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FILE NAME Kent KNT DATE 1951 Feb DOC KNT121 DOCUMENT DESCRIPTION Journal Article - Environmental Lung Cancer Industrial Medicine and Surgery Feb1951 INDUSTRIAL MMEDICINE EDICINE AND SURGERY The Journal of Medicinein Industry With which are consolidated The Industrial Doctor and International Journal n^ Medicine and Surgery FEBRUARY 1951 Number 2 Environmental Lung Cancer W. C. HUEPER M.D. Cancerigenic Studies Section National Cancer Institute Bethesda Maryland ANCER of the respiratory tract had a relatively 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 yo) ~ s-; ;., . 2 ( a a : 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 usider 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 enncers 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 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 gircumstantial and conclusive evidence regarding the role which environmental cancerigenic 2 agents apparently play in the causation of these . tumors o 3y *. ty oe saeFae . Circumstantial Evidence 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 Dr. He's references are identifled in a detailed and tensive bibliography of which a copy ma be obtained by writing him at Cancerigene Stualies Section Cancer Control Aranca U.S. Pulilie Health Service National Institute of Bealth 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 cancer 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 con- sistently high autopsy rate and a competent pathological service there is little reason to attribute 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 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 factora played an important role The available statistical evidence suggests therefore that any real increase in the frequency of lung cancera if such has occurred may most likely be ascribed to the action of exogenous factors which en- oF% Page 50 INDUSTRIAL MEDICINE AND SURGERY February tered the human environment 1951 adenocarcinomatous half century This during the last conclusion receives some ated type and 18 females 11 37 and type support from the fact that the more recently discovered majority of environmental canceri- While Hollingsworth 52 respectively recorded a similar sex dis gens cause cancers of the tribution of adenocarcinomas Mason noted while those respiratory tract adenocarcinomas were that previously fected the skin established mainly af- 6.7 of the male present in this series in cases and in 13.7 of the fe- male cases Lingskog on the other hand re- ported that adenocarcinomas occurred with equal frequency in both sexes and that all adeno- carcinomas observed were present in individuals able rise in the occurrence of lung cancers dur- below the age of 40 A similar ing the past four decades has been dependence of adenocarcinoma on by a definite shift in the sex distribaucticoonmpoafnitehde lung cancer in favor of the age of the individual was noted in the ceedings of the First National pro- the male sex the in- Cancer Confer- crease in lung cancer incidence on agents to which seems to depend males become exposed ence The proportion of adenocarcinoma dropped from 30 in the age group 0-49 years to less often or more intensely than females and more than 20 in the age group 60 years and over are essentially unrelated to which ditioned factors endogenous sex con- There was a corresponding rise in the propor- tion of epidermoid carcinomas while the un- This conclusion is supported by the fact differentiated type of cancer seemed to be un- the female sex ratio of that affected by the age factor Gebauer hibits remarkable local differenlcuensg cancer exvarying be- that adenocarcinomas originate in 90 frreopmorttehde secondary and tween 2 in parts of the Sweden Henschen to 20 in United States O'Keefe while small bronchial branches while the majority of the undifferentiated and epider- averaging most often 5 to 10 moid cancers develop from the main in 1610 cases Fulton 7.3 Clemmesen reported from Den- branches bronchial mark that a shift in the female The proportion of the various histologic has occurred there during recent sex ratio years after of bronchiogenic carcinomas thus types appears to dif- fer according to sex and hinav1i9n4g5 satnoodd isat 4 in 1931 it changed to 1 topography in the age as well as to their expected to become stabilized at bronchial system Their rela- a ratio of 8 in the near future tive sex distribution moreover seems to An exogenous origin of the with different investigators and thus vary with of lung cancer is suggested sex differential ferent areas studied Again it is dif- moreover by ob- servations made in connection with occupational that such variations in the not conceivable manifestations of biologic and anatomic cancers of the respiratory tract