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FILE NAME State of the Art Literature SAL DATE 1951 Feb DOC SAL052 DOCUMENT DESCRIPTION Journal Article - Environmental Lung Cancer INDUSTRIALINDUSTRIAL MEDICINE AND SURGERY The Journal of Medicinein Industry With which saw consolidated The Industrial Doctor and International Journal of Medicine and Surgery FEBRUARY 1951 Number 2 Environmental Lung Cancer W. HUEPER M.D. Cancerigenic Studies Section National Cancer Institute Bethesda Maryland ANCER of the respiratory tract had a rela- : ~ : * 7, -= a XK_... sa 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 last three to four decades Simons Schinz Mason Kennaway Heady and Kennaway Clemmesen 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 ath from cancer in males Many investigators nsider the recent increase in the frequency of fung cancer as purely apparent attributable to the marked shift in age distribution of the population to improvements in diagnostic methods to greater interest of the medical profession in cancers of the lung and to a change in the ratio 4 - ~. of lung cancers to all cancers because of a reduction 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 canceri- genic spectrum starting some 75 years ago related to new occupational hazards and newly acquired habits Halpert Although critical review of the available evidence does not permit * definite conclusion concerning the general question as to the real or apparent nature of the rise in lung cancers it provides much cir- cumstantial and conclusive evidence regarding the role which environmental cancerigenic 2. agents apparently play in the causation of these _* tumors Circumstantial Evidence . ee a7 NUMERICAL out prolongation average Increase of Lung Cancers With- doubt the rapid of the life span has brought in recent decades many more persons into the age group in which OR HUF's refereNETS are identified in a detailed and tensive bibliography of which a copy DAY be obtained by writing Branca him at Cancerigenic U.S. Phonic Health Studies Section Cancer Control Service National Institute " Health Bethesda 14. Maryland lung cancer occurs most often Since approximately 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 1875 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 as 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 1933 to 1944. According to Dorn's calculations on this point the annual percentage increase was 10.5 for males and % for females between 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 economically rather stable patient population a consistently high autopsy rate and a competent pathological service there is little reason to attribute an appreciable portion of this development to improvement in medical service and recording The consistency and increment of the trend moreover would not support such an explanation It was noted on the other hand that the time of onset and degree of the lung cancer rise varied considerably in different countries Casolo and in different parts of the same country Fischer This observation seems to exclude the possibility that racial and hereditary 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- RYToe d . at - tMtol ~ ae. . went? eas Pt a Seth po- \ : hte. piteey = ik a ES 7 tA fs: ral pret Rte teh 3<:, Pagan ae Son 2D FEStes >! se . i we . i Deg TAT TATae he git Pte fee arene. Myr atsk- Page 50 INDUSTRIAL MEDICINE AND SURGERY tered the human environment during the last ated type and 18 February 1951 half century This conclusion receives some females adenocarcinomatous type * support from the fact that the majority of While 11 37 and 52 respectively more recently discovered environmental Hollingsworth recorded a similar sex dis- gens cause cancers of the canceri- tribution of adenocarcinomas Mason noted that while those previously establriesshpeidratory tract adenocarcinomas were present in this series in fected the skin mainly af- 6.7 of the male cases and in 13.7 of the fe- male cases Lingskog on the other hand re- SEX DISTRIBUTION There is ported that adenocarcinomas occurred with equal that lung cancers general agreement are more frequently pres- frequency in both sexes and that all adeno- carcinomas observed in ent males than fernales Since the consider- below the were present in individuals able rise in the occurrence of lung cancers dur- age of 40 ing the past four decades has been A similar dependence of adenocarcinoma on by a definite shift in the accompanied the age of the individual was noted in the pro- lung cancer in favor of sex distribution of the ceedings of the First National Cancer the male sex the in- crease in lung cancer incidence Confer- ence The proportion of adenocarcinoma dropped on agents to seems to depend which males become from 30 in the age group 0-19 years to less often or more exposed more intensely than females and which than 20 in the age group 60 years and over There was a are essentially unrelated to ditioned factors endogenous sex con- tion of corresponding rise in the propor- epidermoid carcinomas while the un- This conclusion is supported by the fact that differentiated type of cancer seemed to be un- the female sex ratio of lung affected by the age factor Gebauer reported hibits remarkable local differences cancer ex- that adenocarcinomas originate in 90 from the tween 2 in Sweden Henschen vtaory2 in0 g bien- secondary and small bronchial branches while the majority of the undifferentiated and parts of the United States O'Keefe while moid cancers epider- averaging most often 5 to 10 Fulton 7.3 develop from the main bronchial in 1610 cases Clemmesen reported from Den- branches mark that a shift in the female _ The proportion of the various histologic types has occurred there during recent sex ratio of bronchiogenic carcinomas thus appears to dif- years after having stood at 5 in 1931 it changed to 3 fer according to sex and age as well as to their topography in the bronchial in 1945 and is expected to become stabilized at tive system Their rela- a ratio of 1 in the near future sex distribution moreover seems to vary An exogenous origin of the sex differential with different investigators and thus with dif- of lung cancer is suggested moreover ferent areas studied Again it is not conceivable servations made in connection with by ob- that such variations in the biologic and anatomic occupational cancers of the respiratory tract Merewether manifestations of lung cancers are due to endogenous causes while they would find found that the female ratio of cancer stands at 2.4 to asbestosis ready explanation in differences of a rather 1. This ratio illustrates exposure to Lindskog the trend toward an equalization of incidence exogenous agents of various types ( rates of cancer for the two sexes whenever RACIAL Distribution the conditions of exposure to an environmental Although neither Jaff^' cancerigen tend to become identical Highly ex- cessive incidence rates of lung or nasal nor Steiner observed any significant differ- ences in the distribution of lung cancers be- hand . cancers among males on the other sinus exist tween whites and Negroes in the Chicago area other investigators noted that whenever for occupational reasons contact with pulmonary can- exogenous cancerigens is restricted to members cers are more frequent in whites than in Ne- of the male sex such