Document MM27zjbVNqeD93jLX5wV1dZwj

C V 2/- i ^ //?4'z_ AN EVALUATION OF CLAIMS FOR OCCUPATIONAL FACTORS IN CANCER OF THE LUNGS BY William E. SMITH (Post-Graduate Medical School, New York University, US.A.) PLAINTIFF'S EXHIBIT I MET-584 EXTRAIT DE ACTA UNION INTERNATIONALE CONTRE LE CANCER VOLUME IX, -- N" 3 1953 * * . Jr AN EVALUATION OF CLAIMS FOR OCCUPATIONAL FACTORS IN CANCER OF THE LUNGS BY William E. SMITH (Post-Graduate Medical School, New York University, U.S.A.J The first intimation that an agent from the external environment might cause cancer in the lungs came from the experience of miners in the Schneeberg region of Saxony. The first diagnosis of lung cancer was made there in 1879 by Harting and Hesse. Among several hundred miners dying over the 37 year period prior to 1913, Arnstein found that carcino ma of the lungs accounted for about 40 % of all deaths. He identified the majority of the lung tumors as squamous cell carcino mata. These findings prompted a search for lung cancer among the neighboring Joachimsthal miners in Bohemia, who handled rather simi lar ores. In 1932, a survey was made of the Joachimsthal miners and 323 of them were examined fluoroscopically. Not a single case of lung cancer was found. Nevertheless, among 89 Joachimsthal miners dying be tween 1928 and 1938, lung cancer was found at autopsy of 43. Although cancer of the lungs has been re cognized as an occupational disease among the miners in these two areas, the specific cause is not entirely clear. These mines con tain radioactive ores, and it has been held that radon is the principle cause of the can cers. An excellent review of the subject has been published by Lorenz (1), who empha sized the possible contributory role of other factors, such as radioactive or arsenical dusts, pneumoconiosis and genetic influence deri ving from inbreeding. Aside from the expe rience in the Schneeberg and Joachimsthal areas, lung cancer has not been associated with mining operations elsewhere. The next association of respiratory tract cancer with occupation derived from the ex perience of a plant in Great Britain engaged in the manufacture of copper sulfate and the refining of nickel. No radioactive materials were present in the ores handled. Up to the present time, 52 cases of cancer of the nose or nasal sinuses and 93 cases of lung cancer have been reported from this plant (2). Since lung cancer is a relatively common disease, notably in Great Britain, detailed data on the population at risk in this plant would be nee ded to ascertain what proportion of the lung cases might be deemed excessive. Cancers of the nose and nasal sinuses are, however, re latively uncommon in the general population and the occurrence of 52 cases of them among employees of one plant signalized the exis tence of an occupational cancer hazard. This matter was reviewed in 1938 by A. J. Amor (3), who stated that over a period of 25 years copper had been extracted in this plant by sulfuric acid which contained arse nic. The arsenic precipitated as a metallic arsenide which escaped as dust in the pro cess of calcining. Amor suggested that arse nic, probably in combination with copper, was responsible for the tumors. Nickel was ex tracted by conversion to the volatile com pound, nickel carbonyl. It has been suggested by some authors, as reviewed by Hueper (4), that nickel, perhaps inhaled as this gas, cau sed the cancers. Amor stated that there was a history of exposure to nickel carbonyl in only one of the cancer cases up to the time of his publication (3). He further argued that there had been no cases of nasal cancer in Canadian nickel refineries where sulfuric acid extraction was not used. He stated that the incidence of cancer of the lung and other sites in workers on the Canadian operations was lower than in the general population. Detailed data on the number of man-years involved in the Canadian experience have not been published, and the same is true of a Norwegian nickel refinery from which 3 ca ses of squamous cell carcinoma of the lungs have recently been reported (5). In 1921, the plant in Great Britain shifted to a grade of sulfuric acid free of arsenic and in 1924 rebuilt the calciners in a manner AN EVALUATION OF CLAIJiS FOR OCCUPATIONAL FACTORS IN CANCER OF THE LUNGS 51 lo decrease escape of dust (5. aiso personal countv where mining was done, the rate was communications). Xo case u' nasal cancer 48.6. A rate of 5.2 was found in a county and only two cases of luny cancer have occur where the major occupation was agriculture, red in workers who were first employed there and a rate of 10.9 in the United States as a after 192k. The latent period of the cancers whole. Hueper calls attention to the large that were recorded is given as 18 to 25 vears quantities of arsenical fumes formerly relea ana only tico cases of limy ciou't > wire ovent-r- sed into the air by smelters in this state and pational tumor hazard