors are most familiar (Table 1). It seems hardly 4 necessary to **.v that, before it can be claimed that any partieuiar form of cancer has an industrial origin, it must be shown that the incidence b significantly higher in exposed workmen than it is in the general population. Thb not always easy, as morbidity statistics of cancer in most countries are not available, hospital statistics being quite fallaciously high. Secondly, in sites where there is a /* high natural incidence, any occupational risk tends to be masked. Received for publication August 31.19M; accepted. Scptem'-er 33. IMA Dr, Banter is Reader in Cancer Research, University of Letds, and Morbid Anatomist to St. James Hospital, I-reds; Dr. Faulds i Vatlmlopsl, Cumi*rland Koynl Infimvirv. Carliilc; and Dr. Stewart is F.meritus Professor of Pathology, University of l.ccds ttt /.v.s.; l.i*r .Sk'i Ar.v'iuc nifwiiiitm (ort aVirk.:l s**ilira .Vnlieiitftt lfm (hematite l^rvllium 1 (rkjf'm n !* I.'iirnnliiix s--r Tar ltuv Ai'ttoic I rueii i.ilfuinnns |i.lr riittni) rvunir ehemc:i l>\\* tttienueOi .V very 'mpltasi/ccf by sriven populate |rn|>ortioHS of xample. th*rp Mtitniit uilK r '-imfumia of r Kumppjui po;j (MepttluflOfl the 'tttptired with ,, 8004 0044 SCF-FA-4550 02/13/2003 THU 10:44 FAX 312 996 1899 UIC LHS CHICAGO of tiie Lung in EBS STEWART, LLD. ngland uable method of lse. This form of oe reproduced in of the carcinogen observation that scessful induction jrcival Pottn do it was not until f an etherextract (der occurring in not until 1937 ancer in dogs by hjgMmcceeded in (Haerti known for cenjection of cobalt tal work. f hazard in any industry of the ; of suspected or nts for effecting Cancer Control his presentation to discussion of t seems hardly r form of cancer is significantly on. This is not e not available, where there is u d. 4. forbid Anatomist Royal Infirmary, of Leeds. Feb. 1965 occupational cancer 127 TABUS 1 List of Some Substances Causing Canchb, Industbt Concisunnd, ano Sits of Cancer Substance ludutof Site ol Cancer Proof Industrial Zroeri- mental Mineral8 Arsenic Chromium (ore) Nickel Silica Asbestos Iron (hematite) Beryllium. Sheepdip manufacture and usage Electroplating, tanning, dyeing Chemical manufacturers Stone blasting Minnnt and users Minors Fluorescent lamps 8km, lung Respiratory, usually lung Respiratory Lung Lung Lung Lung, bones Doubtful Doubtful Doubtful Doubtful + + 0 0 0 0 0 0 0 + Unknown Pitchblende miners Lung +0 Oils Lubricating Petroleum Mule spinners Refiners ' Skin Skin ++ ++ Pitches Soot Tar Chimney sweeps Road workers Skin Skin + ++ Rays Aclinic Farmers, sailorB Roentgen Scientific personnel Luminous paint (ra- Dial painters dium) Skin, exposed sites Skin, exposed sites Skin, exposed sites + + + + + + Organic chemicals Dye intermediates Chemical manufacturers, Bladder and usarg ++ A very significant fact has been observed by many workers and has been emphasized by Kennaway (1950)." The "amount" or incidence of cancer in any given population does not vary greatly, as regards either sex or race, 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 to the female, in contrast with the high rates in lung and stomach in the male. Similarly, primary carcinoma of the liver is high in the Javanese in Sumatra, but insignificant in European populations. "There appears to be a general law that when in a given population the incidence of cancer in one particular organ is markedly increased compared with another population, there is then a compensating decrease in the 128 RONSKET ET Ah. iTol. 25 incidence of cancer in a number of the other organs" (Cramer, 1936). 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 DYESTUJTS 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 mid absorption of these compounds through the skin and yet tho tumors arc 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. Tho knowledge thus gained has altered our conception of the range and mode of 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 associates* (Table 2). They have shown that although there is a small spontaneous incidence of bladder tumors in tho general population (2H tames greater in males than in females and rare under 55 years of age) the risk is 30 times greater in chemical 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 being 2-naphthylamine, benzidine and possibly auramine and magenta. There is no evidence that aniline 1b 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 it is the length and not the severity of exposure that matters, individual susceptibility being a marked feature. There is no special tendency for industrial tumors