as workers in chromate groes Arkin and Wagner Quick and Brindley factories in radioactive mines and in Halpert Likewise Khanolkar reporting on the nickel ore refineries copper- organ distribution of 3,263 cancers of a Bombay hospital does not mention lung cancer ISTOLOGICAL Types Sex and Age Distribu- the for eight types 2,652 of cancers listed that among account tion Probst stated that in recent cancers evaluated However until there has been a shift toward a years proper standardization as to age and sex has more frequent been made these occurrence of epidermoid cancers in pulmonary malignancies of unknown etiology This ob- observations convey no valid information as to differences in racial bility or suscepti- servation may be related to the special types of exposure to exogenous proportionally greater increase of lung cancers among -males cancerigenic agents coinciding populated by different races with regions than females because squamous cell cancers and The various kinds of round cell cancers predominate in males while evaluated circumstantial evidence adenocarcinomas are more frequent in females tal support the concept that environmen- Proc First Nat Cancer Conf The sex dis- factors are involved in the production of cancers of the respiratory tract tribution of the various histologic types of lung lung Boycott While the especially the cancers according to this source is as follows which actual extent to - Males 44 epidermoid type 38 undifferenti- the exogenous agents seem to be active in production of these tumors among the gen- 1 VOL 20 No. 2 INDUSTRIAL MEDICINE ~Iral population and the nature of such agents . ; cannot be deduced from the information avail- -able observations made in the field of occupational cancerigenesis permit a more definite and specific although also more limited view of these aspects of environmental cancers of the respiratory organs AND SURGERY Page 51 Oe ata ea ble of, MA Roy Be EE a Conclusive Evidence ELATION of Lung Cancer to Large Occupational Groups and specific Irritative ~w -S:. e 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- e-. bilities Kennaway and Kennaway argued that the higher mortality from cancer of the lungs in towns noted by Stocks the low mortality in agricultural occupations and the absence of a a 7 social gradient recorded by Stevenson were com- ' patible with an etiological factor in the air such as coal smoke Stephens claimed some years previously that the pollution of the air by carbon monoxide from incomplete combustion of coal bo and gasoline represented a major cancerigenic factor Oldofredi recently revived this conten- tion and pointed to the high incidence of lung i: ws among former members of submarine ta wee oa nO me ae Om e Pore po difficult - crews of World War I when it was exceedingly difficult to control adequately the carbon monoxide content of the air Campbell's experiments on mice exposed to carbon monoxide however failed to show any increased incidence of pulmonary malignancies Green was inclined to attach a similar significance to the pollution of the air with sulfur dioxide from the burning of containing coal and the smeltinogf vari- ous ores Other investigators felt that members of out- . door occupations carrying the hazards of dust and fume inhalation especially dust from tarred roads and exhaust fumes from gasoline engines were especially likely to develop cancer of the respiratory tract McCrae Funk and Jackson Matz Schachter Duguid Ferenczy and Ma- tolczy Hutchison This concept however was disputed by others who pointed out that in some regions Riga an increase in lung cancer was observed before any tarred roads were used Konrad and Franke Kennaway and Kenna- way Guglielminettia Knox and Probst pointed out that not the quantity but the quality of dust was important in lung cancerigenesis A few investigators stated that lung cancer was more frequent among the laboring class than among professions Brockbank Weller There is some evidence indicating that lung cancer is more frequent among the population of indus- trial areas than among that of rural districts Fulton Gerber Several large statistical analy- ses tended to show that some occupations en- gineers mechanics painters decorators Brit Emp Cancer Campaign ; painters and fur- Atypical papillomatous epithelial growth chronic pneumonia such as seen after irritative chemicals in lung with exposure to nacemen Fulton machinists foundry workers metal grinders Turner and Grace metal workers spinners cigar makers Borst exhibit an excessive liability to cancer of the lung Frem information to be given later in connection with the discussion of recognized cancerigenic agents it is apparent that an appreciable part of the membership of the various occupational groups mentioned may become exposed to one of th~ known specific environmental cancerigens mist of lubricating oils soot dust from or pigments of various cancerigenic metals chromium nickel arsenic It is thus possible or probable that in these instances statistical epidemiologic data reflect real causal relations There are finally many students of this subject who could not find any relation between special occupations and lung cancer formation Brockbank Kennaway and Kennaway Simmrosa Shennan Rogers Rice Husted and Billman Jaff^'Bonser Haintz and others However the occupational data on which such statements are based are as a rule too inadequate as to specific type and duration of employment and occupational period which are important because of the long preparatory and latent period of lung cancer to be of any definite value A similar conclusion applies to the claims made concerning the etiologic connection be- tween the inhalation of various irritative gases fumes mists and dusts of various acids and alkalis sulfuric acid hydrochloric acid nitric acid ammonia war gases formaldehyde and cancers of the respiratory tract ( Fig ) While isolated cases of respiratory cancer are bound to occur in occupational groups coming in contact with such agents the existing epidemio- logic evidence does not lend any valid support to a generalization from the observation of a few cases Koeisch However it is worth noting that at least one of the acids mentioned sulfuric acid is often contaminated with appreciable amounts of arsenic This impurity in commerciai sulfuric acid has been blamed by ny r ao) ' sakewe faery 4, : nickel refinery Atypical epithelial Figs 2 and 3 proliferations in fibrotic bituminous lung involving lining of gland Amor for the formations cers among occurrence of lung and nasal can- a Soot Tarry Material workers In view of Produced Incomplete Combustion of Carbonaceous by th Matte among workers exposed to the inhalation of finely dispersed acids alkalies and other tative inorganic and irri- as organic chemicals such especially beryllium and its various pounds formaldehyde glycols isopropyl com- pounds carbamate com- derivatives organic solvents wpehoesdphkoilrlsersalrluobybser paints insecticide sprays There can be accelerators and polishes little doubt from the evidence presented that data obtained by an of large occupational evaluation groups with varying types and degrees of exposure to irritative agents of specific nature yield little definite infor- mation concerning a causal relation between occupational activity and cancer of the tory tract Great