in this plant has been suggests that these may have influenced the substantially reduced. Whether this reduction rates found. reflects a prolongation in the latent period or represents an actual decrease in the even tual tumor rate should be ascertainable wi thin the next decade. Ores of high arsenical content are mined in Sweden. It is possible that studies conduc ted in that country may reveal data as to whether arsenic presents a respiratory can Arsenic, known to be capable of causing cer hazard. I have explored this question with cancer of the human skin t G), has been in Professor Sven Forssjian. Professor Forss- vestigated in several situations for carcino man states that mining of copper ores rich genicity upon other tissues. In studies of mor in arsenic began in Sweden in 1928, and tality data from a British factory handling smelting a few years later. To date, there has inorganic compounds of arsenic. Hill, Per been no evidence of an occupational cancer ry and associates (7), (8) found that 29 per hazard. Since these Swedish operations have cent of deaths were attributed to cancer whe now continued for 24 years under good me reas cancer accounted for death in only 13 dical supervision, an integrated study of ex per cent of instances among control popula posure records of workers, arsenical content tions living in the same area. The proportio of dusts and mortality experience over the nal excess was confined to workers exposed next decade may provide a definitive answer to arsenicals and was not found among em as to hazardous levels of arsenic or indeed as ployees of the same factory whose tasks did to whether arsenic is carcinogenic for the not involve such exposure. Cancer of the res human respiratory tract. The question has piratory tract (7 cases) and skin (3 cases) wide interest, for it will be recalled that ar contributed the majority of the excess. The senical dusts have been thought to play a role authors call attention to the small numbers in the occupational respiratory tract cancers involved in their study. A survey (9) of mor of the Schneeberg and Joachimsthal mines tality records of a plant in the United States and in the nickel refinery discussed above. handling large quantities of arsenic trioxide Furthermore, finished tobacco products have showed that out of 72 deaths from all causes been found to contain considerable amounts over the past 25 years, 18 were due to cancer of arsenic, a large percentage of which is of which 7 were attributed to the respiratory volatilized into the smoke (11). It is probable system. In the age group under 55, there were that arsenic present in tobacco products deri approximately twice as many cancer deaths ves largely from the use of arsenical insec in the plant population than would be expec ticides upon tobacco crops. ted on the basis of mortality data for the state as a whole., The authors concluded, ho wever, that this difference was not statisti cally significant by reason of the small size of the plant population relative to the state population. During the past 20 to 30 years, there have been reports of cancer of the lungs in chro mate workers in Germany, which have been claimed to have occupational etiology. A de tailed study of mortality experience among employees of six major chromate producers Data that may bear on the question of car in the United States was recently conducted cinogenicity of arsenic are contained in a ge by Machle and Gregorius (12). This study neral review of environmental factors in lung concluded that cancer of the lung was sub ' cancer published by Hueper (10). These data stantially more frequent among chromate offer lung cancer mortality rates for males workers than in a control population provided in various counties of a state in the U. S. A. bv the records of a life insurance company. where copper ores of high arsenic content are The diagnostic facilities available to the con mined and smelted. In counties containing trol population may be open to question, but smelters, the rates were 46 and 145. In a there seems little doubt that the lung cancer WILLIAM E SMITH rate among the chromate workers was un duly high. The authors felt that monochro mates presented the hazard, but the exact nature of the carcinogenic material has been discussed further and with differing points of view by others (10). These studies were restricted to chromate producing plants. The re is no data as to whether such a hazard exists for workers exposed to inhalation of chromates in other processes, such as spray ing chromate primers (paints). In view of the German and American ex perience, a survey was recently made of em ployees in three chromate plants in England (13). Chest X-rays were made on 724 men, representing nearly all those employed in these plants. 