to be TABLE 2 Occurrence op Bladder Tuuobb in Manufacturers and Users of Dyestuff Intermediates (Case bt ai*) Population at Risk = 4522 Men Expected deaths in oomparable general population Actual deaths in industry Actual cases in industry Risk in industry Chemical exposure Ago of onset Induction period Degree of maliguanoy Survival after diagnosis Exposure Individual susceptibility 3-5 127 262 30 times that of general population Bensidiue ' Beta .naplithylaminc Alpha-naphUiylamine 15 yearn earlier than in general population 15-20 years Comparable to tumors of bladder in general population 20 pur cent survived 10 years Length, not severity, affects induction time A marked feature of unknown causa Feb.u more c per cei of the In 1 reduce traced engage 1950,i fruit ir Men any tin use. C bladde drawn records It is pi certain bladdei and it t isomers volatili: search and it: mediatt strayed Of gr the loca tion of naphth: develop individi If 2-nap Iffedtc If benzi sonal cc tumors mice, he vation) must bo original tion of tl A atuc a cower the caps these sut 02/13/2003 THO 10:45 FAX 312 896 1899 UIC LHS CHICAGO @005 Vul 25 sr, 1936).* A conlortions are being 1stry manufacture and lop tumors of the and absorption of .ted in the bladder, y workers and we rstand the reasons, range and mode of er in workmen enieraiediates in the > and his associates* ntaneoua incidence er in males than in Oger in chemical ie^Putnufaoturers, y, the noxious subnine and magenta, induction period is dependent upon the he fact that it is the idual susceptibility istriai tumors to be sens or Dy&sxutf J population in general population of bladder in general 0 years induction time uause Feb. 1955 OCCUPATIONA1, CANCER 129 more or less malignant than spontaneous ones. This is a killing disease, only 20 per cent of all cases having survived more than 10 years from the first recognition of the disease. In 1935, certain alterations in plant and teebnio were made and these have reduced the risk just significantly, but another 243 cases (over and above the 262 traced cases in a population of 4622 men) may be expected among British workers engaged in the manufacture of chemicals during tbe next few years. In 1945 and 1950, more drastic plant 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 other industries in'which die dyestuff intermediates are in use. Case and Hosker (1954)* have recently demonstrated an occupational bladder-tumor risk in the rubber industry in England and Wales. Attention was drawn to this by tbe finding of a high incidence of bladder tumors in tbe hospital records of a County Borough which is an important center of the rubber industry. It is probable that the risk was introduced into tbe industry in 1928, when a certain antioxidant began to be used. Tbe latter was known to have caused bladder tumors among the men in tbe chemical industry who manufactured it, and it contained about 2.5 per cent al Tree naphthylamine, both alpha and beta isomers. The treatment of the rubber "mix" containing the antioxidant volatilized quantities of naphthylamiucs. 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 the manufacturers of the antioxidant im mediately ceased its manufacture and the users discontinued its use and de stroyed old stocke. Of great interest to tho experimental worker is the search for the reasons for the 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- naphthylumine is administered by feeding to dogs, all the animals will eventually develop tumors of the bladder, though the number and location will vary in individuals (Hueper and Wolfe, 1937;'* Bonser and her co-workers, 1951')- If2-n&phthylamine is fed to mice, hepatomas or benign cholangiomas will occur. If fed to rats or rabbits, occasional benign papillomas ofthe 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 will be found (Spitz, Maguigan and Dobriner, 1950) if injected into mice, hepatomas only will occur (Bonser and her associates, unpublished obser vation) (Tabic 3). Such localization of tumors suggests that 3 important factors must be at work: (a) species variations in biologic response; (b) excretion of the original chemical or its metabolites along a specific pathway; and (c) concentra tion of these substances in certain sites. ' A study1 of the metabolism of 2-naphthylamine in various species showed that a conversion of the amine to 2-amino-l-naphthol 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 02/13/2003 THU 10:45 FAX 312 996 1899 UIC LHS CHICAGO @006 130 BONHEH BT AL. Vol 95 TABLE 3 Eespouse or Species to Administration op Dyestcfk Ipjtjcumediatbs SpKies Cbenls&l