Document zoeg1G6YOjNKmQovK71KXGNk0

FILE NAME: Owens Illinois Library (OWL) DATE: 1951 Feb DOC#: OWL048 DOCUMENT DESCRIPTION: Journal Article - Environmental Lung Cancer Environmental Lung Cancer W. C^HUEPER, M.O. Cencerigenie Studies Section Netionei Cencer Institute Betkesda, Maryland Cancer of the respiratory tract had a rela tively minor role in the cancer problem before the turn of the century but has become of major importance because of the rapid rise . in the frequency of these tumors during the : lost three to four decades (Simons; Schinz; J,': Mason; Kennaway; Heady and Kennaway; Gemmesen and Busk; Dorn; Herbut and Clerf; Steiner;.* In fact, in a few areas death from cancer of the lung threatens to displace cancer '^of the stomach as the most frequent cause of ^ a t h from cancer in males. Many investigators lasider the recent increase in the frequency of dung cancer as purely apparent, attributable to the marked shift in age distribution of the popu lation, to improvements in diagnostic methods, to greater interest of the medical profession in cancers of the lung, and to a change in the ratio of lung cancers to all cancers because of a re duction of deaths from cancers of other organs. However, this concept is not shared by some investigators, who feel that at least a part of the increased frequency of lung cancers is due to an alteration in the environmental cancerigenic spectrum, starting some 75 years ago. related to new occupational hazards and newly acquired habits (H&lperti. Although critical review of the available evidence does not permit a definite conclusion concerning the general question as to the real or apparent nature of the rise iu lung cancers, it provides much cir cumstantial and conclusive evidence regarding the role which environmental cancerigenic agents apparently play in the causation of these tumors. Grcumstantial Evidence XTUMEUCAL Increase of Lung Cancers: With out doubt the rapid prolongation of the ? average life sp an h a s brought in re c e n t decades 'many more,,persons into the,age group in which <v f O t R t 'p n 'i rrfrM M ir v idcMiAvd in i d f U i ld ta d ' x S - t M b l i o v n w h y of w hich i cony m ay bn obtain! by w ntinc hint at C*nn**m < S ilw ii C an ctf Control hrnet. U.S. TSrirl* Rmith Sorvlr. Notional Inotitulo Remit h, B cth e sd a 14 M a ry la n d . lung cancer occurs most often. Since approxi mately 77% of all lung cancers occur during the ages of 40 to 69 years (Matz), the rise of this age fraction of the population from 18.9% in 1375, to 21.6% in 1900 and-29.9% in 1940 (Sixteenth Census, U.S., 1940), was bound to be reflected in a corresponding increase in the number of lung cancers during the last four decades. However, Dorn as well aa Potter, found in their recent statistical analysis of can cer deaths in the United States that there had occurred a consistent rise in the frequency of lung cancer deaths after eliminating the effect of changes in the age composition. Potter stated that this annual increase amounted to 5.8% for males and to 2.1 % for females during the years 1938 to 1944. According to Dorn's calculations on this point, the annual percentage increase was 10.5% for males and 8% for females be tween 1914 and 1931, and 8.5% for males and 2.5% for females between 1931 and 1940. Since almost all lung cancers are fatal, mortality rates and morbidity rates are practically identical. In view of the observation of this increase in the autopsy material of many large European hospitals which had for many decades an econo mically rather stable patient population, a con sistently high autopsy rate and a competent pathological service, there is little reason to at tribute an appreciable portion of this develop ment to improvement in medical service and recording. The consistency and increment of the trend, moreover, would not support such an ex planation. It was noted, on the other hand, that the time of onset and degree of the lung cancer rise varied considerably in different countries (Ca- solo), and in different parts of the same coun try (Fischer i. This observation seems to ex c lu d e the p o s s ib ility that ra c ia l and h e r e d ita r y factors played an important role. The available statistical* evidence suggests, therefore, that any real increase in the frequency of lung cancers if such has occurred, may most likely be ascribed to the action of exogenous factors which en- r. >1 K **t +*\ u:`; l'4i;VV) , ;! l iT^MTirarnnn Page SO INDUSTRIAL MEDICINE and SURGERY February. 9S1 tered the human environment during the last ated type, and 18% adenocarcinomatous type; half century. This conclusion receives some females: 11%, 37%, and 52% respectively. support from the fact that the majority' of While Hollingsworth recorded a similar sex dis more recently discovered environmental cancerigens cause cancers of the respiratory tract, while those previously established mainly af tribution of adenocarcinomas. Mason noted that adenocarcinomas were present in this series in 6.7% of the male cases and in 13.7% of the fe fected the akin. male cases. Lingskog, on the other hand, reported that adenocarcinomas occurred with equal CSX DISTBIBUT10N: There is general agreement that lung cancers are more frequently pres ent in males than females. Since the consider frequency in both sexes, and that all adeno carcinomas observed were present in individuals below the age of 40. able rise in the occurrence of lung cancers dur A similar dependence of adenocarcinoma on ing the past four decades has been accompanied the age of the individual was noted in the pro by a definite shift in the sex distribution of the ceedings of the First National Cancer Confer lung cancer in favor of the male ?ex, the in ence. The proportion of adenocarcinoma dropped crease in lung cancer incidence seems to depend from 30% in the age group 0-49 years, to less on agents to which males become exposed more than 20% in the age group 60 years and over. often or more intensely than females and which There was a corresponding rise in the propor are essentially unrelated to endogenous, sex con tion of epidermoid carcinomas, while the un ditioned factors. differentiated type of cancer seemed to be un This conclusion is supported by the fact that affected by the age factor. Gebauer reported the male-female sex ratio of lung cancer ex that adenocarcinomas, originate in 90% from the hibits remarkable local differences varying be secondary and small bronchial branches, while tween 2:1 in Sweden (Henschen) to 20:1 in the majority of the undifferentiated and epider parts of the United States (O'Keefe), while moid cancers develop from the main bronchial averaging most often 5:1 to 10:1 (Fulton: 7.3:1 branches. in 1610 cases). Clemmesen reported from Den The proportion of the various histologic types mark that a shift in the male-female sex ratio of bronchiogenic carcinomas thus appears to dif has occurred there during recent years, after fer according to sex and age as well as to their having stood at 5:4 in 1931, it changed to 3:1 topography in the bronchial system. Their rela in 1945 and is expected to become stabilized at tive sex distribution moreover seems to vary a ratio of S:1 in the near future. .with different investigators and thus with dif An exogenous origin of the sex differential ferent areas studied. Again, it is not conceivable of lung cancer is suggested Tnoreover by ob that such variations in the biologic and anatomic servations made in connection with occupational manifestations of lung cancers are due to endo cancers of the respiratory tract. Merewether genous causes, while they would find a rather found that the male-female ratio of asbestoais ready explanation in differences of exposure to cancer stands at 2.4 to 1. This ratio illustrates exogenous agents of various types (Lindskog). the trend toward an equalization of incidence rates of cancer for the two sexes whenever X? acial Distribution: Although neither Jaffe the conditions of exposure to an environmental nor Steiner observed any significant differ cancerigen tend to become identical. Highly ex ences in the distribution of lung cancers be cessive incidence rates of lung or nasal sinus tween whites and Negroes in the Chicago area, cancers among males, on the other hand, exist other investigators noted that pulmonary can whenever for occupational reasons contact with cers are more frequent in whites than in Ne exogenous cancerigens is restricted to members groes (Arkin and Wagner; Quick and Brindley: of the male sex, such as workers in chromate Haipert). Likewise, Khanolkar, reporting on the factories, in radioactive mines, and in copper- organ distribution of 3.263 cancers of a Bombay nickel ore refineries. hospital, does not mention lung cancer among the eight types of cancers listed that account U istolouical Types: Sex an d Age Distribu- for 2,652 cancers