found that Merewether genous lung cancers are due to endo- cancer the female ratio of asbestosis ready causes while they would find a rather stands at 2.4 to 1. This ratio illustrates explanation in differences of exposure to the trend toward an equalization of incidence exogenous agents of various types Lindskog 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- nor Steiner observed any significant differ- cessive incidence rates of lung or nasal sinus ences in the distribution of lung cancers be- cancers among males on the whenever for occupational other hand exist tween whites and Negroes in the Chicago other investigators noted that area reasons contact with cers pulmonary can- exogenous cancerigens is restricted to members 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 hospital does Bombay not mention lung cancer among HISTOLOGICAL Types Sex and the eight types of cancers listed that tion Probst stated that Age Distribuin recent years for 2,652 cancers evaluated proper standardization account However until there has been a shift toward a more frequent been as to age and sex has occurrence of epidermoid cancers in made these observations convey no valid _ malignancies of unknown pulmonary information as to differences in racial servation be etiology This ob- bility or special types of suscepti- may related to the proportionally cancerigenic exposure to exogenous greater increase of lung cancers among -males than females because squamous cell agents coinciding populated by different races with regions round cell cancers and The various kinds of cancers predominate in males while evaluated circumstantial evidence adenocarcinomas are more frequent in females tal support the concept that environmen- Proc First Nat Cancer Conj The sex dis- factors cancers of are involved in the the respiratory tract production of especially the tribution of the various histologic types of lung cancers according to this lung Boycott While the actual source is as follows which extent to- Males 44 epidermoid type 38 undifferenti- the exogenous agents seem to be active in production of these tumors among the gen-  HtBiv>at YOL 20 No. 2 INDUSTRIAL MEDICINE AND SURGERY Page 51 Ya population and the nature of such agents . erate cannot be deduced from the information avail- able observations made in the field of occupa- no tional cancerigenesis permit a more definite and oa | tis. . Eee ne specific although also more limited view of these aspects of environmental cancers of the respiratory organs : Conclusive Evidence ELATION tional of Lung Cancer to Large OccupaGroups and specific Irritative Chemical Agents The remarkable increase in a zee} oie LO are ~ 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- : 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 social gradient recorded by Stevenson were com- ' patible with an etiological factor in the air such as coal smoke Stephens claimed some years ee previously that the pollution of the air by carbon monoxide from incomplete combustion of coal nd and gasoline represented a major cancerigenic factor Oldofredi recently revived this conten- tion and pointed to the high incidence of lung . among former members of submarine en crews of World War I when it was exceedingly difficult to control adequately the carbon mon- difficult oxide content of the air Campbell's experiments a rat on mice exposed to carbon monoxide however failed to show any increased incidence of pul- monary malignancies Green was inclined to at- tach 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- tolezy 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 Gerbe Several large statistical analy- ses tended to show that some occupations en- gineers mechanics painters decorators Brit Emp Cancer Campaign ; painters and fur- Fig . Atypical papillomatous epithelial growth chronic pneumonia such as seen after irritative chemicals in lung with exposure to nacemen Fulton ers metal grinders workers spinners hibit an excessive machinists foundry workTurner and Grace metal cigar makers Borst exliability to cancer of the lung Frem information to be given later in con- nection 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 the known specific environmental can- cerigens 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 Simmross Shennan Rogers Rice Husted and Billman Jaff^' Bonser Haintz and others How- ever 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 ) White 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 Koelsch 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 commercial sulfuric acid has been blamed by B ly i. CAND A) ifapete s 4 bye ae HS eae wtMaeght. 