respira- progress however has been made in elucidating such connections whenever epidemiologic investigations were limited to circumscribed groups of workers and tions either exposed to chemical popula- agents of more or less well defined kind or to identical lar occupational or environmental or simi- conditions DEREKEKECANICHE 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 develop lung cancers Campbell Vorwald and Karr This innocuousness however does not extend to the distillation and fractionation products 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. Commercia Natural Gas Gasoline Die sel Fuel Domestic Industrial and incomplete Soots While the cancerigenic action of soo resulting from the combustion of coa upon the skin is well recognized and best demon strated by the chimney sweep's cancer of the scrotum the causal relation between the inhala tion of atmospheric soot from domestic and in dustrial sources and lung cancer eral and among the gen- industrially employed population is much less definite the lung is not Dorn In fact cancer of unusually frequent among chim ney sweeps Kennaway and Kennaway Al- though Schnurer reported that the incidence lung cancer in a series of 342 of Pittsburgh district increased dniercercotplysiewsitohf tthhee degree of bituminosis Figs 2 and 3 Dorn found in his statistical studies that the lung pared with that of five other large cities Ex- perimental studies conducted by Schnurer and and Seelig and Benignus with the inhalation of smoke from an from a hospital fue eggstove or of soot used as bedding for mice respectively were equally inconclusive convincing On the other or un- little doubt that the hand there can be of soot contained in the air Pittsburgh and other cities is carcinogenic to an extract of soot collected at avnardious localities in the United States Passey Braine found the fraction of hold soot boiling over above 250 most haocutsiev-e in this respect black The question of the possible tion from the inhalation of vacrainocuesrigteynpiecs aocf- commercial soots prepared from natural oil residues and gas or oil black furnace mbelracchkandgiassed as lamp black important cause these paint of the huge production and years be- blacks in the rubber consumption of industry and for and ink manufacture in the making of VOL 20 No. 2 INDUSTRIAL MEDICINE AND SURGERY Page 53 records and because of their use as coloring : matter Some of these blacks have been prepared garage mechanics and automobile drivers do not show an excessive incidence of lung cancer in late rears by the incomplete combustion of oil residues that are obtained from the catalytic fay. cracking process and that possess distinct can- cerigenic properties to mice In addition to the ducers ELEC possible lung cancer hazard involving the loaders shippers and industrial Seaty?: pro- con- > sumers of such carbon blacks there may exist a similar hazard for the general population liv- me ing in the neighborhood of carbon black plants ree because during the production of these materiais 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 cancers of the lungs in rats following prolonged and intense exposure to combustion products of MEA: large amounts of soot may be released into the Wage air A similar environmental cancer hazard may result from the burning of oil dumps Srey perhaps we refineries giving rise to considerable mear .30 amounts of sout Little experimental work S325. .30 far has been done in studying the potential ii cancerigenic properties of the various commer- PRS cial soots which depending upon the production process SEF and raw material used in chemical and physical differ appre- respects and Pigis ciably Miespecially in tar content Mantell iS. Steinbrueck reported the experimental pro- ee~ duction of skin cancers in mice painted with 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 comhustion are rather frequently met future at- tention should be focused on the potential can- cerigenic properties of exhaust fumes emitted from imperfectly operating gasoline and Diesel et black of printing ink Seelig and Benignus on in in is the other hand failed to see any lung cancers mice exposed to the inhalation of lamp black of Miescher and Schwarz using an igsExperimentscontaining a benzene extract of oil Ze ointment Se burner soot applied to the skins of mice were equally negative Since the carbon black indus- try is supporting experimental investigations on {epi So the potential pulmonary cancer hazard connected blacks with eb more igibtgoe: the inhalation of various carbon definite information may soon become ORE aay : 4: . = pate, available available i Gasoline b Diesel and Gasoline Engine Exhaust A + similar degree of uncertainty exists in regard to % the potential cancerigenic properties of the and abnormal exhaust products of low eS eat 2s: normal LZ compression internal combustion gasoline en- aoees gines and of high compression Diesel engines INCIoi rytit ste in connection with the development of occupa- va tional ean;o, and environmental respiratory cancers Shaan ot Ferenszy Pe Heilmann Duguid and Lorentz *. Ried)S, one. Diesel , fe Matolcsy of iS nd exhaust The contention that the fumes from gasoline and inhalation en- 4 4 le Ry* "7 7) kd automobile traffic gines a. ~~ and thus the increased is causally related .of lung cancers in to the recent rise in the incidence decades has been at- Hg= thereby Pagte owits tacked on various grounds 6d 8 i Whe ~ It was pointed out that the exhaust fumes pe bo mit 2 of these engines when operating perfectly and eres generating products of complete com- contain little or no ingredients of po- 4c: bustion tential fese-ts: cancerigenic qualities Bloch and Wid- made TEEeNL mer Probst Mention moreover was of parallelism weet e the fact that there does not exist a the rise in automobile traffic in differ- T*SSST bLeetwhemenann Seer and Fent countries and the increase in lung cancer Konrad and Franck Syreck f Be oe rebee eka that occupations particularly exposed to engine exhausts such as policemen street cleaners 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 considerable speculation since such a hazard if present would be of great practical importance Brandt Kling Samssonov and Heros and others However this concept finds little support from the epidemiologic studies of Lehmann Husted and Billmann Fischer and Kennaway and Kennaway There was no consistent relation between the lung cancer frequency and the extent of tarred roads in different countries ---- --was there any excessive lung cancer incidence among workers especially exposed to the inhalation of tar dust and fumes in several countries Hugounenq Husted and Billmann M^...llschitzky More recent observations however indicate that the inhalation of hot tar fumes such as those encountered in the operation of gas generators in connection with the production of illuminating gas and coke is associated with an increased liability lung cancer It was shown that retort workers seem to be especially subject to pulmonary malignancy Kuroda and Kawahata Kawahata Sunderland According to Japanese experience the gases emitted from the stoking holes contain 0.7 tarry matter Within a year period there came to observation 21 cases of lung cancer among a total of 100 workers employed for more than 10 years ID 14 of the 21 cases the age of the patients was from 35 to 15 years thus showing a definite ex 4b be ap r etd ) as oo we . . moeTepa 8 rege 1 nd pegs TAL eeeame as iis: wh - te 42 AyAy 4 Y a * a ne eee a 8 Bibs 4 of Hee a a : Pie. ne 4 . 