evaluated. However, until A tion: Probst stated that, in recent years, proper standardization as to age and sex has there has been a shift toward a more frequent been made, these observations convey no valid occurrence of epidermoid cancers in pulmonary information as to differences in racial suscepti malignancies of unknown etiology. This ob bility or special types of exposure to exogenous servation may be related to the proportionally cancerigenic agents, coinciding with regions greater increase of lung cancers among .males populated by different races. than fem ales, b ecau se sq u am o u s cell cancers and The various kinds of circumstantial evidence ~- round cell cancecs^predominate in males, while evaluated~support the concept that environmen adenocarcinomas are more frequent in females tal factors are involved in the production of tProe. First Sat. Cancer Conf.). The sex dis cancers of the respiratory tract, especially the tribution of the various histologic types of lung lung (Boycott). While the actual extent to cancers according to this source, is as follows: which exogenous agents seem to be active in Males: 44% epidermoid type. 38% undifferenti- the production of these tumors among the gen- YOU.20, No. 2 INDUSTRIAL MEDICINE AND SURGERY Page 51 )r*i population, and the nature of such agents 'cannot be deduced from the information avail* " able, observations made in the field of occupa tional cancerigenesis permit a more definite and specific, although also more limited view of these aspects of environmental cancers of the respiratory organs. Conclusive Evidence D elation of Lung Cancer to Large Occupa- AV tional Groups and Non-specific Irritative Chemical Agents: The remarkable increase in the number of lung cancers observed during recent decades induced many investigators to search for possible environmental causes for this development. In considering the various possi- Rg. I. bilities Kennaway and Kennaway argued that Atypical papiliomatou* pitheliei growth in lung with the higher mortality from cancer of the lungs chrome pnoomonio such u soon ofior ospoturo to il. in towns noted by Stocks, the low mortality in irritative chemicals. agricultural occupations and the absence of a nacemen (Fulton); machinists, foundry work social gradient recorded by Stevenson were com ers, metal grinders (Turner and Grace); metal patible with an etiological factor in the air such workers, spinners, cigar makers (Borstl ex as coal smoke. Stephens claimed some years hibit an excessive liability to cancer of the previously that the pollution of the air by carbon lung. monoxide from incomplete combustion of coal From information to be given later in con and gasoline represented a major cancerigenic nection with the discussion of recognized can factor. Oldofredi recently revived this conten cerigenic agents it is apparent that an apprecia tion and pointed to the high incidence of lung ble part of the membership of the various occu '-v cancer among former members of submarine pational groups mentioned, may become exposed | crews of World War I, when it was exceedingly to one of th^. known specific environmental can- / difficult to control adequately the carbon mon cerigens (mist of lubricating oils, soot, dust oxide content of the air. Campbell's experiments from or pigments of various cancerigenic metals on mice exposed to carbon monoxide, however, (chromium, nickel, arsenic). It is thus possible failed to show any increased incidence of pul or probable that in these instances statistical monary malignancies. Green was inclined to at epidemiologic data reflect real causal relations. tach a similar significance to the pollution of the There are, finally, many students of this sub air with sulfur dioxide from the burning of ject who could not find any relation between sulfur-containing coal and the smelting-of vari special occupations and lung cancer formation ous ores. (Brockbank; Kennaway and Kennaway; Siram- Other investigators felt that members of out rose; Shennan; Rogers; Rice; Husted and Bill- door occupations carrying the hazards of dust man; Jaff; Bonser; Haintz; and others). How and fume inhalation, especially dust from tarred ever. the occupational data on which such state roads and exhaust fumes from gasoline engines, ments are based are, as a rule, too inadequate were especially likely to develop cancer of the as to specific type and duration of employment respiratory 'tract (McCrae, Funk and Jackson: and occupational period, which are important be Matz; Schchter; Duguid; Ferenczy and Ma- cause of the long preparatory and latent period tolczy; Hutchison). This concept, however, was of lung cancer to be of any definite value. disputed by others, who pointed out that in A similar conclusion applies to the claims some regions (Riga) an increase in lung cancer made concerning the etiologic connection be was observed before any tarred roads were used tween the inhalation of various irritative gases, (Konrad and Franke; Kennaway and Kenna fumes, mists and dusts of various acids and way; Guglielminettia). Knox and Probst pointed alkalis (sulfuric acid, hydrochloric acid, nitric out that not the quantity but the quality of dust acid, ammonia, war gases, formaldehyde and was important in lung cancerigenesis. A few cancers of the respiratory tract Fig. 1). While investigators stated that lung cancer was more isolated cases of respiratory cancer are bound frequent among the laboring class than among to occur in occupational groups coming in con professions (Brockbank; Weller). There is tact with such agents, the existing epidemio some evidence indicating that lung cancer is logic evidence does not lend any valid support more frequent among the population of indus to a generalization from the observation of a trial areas than among that of rural districts few cases Koelsch >.' However, it is worth iFulton: Gerbe. Several large statistical analy ses tended to show that some occupations 'en gineers, mechanics, painters, decorators (Brit. noting that at least one of the acids men tioned. sulfuric acid, is often contaminated with appreciable amounts of arsenic. This impurity Emp. Cancer Campaign ); painters and fur- in commercial sulfuric acid has been blamed by iMrtattBH Page S INDUSTRIAL MEDICINE and SURGERY February, l'j. R . 2 *sd 3. Atypical p HImIm profifacstiom in fibrati bitumino* lung. i*ol*ig lining of gUnAiik* formation. Amor for the occurrence of lung and nasal can cers among nickel, refinery workers. In view of the absence of reliable epidemiologic studies it is desirable that thorough surveys of operations showing respiratory hazards of the above type be made so as to obtain adequate information on the incidence rate of respiratory cancer among workers exposed to the inhalation of finely dispersed acids, alkalies, and other irri tative inorganic and organic chemicals, such as, especially, beryllium and its various com pounds, formaldehyde, glycols, isopropyl com pounds, carbamate derivatives, organic solvents, phosphors, alloys, paints, insecticide sprays, weed killers, rubber accelerators, and polishes. There can be little doubt from the evidence presented that data obtained by an evaluation of large occupational groups with varying types and degrees of exposure to irritative agents of non-specific nature yield little definite infor mation concerning a causal relation between occupational activity and cancer of the respira tory tract. Great progress, however, has been made in elucidating such connections whenever epidemiologic investigations were limited to circumscribed groups of workers and popula tions either exposed to chemical agents of more or leas well defined kind or to identical or simi lar occupational or environmental conditions. O&CANIC chemicals: The inhalation of coal ^ dust is in general not credited with being inducive to cancer of the lung, since statistical studies conducted in coal miners were negative in this respect (Feil; Jordan; Kennaway and Kennaway; Gerbe; Schulte), and mice and guinea pigs exposed to coal dust did not de velop lung cancers (Campbell; Vorwald and Karr). This innocuousnetw, however, does not extend to the distillation and fractionation produets of coal, oil shale, and petroleum (tar, asphalt, pitch, oil) and their incomplete combustion products, such as domestic, industrial and com mercial soots (lamp blacks, carbon blacks, oil blacks, etc.). (a) Soot, Tarry Material Produced by th Incomplete Combustion of Carbonaceous Matte (Coal, Mineral Oil, Natural Gas, Gasoline. Die sei Fuel) (Domestic, Industrial and Commercia Soots) : While the cancerigenic action of soo resulting from the incomplete combustion of eoa upon the skin is well recognized and best demon strated by the chimney sweep's cancer of th* scrotum, the causal relation between the inhala tion of atmospheric soot from domestic and in dustrial sources and