4 a. ow.. : es o Rpt eel a - ? id wee Pre OP ? esti.aera7s INDUSTRIAL MEDICINE AND SURGERY February 1 wr Sensor hi Dregs ART TT sah Atypical spithelial Figs 2 and 1 Amor for the proliferations in fibrotic bituminous lung involving lining of gland formations occurrence of lung and nasal workers can- a Soot Tarry Material Produced by th Incomplete Combustion of Carbonaceous Matte is desirable that thorough surveys of Coal Mineral Oil Natural Gas Gasoline Di showing respiratory hazards of the be made so as to obtain adequate operations above type sSeol oFtusel Wh( iDloemetshteic Industrial and Commerci cancerigenic action of soc information on the incidence rate of resulting from the incomplete combustion of among workers respiratory cancer upon the skin is well co finely dispersed aecxipdossed to the inhalation of recognized and best demon strated by the chimney tative alkalies and other irri- scrotum the sweep's cancer of th inorganic and organic chemicals such tion of causal relation between the inhala as especially beryllium and its various atmospheric soot from domestic and in pounds formaldehyddereivatives pounds carbamate glycols isopropyl organic comcom- dustrial sources and lung cancer among the gen eral and industrially employed population i phosphors alloys paints solvents much less definite Dorn In fact weed killers rubber insecticide sprays accelerators the lung is not unusually frequent cancer o There can be little doubt from atnhde peovliidsehnecse presented that data obtained among chim ney sweeps Kennaway and Kennaway Al though Schnurer reported that the of large occupational by an evaluation lung cancer in a series of 342 incidence of Pittsburgh and degrees of groups with varying types necropsies of the district increased exposure to irritative agents of degree of directly with the specific mation nature yield little definite infor- bituminosis Figs 2 and 3 Dorr found in his concerning a causal relation between statistical studies that the lung occupational activity and cancer of the cancer rate was low in Pittsburgh when tory tract Great respira- pared with that of five other com progress however has been made in elucidating such connections whenever perimental studies conducted Haythorne and Seelig and large cities by Schnurer Ex and epidemiologic investigations were limited to circumscribed inhalation of smoke from Benignus with the tions either groups of workers and popula- exposed to chemical agents of more from a an eggstove or of soot hospital flue used as bedding for mice or less well defined kind or to identical respectively were equally inconclusive lar occupational or environmental conditoironssimi- convincing little doubt On the other that the hand there or un- can be of soot contained in the air TERKECHANICK CHEMICALS The inhalation of coal Pittsburgh and other cities is carcinogenic to dust is in general not credited with inducive to cancer of the lung since being mice since Leiter Shimkin and Shear and Lei- ter and Shear could elicit skin studies conducted in coal miners statistical animals with an extract of cancers in those in this were negative various localities in the soot collected at respect Feil Jordan Kennaway and Kennaway Gerbe Schulte and mice and and Braine United States Passey hold found the fraction of house- velop lung guinea pigs exposed to coal dust did not de- soot boiling over above 250 in this respect most active Karr cancers Campbell Vorwald and The question of the This tion from the possible cancerigenic ac innocuousness however does not extend to the distillation and fractionation products inhalation of various commercial soots types of oil prepared from natural gas or of coal oil shale and petroleum tar asphalt oil residues and merchandised as lamp black pitch oil and their incomplete combustion black furnace black gas black black has become important in or recent channel products such as domestic industrial and commercial soots lamp blacks carbon cause of the huge production and years be- blacks etc. blacks oil these blacks in the rubber consumption of paint and ink industry and for manufacture in the making of eB + ate + WA oy VOL 20 No. 2 INDUSTRIAL MEDICINE AND SURGERY Page 53 coloring Sate gs records gi and because of their use as matter Some of these blacks have been prepared in late years by the incomplete combustion of oil + an mm residues that are obtained from the catalytic dee and that possess distinct can- Py? A -cracking process aon 7 -@.