1% oa . ny ATER, GIS PARES Nia at i PLE ar CN - ee mt Hy eres OO Da ae t a Vivekoo Fs3 . ere: Si oat, eh Mr FR x : t EI BOB ek Page 54 INDUSTRIAL MEDICINE AND SURGERY February 1951 shift into a younger age group than that found with the tissues for lung cancer in the general of the respiratory tract In the majority of cases population where view of the existing tendency to relate from 45 to 65 occurs in the group of years Similar observations have the recent increased frequency of lung cancers to the action of a single widely distributed can- noted that Kennaway and Kennaway _ gas stokers and patent fuel workers who have a similar exposure to tar fumes and dust have a more than nine incidence of lung cancer rate 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 exposed 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 development 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 unsuccessful in regard to pulmonary tumor for- mation Staufer Intratracheal insulation 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 Tedeschi as well as Simonds and Curtis observed merely atypical proliferations of the bronchial epithelium of rabbits after re- peated intravenous administration of tar similar result was obtained after the direct A in- troduction of tar into the pulmonary parenchyma of rabbits Gerschin and Pigalew Since none of the called carcinomas produced by insuf- flation or intravenous or intrapulmonary in- jection of tar gave rise to metastases it is doubt- ful whether any of the reported atypical liferations of the bronchial and pulmonary enchyma were actually malignant pro- par- . It is noteworthy on the other hand that the cutaneous application of tar to mice was followed by the appearance of adenocarcinomas of the lung Murphy and Sturm Koose and Cordes Lynch Schabad Watson and Mellanby Campbell Samssonow Puccinelli Pucinelli as well as M^ller obtained with the same method lung cancers in rats These remote cancerigenic effects of cutaneously applied tar on the lung suggest the possibility that in man also cancer of the respiratory tract may result from con- tact with environmental cancerigens by other than the respiratory route < Smoking d Tar Fumes from Tobacco Smoking The tobacco smoking habit provides an additional tarry environmental source through which ma- terial in the form of hot fumes comes in contact cerigenic 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 last three to four decades Bogen and Loomis Sch^...rch and Winterstein Hruby and Sweany Roffo McNally Lickint M^...ller Arkin and Wagner Ferrari Mertens Ochsner Dixon and DeBa- key Fulton Grace Hoffman Schrek Baker Ballard and Dolgoff Wynder and Graham Jack- son 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 cancer to cigarette smoking others claimed that the inhalation of tobacco smoke is merely one of the factors that is involved Hoffman 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 ered The complete exclusion of these when investigating tabagism must lead considfactors to seri- our errors It is moreover evident that the present trend in the sex ratios of lung cancer and of cigarette smoking run in opposite directions is while the sex ratio of lung cancer becomes more heavily weighted in favor of the cigarete the male sex that of cigarette smoking doubtlessly favors increasingly 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 Sch^...rch and Winterstein It is obvious on the other hand from measurements of the temperatures obtained in pipes cigars and cigarettes during the smoking process that temperatures are reached 400 to 700 which might cause the production of aromatic compounds of canceri genic nature through 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 contradictory While Roffo claimed rather uniform and con- sistent cancerigenic action of various tobacco tars in mice and rabbits the great majority of other experimentalists either obtained only carcinomatoid growths in the ears of rabbits and an occasional skin cancer in mice t Cooper Lamb Sanders and Hirst Campbell Flory Hua Sch^...rch and Winterstein Chiha- Hoffmann matau or no tumors at all Bogen and Loomis Schreus and Zurhelle Mertens  VOL 20 No. 2 INDUSTRIAL MEDICINE AND SURGERY Page 55 It appears from the evidence reported that at nn- at the present time only suggestive epidemiologic data exist connecting the inhalation of tar fumes in tobacco smoke and thereby the smok- ing habit with the development of lung or larynx cancer in man Hueper It is unlikely moreover that this type of respiratory contact with a variety of vegetable tar plays a dominant role . in the production of lung cancer since experimental observations place tobacco tar at best -* 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 residues of arsenical insecticides The smoking of such a tobacco therefore would entail the inhalation of arsenical vapors or fumes which by themselves seem to represent a respiratory can- . cer hazard Although the exposure to tobacco dust does not entail contact with tarry combustion prod- ucts of tobacco mention is made in this connection of the claim that the inhalation of tobacco dust tobacco workers cigar makers tobacco dealers creates an increased liability to lung cancer Seyfarth Krompecher Heilmann Beh- la Benda Ferenczy and Motolcsy Brinkmann Enger Langbein Borst Jaeger and Kolb Rottmann Koelsch Wacher and Schmincks Lickint Lehmann however pointed out that persons engaged in the tobacco trade are in general heavy smokers The entire statistical evidence as to a lung cancer hazard from to- fark bacco dust is unreliable and requires confirma- > tion before such allegations can be entertained af pean Re seriously e Petroleum and Shale Oils Inhalation of renga processed mineral oil mists and fogs occurs for occupational as well as medical reasons The question therefore has arisen as to whether such exposures may result in the production of cancers of the respiratory tract Kennaway and Kennaway stated that there exists a rela- tively high incidence of laryngeal cancer in mule spinners who during their work inhale a mist of cancerigenic shale oil used in lubrication of the spindles While the use of mules has long been discontinued in the United States in textile manufacturing using fibers of vegetable animal or synthetic chemical origin mules are still employed in asbestos mills for the production of asbestos threads having a minor addition of other fibrillar material cotton rayon Southam noted that mule spinners exposed to a spray of shale oil occasionally develop not only cancer of the scrotum but also of the stomach and lung Scott on the other hand stated that he had not seen a single case of lung cancer in shale oil workers of whom those employed in the press rooms of paraffin departments may be- come exposed to the inhalation of oil fogs Roesch reported a case of triple cancer lung skin stomach in a paraffin worker of a lignite oil operation An inhalation hazard from lubricating oil mist and fog cutting oil has been incriminated in the excessive incidence of lung cancer among French turners millers planers mechanics and fitters Huguenin Fauvet and Bourdin Touraine and