lung cancer among the gen eral and industrially employed population .much less definite (Dorn). In fact, cancer ot the lung is not unusually frequent among chim ney sweeps (Kennaway and Kennaway). Al though Schnurer reported that the incidence oi lung cancer in a series of 342 necropsies of the Pittsburgh district increased directly with the degree of bituminosis (Figs. 2 and 3) Doni found in his statistical studies that the lung cancer rate was low in Pittsburgh when com pared with that of five other large cities. Ex-, perimental studies conducted by Schnurer and Haythorne, and Seelig and Benignus, with the inhalation of smoke from an eggstove or of soot from a hospital flue used as bedding for mice, respectively, were equally inconclusive or un convincing. On the other hand, there can be little doubt that the soot contained in the air of Pittsburgh and other cities is carcinogenic to mice, since Leiter, Shimkin and Shear and Leiter and Shear could elicit skin cancers in those animals with an extract of soot collected at various localities in the United States. Passey and Carter-Braine found the fraction of house hold soat boiling over above 25Q'C most active in this respect. The question of the possible canceri genie ac tion fro m the inhalation o f various types of commercial soots prepared from natural gas or oil residues and merchandised as lamp black, oil black, furnace black, gas black, or channel black, has become important in recent years be cause of the huge production and consumption of these blacks in the rubber industry and for paint and ink manufacture, in the making nf v SOL. 20, NO. 2 INDUSTRIAL MEDICINE and SURGERY Page 5J $ records and because of their use as coloring - matter. Some of these blacks have been prepared in late rears by the incomplete combustion of oil yresidues that are obtained from the catalytic ^cracking process and that possess distinct can- pAcerigenic properties to mice. In addition to the possible lung cancer hazard involving the pro- >4>ducer*. loaders, shippers, and industrial con sumers of such carbon blacks, there may exist a similar hazard for the general population Uv- %, ing in the neighborhood of carbon black plants, '-y because during the production of these materials large amounts of soot may be released into the -v air. A similar environmental cancer hazard may perhaps result from the burning of oil dumps ear refineries giving rise to considerable amounts of soot. Little experimental work ^jo far has been done in studying the potential csncerigenic properties of the various commer cial soots which, depending upon the production ^process and raw material used, differ apprc- `rciably in chemical and physical respects and especially in tar content (Mantell). Steinbrueck reported the experimental pro- 'r tfuction of skin cancers in mice painted with ,,-black of printing ink. Seeiig and Benignus, on .the other hand, failed to see any lung cancers in mice exposed to the inhalation of lamp black. ^ Experiments of Miescher and Schwarz, using an ^.ointm ent containing a benzene extract of oil "" burner soot applied to the skins of mice, were siTequally negative. Since the carbon black indus- v1try is supporting experimental investigations on `the potential pulmonary cancer hazard connected "with the inhalation of various carbon blacks, more definite information may soon become 'available. f%t:''s-i(mbi>larDdieesgerleeanodf Gasoline Engine Exhaust: A uncertainty exists in regard to the potential cancerigenic properties of the ^ normal and abnormal exhaust products of low `' compression internal combustion gasoline en- vr ginea and of high compression' Diesel engines put connection with the development of occupa- SCK" tiooal and environmental respiratory cancers %[ (Lorentz; Heilmann; Duguid; Ferenszy and Matolcsy. The contention that the inhalation of exhaust fumes from gasoline and Diesel en gines and thus the increased automobile traffic, ,,...-- causally related to the rise in the incidence lung cancers in recent decades has been at- *" tacked on various grounds. It was pointed out that the exhaust fumes k these engines when operating perfectly and "^thereby generating products of complete com- .bastion contain little or no ingredients of po- `^Jtwtiai cancerigenic qualities (Bloch and Wid- mer; Probst). Mention, moreover, was made vf the fact that there does not exist a-parallelism ^between the rise in automobile traffic in differ- countries and the increase in lung cancer ^(L e h m an n ; Konrad and Franck; Syreck), and i^ihat occupations particularly exposed to engine ^exhausts, such as policemen, street _cleaners, garage mechanics, and automobile drivers, do not show an excessive incidence of lung cancer i Passey and Holmes; Probst; Katz; Brandt). Experimental attempts to produce cancer of the skin or of the lung by exposing mice to exhaust gases or to extracts from the fumes of such engines gave negative results (Campbell; Smith; Schmidtmann; Twort and Twort) in the hands of most investigators, although Pessano reported the development of metastasizing can cers of the lungs in rats following prolonged and intense exposure to combustion products of fuel oils. In evaluating the experimental evidence it may be well to note that the products of exhaust of a well functioning gasoline or Diesel engine differ doubtlessly in many respects from those of an engine with imperfect performance, which generates considerable amounts of soot and other matters of incomplete combustion at high temperature. Since engines with defective com bustion are rather frequently met, future at tention should be focused on the potential cancerigenic properties of exhaust fumes emitted from imperfectly operating gasoline and Diesel motors, before definite conclusions as to the existence of an environmental and occupational lung cancer hazard from this source can be reached. (c) Tar Dust and Fumes: The existence of an environmental lung cancer hazard from the inhalation of dust, mist and fumes of tar and tar oils generated during the construction and use of tarred roads has been a matter of con siderable speculation, since such a hazard, if present, would be of great practical importance (Brandt: Kling, Samssnnov and Heros, and others). However, this concept finds little sup port from the epidemiologic studies of Lehmann; Husted and Billmann: Fischer, and Kennaway and Kennaway. There was no consistent rela tion between the lung cancer frequency and the extent of tarred roads in different countries, nor was there any excessive lung cancer in cidence among workers especially exposed to the inhalation of tar dust and fumes in several countries (Hugounenq; Husted and Billmann; MQllschitzky). More recent observations, however, indicate, that the inhalation of hot tar fumes, such as those encountered in the operation of gas gen erators in connection with the production of illuminating gas and coke, is associated with an increased liability to'lung cancer. It was shown that retort workers seem to be especially subject to pulmonary malignancy (Kuroda and Kawa- hata: Kawahata; Sunderland). According to Japanese experience the gases emitted from the stoking holes contain 0.7% tarry matter. With in a six-year period there came to observation 21 cases of lung cancer among a total of 100 workers employed for more than 10 yearer* In 14 of the 21 cases the age of the patients was from 35 to 45 years, thus showing a definite .$4ij1l it "jin rt m I I ss frjff 0S5 m ' -if t y % *y-> $ ki v.;(L\ K 'i 'M i u t . ' H '*!?*' ; t-3 tv; " il* --. r* t i- 'iV , f3` .-I J ?*-' ! I 'V .P- t ! 4: *1, ir* y - 1- i ?