> cerigenic properties to mice In addition to the AT det : possible lung cancer hazard involving the pro- ag loaders shippers and industrial con- ducers Aeats, oy vereee OULBat BR SY hs SA von <7," sumers of such carbon blacks there may exist a similar hazard for the general population liv- ing in the neighborhood of carbon black plants < en because during the production of these materiais garage mechanics and automobile drivers do not show an excessive incidence of lung cancer 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 ele fe Jarge amounts of soot may be released into the et wd . ee air A similar environmental cancer hazard may result from the burning of oil dumps aed orden be eres pmaeemraohruanpsts ter-t27t ' & Aten refineries giving rise to considerable of sout Little experimental work ~ so so far has been done in studying the potential tthh vueraeusa cancerigenic properties of the various commer- > cial soots which depending upon the production ae. Bete i See MY and raw material used differ appre process ciably in chemical and physical respects and se" Steinbrueck especially Tykdets: 3 i 2 duction in tar content ( Mantell reported the experimental of skin cancers in mice painted prowith black of printing ink Seelig and Benignus on the the - oui other hand failed to see any lung cancers ( in mice exposed to the inhalation of lamp black Experiments of Miescher and Schwarz using an ox Experiments <&- cintment containing a benzene extract of oil burner soot applied to the skins of mice were equally negative Since the carbon black indus- 72 Etry is supporting experimental investigations on the potential pulmonary cancer hazard connected with the inhalation of various carbon blacks SM more definite information may soon become 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 combustion 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 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 Samssonov and Heros and gke: Available and Gasoline Engine Exhaust A me: b Diesel tet) Omilar ; h degree of uncertainty exists in regard Ke aeacy ES to the potential cancerigenic properties of the aw sel! % normal and abnormal exhaust products of low wal nha my compression internal combustion gasoline en- ee and of high compression Diesel engines fi iginnecsonnection with the development of occupa- CeePa Te tional and environmental respiratory cancers Le ha 5. Heilmann Duguid Ferenszy and LY ~~ Lorentz The contention that the yrs inhalation tke. Matolcsy hartSWyEA of exhaust fumes from gasoline and Diesel en- > psgines traffic rx. and thus the increased automobile causally Ss is related to the rise in the incidence of lung cancers in recent decades has been at- 8 Sip 1 ttahcekreebdy complete E fate1 on various grounds 1 es tag 1 1 . It was pointed out that the exhaust fumes of these engines when operating perfectly and generating products of com- bustion contain little or no ingredients of po- i tential cancerigenic qualities Bloch and Wid- mer Probst Mention moreover was made of the fact that there does not exist a parallelism between the rise in automobile traffic in differ- ent countries and the increase in lung cancer and : Konrad and Franck Syreck Lehmann : exposed to engine street cleaners 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 relation 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 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 to lung cancer It was shown that retort workers seem to be especially subject to pulmonary malignancy Kuroda and Kawabata 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 In 14 of the 21 cases the age of the patients was from 35 to 45 years thus showing a definite we, A v RE ee EB cel . . BES AL by el te cakew l s on ra 4asuy, ly ise ror ar ca are tog : od. AR? dy % e -5S wes February 1951 Kennaway recently been made workers in Canada among gas house retort Kennaway and noted that gaa stokers and who have a similar patent fuel workers dust have exposure to tar fumes and a more than nine incidence 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 intravenous administration of tar | Campbell's experiments showed that mice ex- posed to dust from tarred roads of the skin and of the lungs dSeivmeilolpaerd ecxapnecrei-r ments of Staufer Barnewitz and Bonne using mice however were negative as to the ment of lung tumors although resulting dienvesloompeof 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 formation 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 A similar result was obtained after the direct introduction 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 pro- liferations of the bronchial and pulmonary par- enchyma were actually malignant 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 can- 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 cancer 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 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 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 parent that in no instance have occupational ao pr - 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 ous seri- 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 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 Cooper 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 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 The Smoking d Tar