Bour Kling Samssonow and H^'ros Statistical data cited previously indicate that painters who are exposed to the inhalation of mists from petroleum fractions used in paints have an excessive lung cancer incidence rate No information on this point is available in regard to printers and construction workers who spray impure paraffin Humperdinck Brodnitz and in workers in match and proofed paper factories using impure paraffin for impregnation While there does not exist any information on the pulmonary effects of oil mists and fogs nebulized oil in experimental animals Schabad Campbell Twort and Lyth and Kling Samssonow and H^'ros reported an increase of lung tumors in mice following the cutaneous application of shale oils and lubricating oils of petroleum derivation There was however no direct correlation between the degree of cutaneous cancerigenicity of these oils and the extent of pulmonary tumorigenesis f Isopropyl Oil The only aliphatic chemical that may be involved in the development of cancer of the nasal sinuses and of the lung when inhaled as a vapor is apparently isopropyl oil which is a crude product of the manufacture of isopropyl alcohol Although neither the actual existence of these occupational respiratory cancers nor the nature of the causal agent is as yet entirely established the observations made in two plants known to us are of sufficient significance to deserve further study If confirmed these findings would open a large new field of environmental chemical agents straight chain and cyclic aliphatic hydrocarbons that would require intensive scientific and epidemio- logic investigations for evidence of potential cancerigenic properties NORGANIC CHEMICALS Observations made during rather recent years in the occupational field indicate that respiratory exposure to inhaled dusts fumes vapors and gases of various metals or metal compounds seems to convey an excessive liability to cancer of the respiratory system a Arsenie While cancer of the skin through medicinal environmental or occupational contact with inorganic or organic arsenicals has become a well recognized fact Hueper Neubauer cancer of the respiratory organs following exposure to arsenical dust fumes or spray or after medicinal ingestion of arsenicals represents a sequela of more recent observation and of less firmly established nature The total number of lung cancers after medicinal or occu- pational exposure to arsenicals stands at present at 13 cases with one additional case listed as Coby? pA AUDfs WY Barhead ah br AOE Po a i". . t iM ei s as vated Fe Aatyer at Fak e? { 3 ee. } L eas ad . ad 2 M2ehd aegi NrFey teNe 42, yaa rh LE ig Sige Abe 6 Page 56 INDUSTRIAL MEDICINE AND SURGERY February LUNG CANCER MORTALITY IN SEVERAL OF MONTANA 1947-1948 OUTS COUNTIES < RS Ss 1951 .Ss County Population 1940 Der Lage 13,627 Silver Bow 53.207 Cascade 41,999 Major Major Industry Copper Smelting Copper Mining Copper Mining i Number Lung Cancers Male Femain : r 27 z . 20 3 Total 21 a | Total Cancer Deaths 98 239 23 209 L> ung Cancer Femal Mala Femal 30.8 0.0 po] 13 127 127 33 Annual Lang Cancer Death Rate 100,00 100,00 Mate 145.7 Female LR.G 3.3 18.3 12.3 Smelting Cailatin Agriculture t) 11.259 1 i 82 3.0 0.0 3.2 The estimated crude death rate for lung cancer among white male in the entire United States population in 1947 is 14.9 ppp odleb ; cancer of the larynx Two of these curred after medicinal use of cancers oc- County where about 25 of the population Montgomery and arsenicals - Semon Waisman Russell and Kla- 13,627 is engaged in smelting of copper ores containing 0.5 arsenic and where from the ber the other followed after occupational ex- posure to dust of past industrial history of this region arsenical pesticides manu- pational as well an occu- facture and use sheep dip manufacturers as environmental arsenic hazard may be assumed vineyard workers or smelter fumes wether four cases Hopkins and Mere- to exist In the adjacent Silver Bow County where ex- one case Saupe two Studdiford tensive copper and zine mining activities are car- case von Pein one cases Frommel one ried on the proportion of lung cancer deaths case and Faning five cases of lung three apparently identical with eancer deaths was 20.6 and 1.5" two 27 cases to for males Merewether'si one case of larynx In the cases for females total number jority of the lung cancer ma- of cancer deaths 259 total population 53.207 occupational origin there cases of apparently existed There was in contrast in the adjoining Gallatin lesions characteristic of chronic cutaneous County which is agricultural in character and arsenicism The cancers of the respiratory tract observed which has a population of 18,269 one male lung cancer death while again in Cascade County by Hill and Faning among facturers represented sheep dip manu- with a population of 41,999 and with 31.8 of all cancers ob- arsenic ore copper- served in this group engineers packers chem- mining and smelting activities the ists proportion of lung cancer deaths to all deaths These occupational observations are of from cancer was 12.7 for males 20 cases tinct environmental importance since dis- and at 3.5 five cases for females with a from Germany have related serious reports total number of 209 cancer deaths These ob- injuries in domestic and wild arsenical servations are of only limited value since within the fume of animal life living cover too short a period of time too they zone silver and lead smelters number of small a to arsenic containing fumes released into the air cases and no detailed data on the from these plants Preil Nieberle also occupational and environmental aspects of the ported from the same region the endemic re- individual lung cancer cases However the high rence of adenocarcinomas of the occur- frequency of lung cancer in counties where ar- nasal sinuses in a flock of sheep and stated that a certain senic contamination of the environment is known to exist is of sufficient importance to call connection of this disease with the locality and with an injury by arsenic can scarcely he ex- for a of thorough and extensive study of the presence cluded a potential arsenic lung cancer hazard in Similar environmental and industrial health all those regions in which existing occupational and environmental conditions warrant such in- conditions may exist in this country for those vestigations : parts where arsenic containing flue dust or ar- senical insecticides have been and are re- leased 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 past years entered the air from copper smelting operations may be of significance in this respect Lull Wallach Mortality and morbidity records for the years 1947 and 1948 revealed that 30.8 21 cases of all male cancer deaths total cancer 98 deaths were listed as due to cancer of the respiratory tract in Deer Lodge 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 meth- ods Neubauer Hueper b Asbestos There occurs tact with three different typesreosfpirsailtiocray ccoomn-- pounds namely inorganic crystalline or amorphous silicates organie silicones and asbestos Since silicotic pneumoconiosis is characterized by a chronic granulomatous inflammatory re- . VOL VOL 20 No. 2 INDUSTRIAL MEDICINE AND SURGERY theory and thus seems to fulfill remarkably well _ , he basic requirements of the chronic irritation " theorytheory of cancerigenesis