-tv! S` . <r y -.. tuli Page Si INDUSTRIAL MEDICINE AND SURGERY February, lOSl shift into a younger age group than that found for lung cancer in the general population where the majority of cases occurs in the group of from 45 to 65 years. Similar observations have recently been made among gas house retort workers in Canada. Kennaway and Kennaw&y noted that gas stokers and patent fuel workers, who have a similar exposure to tar fumes and dust have a more than nine-fold incidence rate of lung cancer. These relatively meager findings in man are repeated by the experimental evidence obtained in mice and other species exposed to tar dust or subjected to cutaneous, intrapulmonary or in travenous administration of tar. , Campbell's experiments showed that mice ex posed to dust from tarred roads developed cancer of the skin and of the -lungs. Similar experi ments of Staufer; Barnewitz: and Bonne, using mice, however, were negative as to the develop ment of lung tumors, although resulting in some of the animals in the development of cutaneous carcinomatosis. Inhalation experiments with dust from tarred roads in which rabbits, guinea pigs and rats .were employed were equally un successful in regard to pulmonary tumor for mation (Staufer.i. Intratracheal insurilation of powdered tar into mice, and guinea pigs yielded negative results (Bonne; Schabad). Kimura, on the other hand, using the same experimental method in rabbits and guinea pigs, reported the development of lung cancers in both species. Nakano obtained a similar result in rabbits in jected intravenously with a ,,solution of tar in lanolin, while Tedescbi, as well as Simonds and Curtis, observed merely atypical proliferations of the bronchial epithelium of rabbits after re peated intravenous administration of tar. A similar result was obtained after the direct in troduction of tar into the pulmonary parenchyma of rabbits (Gerschin and Pigalew). Since none of the so-called carcinomas produced by insuf flation, or intravenous or intrapulmonary in jection of tar gave rise to mtastass, it is doubt ful. whether any of the reported atypical pro liferations of the bronchial and pulmonary par enchyma were actually malignant. It is noteworthy, on the other hand, that the cutaneous application of tar to mice was fol lowed by the appearance of adenocarcinomas of the lung (Murphy and Sturm; Koose and Cordes; Lynch; Schabad; Watson and Mellanby; Campbell; Samssonow; Puccinellil. Pucinelli as well as Moller obtained, with the same method, lung cancers in rats. These remote cancerigenic effects of cutaneousiy applied tar on the lung suggest the possibility that in man also cancer of the re s p ir a to r y tr a c t may result from con tact with., environmental cancergena by other than the respiratory route. (d) Tar Fumes from Tobacco Smoking: The tobacco smoking habit proyides an additional environmental source through which tarry ma terial in the form of hot fumes comes in contact with the tissues of the respiratory tract. In view of the existing tendency to relate the recent increased frequency of lung cancers to the action of a single, widely distributed canceri genic agent, it was to be expected that some investigators would point to the parallelism be tween the phenomenal growth in the cigarette smoking habit and the rising incidence of can cer of the respiratory tract during the laat three to four decades (Bogen and Loomis; Schrch and Winterstein; Hruby and Sweany: Roffo; McNally; Lickint; Mller; Arkin and Wagner; Ferrari: Mertens; Ochsner. .Dixon and DeBakey; Fulton; Grace; Hoffman; Schrek; Baker; Ballard and Dolgoff; Wynder and Graham: Jackson and Jackson: Hermann and others*. While some of these investigators (Roffo; Wynder and Graham) went so far as to attribute the chief responsibility for the development of lung can cer to cigarette smoking, others ciaipied that the inhalation of tobacco smoke is merely one of the factors that is involved <Hoffman 1. In analyzing the statistical evidence advanced in support of these contentions, it becomes ap parent that in no instance have occupational or environmental exposures to the various known or suspected cancerigenic agents been consid ered. The complete exclusion of these factors when investigating tabagism must lead to seri ous errors. It is, moreover, evident that the present trend in the sex ratios of lung cancer and of cigarette smoking run in opposite direc tions--that is, while the sex ratio of lung cancer becomes more heavily weighted in favor of the male sex, that of cigarette smoking doubtlessly favors increasingly the female sex. The claim of Roffo that the spectrographic examination of tobacco tar demonstrates the presence of can cerigenic -aromatic hydrocarbons, such as 3,4 benzpyrene, has not been substantiated by Coop er, Lamb, Sanders and Hirst, and Schrch and Winterstein. It is obvious, on the other hand, from measurements of the temperatures ob tained in pipes, cigars and cigarettes during the smoking process that temperatures are reached (400 to 700C) which might cause the production of aromatic compounds of canceri genic nature through thermo-cracking (Flory: McNally; Cooper. Lamb, Sanders, and Hirst). Attempts to produce cancer of the lung in mice by the inhalation of tobacco smoke have failed (Lorenz. Stewart, and Daniel). The results of cutaneous applications of tobacco tar to the skin of mice and rabbits have been contradictors'. While Roffo claimed rather uniform and con sistent cancerigenic action of various tobacco tars in mice and rahbits. the great m a jo r ity of other experimentalists either obtained only car- cinomatoid growths in the ears of rabbits and an occasional skin cancer in mice t Cooper. Lamb, Sanders and Hirst: Campbell: Flory: Lu-Fu-Hua: Schrch and Winterstein; Chihamatau i or no tumors at all (Bogen and Loomis; Hoffmann; Schreus and Zurhelle: Mertenst. | | u Voi 20. N a 2 INDUSTRIAL. MEDICINE and SURGERY Page 55 U appears from the evidence reported that oil operation. An inhalation hazard from lubri _ W the present time only suggestive epidemio-.. cating oil mist and fog (cutting oil) has been w logic data exist connecting the inhalation of tar incriminated in the excessive incidence of lung fumes in tobacco smoke and thereby the smok- cancer among French turners, millers, planers, ing habit with the development of lung or larynx mechanics, aasti fitters (Huguenin. Fauvet and if**. cancer in man (Hueper). It is unlikely, more Bourdin; Touraine and Bour; Kling, Samssonow over, that this type of respiratory contact with and Hros). Statistical data cited previously a variety of vegetable tar plays a dominant role f e u in the production of lung cancer, since experi -*>- ' mental observations place tobacco tar at best indicate that painters who are exposed to the inhalation of mists from petroleum fractions used in paints have an excessive lung cancer $y: gSr:>jr * among the weak exogenous cancerigens. It is essential in any consideration of this question to take cognizance of the fact that all tobaccos grown in the European and American countries are apt to be contaminated with resi dues of arsenical insecticides. The smoking of such a tobacco, therefore, would entail the in incidence rate. No information on this point is available in regard to printers and construction workers who spray impure paraffin (Humper dinck; Meyer-Brodnitz) and in workers in match and water-proofed paper factories using impure paraffin for impregnation. While there does not exist any information halation of arsenical vapors or fumes which by on the pulmonary effects of oil mists and fogs ii'-v themselves seem to represent a respiratory can (nebulized oil) in experimental animals, Scha- l-*2. cer hazard. Although the exposure to tobacco dust does bad, Campbell, Twort and Lyth; and Kling, Samssonow and Hros reported an increase of .'X .* not entail contact with tarry combustion prod lung tumors in mice following the cutaneous ucts of tobacco, mention is made in this connec application of shale oils and lubricating oils of tion of the claim that the inhalation of tobacco petroleum derivation. There was, however, no dust i tobacco workers, cigar makers, tobacco direct correlation between the degree of cutane *&. dealers) creates an increased liability to lung ous cancerigenicity of these oils and the extent tfri- cancer (Seyfarth; Krompecher; Heilmann; Beb of pulmonary tumorigenesis. a; Benda; Ferenczy and Motolcsy; Brinkmann; (f) Isopropyl Oil: The only aliphatic chemi Jiv Eager; Langbein; Borst; Jaeger and Kolb; cal that may be involved in the development of _^ _ Rottmunn; Koelsch; Wacher and Schmincks; cancer of the nasal sinuses and of the lung Lickint ). Lehmann, however, pointed out that when inhaled as a vapor is apparently isopropyl I persons engaged in the tobacco trade are, in oil which is a crude product of the manufacture j, general, heavy smokers. The entire statistical of isopropyl alcohol. Although neither the ac evidence as to u lung cancer hazard from to- tual existence of these occupational respiratory 2 bacco dust Is unreliable and requires confrma cancers nor the nature of the causal agent is l a ' tion before such allegations can be entertained as yet entirely established, the observations I .' seriously. made in two plants known to us are of sufficient ^ ie) Petroleum and Shale Oils; Inhalation of significance to deserve further study. If con Lr; processed mineral oil mists and fogs occurs for firmed these findings would open a large new r.; occupational as well as medical reasons. The field of environmental chemical agents (straight .question, therefore, has arisen as to whether chain and cyclic aliphatic hydrocarbons) that c - such exposures may result in the production would require intensive scientific and epidemio $.: of cancers of the respiratory tract. Kennaway logic investigations for evidence of potential f and Kennaway stated that there exists a rela- cancerigenic properties. i tively high .incidence of laryngeal cancer in mule T spinners who, during their work, inhale a mist of in o r g a n ic c h e m ic a l s : Observations made dur- \ ' cancerigenic shale oil used