165 had worked in the industry for more than 20 years. Only one case of lung cancer was found. Another man died of lung cancer in the year following the survey. The author states that the examined men will be followed for mortality experience. It is temp ting to recall the situation referred to above in which a fluoroscopic survey of Joachimsthal miners failed to detect any cases of lung cancer although many deaths from this di sease occurred among these miners over the succeeding few years. The 1947 report of the Chief Inspector of Factories in Great Britain (14) called atten tion to the occurrence of primary lung cancer in 31 instances among 235 cases of asbestosis. The lung cancer rate (13.2 r/c) in these asbestotic lungs contrasted with a rate of 1.32 9e found in a large group of silicotic lungs reported through similar channels to the Inspector's Office. The mortality rate for lung cancer in the general population of Eng land and Wales can be calculated as 1.36 % on the basis of death statistics published by the Registrar General. For these considera tions, the question has arisen as to whether asbestosis predisposes to carcinoma of the lungs. I have elsewhere presented a detailed discussion of evidence available on this sub ject (15). Lung cancer has occasionally been described in autopsies upon asbestotics in Germany, the United States and Canada, but the cases have been too few to provide con vincing evidence of the existence of an occu pational tumor hazard for asbestos workers in these countries. It must be remembered that working conditions tend to vary in dif ferent countries and at different times within a single country. For example, ventilation regulations for control of dust in asbestos work rooms were adopted in Great Britain in 1931. The number and severity of cases of asbestosis has decreased markedly since that time. In 1950, the Factory Inspector's Office had a record of only a single case of lung cancer among individuals whose employment in the asbestos industry in Great Britain had taken place wholly in the period since venti lation regulations were instituted. Immedia tely prior to the present conference, I visited the Senior Medical Inspector, Dr. E. R. A. Merewether, and learned that additional cases had subsequently occurred. These, as well as the earlier ones, will require careful analysis with reference to the population at risk. In a series of 126 cases of asbestosis re ported from Finland by Wegelius (16), the re were no instances of carcinoma. Work with asbestos in Finland has, however, been con ducted for a period of only 20 years. The British cases of asbestosis dying with carci noma of the lung had a mean exposure of 16.5 years compared with 13.4 years expo sure for asbestotics dying with no evidence of lung cancer, according to the Factory In spector's Report for 1947. The most advan ced cases of asbestosis in the Finnish series had an average exposure of only 11.5 years and there were only 9 individuals in this group. Furthermore, it must be noted that the British figures are based on autopsy re cords whereas the Finnish survey was based on radiographic examination of living per sons who were actively at work. I am unaware of observations for lung cancer in asbestos workers in countries other than the above where mining of asbestos or manufacturing of asbestos articles is carried out. Russia and Rhodesia are countries where such studies might be possible. It is noteworthy that our consideration of environmental factors in lung cancer has thus far taken up only inorganic compounds. This is unusual in that the great majority of oc cupational tumors of other tissues have been traced to organic compounds. Several types of exposures involving organic compounds notably tar and tarry materials, have been considered to present occupational respirato ry tract cancer hazards as reviewed by Hue- PER (4) who cites a Japanese paper listing 21 cases of lung cancer found over a period of 6 years in workers exposed to inhalation AN EVALUATION OF CLAIMS FOR OCCUPA7IC NAL FACTORS IN CANCER OF THE TONGS ol distillation products of coal tar in genera tor gas plants of steel mills. A greater than expected frequency of lung cancer was attri buted to gas worlcs stokers and coke oven chargers in Great Britain by the Ke.xxaways (17). Their paper presents an exten sive analysis bv occupational groups of all death certificates filed in the General Regis ter Office for cancer of the lung and larynx in males between 1921 and 1938. The population at risk in the various occupations, from which the expected number of deaths for each occupational group was calculated, was esti mated from census returns. Judged on this basis, there was a less than expected frequen cy of lung cancer among cotton sninners and piecers. This finding, as the Kennaways point out. is of unusual interest in that such persons are engaged in an industry that has for many years had a serious skin cancer problem from use of carcinogenic oils to lu bricate the spindles. Skin exposure in these textile mills has been attributed in part to spray of oil from the spindles, but I am una ware of anv measurements of the amounts of oil mist. The question has importance, for Huguenin has recently described a series of cases of lung cancer in metal workers in France and suggested a relationship to their exposure to mists of cutting oils (18). Quite recently, a new and previously unsus pected respiratory cancer hazard has been discovered and is about to l)e described in the A. .1/. A. Archircs of Industrial Hcpienc and Occupational Medicine by Weil. Smyth and .Vale. These authors have permitted me to present their experience to this conference. (Addendum : their paper has appeared in A. M. A. Arch. Indust. Hyp. and Occup. Med. 1952. 