several investigators bave incriminated this frequent type of occu- pational pneumoconiosis in the development of _ cancer of the lung Fine and Jaso Anderson _ xy... rete paeg . | Syeey e . ae two as Sead _ and Dible Charr Klotz Dible There are in fact some 50 cases on record in which cancer of the lung or larynx and silicosis were existing Dible Fine and Jaso Klotz and Simpson Maxwell Sladden Middleton Sweany Porsche and Douglass Vorwald and Karr Allen Sokoloff Pancoast and Pendergrass Simons Schnurer Charr Harris However the great majority of investigators have come to the con- clusion that there does not exist any causal re- lation between silicosis and pulmonary or laryn- += geal malignancy Vorwald and Karr Allen Feil Harris Pancoast and Pendergrass Saupe Schulte Schulz Berblinger Schulte and Schulz noted that coal miners in the Ruhr district among whom silicosis is frequent have no unusual frequency of lung cancer while Allen : _ ee ot - t+ A recorded a similar observation for the coal miners of Pennsylvania Corresponding negative observations were made by Vorwald and Karr on individuals who came to necropsy with silicosis at the Saranac Laboratory and have ey oe ray .. yom ( pee . been reported by the Miner's Phthisis Medical Bureau of South Africa based on studies made among the South African gold miners in the Johannesburg district These conclusions are supported by the results of experimental investigations in which mice rats guinea pigs rabbits chickens and perp a. cats were exposed to the inhalation of silica orn is f e' dust Campbeil Vorwuld and Kare Willis and Brutsaert . A fundamentally different situation on the other hand seems to prevail in regard to the causal relation between asbestosis and cancer of tye the lung Because the recognition of asbestosis as a special form of pneumoconiosis is of rather r recent the analysis of 18,280 death cer- 122 122 tificates cancer of the lung and larynx in maies from England and Wales from 1921 to ra | iea s 1932 did not reveal any cases of lung cancer in asbestos workers Kennaway and Kennaway Since 1935. however an appreciable number 55 of cases of asbestosis complicated with po a }- jon avisage a: ar oP ww 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 Merewether Luton and Champfix Linzbach and Wedler Dominici Baader Homburger Holleb and Angrist Desmeules Rousseau Giroux and ners Sirosis Cureton Figs 4 5 and 6 re The proportion rate of lung cancer in per- song with asbestosis who came to necropsy 7) stands between 13 and 15. The exposure time ranged from three to 27 years average 15 , i aee years Rend 9 r~ + 9 ee BEER. Bi Pedpce A. Bien tat 2 ergata; Fig 4 Atypical glandular spithelial formations in fibrotic and chronically inflamed lung with asbestosis bodies within desquemated epithelial cells located within lumen of cystic gland formations ~_e oe, + eee SO wo P Te aoAeec - rg Ot ee =e oe AP a SK, SPOS Squamous cell cancer adjacent to Fig 5 of lung with asbestosis epithelial cell pegs bodies eS BO AES se. tS . 5 ae? Rex Wao 2, S YY aS te Sa tt we Piet ee PAS TRS Ses yr 345 Ke te po ae a is po i Ra ath ' > ore T ~~ e Combination squamous Fig 6 of atypical glandular formations cell carcinoma in asbestotic lung and The latent period after cessation cessation of exposure was from 10 to 12 years Multiple cancers were found in several cases and both male and female workers were affected The female sex while ratio arcording to Merewether is 2.4 while the mean age is about 52 years Although Warren rather recently maintained that the con- ee Pod Pots et q Rare - . ' ge ae one er 7 oe wsv t te ge any Wy ot ri . ~~, waligg > - 3 18 E say 2 PUY wb OA ie 3 . C 45 ae .g4ac _ tea. Re Page 58 INDUSTRIAL MEDICINE AND SURGERY February 1951 oo. AGE DISTRIBUTION OF ASBESTOSIS Cancer Age Casen : in cancer 30-40 41-50 2 i nuteworthy is relatively that the young 51-60 61-70 6 3 manifestation age 71-80 1 years of abertos . . SE; SSs & ae js Exposure Time or ^ sbestosis CANCER > ~~ Exposure Casso 12 610 I ti 2 16-20 3 21-25 5 25-30 _ I peare nection 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 The reason for the different behaviour of silica and asbestos in regard to pulmonary can- cerigenesis is unknown The various metallic constituents of asbestos may possibly play a role NS he ~ * 3 ye. oe * ^' . ow af:bas ry a -38 x4 ore soe Fig 7 ' el Round cell carcinoma of the lung in a chromete worker with black chromite deposits in adjacent lung tissue WA ale While the experiments of Vorwald and Karr Ae performed on guinea pigs that were exposed to a MO asbestos dust gave negative results those con- ducted with mice by Nordmann and Sorge ap- ek parently yielded positive results since a few RA of the animals surviving the inhalation of as- . bestos dust sufficiently long showed at E A autopsy pulmonary lesions interpreted as squamous cell AE cancers of bronchiogenic nature All spontane- e ous pulmonary tumors occurring in mice on one the other hand are of glandular type and alveo- . ke lar origin . e 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 chromate While Fig 8 Re the first two cases of chromate cancer of the Spodogram of lung with chromite pneumoconi sisshow- tn lung were observed in 1914 in Germany Leh- ing the black chromite deposits within the white min- Mit mann it was not until 1936 that their number eral sketeton of the ashed lung saction hae ea) industry had become sufficiently large for establishing making establishments and a definitely the causal relation between exposure and processing of in the production to chromate dust and lung cancer in German mium alloys It is metallic chromium and chro- chromate plants Alwens and Jonas Alwens Goldblatt and remarkable that according to an Bauke and Jonas Bauke and Alwens Baader Wagstaff the English chromate Gross and Koelsch Gross Pfeil Teleky Bauer these apparently has remained free from eye Carozzi Koelsch Lecoeur Saita Staemmler respiratory cancer hazards mated that the Gross esti- Teutschlaender Kennaway and Kennaway rate chromate lung cancer incidence eer the While the exposure in the chromate plants was among Se approximately 1,000 effectively to dust of chromite ore and of exposed German workers stands at 3.0 It ap- ee ee monopcohtarsosmiautme and bichromate salts of sodium or pears to have risen in more recent years to re about % since Baader placed the total Se the respiratory contact in the chromium pig- of chromate number ment manufacture which resulted in lung can- No cancers in Germany at above 50 ee cer was in all cases eight to zinc chromate similar figures are available from this ee, Koelsch Baader zinc yellow Gross and country However the epidemiologic studies of Pees Machle and Gregorius have shown that the noted moreover that there were nine cases of cancer incidence rate lung lung cancer on record among workers of the workers is from 10 among American chromate Germany chromate consuming industries in parable industrial to 40 times that of a comgroup or an The more recent observations of similar na- times the expected rate average of 16 A recent analysis of workers ture among American chromate cover the final fate of some 150 former so far only chromate manufacturing operations workers chromate In neither country is there any information engaged in chromate production for at least six months and having passed a latent