iu lubrication of the 1 ing rather recent years in the occupational \ spindles. While the use of mules has long been field indicate that respirator)' exposure to in discontinued in the United States in textile haled dusts, fumes, vapors and gases of various manufacturing using fibers of vegetable, animal metals or metal compounds seems to convey or synthetic chemical origin, mules are still em an excessive liability to cancer of the respiratory ployed in asbestos mills for the production of system. asbestos threads having a minor addition .at (a) Arsenic: While cancer of the skin through other fibrillar material (cotton, rayon). Southam medicinal, environmental, or occupational con T noted that mule spinners exposed to a spray tact with inorganic or organic arsenicais has be of shale oil occasionally develop not only cancer come a well recognized fact. (Hueper; Neu- of the scrotum but also of the stomach and bauer), cancer of the respiratory organs fol lung. Scott, on the other hand,, stated that he lowing exposure to arsenical dust, fumes or had not seen a single case of lung cancer in spray or after medicinal ingestion of arsenicais ) shale oil workers, of whom those employed in represents a sequela of more recent observation VT** the press rooms of paraffin departments may be and of less firmly established nature. The total come exposed to the inhalation of oil fogs. number of lung cancers after medicinal or occu & Roesch reported a case of triple cancer (lung, pational exposure to arsenicais stands at present skin, stomach.) in a paraffin worker of a lignite at 13 cases with one additional case listed as m Page 56 INDUSTRIAL MEDICINE ANO SURGERY t'v h ru a n j, !>.i Lusa Ca n c o Mortality in Several Counties o r Montana, 1947-1948 . C anqr m 4 Tout Popaietkm N im bar L ana Canoera Total C aacrr Aanual Lane Cancer Death S a ta / loo.no* O** S 1 \ me iM tairr Mala "aoja Total Dtmhft Nata Kemai* Naia fem ata ban 1 am Slhw* B w U Jttfl Cmtmdm Copper S m altine Co#HT M ims Copper M inine 11 ti . - 20 21 0.0 116.7 a 2X6 U 4A.6 U a 29* 1X7 44JK 1X3 Sancitine G allatin A cncultur# 1 9 I SI Vo 0.0 3.2 .26 T h e an im a te d cruda S talli rale for Km c s n rv r meima b it a malee ia th s cn tir# t.''filled Slat#* is 194? ia la. pee panatati. cancer of the larynx. Two of these cancers occurred after medicinal use of arsenicals (Semon: Montgomery and Waiaman: Russell and Klaber), the other followed after occupational exposure to dust of arsenical pesticides. (manufacture and use) (sheep lip manufacturers, vineyard workers) or smelter fumes (Merewether (four cases); Hopkins and Studdiford (one case); Saupe (two cases); Frommel (one case); von Pein (one case); and Faning (five cases of lung (three apparently identical with Merewether'si, one case of larynx. In the ma- jority of the lung cancer cases of apparently occupational origin there co-existed cutaneous lesions characteristic of chronic arsenicism. The cancers of the respiratory tract observed by Hill and Faning among sheep dip manufacturers represented 31.8V of all cancers observed in this group (engineers? packers, chemists). These occupational observations are of distinct environmental importance, since reports from Germany have related serious arsenical injuries in domestic and wild animal life living within the fume zone of silver and lead smelters to arsenic containing fumes released into the air from- these plants (Prell). Nieberle also reported from the same region the endemic occurrence of adenocarcinomas of the nasal sinuses in a flock of sheep, and stated that "a certain connection of this disease with the locality and with an injury by arsenic can scarcely be exeluded." Similar environmental and industrial health conditions may exist in this country for those parts where arsenic containing flue dust or arsenical insecticides have been and/or are released into the air in appreciable quantities, Recent observations made in regard to the lung cancer incidence in certain counties in Montana where huge quantities of arsenical fumes in paat years entered the air from copper smelting operations may be of significance in this respect (Lull, Wailach). Mortality and morbidity records for the years 1947 and 1948 revealed that 30.8rr (21 cases of all male cancer deaths total cancer 98 deaths were listed as due to.. cancer of the respiratory tract in D*er Lodge County where about 25V of the population (13,627) is engaged in smelting of copper ores containing 0.3V arsenic, and where from the past industrial history of this region an occupational as well as environmental arsenic hazard may be assumed to exist, In the adjacent Silver Bow County where ex tensive copper and zinc mining activities are car* ried on, the proportion of lung cancer deaths to cancer deaths was 22.6', (27 cases for males and 1.5V (two cases) for females (total number of cancer deaths 2.*>i), total population 53.207). There was in contrast in the adjoining Gallatin County which is agricultural in character, and which has a population of 18,2(1!). one male lung cancer death, while again in Cascade County with a population of 11.009 and with enpperarsenic ore mining and smelting activities the proportion of lung cancer deaths to all deaths from cancer was 12.7V for males (20 cases and at 3.5V (five cases) for females, with u total number of 200 cancer deaths. These obserrations are of only limited value since they cover too short a period of time, too small a number of cases, and no detaileddata on the occupational and environmental aspects of the individual lung cancer cases. However, the high frequency of lung cancer in counties where arsenic contamination of the environment is known to exist is of sufficient importance to call for a thorough and extensive study of the presence of a potential arsenic lung cancer hazard in all those regions in. which existing occupational and environmental conditions warrant such in vestigations. Such epidemiologic studies are especially in- dicated because of the difficulties encountered in the production of arsenic cancers in experimental animals and because of the complete lack of any investigations of the pulmonary cancer aspects of arsenic hazards by experimental methods (Heubauer; Hueper). <b) Asbestos: There occurs respiratory con- tact with three different types of silica corn- pounds, namely, inorganic crystalline or amor- pilous silicates, organic silicones aud asbestos. Since silicotic pneumoconiosis is characterized ly a chronic granulomatous inflammatory re- K- fi-$ ' Voi 20, No. 2 IN D U STRIA L M E D IC IN E a NU SURGERY Page 57 fUcr:--vactioii. and thus w m n to fulfill remarkably well fc* Ah basie. requirements of the chronic irritation " ^theory of cancerigenesis. several investigators have incriminated this frequent type of occu- pationai pneumoconiosis in the development of cancer of the lung (Fine and Jaso; Anderson and Dible; Charr; Klotz; Dible). There are in fact some 30 cases on record in which cancer of the lung or larynx and silicosis were coexist* ing (Dible; Fine and Jaso; Klotx and Simpson; Maxwell; Sladden; Middleton; Sweany,. Porsche and Douglass; Vorwald and Karr; Allen; Soko- j-gr loff; Pancoast and Pendergrass; Simons; Schnu- rer; Charr; Harris). However, the great ma- jority of investigators have come to the conelusion that there does not exist any causal relation between silicosis and pulmonary or larynjpeai malignancy (Vorwald and Karr; Allen; ' Feil; Harris; Pancoast and Pendergrass; :C.' Saupe; Schulte; Schuler Berblinger). Schulte Rg. 4. Atypical gUnduler opitheliei lonMtlwH in fibrati end chromcoHy infUmed lung hh sbottasi* badi within de*quemted epithe)il cefi* located within lemon ol 1 cystic glnd4ite formations. '7 and Schulz noted that coal miners in the Rohr \ district, among whom silicosis is frequent, have J no unusual frequency of lung cancer, while Allen V recorded a similar observation for the coal miners of Pennsylvania. Corresponding nega r : tive observations were made by Vorwald anti j ' Karr on individuals who came to necropsy with I silicosis at the Saranac Laboratory and have \ been reported by the Miner's Phthisis Medical ' /; Bureau of South Africa based on studies made C ^Vimong the South African gold miners in the f Johannesburg district. * These conclusions ure supported by the re- suits of experimental investigations. In which mice, rats, guinea pigs, rabbits, chickens and cats were exposed to the inhalation of silica dust tCampbell; Vorwald and Karr; Willis ami Squamous call cancer of lung with asbestos!