Fumes from Tobacco tobacco smoking habit provides an additional tarry environmental source through which ma- terial in the form of hot fumes comes in contact production of aromatic compounds of genic nature through cracking McNally Cooper Lamb Sanders and canceri- Flory Hirst Hoffmann cinomatoid 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 While Roffo claimed contradictory rather uniform and con- sistent cancerigenic action of various tobacco tars in mice and rabbits the great other majority of experimentalists either obtained only car- growths in the ears of rabbits and an occasional skin cancer in mice Cooper Lamb Sanders and Hirst Campbell Flory Hua Schurch and Winterstein Chiha- matsu or no tumors at all Bogen and Loomis Schreus and Zurhelle Mertensi Wai ee < Wieaoy a "y ot * VOL 20 No. 2 INDUSTRIAL MEDICINE AND SURGERY Page 55 It appears from the evidence reported that atat the present time only suggestive epidemio logic data exist connecting the inhalation of tar wv fumes in tobacco smoke and thereby the smok- ing habit with the development of lung or larynx Lor;| ~S%.~ cancer in man over that this Hueper It is unlikely moretype of respiratory contact with a variety of vegetable tar plays a dominant role +1. in the production of lung cancer since experi- mental observations place tobacco tar at best among the weak It is essential exogenous cancerigens 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 products 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 Behla 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 tobacco dust is unreliable and requires confirmation before such allegations can be entertained seriously e Petroleum and Shale Oils Inhalation of processed mineral oil occupational as well mists and fogs occurs for as medical reasons The question therefore has arisen such exposures may result in as to whether 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 em- ployed 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 hand stated lung Scott on the other that he had not seen a single case of lung cancer in shale oil workers of whom those employed in the press rooms of come exposed to Roesch reported a paraffin departments may be the inhalation of oil fogs case of triple cancer lung skin stomach in a param n worker of a lignite oil operation An inhalation hazard from lubrieating 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 Humper- dinck match Brodnitz and proofed and in workers in 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 cutane- ous cancerigenicity of these oils and the extent of pulmonary tumorigenesis f Isopropyl Oil The only aliphatic chemi- cal 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 epidemiologic investigations for evidence of potential cancerigenic properties NORGANIC [ ing CHEMICALS Observations made dur- rather recent years in the occupational field indicate that respiratory exposure to in- haled dusts fumes vapors and gases of various metals or metal compounds seems to convey an excessive liability to cancer of the respiratory system a Arsenic While cancer of the skin through medicinal environmental or occupational con- tact with inorganic or organic arsenicals has be come a bauer lowing well recognized fact Hueper Neucancer of the respiratory organs folexposure 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 re ye . wet . Fy : abporey4 Spe py tele. ee Seayed og ae aa OE yr<iRTS Fab ? t 2 i oa Sens 4 chad Pp ey 8 4, S & , Bi Sey 2 om ari ayir 4 C wtalts riow. 9 . Bigiy: arm Soche s te Ba "ee hs F423 5 6 Sty tt,te > azack2 > eC, * aa sy =4. 5 ta esJ j AP a is: a Ten Sel. ee SALES i Page 56 INDUSTRIAL MEDICINE AND SURGERY LUNG CANCer MortalitY op Montana IN SEVERAL 1947-1948 COUNTIES February February 1951 SSS = =. County Population Total Population Deve Lodge 11,677 Silver Bow 61.207 Major Industry Industry Industry ~~ Copper Starting Copper Mining Number Lang Canceri Wale Fema 21 27 2 . Total 21 " Total CCFT Dentha 98 139 > Lung Candet Femal Main Femal 30.8 0.0 s26 EK Annual Long Cancer Death Bata 100,000 Xab 143.7 Perale Cascade 41,999 Cooper Xining Xining Smelting 20 3 LR.C 3.0 - 199 127 EK 16 12.3 Cailatin Agriculture 1 Illu^ n 18269 t Q H The mtimated crude death rate for lung 1.0 0.0 3 population cancer among white males in the entire United . States in 1947 in 149 per Illu^ n cancer of the larynx Two of these curred after medicinal use of arsenicalcsanSceerms oon c- Montgomery and Waisman Russell and Kla- ber the other followed after occupational ex- posure to dust of arsenical pesticides facture and use vineyard workers sheep dip manu- manufacturers or smelter fumes Mere- wether 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's ) one case of larynx In the ma- jority of the lung cancer cases of occupational origin there existed acpuptaarneenotulsy