5. 535-547). Among 71 men employed 5 or more years in a unit for production of iso propyl alcohol, there have occurred 4 cases of nasal sinus cancer, one case of lung cancer, one case of laryngeal cancer and one papillo ma of a vocal cord. It would seem clear that an occupational factor must have operated to yield such a series of respiratory tract tu mors in this small group of men. Animal ex. periments have disclosed no carcinogenic ac tion on the part of the alcohol itself, but an increase over the expected number of pulmo nary adenomas was observed in a few groups of mice exposed to inhalations of isopropyl oil . This is a highly complex mixture of ma terials encountered as an intermediate in the course of production of the alcohol. The present paper has oeen concerned u ith evaluation of data derived from human ex perience. but investigations conducted unon animals have contributed to our knowledge and much additional information can be ex pected from them. I have elsewhere publis hed a review of experimental studies of lung cancer (19). To date, most experimentally induced lung tumors have been the pulmo nary adenomas of mice, which bear little re semblance to the majority of human lung can cers. Direct introduction of potent carcino gens into the lungs have generally elicited sarcomas rather than carcinomas. I should like to comment briefly upon a procedure we developed which has proved useful for experimental production of carci nomas from lung tissue. Lungs are removed from mouse embryos, cut fine, and implanted into the thigh muscles of adult animals of the same inbred line (the C strain, obtaina ble from Jackson Laboratory, Bar Harbor, Maine. U. S. A.). When such tissue is implan ted together with methylcholanthrene, benz pyrene or dibenzanthracene, the bronchial epithelium undergoes metaplasia and carcino mas of transitional cell or frankly squamous cell type develop. This method, the tissue transplant technique has been described in detail elsewhere (20), (21). Obviously, inha lation techniques are essential for adequate study of materials suspected to present inha lation hazards. These, however, require ela borate equipment. The tissue transplant tech nique is mentioned merely as an inexpensive and simple procedure that may serve as a use ful screening measure for test of substances suspected to play a role in lung cancer. In closing, it may be pertinent to emphasi ze a general concept that is evident from the foregoing attempts to evaluate claims for oc cupational factors in cancer, namelv that such studies require the integrated efforts, not on ly of physicians, but also of industrial hy gienists. statisticians and personnel familiar with the technologv of the various industrial operations involved. Further, the interest and cooperation of management and labor is nee ded for effective study and control of such hazards as mav exist. In an endeavor to bring together individuals from such diverse fields, the Cancer Prevention Committee was esta blished in 1948 for the purpose of studying environmental, particularly industrial fac tors. in cancer. The Proceedings of this com mittee were published in 1952 as the March 54 WILLIAM E. SMITH issue of the A. M. A. Archives of Industrial Hygiene and Occupational Medicine. It is conceivable that studies in this field may disclose occupational tumor hazards not presently recognized and thereby afford fur ther means for effective prevention of can cer. On the other hand, the widespread occur rence of cancer, and especially of lung cancer, makes evident that many cases of this disease would occur no matter what the occupation of its victims. Many such cases have no doubt been wrongly attributed to occupation. For scientific progress as well as for proper com pensation practice, the reporting of occasio nal cases with implication of occupational etiology must be replaced by sound statistical study of occupational group experience. Stu dies of inbred lines of mice have shown that genetically different strains living under nor mal conditions develope tumors of certain tissues with differing and predictable fre quencies. Exposure of such animals to carci nogens increases the frequency and time of appearance of the