* bodies w.f. Brutsaert/. ti- A fundamentally different situation, on the adjacent to epithelial cell pegs. other hand, seems to prevail in regard to the *2-' causal relation between asbestosis and cancer of the lung. Because the recognition of asbestosis as a special form of pneumoconiosis is of rather tt recent date, the analysis of 18,280 death cer tificates for-cancer of the lung and larynx in U - males from England and Wales from 1921 to [ 1932 did not reveal any cases of lung cancer yl . in asbestos workers (Kennaway and Kennaway). * Since 1935. however, an appreciable number <551 of cases of asbestosis complicated with | ''. cancer of the lung have been recorded from England, Germany, Canada and the United States (Lynch and Smith; Lynch; Lynch and Cannon; Egbert and Geiger: Gloyne: Wood; , Horning; Welz; Wedler; Nordmann; Mere- * :- wether; Luton and Champftx; Linzbach and L Wedler; Dominici; Baader; Homburger; Holleb Fig. 6. Combination of atypical glandular formation* and tqoemou* ceil carcinoma in asbastotic lung. 1 ' and Angrist: Desmeules, Rousseau. Giroux and The latent period after cessation of exposure T" Sirosis: Cureton) (Figs. 4. 5 and G). Was from 10 tit 12 years. Multiple can cers w ere | X The proportion rate of lun cancer in per- found in several rases, and both male and fe j l.'ima with asbestosis who came to necropsy male ivurkt*r> were affected. The male-female *r L stands between 13 and 15'. The exposure time -sex ratio, acc or di ng to Merewether is 2.4:1. JK I ranged from three to 27 years average 15 "hilv the mean a ge is about 52 years. Although * year3). Warren rather recently maintained that the con- & *V- 111 Pag SS INDUSTRIAL MEDICINE A.ND SURGERY F ebruary. I OSl A ge D istribution' of A sb esto sis Ca n c er A**: S M I 4140 Cm : I 1 1: U nwUwonSr UMkt IK* t u w t r M rtk U u q r il-SO 41-70 1 1 m iM laulim 71-S0 y a en 1 ol u b u w Exrosusx T im e o r A s b e s t o s is C a n c e * Baronire: C uo 1-4 t-10 ll- U t*z It-JO j Jl-tt * to o * m n 1 neetion between asbestosis and lung cancer is of coincidental nature, the actual existence of a causal relation appears to be very likely (Le- coeur; Koelsch; Saita; Hueper; Teleky; Edi torial) ; Gross I. The reason for the different behaviour of silica and asbestos in regard to pulmonary can cer! genesis is unknown. The various metallic constituents of asbestos may possibly play a role. While the experiments of Vorwald and Karr performed on guinea pigs that were exposed to asbestos dust gave negative results, those con ducted with mice by Nordmann and Sorge ap parently yielded positive results, since a few of the animals surviving the inhalation of as bestos dust sufficiently long showed at autopsy pulmonary lesions interpreted as squamous cell cancers of bronchiogenic nature. All spontane ous pulmonary tumors occurring in mice, on the other hand, are of glandular type and alveo lar origin. (c) Chromium: Another member of the group of respiratory metal cancers is the cancer of the lung observed in the manufacture of chromates and chromium pigments (zinc chromatei. While the first two cases of chromate cancer of the lung were observed in 1914 in Germany (Leh mann), it was not until 1936 that their number had become sufficiently large for establishing definitely the causal relation between exposure to chromate dust and lung cancer in German chromate plants (AJwens and Jonas; Alwens, Bauke and Jonas; Bauke and Alwens; Baader; Gross and Koelsch r Gross; Pfeil; Teleky; Bauer; Carozzi; Koelsch; Lecoeur; Saita; Staemmier; Teutschlaender; Kennaway and Kennaway). While the exposure in the chromate plants was to dust of chromite ore and of monochromate and bichromate salts of sodium or potassium, the respiratory contact in the chromium pig ment manufacture which resulted in lung can cer was in all cases (eight) to zinc chromate (zinc yellow) (Gross and Koelsch). Baader noted moreover that* there were nine cases of lung cancer on record among workers of the chromate consuming industries in Germany. The more recent observations of similar na ture among American chromate workers cover 30 far only chromate manufacturing operations. In neither country is there any information available as to the existence of lung cancer hazards for workers employed in chromium plating operations, in the manufacture of inks and paints, in printing, painting, dyeing, dye Fig. 7. Round cod coreinomo of (Ito lung in citroinct* wortor ridi bieck chromite deporta io djecent lung tiisuo. Fig. I. Spodogrcm of long with chromite pitoumocooiotif bow0 9 tho block chromite depoiiti within the whito min. ecel tkoieton of tho eihed lung taction. making establishments, and in the production and processing of metallic chromium and chro mium alloys. It is remarkable that, according to Goldblatt and Wagstaff, the English chromate industry apparently has remained free from these respiratory cancer hazards. Gross esti mated that the chromate lung cancer incidence rate among the approximately 1.000 effectively exposed German workers stands a t 3.9'c- It ap pears to have risen in more recent years to about 5fc, since Baader placed the total number of chromate cancers in Germany at above 50. No similar figures are available from this country*. However, the epidemiologic studies of Machle and Gregorius have shown that the long cancer incidence rate among American chromate workers is from 10 to 40 times that of a com parable industrial group, or an average of 16 times the expected rate. A recent analysis of the final fate of some 150 fo rm e r chromate workers engaged in chromate production for lit least six months, and having passed a latent period of more than four years, demonstrated that of 25 deaths that had so far occurred in this group, five were caused by cancer of the respiratory tract i20f<) (Figs. 7 and 81. . Vol. "20, No. .2 INDUSTRIAL MEDICINE and SURGERY Page SO n Acs .*1-30 H -tO Distribution o p C h r o m a t e C a n c e r s OP THI Lung H 4 I S M 0W0 71 u id i ito v Y f n Total M ota 1 t . 1 u M 12 I t T 1 1 11 * t u 21 1 TW fir dtocributto of i to ckm M W idenoeni 1KMM var iROd K n u w t y > M fM 9 I.S14 hm c tr a ( M tbnw d by M iti, C am u 4 A um cM i t ll.T Tatml 100 (U M w m) pr**tteaUy witk tto l MM i t * ttofavr tto l. U E x po su re P xsiod op C hro m a te Ca n c ers op th e L ung *-HI 11-10 21.30 1-40 41and a h o y Y u r t____________ 10 I I I It 1 Gorman IS r a n 10 22 N 2 American K .l Tbc Is u l noratwr of okacr*d cam of chroraato caar of the tunc from botk tbc United S u m mod Germany io bow U abo*c 100. tinea additional e a a n have bean d ia m o n d after the above Amina w e n reported. Although ulcers and perforations of the nasal septum are frequently observed in chromate workers, there is only one case of carcinoma of the nares in a chromate worker on record (Newroam. The statement of Machle and Gregorius that apparently the monochromate only is cancerigenic does not seem to be supported by obser vations made in German plants where in Lever kusen 10 cases and in Uerdingan 14 cases were found among workers in dichromate plants, --uch a selectivity of monochromate is, moreyer, scarcely conceivable from a biochemical Viewpoint since both monochromates and bi chromates are readily ionized in the body. Whether chromite ore dust represents a can cerigenic factor in chromate workers is still an open question although it may produce a chemi cal pneumoconiosis ( Lukanin . Likewise it is uncertain whether chromium plays an essential role in the production of other human cancers, although Dingwall and Beans some IS years ago demonstrated spectroscopically chromium in various human cancers. The exposure of rabbits- and cats for several months to chromite and chromate dust present in a chromate-factory did apparently not elicit any cancerous responses (Lukanin). The im plantation of metallic chromium into the marrow cavity of the femur of rabbits (Vollmannt, on the other hand, gave rise in animals surviv ing for more than three years to cancers at the site of deposition and in the lung (Schinz).. id Nickel: The occurrence of cancers of the nares, nasal sinuses and of the lung among workers in Clydach, South Wales, engaged in processing Canadian coppernickel matte of the Sudbury mines by the Mond nickel carbonyl process was first observed in 1924 (Baaderi. During the following 15 years several reports on the continued appearance of such cancers 1 V er* made by various investigators iGrenfell: Tooper; Stephens; Bridge; Amor; Merewether). Up to 1939 there were recorded with the Chief Inspector of Factories 34 cases of nasal sinus cancer and 24 cases of cancer of the lung. These figures have risen to 47 cases of cancer of the nose and 82 cases of cancer of the lung for the period of 1923 to 1948 (Merewether). No simi lar observations have been made or recorded so far from -German, Canadian and American nickel refineries using the same process. According to Amor, the average employment period for the nasal sinus cancer cases was 19.4 years (range: 6.0 to 30.0 years) and that * of the lung cancers 21.4 years (range 7.0 to 32.0 years). The average exposure time to dust was 11.3 years for the nasal sinus cases (range 3.0 to 26.0 years) and 11.6 years