available as to the existence of lung cancer period of more than four hazards for workers employed in chromium years demonstrated that of 25 deaths that had so far occurred in plating operations in the manufacture of inks and this group five were caused by cancer of the paints , in printing painting dyeing dye . respiratory tract 20 Figs 7 and 81 VOL No. 2 INDUSTRIAL MEDICINE AND SURGERY Page 59 ~~, { AGE DISTRIBUTION OF CHROMATE OF THE Lung CANCERS 21-30 31-40 41-50 51-80 61.70 71 and above Tran Tusal Mane 4 6 le 18 tS 4 13 16 } e Germa 44 i BETHES 12 61.7 1 The 11 age 2 H distribution 21 of the 1 chromate Total cancere 100 in practically identien Kennaway and KennawLY with that seen in a serve of 1,514 long caneers of unknows etiology that wae saba by Mats EXPOSURE PERIOD OF CHROMATE CANCERS OF THE LUNG G10 11-20 21-30 31-40 41 and above Yan 10 18 10 4 3 12 a 1 German 15 years 2 American 16.6 The total number of observed cases of chromate cancer of the lung from both the United States and Germany is now well above 100 since additional CASEI have been discovered after the above Ares were reporteil 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 New- ran The statement of Machle and Gregorius that apparently the monochromate only is cancerigenic does not seem to be supported by observations made in German plants where in Leverkusen 10 cases and in Uerdingen 14 cases were found among workers in dichromate plants Such a selectivity of monochromate is more- ( hewpoint _ scarcely conceivable from a biochemical hewpoint since both monochromates and bi- . chromates are readily ionized in the body Whether chromite ore dust represents a cancerigenic factor in chromate workers is still an open question although it may produce a chemical pneumoconiosis Lukanin Likewise it is uncertain whether chromium plays an essential role in the production of other human cancers although Dingwall and Beans some 15 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 implantation of metallic chromium into the marrow cavity of the femur of rabbits Vollmann on the other hand gave rise in animals surviving for more than three years to cancers at the site of deposition and in the lung Schinz d 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 Baader During the following 15 years several reports on the continued appearance of such cancers _ 7 iN wwere made by various investigators i Grenfell Merewether Cooper Stephens Bridge Amor 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 1924 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 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 refinery 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 arsenical 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 cell 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 containing nickel dust obtained as concentrated matte from the Mond Company gave results of doubtful statistical significance since the ratio of lung tu- mors in the test series and in the controls was 14 It is uncertain whether these experiments actually duplicate the conditions of exposure fe ial aa a!rd Sax Bhi oy ag: she on. ie nd 4 Pod Pi hE ii pi sebaes { part ELEC Os ae ee 4 4 at e a rN TL bias Re te. SUE ee if ET Oa - BS PR Sarn EE Eo A 4, e oo : tS A Bb 1 pada ae!4 yi ayopyree, a Ag 4 at:re at . tone f 4 rhs at Sr . Mon ale hee ae rae He ane Rae % dae rom i on h tar ear oes3t . Pape Fe spore; Alaa Ss Fe te: Nos os Cor foe ot no aesat. Feed ? r, - oyPo On WoT. SPN gee ON mt Soe a date he 4,Bsie 7h 7. Rear Bike eps Page 60 INDUSTRIAL MEDICINE AND SURGERY February February 1951 sustained by the workers in the nickel refineries since the copper matte manufactured in Canada and used in England contains only minute amounts of arsenic The origin of the ar- PR engt re yee oe awit MLR SA eS uo. USS 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 epidtiecmailolaosgiwcelal ndas exscpieernitimfeinctal methods for prac- reasons Definite information 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 and in the polishing of nickel may aid in clarifying the presently con- troversial etiologic aspects of the cancers oc- curring workers among the copper refinery Fig 9 Highly anaplastic carcinoma in a Schneeberg miner lining showing many grotesque cells which are commonly seen but not specific for an irradiated mucosal and the air in the mine ducts contains radioactive gases and dust strongly indicates that a prolonged exposure to these agents is causally related to the occurring pulmonary malignancies PHYSICAL AGENTS ca radiation Despite the large number of persons whose lungs have been subjected to intensive irradiation by rays for medicinal reasons cancer of the breast or lung there is not a singie case of medicinal 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 and stratifica- tion giant cell formation and squamous cell metaplasia of the bronchial epithelium Bauer and Schaer Warren and Spencer Warren and Gates Widmann Mcintosh and Spitz Leach Farrow and Foote Jacobsen Freid and Gold- berg Bauer -Engelstad produced similar re- actions in the pulmonary parenchyma and bron- chial epithelium of cancerous responses rabbits without obtaining Warren and Gates reported corresponding acute lesions in rats The development of a squamous cell cancer of the larynx on the basis of a chronic ray in- jury produced by 86 ray treatments given for a skin disease of the neck was reported by von Eicken b There Radiation of Radioactive Substances are only two cases on record in which prolonged inhalation of radioactive gases and luminous chemist dust by a laboratory technician and a engaged in the production of medicinal radium preparations or in the manufacture of paint respectively Tonges and Kalbfleisch Kalbfleisch Belt Doenecke caused fatal fibro- sis of the lungs The high incidence of pul- Schneeberg monary cancer among miners in Joachimsthal where radioactive ores are and mined Weber Uhlig Thiele Rostoski Saupe and Schmor Thiele Stocklasa and Penkava Stocklasa Schmort Scheffler Rustoski and _ Saupe Rostoski Saupe and Schmort Rajewski Neitzei Ludewig and Lorensen Lorenz Lin- demann Lange Koelsch Hueck Hopmann Beyreuther Agricola Aucke Arnstein Baa- der Bauer Epstein Henckel H^/rtung and Hesse Fischer Teleky Doubrow Pel- ler Saupe Behounek and Fort Czechoslovakian Commission Ziel Woldrich Tschelnitz Sickl Behounek Pirchan and Sickl L^wy Humphries Beutel and Woldrich Fig ) 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 L^wy 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 exist for employees of may mesothorium refineries and thorium mantle factories who inhale thoron since the degree of atmospheric radioactivity in auch plants was found to be in quantitative x agreement with the experiences in Schneeberg and Joachimsthal mines 40 to 10x-11 0-1 11 curies of thoron per liter of air in thorium ations against 40 to 10-110-1 11 curiesoperi-n Schneeberg mines and 80 to 560 x 10-11 curies in Joachimsthal mines Since Bryan and Silver- man recently pointed out that electrostatic eliminators covered with a gold film either polonium or radium containing inhalation hazard by contapmriensaetnitonan ofindtuhsetraiiarl with fine particles containing radioactive mast terial the possible development of pulmonary cancers in workers engaged in operations where . 