tumors for which they pos sess inherent potentialities. Evidence for increase in tumor frequency over and above that found in properly selected control popu lations is needed when claims for new occu pational factors in human cancer are conside red. DISCUSSION Dr. Morgan : I should like to say some thing more about the nickel risk. The process for manufacturing nickel carbonyl was first evolved in 1900. The first cancer cases occur red in 1923. Earlier records showed a num ber of cases of lung fibrosis but these have diminished since cancer has been occurring. The nickel ore comes from Canada to Swan sea. It contains very many other metals. It is first ground into a very fine powder and in the old process the dust was very profuse. The new type of calciner is nearly dust-freeas is also the present crushing and grinding process. Sulphuric acid is then added and un til 1923 this contained arsenic -- but it is now arsenic free. Other dust prevention measures were also instituted in 1924, i.e. the men wear gauze masks. Since then there have been no cases in men engaged since 1924 and only two or three new lung cases which would have been expected anyhow. The shortest period of work in dust among the cases seen is 1-1 1/2 years. The lag period is 18 to 25 years. The particle size of the dust is 1 to 10 pl. The ratio of lung to nose cases is 100 : 50. The nickel made at Swansea goes to other factories in London, Birmingham* and Glas gow, where precious metals are extracted, al loys made and so on. No unusual incidence has been seen in these factories. The condi tions seem, therefore, to be associated with the refining process at Swansea. All the cases have been in calciners and grinders. The pa thological type of lung cancers have been mixed. Dr. Levin : Do your findings support the hypothesis that arsenic is the cause ? Dr. Morgan : They could do. Dr. Doll : I have had the opportunity of seeing Dr. Morgan's figures and I think they show that there is a definite lung risk in ad dition to the nose risk. The incidence -- as far as one can tell -- is twenty times the expected incidence. With regard to arsenic I would mention a study made by Professor Bradford Hill of a small factory outside London, which has been handling arsenic for many years. A greatly increased proportion of deaths from cancer was found among people who had been em ployed there and was due to skin and lung cancer. With regard to chromates, I would strongly support Dr. Smith's remarks regarding the perils of relying on mass X-ray of present industrial populations. Dr. Bidstrup in her British survey found only one case in a chro mate factory. But she is now following up the employees and is finding some deaths and we begin to think that our experience may not be so different from Dr. Machle's. Our study of gasworkers was based on 831 deaths among pensioners who had been em ployed in a gasworks. There were 25 deaths from lung cancer against an expected 13.8. I think we can attach some significance to this result as the experience of our population of 831 was comparable with that of the gene ral population at similar ages for all other causes of death. Dr. Levin : Am I right in thinking that arsenic is not an experimental carcinogen ? Dr. Stewart : As far as I know it is not. AN EVALUATION OF CLAIMS FOR OCCUPATIONAL FACTORS IN CANCER OF THE LUNGS Dr. Firket : I have seen severai specimens of asbestos cancer of the lung in Professor Gough's laboratory in Cardiff. The lower lobe was always the one affected. Is this special localisation always found ? Dr. Smith : No, but I can give you no fi gures on distribution. Dr. Firket : The suggestion has been ma de that beryllium is cancel-producing. Profes sor Chevremont has done some tissue culture experiments which are very interesting biolo gically (*). Dilute berylliums will inhibit al kaline phosphates. It acted like an antimitotic poison -- as will many other poisons. But it is interesting that many of the cells in his tissue culture were not killed but recovered and became resting cells. Of course most car cinogenic poisons are anti-mitotic. Dr. Clemmesen : Has Dr. Smith got more detailed statistical information on the mate rial he presented ? For instance the minimum and maximum latent periods -- the age when tumours occurred etc. Dr. Smith : There is additional material on the chromate work in U.S. Public Health Ser vice report in 1948 by Machle and Gregorius. The asbestos cases have not yet been reported in detail except in a short posthumous paper by Gloyne in the Lanct 1951. Dr. Clemmesen : Would Dr. Morgan's material justify the precise definition of a latent period ? DR. Morgan : I have some difficultv in presenting details as the material comes from an industrial firm, but I hope to as soon as possible. Dr. Maisin : Could Dr. Denoix give some information on the French workers who used Bordeaux mixture in preparing their vi neyards ? Dr. Denoix : I have no information on this at present, but cannot give a negative answer. I will look into the question in S. and (*) M. Chevremont & H. Firket: Action du berylHum sur la croissance ct la mito^e culture fie tissue. Oompt. Rend. Assoc. Anatom.. .''3. 