for the lung cancer cases (range 1.0 to 33.0 years). With a few exceptions all workers who developed nasal or pulmonary cancers had entered employment be fore 15)24 (Merewether). The average age at death was 51.0 years for the nasal cancer cases (range: 36.0 to 66.0 years) and 53.0 years for the lung cancer cases (range: 48.0 to 66.0 years). As to the causative agent. Amor emphasizes that only one case has been observed in a worker who had contact with nickel carbonyl, while all others had been exposed to arsenic-containing dust originating from commercial sulfuric acid contaminated with arsenic and used for the extraction of copper. The absence of similar cancers among the nickel refiner}- workers in Canada is explained in the opinion of Amor therefore by the fact that in Canada the sul furic acid extraction process is not used. The concept of an arsenical origin of these respiratory cancers, however, is not supported by the apparent absence of arsenical derma toses and cancers of the skin among the affected nickel refinery workers. Such manifestations rather regularly accompany the cancers of the lung' in arsenic workers and thus represent a part of the environmental arsenic lung cancer pattern. There is. moreover, no evidence from any other source that the industrial use of com mercial sulphuric acid usually containing ar senical impurities has given rise to cancer of the respiratory tract. Exposure to arsenical dust, while having frequently caused ulceration and perforation of the nasal septum, has not given rise to nasal cancers. The cancers of the nares and nasal sinuses in the nickel workers involved the middle tur binates and the ethmoids and were histologically of squamous, undifferentiated or papillary colum nar cell types. One columnar ceil cancer involved the nasopharynx. The four pulmonary cancers that were studied histologically were of small round cell or squamous cell types. The inhalation experiments conducted by Campbell on mice exposed to arsenic-containing nickel dust obtained as concentrated matte from the Mond Company gave results of doubtful sta tistical significance, since the ratio of lung tu mors in the test series and in the controls was 14:8. It is uncertain whether these experiments actually duplicate the conditions of exposure r f - '.--w * v. uanit'-iiag? & & s s s & m ^ j- ..= y . Pun 60 INDUSTRIAL MEDICINE and SURGERY February. IOH sustained by the workers in the nickel refineries, since the nickel-copper matte manufactured in Canada and used in England contains only min ute amounts of arsenic. The origin of the ar senic. according to Amor, is not from the matte but from the sulfuric acid used. Since cancers of the respiratory tract seem to continue to occur in English nickel refinery workers, there is sufficient indication to investi gate thoroughly their causal aspects by epi demiologic and experimental methods for prac tical as well as scientific reasons. Definite in formation should be obtained whether these cancers are of arsenical causation as claimed by Amor or are attributable to the inhalation of nickel carbonyl vapors and thus represent a separate type of metal cancer. A study of the respiratory cancer incidence in workers engaged in nickel plating, manufacture and use of nickel pigments and alloys, ami in the polishing of nickel may aid in clarifying the presently con troversial etiologic aspects of the cancers oc curring among the copper-nicke! refinery workers. PHYSICAL acKNTs: >n X-radiation: Despite the large number of persons whose lungs have been subjected to intensive irradiation by x-rays for medicinal reasons (cancer of the breast or lung), there is not a single case of medicinal x-ray cancer of the lungs on record. Chronic radiation pneumonitis, on the other hand, has been of relatively frequent occurrence. Apart from the extensive hyalinizing and fibrosing changes characterizing this process, there occurred swelling and transformation of the alveolar epithelium into cuboidal and columnar cells and cellular monstrosities, andl stratifiestion, giant cell formation and squamous cell metaplasia of the bronchial epithelium (Bauer and Schaer; Warren and Spencer: W'arren aad Gates; Widmann; McIntosh and Spitz; Leach, Farrow and Foote; Jacobsen: Freid and Goldberg; B auer).'Engelstad produced similar reactions in the pulmonary parenchyma and bronchial epithelium of rabbits without obtaining cancerous responses. Warren and Gates reported corresponding acute lesions iu rats. The development of a squamous cell cancer of the larynx on the basis of a chronic x-ray injury produced by 86 x-ray treatments given for a skin disease uf the neck was reported by von Eicken. <b) Radiation of Radioactive Substances: There are only two cases on record in which prolonged inhalation of radioactive gases and dust by a laboratory technician and a chemist engaged in th production of medicinal radium preparations or in the manufacture of luminous paint, respectively, (Tonges and Kalbfieisch; Kalbfteisch: Belt: Doeneekei caused fatal fibrosis of the lungs. The high incidence o f. pulmonarv cancer among miners in Schneeberg and Joachimsthal where radioactive ores are mined Fig. . Highly in tp lu tic c o c i w n t in I Schnnnbnrg minr showing mny grotw qu* e*ll* which t t * commonly scon but not specific for on irrc ctcd mucosci lining. and the air in the mine ducts contains radio* active gases and dust strongly indicates that a prolonged ex(insure to these agents is causally related to the occurring pulmonary malignancies OVeber; L'hlig: Thiele. Roatoski. Saupe and Schmori >: Thiele; Stocklaaa and Penkava: Stooklaaa: Schmori: SchetHer; Rostoski and Saupe : Rustoski, Saupe and Schmori : Rujewski : Neitzel; Ludewig and Lorensen: Lorenz: Lindemanu: Lange; Koelsch: Hueck: Hopmann: Beyreuther; Agricola; Aucke: Arnstein: Baader; Bauer: Epstein; Henckel: Hrtung and Hesse: Fischer-Wasela; Teleky; Doubrow; Pel1er; Saupe: Rehounek and Fort: Czechoslovakian Commission; Ziel: Woldrich: Tschelnitz: Sickl: Behounek; Pirchan and Sickl: Lowy: Humphries; Beutel and Woldrich) (Fig. 9*. Work in radium laboratories may represent an additional source of occupational cancer of the lung through inhalation of radioactive gases* and dust. Three cases of this type have been observed in chemists (Neitzel; Lowy). Martland, moreover, reported the occurrence of a carcinoma in a nasal sinus in a luminous dial painter, who sustained a similar exposure. It is apparent from the discussion of Evans and Goodman that a similar respiratory hazard may exist for employees of mesothorium refineries and thorium mantle factories, who inhale thoron. since the degree of atmospheric radioactivity in such plants was found to be in quantitative agreement with the experiences in Schneeberg and Joachimsthal mines (40 to 600 x 10-11 curies of thoron per liter of air in thorium operations against 40 to 1800 x 10-11 curies in Schneeberg mines and SO to 560 x 10-u curies in Joachimsthal mines). Since Bryan and Silverman recently pointed out that electrostatic eliminators covered with a gold film containing either polonium or radium present an industrial. inhalation hazard by contamination of the air with tine particles containing radioactive mu. , terial, the possible development of pulmonary cancers in workers engaged in operations where ' Vod 20, No. 2 INDUSTRIAL MEDICINE and s u r g e r y Page 6t devices are used (textile, paper) might ^ N ll be kept in mind. Most of the recent in* Itigaton of the Schneeberg and Joachimsthal Kmi cancers agree that their radioactive can* sation can be considered as almost definitely established. A critical evaluation of the evidence advanced in favor of other factors, such as silica, arsenic, bismuth, chromium, nickel and cobalt, shows that little or no factual and valid evidence sup* ports such claims. Perhaps the most objection able contention that has been put forward in this respect is the speculation that the lung cancers among the Schneeberg and Joachimsthal miners are the result of inbreeding and thus of hereditary predisposition (Macklin). The facts are quite different. The majority of the Schneeberg miners reside in Schneeberg, a community of some 10,000 inhabitants located at the end of a railroad branch line, aud thus are living in a remote but not isolated mountain region of Saxony, which has been for many years the most densely populated state of Germany. Even a limited type of inbreeding that would be remotely comparable to the hereditary and abnormal conditions created in inbred strains of mice is scarcely conceivable under such circum stances. A study of the names of 53 miners listed by Harting and Hesse supports this con clusion, since there were 44 different names 'S n this group. Duplications existed seven times, liplication and quadruplication once each. This >regree of repetition of names is not unusually high and is plausibly