Tumor Man Dog Cat Ferret Mouse Rat Rabbit 2 Naphthylamine Benzidine 2-N aphthylamlne Bessitline 2-Naph.thyIamine Benzidine 2-Naphthylamine Benzidine 2-Naphthylamine Benzidine 2-N aphthylomi ne Benzidine 2-Naphlhylaminc Benzidine Bladder carcinoma Bladder carcinoma Not known Not known Hepatoma Bladder papilloma Hepatoma, acoustic carcinoma, intestina carcinoma Bladder papilloma Not known metabolites was approximately 200:1. In addition, the dog was found to have a high level of urinary sulfatase, which would aid in the liberation of free 2- amino-l-naphtiiol from the conjugates. A consideration of these factors has led to the hypothesis that aromatic amines and azo-compounds 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 of action (Clayson, 1953)." ' OCCUPATIONAL CANCEH OF THE LUNG Two aspects only will be considered: its occurrence in (I) asbestos textile workers; and (2) hematite miners. The series of cases presented here are, ss yet, unpublished. For published series the reader is referred to Hueper's thorough survey (1952) in which he cites 60 cases of cancer associated with asbestosia, 33 of which were reported in Britain. Hueper also refers to 8 cases with coexistence of sideresis and cancer of the lung. 1. Cancer cf the Lung in Asbestos Textile Workers In 1928, 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 early in the field in describing the peculiar hndies and the significance of their occurrence, especially in dumps, in the sputum (Stewart, 1928;" Stewart and Haddow, 1020;*" Stewart, Taltersall and Kaddow, 1932*). Stewart's series consists of postmortem material from 80 perouus who had worked in the 2 factories, and were thus likely to inhale asbestos fibers. In 8 persons no pulmonary asbestosis could be demonstrated, though mnull numbers of bodies were usually present. The effective number for consideration is thus 72,46 males Feb. 1955 Incidence q: Number at ca Incidence of) Average age i Average age I Average peril Total Prior to 19! In cases en * One man f Vigores wob uvailablt and 26 fern: cancer are present in! higher inch before the culosis. Th of exposun asbestosis: in the dye cancer. It cancer tha A fair u Taking in applied tc malignant factory ui factory ft access to developed Two in of the 13 Four wer iicleristic in the pei lymph at these we possibly Raeburn Vol.$5 p Intermediates; Tbmor idsr carcinoma ider carcinoma known known tatotnA dder papilloma mtoma, acoustic gland trcinowa, intestinal lrcinoma dder papilloma v known log was found to have a he liberation of free 2- ese factors has led ids produce their excretion because they i, coupled with certain Hayson, 1953)." tea s in (1) asbestos textile esented here are, as yet, d to Hueper's thorough i&ted with aabestosis, 33 8 cases with coexistence 5 Workers i (MJS) began to collect ts, and it will be remempeculiar bodies and tbe in tbe sputum (Stewart, iU and Haddow, 1932**). persons who hod worked is fibers. In 8 persons no small numbers of bodies ition is thus 72,46 males Feb. im OCCUPATIONAL CANCER 131 TABLE 4 Incidence or Canceb m Asbestos Textile Workers at Postmortem Examination 'ctmmOuac-ataJ Ashwlosii Tuber culosis end Asbcstails LuAsAgaCentdminclclr Crcarnictoernacnidi Asbcstoeis Number of vases investigated postmortem (72) Inoideuce of lung cancer (per cent) Average age at death Average age at starting work Avorage period o! exposure (years) Total Prior to 1331 In oases entering after 1031 MF 23 18 54(21)f 31(21) 23(21) 14(10) 5(2) MF 12* 3 47(12) 28(12) MF 12* 2 26.1 8.7 56(11) 27(10) 18(12) 14(7) 7(5) 26(10) 12(10) MF 13 One man bod aabeBtosis, tuberculosis and lung cancer. f Figures in parentheses represent the number oI cases for which the information was available. - and 26 females. In Table 4 the data in regard to the association of asbestos's and cancer arc given. Cancer arising primarily in pleurae, lungs or bronchi was present in 26.1 per cent of males and 8.7 per cent of females. This significantly higher incidence in males may be accounted for by the fact that 7 women died before the cancer age, 4 following 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 starting work between males with uncomplicated aabestosis 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 degreo of fibrosis was rather Ices in the lungs with cancer than in those without. Tuberculosis significantly lowered the age at death. A fair assessment of the period of exposure is difficult in such a series of eases. Taking into account the known fact that afteT a carcinogen has ceased to be applied to a tissue a latent period is required before the development of the