19 mars 1951. M. Chevremont & H. Firket : Etude histochimique de I'aetion du beryllium sur la mitose en culture de tissus (phosphatase alcaline et acides nuc16iques). Corapt. Rend. Soc. Bioi.r 145, juin 1951. p. 938. S. E. France where many people work in a fog of copper sulphate. REFERENCES 1. Lorenz, E. : Radioactivity and lung can cer : A critical review of lung cancer in the miners of Schneeberg and Joachimsthal. Joum. .Vat. Cancer Institute. 1944. 5. 1-15. 2. Annual Report of the Chief Inspector of Factories. 1950. pp. 145-146. H. M. Sta tionery Office, London. 3. Amor, A. J. : Growths of the Respiratory Tract. Dcricht iiber den VIII. Internationalcn Kongrcss fiir Vnfalimedizin und Berujskrankheiten. Frankfurt a. 1938, 941-962. G. Thieme. Leipzig. 4. Hueper. \Y. C. : Occupational Tumors and Allied Diseases. Chas. C. Thomas. Baltimore. V. S. A.. 1942. 896 pp. 5. LoKEN, A. C. : Lung carcinoma in nickel workers. Tidskr. Norske Laegefor.. 1950, 70, 376-378. 6. Neubauer. 0. : Arsenical Cancer : A Review. British Joum. Cancer. 1947. 1. 192-251. 7. Hill. A. B. and Faning, E. L. : Studies in the incidence of cancer in a factory handling inorganic compounds of arse nic. I. Mortality experience in the factory. British Joum. Industrial Medicine. 1948, 5. 1-6. 8. Perry. K. et al. : Studies in the inci dence of cancer in a factory handling inortranic comnounds of arsenic. II. Clinical and environmental investiga tions. British Joum. Industrial Medicine. 1948, .J. 6-15. 9. Snegireff, L. and Lombard, 0. : Arse nic and Cancer. A. M. A. Arch. Indust. Hyg. & Occup. Med. 1951, 4, 199-205. 10. Hueper. W. C. : Environmental lung cancer. Industrial Medicine and Surge ry. 1951. 20. 49-62. 11. SUGIURA. K. : (in discussion of paDer by E. L. Wynder. A. M. A. Arch. Indust. Hva. & Occup. Med. 1952. J, refer to p. 227). 12. Machle. W. and Gregorius, F. : Can cer of the respiratory system in the Uni- -lt> .YTLLl-- ; SMITH red Stares chromate-producm-,: :inius:. C. S. Public Health Reports. l'.)4S. 1114-1127. 13. Bidstrup. P. L. : Carcinoma or the It::'.; in chromate workers. British -fount. .' dustr. Med. 1951. 6. 302-305. 14. Annual Report of the Chief Inspector Factories. 1947, pp. 79-81. H. M. Strr nery Office. London. 15. Smith. \V. E. : Survey of some cuit::.: British and European studies of occir.v.tional tumor problems. .4. M. A. .1,<Indust. Hug. A Ocnto. Medicine. IP".. .'. refer to pp. 249-254 and 262-2G3. 16. Wegelius. C. : Changes in the lungs `. 123 cases of asbestosis observed in Fin land. .4cfn Radiologiea. 1947. 2,s'. 139-152. 17. Kennaway, E. and Kenn'away. X. : A further study of the incidence of cancer of the lung and larynx. British Jour.:. Cancer. 1947. 1. 2G0-2C8. 18. Huguenin, R., Fauvet. J. and MazaBRAND, M. : Role eventuel des nebulisations d'huiles industrielles dans la pathogenie des cancers broncho-pulmonaires. .4rc/i. mal. profess. 1950. 2, 4S-51. 19. Smith, W. E. : Lung cancer with specir.i reference to experimental aspects. .4. .1/. A. Arch. Indust. Hyg. & Oecup. Med. 1952. 5. 209-217. 20. Smith, \V. E. : The tissue transplant tech nic as a means of testing materials for carcinogenic action. Cancer Research. 1949. .9. 712-723. 21. Smith, W. E. : The neoplastic potentiali ties of mouse embryo tissues. V. The tu mors elicited with methylcholanthrene from pulmonary epithelium. Joum. Exper. Med. 1950, 91. 87-104. ZrSAM.MKXFASSCXd l>in Karzinoinp dor Atemweec warden mir incur "dor uemecr plnnsihlcr Artrumenratinn den vcr-rhiiden-ten lientrlichen Kinfliissen zutreschrielicn. In An- hefrnchr dcr Yerschiedenhcircn dcr Tmlit-rri<*n. w-c mien dcr Matenalien und der Ycrarlteitiimr-nieihniie' ill den vpisclncdcnrn hiindprn -ollrcn dip niirtrcwor- tpiipn Pinnleme in trewissen bcvorzu<rtcn dci-endcr srudipn werden und e- wine wuuschcnswerT dip F.rialirmisren dpr verschiedenen Geirrndcn ztt verrrlpiehen. Per KernI-krebs diT I.MiurPii I>< I Mineuiin 'lid in den deur-plicii uml hiilnnischcn (rammnin up!"'-.- dun. 1 Mi- Autmcrksamkcit wird mil dip Anmndmic mlpr Verhiituntr lilmlirlior Karzinome I>pi Minpurpn "dpr nndei-pti Arhettern mir rndiiiakrivpii .-rutten mi iiii'ipii i ii reii inuzp'i nu;. f'ii- I rmip. -m." , inr-bedmrric Km.mill'll '"ii m-i iiiimiiz'pii pin Kiirzinmiip or Alemueirc 'ii'iir-;ni!i "iiurpii. mu-- " 1'irpi'iiiii mi'z'ekiaiT ppntpti. *u -- ' "I'kommni--c in C..-.A. mid m >p|i"piipn :.p::u p-riminrp Aiii-ehlii--e in dip'i-r Kielumur -.... .. vdiiiPM. Man liar le-rrrc-rellr. da-.- unipr .ii-n A-in "in von Xickeirn t r incneii in dr.o--hrirnmiicti Kur "iiip dp- l!c-pirnrinii-rrnkrc- al- Berur-krankhii' :r: reten. nipiir alter in Kaitada. Ill < Ini-.-britanmeu :- :p pIipiitails dip A-bc-rosi- nut Lunscnknmttom .'