explained by the fact that in some instances several members of the same family were probably employed in the mines. The occurrence of "familiar' cancer under such conditions is not due to heredity but due to identity of exposure to an environmental can e e n gen. Similar circumstances of exposure to soot have been in past decades the reason for the appearance of scrotal cancer among several members of the .ame family engaged as chim ney sweeps in England. To introduce the con cept of heredity into such a picture is totally unjustifiable and merely acts to obscure or con fuse rather clearly established facts of environ mental canceri genesis. There were approximately 400 coses of lung cancer among the Schneeberg miners between 1876 and 1930, while 42 cases of this disease came to observation among the Joachimsthal miners during 1929 to 1938 (Peller). It ap pears from the epidemiologic studies made that between 75 and 80% of the deaths among the Schneeberg miners and from 47 to 50% of the deaths of the Joachimsthal miners were caused by cancer of the lung. The recorded age distribution clearly demon strates a shift toward the younger age groups in individuals dying from lung cancer following Exposure to radioactive dust and gases. ^ The period of exposure ranged for the ma jority of the Schneeberg miners from 20 to 50 Ad D ist r ib u t io n or L u n g C a n c e r s in R adioactive O r s M in e r s ! * . 1*41 4*-4 9<M>9 4*4-49 70 ta d r r r n 4* 1 IT 9 9 t9 Total (9 Scbnooborr H JoacbioutfaaJ years, but was occasionally as short as seven years. The exposure time of the Joachimsthal miners was from 13 to 23 years. No information is available on the occurrence of lung cancers among the miners employed in the Katanga mines in the Congo, which are open pit mines, in the Canadian mines at the Great Bear Lake region and in the vanadium-uranium mines in the Rocky Mountain area (Warschwa- aki; Mainsin). It seems to be characteristic of the Schnee berg and Joachimsthal lung cancers that many of them are of the small cellular or highly ana plastic type, which accounts for the fact that they were first diagnosed as sarcomas. The topographical restriction of these cancers to the lung suggests that the cancerigenic agent mainly responsible for these tumors occurs either in the form of a dust or is adsorbed to the surface of dust particles, because canceri genic vapors or gases in the absence of dust seem to cause cancers of the lungs as well as of the nares and nasal sinuses (.nickel, carbonyl and isopropyl .oil workers). While the experiments of Schmidtmann and Lowy aimed at the production of pulmonary cancers in mice exposed to radioactive dust and gases were negative, subsequent ones conducted by Dohnert, Rajewski, Schraub and Kahlau; Lorena, Heston, Eschenbrenner and Deringer gave suggestive results. Of definitely more con clusive character are the observations reported by Lisco and Finkel who obtained malignant pul monary tumors in rats exposed to an aerosol of radioactive cerium. The greatly and rapidly increasing production and uses of radioactive substances of natural and synthetic character for research, industrial and military purposes that has taken place dur ing the last 25 years in this country have brought along exposures to radioactive material for an appreciable number of individuals. The conditions of such contacts are of a quality and order that the appearance of cancers of the res piratory organs in some members of this group must be anticipated. Comments 'THE data presented permit the conclusion that some of the cancers of the respiratory tracr are attributable to the inhalation of a number of more or less well defined chemical or physical agents. Although the total number of these respira tory cancers is relatively small when compared with the total number of cancers of this organ system, the proved environmental origin of these tumors lends strong support to .the great amount w*r-st .'..ft T* ' .1. :*7 ym V-; : 'U-si :j>2* 5`. **' *' ft * -I i Page 62 INDUSTRIAL MEDICINE AND SURGERY . February, lo st of merely circumstantial evidence indicating of occupational lung cancers mistaken for many that environmental factors piav a significant years for tuberculosis or silicosis. role in the production of pulmonary, nasal and Future studies of environmental pulmonar}* laryngeal malignancies. cancerigenesis might well include proper con The available information on the recognized and suspected respiratory carcinogens, moreover, suggests that the known numbers of environ* mental respiratory cancer represent only a fraction of the actual ones, since existing epi demiologic studies on this point are highly de fective. Although all known environmental cancers have followed upon the inhalation of exogenous cancergena present in the form of dust, fume, mist, fog, vapor or gas, serious consideration sideration of local atmospheric conditions for air pollution with cancerigenic agents. In view of the long latent period of environ mental respiratory cancers which ranges from ve to 40 years and because of the fact that these cancers may develop many years after cessation of exposure to the cancerigenic exo genous agent, it is essential that arrangements are made for the medical supervision and con trol of effectively exposed persons to extend be yond the period of employment. Likewise, it is should be given to the possibility that some or pertinent that detailed employment and exposure many cancers of the respiratory tract may be data in addition to name, birth date and place, due to agenta entering the organism through the alimentary or cutaneous route and being either excreted through the respiratory organs and social security number are recorded and kept for all persons who had effective exposure to environmental respiratory cancergena, so as or having special metabolic or chemical aifini- to ascertain in future investigations reliable and ties to these tissues. valid epidemiologic evidence on the existence The past history of the discovery of environ and extent of cancers of the respiratory tract. mental respiratory cancers has shown that the While such procedures will prove to be tedious, rst indication of their existence is usually pre and expensive, they will amply repay all efforts sented by the occurrence of a crowding of such by improving the health of our people not only tumors among members of restricted occupa through prevention of environmental canceri * tional groups. Industrial physicians and special genesis, but through resultant fundamental con ists in pulmonary diseases might, therefore, tributions to the etiology of human cancer. make valuable contributions to the etiology and The experiences made in connection with en epidemiology of respiratory cancers by investi vironmental respiratory cancers suggest that the rt tm gating thoroughly the entire occupational his regional variations in lung cancer among the it# tory of their respiratory cancer patients for general population may be attributable to locally if* evidence of a previous exposure to an environ restricted quantitative and qualitative differ f i mental cancerigen. Special attention should also ences in the environmental cancerigenic spec iff be given to all those patients who enter medical trum. care with the diagnosis of tuberculosis or sili Likewise, the evidence related to environmen cosis or both and who have been employed in in tal lung cancers indicates that the increased fre dustries where they became exposed to various quency of these tumors observed during recent cancerigenic metals, such as arsenic, aranium decades is apparently not caused by the appear ores, chromates, nickel, asbestos, and bituminoua ance of one new environmental cancerigen re substances. The history of occupational res lated to occupation or habits, but rather re piratory cancers offers several vivid examples flects the action of several or many cancergena. He Says He Did It To Save Money I **> LLINOIS' Governor Stevenson on December 28 ordered the liquidation of the Bureau of Industrial Hygiene in the State Department of Public Health, on S recommendation of the Schaefer Commission to Study State Government. The % commission pointed out that "one of the more obvious cases of overlapping and duplication of activities" between separate state agencies existed in the competing activities of the bureau and the Industrial Hygiene Unit of the Department of dLaatbeodr'bsyDniveixstioJnunoef 3F0a.ctthoeryenIndspoefcttihoen,prTehseentgobvieenrnnoiurmo.rdTerheed BthuerebauureoafuInlidquusi trial Hygiene currently employs 16 persons and has a biennial*appropriation of $133,735. The commission's report recommended and the governor directed that the facilities of the health department's central laboratory be made available to u the Department of Labor to review findings made in the course of its inspections. ' Vi &