lesions characteristic of chronic arsenicism The cancers of the respiratory tract observed by Hill and Faning among sheep dip manufacturers represented 31.9 of all cancers observed in this group engineers packers chemists These occupational observations are of dis- tinct environmental importance since reports ifnrjoumrieGs eirnmadonmyesthiacveanrdelated serious arsenical wild animal life living within the fume zone of silver and lead to arsenic containing fumes released intosmtehletearisr from these plants Prell Nieberle also reported from the same region the endemic occur- rence 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 he ex- cluded Similar environmental and industrial health conditions may exist in this country for those 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 tact records for the years 1947 and 1948 revealed that 30.8 21 cases of all male cancer deaths Stotal cancer 98 deaths were listed as due to cancer of the respiratory tract in Deer Lodge County where about 25 of the population 13,627 is engaged in smelting of copper ores containing 0.5 arsenic and where from the past industrial history of this region an occupational as well as environmental arsenic hazard may be assumed to exist environmental In the adjacent Silver Bow County where ex- tensive copper and zinc mining activities ried on the are car- proportion of lung cancer deaths to cancer deaths was 20.67 27 cases for males and 1.5 two cases for females total of cancer deaths 239 total number population 53.207 ) There was in contrast in the County which is adjoining Gallatin agricultural in character and which has a population of 18,269 one male lung cancer death while again in Cascade with a population of 41,999 and with County arsenic ore mining and smelting activiticeosppetrhe- proportion of lung cancer deaths to all deaths from cancer was 12.7 and at 3.5 five for males 20 cases cases for females with a total number of 209 cancer deaths These ob- servations are of only limited cover too short a period of value since they number of time too small a cases and no detailed data on the occupational and individual lung cancer aspects of the frequency of lung cases However the high cancer in counties where ar- senic contamination of the environment is known to exist is of sufficient importance to call for a thorough and extensive study of the of a potential arsenic lung all those regions in which cancer presence hazard in and existing occupational environmental conditions warrant such in- vestigations Such epidemiologic studies are especially indicated because of the difficulties encountered in the production of arsenic cancers in experi- mental 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 respiratory con- with three different types of silica com- pounds namely inorganic crystalline or amor- phous silicates organic silicones and Since silicotic asbestos pneumoconiosis is characterized by a chronic granulomatous inflammatory re- VOL 20 No. 2 . INDUSTRIAL MEDICINE AND SURGERY BS and thus seems to fulfill remarkably well theorythe basie requirements of theory of cancerigenesis the chronic irritation several investigators ~ have incriminated this frequent type of occu- pational pneumoconiosis in the development of cancer of the lung Fine and Jaso Anderson 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 exist , Peet ; sv.. oe tal room ing Dible Fine and Jaso Klotz and Simpson Maxwell Sladden Middleton Sweany Porsche and Douglass Vorwald and Karr Allen Sokoloff Pancoast and Pendergrass Simons Schnu- rer Charr Harris However the great ma- (38 jority of investigators have come to the con- clusion that there does not exist any causal re- =ss, lation between silicosis and pulmonary or laryn- geal malignancy Vorwald and Karr Allen befwFeil Harris Pancoast and Pendergrass fer. Saupe Schulte Schulz Berblinger Schulte - * a : and Schulz noted that coal miners in the Ruhr district among whom silicosis is frequent have no unusual frequency of lung cancer while Allen . recorded a similar observation for the coal ss miners of Pennsylvania Corresponding nega- py vs tive observations were made by Vorwald and Karr on individuals who came to necropsy with \. silicosis at the Saranac Laboratory and have t been reported by the Miner's Phthisis Medical ty . Bureau of South Africa based on studies made - among the South African gold miners in the ( aye wee S Johannesburg district These conclusions are supported by the results of experimental investigations in which mice rats guinea pigs rabbits chickens and cats were exposed to the inhalation of silica dust Campbell Vorwald and Karr 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 the lung Because the recognition of asbestosis as a special form of pneumoconiosis is of rather recent date the analysis of 18.280 death