malignant change, it was decided to use the period from the first entry into the factory until death as the period of exposure. This disregards absences from the factory for any reason. It also presupposes that once the fibers have gained access to tho lung the carcinogenic process is sot in motion, becoming fully developed at the end of the latent period. Two interesting features deserve mention. The morbid anatomy and histology of tbe 13 lung cancers of which full notes were available was unusually varied. Four were large tumors situated near tho lung hilura, disseminating in char acteristic fashion and of adcnocareinomatous or oat-cell type. Seven wore situated in the periphery of the lung, usually near the base, 3 disseminating by blood and lymph streams and tbe other 4 remaining confined to the lung substance. Six of these were adenocarcinomatous or of oat-coll type, 1. being spindle cell and possibly a rhabdomyosarcoma. Small peripheral cancers were described by Raeburn and Spencer (1953)u as the likely precursors of the large hilar masses 02/13/2003 THU 10:46 FAX 312 996 1899 UIC LHS CHICAGO @008 132 OONSER ST AL. Val. 25 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, 1 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 cited is very high and by comparison with the incidence in iron-ore miners must be highly significant. The occurrence uf 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 1931, the amount of exposure of the workers to dust has been enormously reduced and we shall therefore expect to sec a disappearance of those severe degrees of pulmonary fibrosis that have been described heretofore and possibly a disappearance of associated cancer. All the present cases that had asbestosis aud cancer hod been exposed prior to 1931. . Cancer of the Lung in Inm-Orr- Miners One of the authors (JSF) has had a unique opportunity to study this disease (Stewart and Foulds, 1934).l Ho has personally conducted postmortem exami nations on 192 Cumberland hematite miners during the last 20 years and in addition has performed postmortem examinations on 2378 Cumberland males above the age of 20 years, unselected in regard to cancer or lung disease. The dif ference in incidenoe of lung cancer in these 2 groups is statistically significant (Table 5). The age of onset is not significantly delayed, moat of the miners having entered the mines under the age of 30 years. AH the miners' lungs contained much silica and iron at death, but there was no significant difference in the content of either mineral in the lungs with and without cancer. There was, however, an interesting difference in the degree of fibrosis (Table 6) and this has greater significance when a similar occurrence in relation to asbestosis is remembered. All the tumors were classified as oat-oell or squamous cancers. . TABLE S Canceb of Tax Luno in Ibon-Ore Mimebs Number IcUng Cancers Ptrceatagt Incidents Iron-ore miners Cumberland rnales over 20 years 102 2378 17 8.8$ 2 a 1-8S 2 Feb. /95 MlOT'.TiA.L Bronchial card Fibrosis alone Fibrosis and t\ tfo fibrosis &ni Figures in I available- The oomm it is suggeste silicic aoid) c naot process which canoe: lationship b than in silic examined th availablo ev. the lung is u asbestos or chemical act nature of th The vaht cancer In th 2 aspects, any popula tional cancc More tie In regard t involved ar latter, the > textile wor scribed. 1. Bowses, cause 2. Bohse&. propei amine 02/13/2003 THU 10:46 FAX 312 996 1899 UIC LHS CHICAGO V61.26 in this series tumors were loarcinoroaa, sale and 3 in cs. All these mod in any 1 epithelium but without rking under th which to 'idence here ninern must the exposed lust be exntbestos dust enormously hose severe i possibly a and this disease bem examiars and in land mains >e. The difsignificant lers having dned much content of iwaver, an .as greater lbered. All We Incidence 85 2 85 2 Feb. 1965 OCCUPATIONAL CANCfiB 133 TABLE 5 Mineral Content, Duration op Occupation and Pulmonary Fibbosib in Iron-Ore Miners NuCmrboeurpto Avtljsc Aft II Petth DAurvaetriaogneof Occupation (Yews) Avenue Per. centageMineral ConigLainl tgo Dry Silica Iron Decree ot Ftbzosb Bronohial carcinoma Fibrosis alone Fibrosis and tuberculosis No fibrosis and no tuberculosis 15 59 75 26 61 32 (11) 1.11 6.3 ' + 60 34 (20) 1.15 6.3 +++ 57 28 (48) 1-H 5.4 ++ 62 26 (19) 0.59 4.04 0 Figures in parentheses 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 caroinogtmic agent. The presence of silica, (os silicic add) causes pulmonary fibrosis, which precedes the initiation of the malig nant process. The fibrosis is usually of lesser degree, however, in those lungs in which cancer supervenes. On published evidence the case for an etiologic re lationship between nodular silioosis per se and lung cancer is much loss strong than in silicosis associated with siderosis 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 the fibrous nature of asbestos or the presence of hematite dust may exert a modifying effect on the chemical action of the silica or on the fibrotic process itself. Furthor study of the nature of the carcinogenic process in pneumoconioses is thus obviously needed. 