7 Vol 20 No. 2 INDUSTRIAL MEDICINE AND SURGERY Page 61 7 i . Noe. ' - these devices are used textile paper might ll be kept in mind Most of the recent instigators of the Schneeberg and Joachimsthal lung cancers agree that their radioactive can- sation can be considered as almost definitely established AGE DISTRIBUTION OF LUNG CANCERS IN RADIOACTIVE ORE MINERS 12 12 16:31 40-49 50-69 64-69 and over a 11 x li 9 , fi 6 2 fi Total 83 Schneeberg 10 Joachimsthal - 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 supports such claims Perhaps the most objectionable contention that has been put forward in _ ax this respect is the speculation that the lung . cancers among the Schneeberg and Joachims- Ln thal 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 s* community of some 10,000 inhabitants located . at the end of a railroad branch line and 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 H^/rtingand Hesse supports this con- ! clusion since there were 44 different names a this group Duplications existed seven times ~ iplication and quadruplication once each This fegree 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 familial cancer under such conditions is not due to heredity but due to identity of exposure to an environmental cancerigen Similar circumstances of exposure to soot have been in past decades the reason for the appearance of scrotal cancer among several members of the same family engaged as chimney sweeps in England To introduce the concept of heredity into such a picture is totally unjustifiable and merely acts to obscure or confuse rather clearly established facts of environ- mental cancerigenesis There were approximately 400 cases of lung cancer among the Schneeberg miners between 1876 and 1939 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 rc Schneeberg miners and from 47 to 50 of the deaths of the Joachimsthal miners were caused e , by cancer of the lung The recorded age distribution clearly demon- en strates a shift toward the younger age groups as in individuais dying from lung cancer following we _ exposure to radioactive dust and gases . The period of exposure ranged for jority of the Schneeberg miners from the ma20 to 50 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 mines in the Rocky Mountain area Warschwa- ski 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 anaplastic 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 genic vapors or gases in the because absence canceriof 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 L^wy aimed at the production of pulmonary cancers in mice exposed to radioactive dust and gases were negative subsequent ones conducted by D^hnert Rajewski Schraub and Kahlau Lorenz Heston Eschenbrenner and Deringer gave suggestive results Of definitely more conclusive character are the observations reported by Lisco and Finkel who obtained malignant pulmonary 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 during 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 tract are attributable to the inhalation of a number of more or less well defined chemical or physical agents Although the total number of these respiratory 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 teje gh tT. yt Ed we n we ecrh en 4 br. ono ee, 7 . Pre t a ay wea seat ay Be aE, Ee sagt ye a Pay, or &, a ot of See.e hi te eee a ae at <i vgs en Page 62 INDUSTRIAL MEDICINE AND SURGERY February 1951 of merely circumstantial evidence that environmental factors play a indicating significant of occupational lung cancers mistaken for many years for tuberculosis or silicosis role in the production of pulmonary nasal and laryngeal malignancies The available information on the recognized Future studies of environmental pulmonary cancerigenesis might well include proper con- sideration of local atmospheric conditions for and suspected respiratory carcinogens moreover suggests that the known numbers of environ- agents air pollution with cancerigenic In view of the long latent period of environ- mental respiratory cancer represent only a mental respiratory cancers which ranges from fraction of the actual ones since existing epi- five to 40 years and because of the fact that demiologic studies on this point are highly de- these cancers may develop many years after fective cessation of exposure to the cancerigenic exo- Although all known environmental cancers genous agent it is essential that arrangements have followed upon the inhalation of exogenous are made for the medical supervision and con- cancerigens present in the form of dust fume trol of effectively exposed persons to extend be- mist fog vapor or gas serious consideration should be given to the possibility that some or yond the period of employment Likewise it is pertinent that detailed employment and exposure many cancers of the respiratory tract may be due to agents entering the organism through data in addition to name birth date and place and social security number are recorded and the alimentary or cutaneous route and being kept for all persons who had effective exposure either excreted through the respiratory organs to environmental respiratory cancerigens so as or having special metabolic or chemical atfini- to ascertain in future investigations reliable and ties to these tissues valid epidemiologic evidence on the existence The past history of the discovery of environmental respiratory cancers has shown that the first indication of their existence is usually pre- and extent of cancerosf the respiratory tract While such procedures will prove to be tedious 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 make valuable contributions to the etiology and tributions to the etiology of human cancer The experiences made in connection with en- epidemiology of respiratory cancers by investi- vironmental respiratory cancers suggest that the gating thoroughly the entire occupational his- regional variations in lung cancer among the tory of their respiratory cancer patients for general population may be attributable to locally evidence of a previous exposure to an environ- restricted quantitative and qualitative differ- mental cancerigen Special attention should also be given to all those patients who enter medical ences in trum the environmental cancerigenic spec- care with the diagnosis of tuberculosis or sili- Likewise the evidence related to environmen- cosis or both and who have been employed in industries where they became exposed to various cancerigenic metals such as arsenic uranium ores chromates nickel asbestos and bituminous substances The history of occupational res- tal lung cancers indicates that the increased fre- quency of these tumors observed during recent decades is apparently not caused by the appearance of one new environmental cancerigen related to occupation or habits but rather re- piratory cancers offers several vivid examples flects the action of several or many cancerigens | I. # # er Or eT ue + NNSae rane ob eke Sci st? 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 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 Labor's Division of Factory Inspection The governor ordered the bureau l^fiquidated by next June 30 the end of the present biennium The Bureau of Industrial 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 the Department of Labor to review findings made in the course of its inspections , pe rg ~ e rat $s A. gE 5. = bord Hesedy