.ii-aninipiiiiam; itcbraciit. -misr alipr nii'irpnd.-"". l.r.r. .'piikaizininii tiar al- KiTtu.-kranklipir mir Iipi i rheircrn in I)i ur-< 11i:111d mid ill I ..'-.A., iin-lii mu' n urn-brirnnmeii. K- i-t -pin' wnn-cucn-upiT "pu.ii l iitpr-iipliitii'Ti'ti fiber dip-p 1'rolilpinp miznsipllpii nr pr In--oinicrpr llpriipk-ipliricuiicr dpr \ er.-chipilenhi' pii in dim Ailipit-cmiepii und in dpi- iinnlitmiwm u:v iiianrirarivon Kxpn-irinii in vpr-pliipdpiipii iii-jri'iii!:: In niplfPiPii l.iitidcrn warden Tecrdiintpic ;iir : Luuienkarzinomc vcrnntwortlich rremneht. In Anhe- 'rnelir dpr lM`kniintPii karzinorrenen Fiireii-ehaiipn ire wis-cr Teenlcrivare soilte allps scum werden mil -" .'up Tumoren aufzurinden und zu verhiiteu iilterni. dart, wo eiirsprechende Fxposirinncn vorkomnieit X'cuerdiirrs wurde in C.S.A. Iipliauprpr. da.-- Itct dvr ircrsfellmi!r von Isopropylnlkohol Karzinuiiip dpr l.ufrwerre pnr-tplipn kiimipii. SUMMAKY Cancers of thp rp-piraforv trncf liavp. ivith varvine desrpps of plansiliility, Iippii iinritiutrd to a varipiv of occupational factors. Since the rypps of industrial operations us well as the materials and methods em ployed vary in distribution niiinni various count rie-. the several problems involved present certain prefer red areas for study and in -nme instance- inert! comparison of experience ill different areas. Occupational lumr cancer ammi; miners has lints far lieen restricted to the Herman and Itiihemian uranium mines. Attention is required for the deter non or prevention of similar cancer amon'' miners m other workers with radioactive materials elsewhere. The question of whether inhalation of arsenical dusts presents an occupational liasard of respirators tract cancer requires further study. Certain -itualionin the I'nited States and in Sweden arc'indicated aaffordinT approaches to this problem. Cancers of the respiratory tract have been tniinii 'o occur on an occupational ba-is utnonsr nickel reii uery workers in drear l'.ntain. but im -uch hazard lialicen evident in t'anada. A-lMisto-is has been a-socia red with limtr paticer m drear Hritain. hut no -ucii association has lns>n manifest elsewhere. Lunar cancel has appeared as an oeeupnrional hazard for chroitiaip vorkers in dermnny and the I'nited .'-late- lint tint n dreat Kritain. Further -rudic- ol tlte-e problem' un desirable with special lplcrence to differences in ope rations and to qualitative and quantitative differencein extiosiire m the various areas. AN EVALUATION OF CLAIMS FOR OCCUPATIONAL FACTORS IN CANCER OF THE LUNGS ( V>al tar Mime- have been associated with lunar can cer m several countries. In view ot the known car cinogenicity ot certain coal tar tractions, close atten tion should he given to detection and prevention oi such tumors >11 anv localities where such exposures may occur. Production ot isopropyl alcohol has recently been claimed to involve a respiratory traet earner hazard in the I'nited States. RESUMEX Los eaneeres de las vias respiratorias hnn sido asoeiados. por rnzones mas o mesnos justificadns. a diferentes npos de agenres iirot'esionales. Dado quo Ins tipos tie operactones industriales, y que las matcrias primns y los metodos empleados varian do tin puis a otro sera preterible estudiar los diferentes problemas en ciertas regiones y. on determmadas cirennstaneias. serii nltil eomparar los resnltados ohtenidos en las diferentes regiones. El cancer profesional del pulmon se encuentra unicamente en las minas de nranio de Boliemia y de Alemania. Hay que llamar la atencion sobre el ilcseubrimiento y la preveneidn de estc tipo de cancer en los obreros que utiliznn otras substancias radioactivas en otros lugares. Son indispensables juevos estudios para determinar si el pdlvo de arsenico constituve un peligro profesional eapaz de barer npareeer eaneeres de vias respiratorias. Se ban observado eaneeres de vias respiratorias en los obreros de las refinerias de niquel en Inglaterra. Este fendmonos no ha sido observado nunca en el Canada. En Inglaterra se ha asociado la asbestosis al cancer de pulmon pero esta sociacidn na se ha comprobado on ninguna otra parte. El cancer de pulmon se seiiala eomo un peligro profesional en los obreros de la industria del eromo en Alemania v en los Estados I'nidos pero no en Inglaterra. Son indispensables otros estudios para elucidar cstos problemas. Seria preeiso insistir. sobre todo, en el analisis de las diferencias cualitativas v cuantitativas en los proeedimientos v las diferencias en el tiempo de exposieion al agente toxico en las distintas regiones. Los vapores de alquitran se ban considerado como responsables de la apairiedn del cancer pulmonar en diversos paises. Teniendo en euenta esta accion cancerigena de dcrerminadas fracciones del alquitran se deberia dedi ear 1111a gran atencion al desoubrimiento y la preveneidn de c-tos tumores en los litgares en que es posihlc tal exposieion. Reeientemente se ha pretendido en los Estados I'nidos que la produoeion de alcohol isopropilico eonstituiria un peligro para las vias respiratorias en p1 terreno del cancer. RESUME Les cancers des voies respiratoires ont. pour dcs raisons plus ou moins plausibles. etc assoeiees a dif ferent types d'agents professionnels. Etant donne que les type.