6UMMABY The value to the cancer problem as a whole of die study of occupational cancer in the field and by experiment, together with the time 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. In regard to the former, the extent of the hazard, the nature of the chemicals involved and their metabolism in various species are discussed. In regard to the Litter, 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 scribed. REFERENCES 1. Bonser, 6. M., Claybon, D- B., and Jull, J. W.: Ad experimental inquiry inln Iho Ranee of industrial bladder cancer. Lancet. 2:286-287,1951. 2. Bonser, G. M., Claybon, D. JS-, Jull, J. W., and Pybah, L. N.: The carcinogenic properties of 2-amino-l -naphthol hydrochloride and its parent amine 2-naplithyIamine. Brit. J. Cancer, 6: 412-424, 1952. @009 02/13/2003 THU 10:47 FAX 312 996 1699 UIC LHS CHICAGO @1010 6r Case, R. a. M., and Hoskeb, M. Ur: Tumour o! tbe urinary bladder as au oeeupatiooiU disease in the rubber industry in England and Wales. Brit. J. Prevent. A Sue. Med 8:39-50,1934. 4. Case, R. A. M., Huskkb, M. E., McDonald, D. B., and PeabboN, J. T.: Tumours 0f the urinary bladder in workmen engaged in the manufacture and use of certain dyestuff intermediates in tbe British chemical industry. Fart I. The role of aniline benaidioe, alpha-napbthylamine and bcta-naphthyiaminc. Brit. J. Indust. Med' 11: 75-104,1964. ' 5. Clatbon, D. B.: A working bypotbesis for the mode of carcinogenesis of aromatic amines. Brit. J. Cancer, 7:460-471,1953. 6. Cbamsb, W.: The importance of statistical investigations in the campaign against cancer. Report of the 2nd Internet. Congress against Cancer, 1:441-469, 1936. 7. Haeuttnc, F. H., and Hesse, W.: Dor Lungeahrebs, die Bergkrenkhcit in den Schnee- berger Grubeo. Vrtljschr. f. geriohU. Mad., 30: 295-309; 31; 102-134; 313-337, 1879. 8. Heath, J. C.: Cobalt as a corcmogeu. Nature, 173: 822,1954. 9. Hueper, W. C-: Occupational and euviranmeutal pulmonary cancer with special - reference to pneumoooniosis. Proceedings of the 7th Saranac Symposium of Pneu moconiosis, 1952, in press. 10. Hueper, W. G, and Wolfe, H. D.: Experimental production of onilino tumors in dogs. Am. J. Path.,13:656-673,1937. 11. Eennawat, E. L.; The data relating to cancer in tbe publications of the General - Registrar's Office. Brit. J. Cancer, 4; 158-172,1950. 12. Passbv, R- D.: Experimental soot cancer. Brit. Med. J., 2:539-540,1922. 13. Pon, P.: Chirurgfcal Observations Relative to the Oatanust, the Polypus of the Nose, the Cancer of the 8crotum, the Different Kinds of Ruptures, and the Mortification of the Toes and Feet. London: T. J. Carnegie, Ilawer, Clark and PolUns, 1776, p. 63. 14. Rabbubn, C., and Spencer, H.: A study of the origin and development of Jung cancer. Thorax, 8: 1-10, 1953. 15. Rrrv, L.: Blasengeeohw&Iate bei Fuehsin-Arbeitcru. Arch. f. kiln. Cbir., 60: 588-000. . 1895. ^ 16- Sntx, H.: Tiber der Lungenkreba der Bergleute in Joaehimstal (Tschcohowlowakei). Zteohr. f. Krebsfotseh.,.22:609-613,1980. 17. Stewart, M. J.: Diagnosis of pulmonary asbestosis at necropsy. Brit. Med. J., 2:509, 1928. . 18. StkwaBt, M. J., and Faulds, J. S.: The pulmonary fibrosis of haematite miners. J. Path. & Beet., 39: 233-263, 1934. 19. Stewart, M. J., anti Haddow, A. C.: Demonstration of the peculiar bodies of pul monary asbestosis ("asbestosis bodies") in material obtained by lung puncture and in tbe sputum. J. Path. 5c Boot., 33: 172, 1929. 20. Stewabt, M. J., Tattkkhai.i., N., and Hadoow, A. C.: On the occurrence of oluraps Of asbestosis bndiea in the sputum of asbestos workers. J. Path, dr Boot., 35: 737 741, 1932. 21. Symposium on a Cancer Control Program fur High-Boiling Catalytically Cracked Oils. Arch. Induet- Hyg. & Occup, Med., 4:297,1951. 22. Spite, B-, Maguioan, W. H., and Dobbineb, K.:The carcinogenic action of benzidine. Cancer, 8:789-804,1950. nor; Chan Ye aem clinic path' and and ' defici globi anuri Ex of Pj origii term and t ing r railee of th Alt Novt quire scare obtai yello A: nano the I yollo' did i rema few { Indie An progi majo Rv Co is Ch Clinii