- d'opcrntioiis indtistriellcs. que a- maticres premieres et les merhodes employee- lancir <l'un pays ii 1'aurre. il serair preferable d'emdier lrdifferents problemes dans eertaines regions c' danlertaine oireoustanees. il -emir utile de eompurer K-- resultats obtenus duns ditlcmitcs regions. Le cancer proiessiounei dll pom.ton iiiiroinrc uniquemeut dans les mines d'uninium de Hohcinr el d'Allemagne. Il taut attirer ('attention -ur le depistage et la prevention d'un pareil cancer chez les 011vriers utilisant d'autres substances railio-ncrives dans d'autres endroits. Do nouvelles etudes sont indispensables pour determiner si les poussieres d'arsenic constituent un danger profcssionnel capable de taire apparaitre des eanccrs des voies respirarmre-. Aux Etats I'nis ct en Suede, certains cas 1'imposenr eomme apportant des vues nouvelles sur ee problem)-. On a observe des cancers des voies respirarmre? ebe7. les ouvriers des ratfincries de nickel cu ilrande-Bretagne. Jamais ee phenomena nil eie mis en evidence au Canada. On a assoeie en Angleterre. I'asbesto-e au cancer du poumon. mais ccttc association lie se revele nullc part aillettrs. Le eaneer du poumon est signale eomme un danger professioiinel chez les ouvriers de l'industrie du chrome en Allemagne et mix Etats Cnis mais pas en Angleterre. D'autres etudes sont indispensables pour clucidcr ees problemes. Il faudrait s'attacher specialenicnt a 1'analvse des differences qualitatives et quantitatives dans les precedes et les differences dans le temps d'exposition a l'agent toxique dans les ditferentes re gions. Les fumces du gowiron ont etc rendues rcsponsables de 1'appnrition du cancer du poumon dans divers pays. Tenant eompte de cctte action cancerigetie de eer taines fractions du goudron. on devrait porter grande attention pour la detection et la prevention de ces tumeurs dans les endroits oil line pareillc exposition est possible. Recemmenf on a pretendu. aux Etats Unis, que la production de Talcool isopropvle eonstituerait un danger du point de vue cancer pour les voies respiratoires. RI ASSUNTO I cancri delle vie respiratorie. per ragioni piii o meno plausihili. sono stati attribniti alle piii svariate cause professional!. Poiche le attivita industriali. co me pure i materiali lavorati ed i metodi impiegati variano in distribuziom* a seconda dei paesi. i diversi problemi eonnessi mosrrauo logicamente nree preferenziali di studio ed. in alcuni casi. meritnno lino studio comparative delle diverse esperienze a seconda delle differenti regioni. Il cancro professionnie del polmone e state fino ail ora eircoscritto alle miniere di uranio della Germania e della Boemia. E' percib necessario inettere in rilievo questa coincidenza onde prevenire inI allontanare I'insorgcnza di un eancre del genere negli operai ebe lavorano materiali radioattivi in nitre regioni. Ulteriori studi sono oggi indispensabili onde aceertare se la polvere di arsenico eostituisea un seno 58 'VTLUAM E. SMITH IMTicolo proiessionale. tale tin uvonre I'lasorzeuza lei rancro del polmone. Sesrli C.s.A. si m Svezia si sono verificati cast tali da suesenre nuove !nf su questo problema. Sono stnti osservatt canon .Vile vie respiratorie fra gli operai delle rarrinene di nickel in (Iran Bretagna. Tale evemenza non si e roru r.-nin- frata nel Canada. In Iughelterra 1'asbestosj e 'tata messa in rapporto con 1 msoreroza del caneto del polmone, ma tale assoctazione non e stata mu- nscontrata altrove. II cancro del polmone d'altra pane none seenalato come un rischio professional need operai deirinilnstria del cromo sia negli Stati t'niri die in Germania, ma non in Inghilterra. Ultenori studi si irapongono in proposito con particoiare rieuardo alia analisi detle differenze qualitative e quantitative sul tipo di industria e sul tempo di esposizione all'aeente rossico nei diversi paesi. Le esalaztom del fumo del catrarae sono ritenute responsabili deil'insoreenza del cancro del i'.iinioue in dirers; 7. i-onio .... ..a a/.ionc cauceneetia di detemur.sre : "r-voiti del . Jininic, e mdispensabile a.iotrare contn'i.o aivuraus- strap onde mettere tr. . .. oreicnire oucstt in ruon nelle zone i:; .l't->vsts:.-.;one ana ert. ii/.ionc e pui facile a wmicars:. Attermazione reeer.io r.ec.i l ..'.A. c .in. :ia die la proiluzione dell'aloooi .soptvt'u.eo pos.Ni mstituirr nn notevole pencolo dal :'.:nro d: ' ism della .nsonnwa del eancro delle \ie respiratorie. It nous a tie ihi iiossr. or xatc tie ' 'ri nn.t/iinrrs >ndeptndantes de <u.;rt r.u.mtr. ile fairr "purer In totality des tr<uini`tuw< oVs fl. -w/nes. A oits /c reprethms .; h.ih. ... txcusotis rrtarnl. La 5Vdavtiun.