cer- tificates cancer of the lung and larynx in males from England and Wales from 1921 to 1932 did not reveal any cases of lung cancer c } fFyo r* i . . \ 1. wee in asbestos workers Kennaway and Kennaway Since 1935. however an appreciable number 55 of cases of asbestosis complicated with cancer of the lung have been recorded from Engiand 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 Sirosis Cureton Figs 4 5 and ) The proportion rate of lung cancer in per- Song with asbestosis who came to necropsy standa between 13 and 15 ranged from three to 27 years The years exposure time average 15 , Fig 4 Atypical glandular epithelial formations in fibrotic and chronically inflamed lung with asbestosis bodies withie desquamated epithelial cells located within lumen of t cystic gland formations Squamous cell cancer adjacent to Fig 5 of lung with asbestosis epithelial call pegs bodies PT a OE OPT oe. fad Oe Bae Combination of atypical glandular formations and squamous cell carcinoma in asbestatie lung The latent period after cessation of exposure was from 10 to 12 years Multiple cancers were found in several cases and both male and fe male workers were affected The female sex ratio according to Merewether is 2.4 while Although the mean age is about 52 years Warren rather recently maintained that the con- rn re) a i bite 2 ve waaay Od OO eredoe OP eOe ST AedsA ~: ta ed a ET ves Eteniv esas 2 5, F. yelke j ~yee : Hose.ee we ve wee aS a sop ty pS , , Page 58 INDUSTRIAL MEDICINE == ee AGE DISTRIBUTION OF ASBESTOSIS CANCER Age Cases is caneer 30-40 2 2 41-50 3 3 noteworthy in every that the youRR 51-60 s 51-70 I manifestation age 71-80 yean 1 of berts Exposure Expornre fs Conan 2 Time of ASBESTOSIS CAN 31-16 3 t 14-20 1 21-25 S 25-30 i year AND SURGERY February 1951 nection between asbestosis and lung cancer is of coincidental nature the actual existence of a causal relation appears to be very likely Lecoeur Koeisch Saita Hueper Teleky Edi- torial; Gross The reason for the different behaviour of silica and asbestos in regard to pulmonary cancerigenesis is unknown The various metallic constituents of asbestos may possibly play a role oy aXe S.2 SMS Fig 7 Round cell carcinoma of the lung in a chromate worker with black chromite deposits in adjacent lung tissue While the experiments of Vorwald and Karr performed on asbestos dust guinea pigs that were gave negative results exposed to those con- ducted with mice by Nordmann and Sorge apparently 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 chromate 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 Alwens and Jonas Alwens Bauke and Jonas Bauke and Alwens Baader Gross and Koelsch Gross Pfeil Teleky Bauer Carozzi Koelsch Lecoeur Saita Staemmler Teutschlaender Kennaway and Kennaway While the exposure in the chromate plants was to dust of chromite ore and of monochromate and bichromate saits 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 Koelsch Baader zinc yellow Gross and 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- manufacturing operations ture among American chromate workers cover so far only chromate 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 seq tows sea See oe 2 oon aes Ress ety c are te he i] et Fig 8 Spodogram of lung with chromite pneumoconiosis showing the black chromite deposits within the white min- erel skeleton of the sshed lung saction making establishments and in the production and processing of metallic chromium and chromium alloys It is remarkable that according to Goldblatt and Wagstaff the English chromate industry apparently has remained free from these respiratory cancer hazards Gross estimated that the chromate lung cancer incidence rate among the approximately 1.000 effectively exposed German workers stands at 3.9 It appears to have risen in more recent years to about % 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 lung cancer incidence rate among American chromate workers is from 10 to 40 times that of a comparable industrial group or an average of 16 times the expected rate A recent analysis of the final fate of some 150 former chromate workers engaged in chromate production for at least six months and having passed a latent period of more than four years demonstrated that of 23 deaths that had so far occurred in this group five were caused by cancer of the respiratory tract 206 Figs 7 and 81 VOL No. 2 INDUSTRIAL MEDICINE AND SURGERY Page 59 Age DistribUTION OF CHROMATE CANCERS ( OF THE LUNC 2140 31-40 41-50 51-68 81-70 71 and above Year Tota) Mean 1 e t The 6. ae 18 6 12 14 ou 14 age distribution 14 , 21 of the 6 1 1 chromasa Germa Ameraan Total essers is 4a 42 1.7 100 practies ideaonal Kennaway and Kennaw Y with that betn in a series of 1,314 long as of saknOWA etiology that was sambysed by Mate EXPOSURE PERIOD of Chromate CANCERS OF THE Lung 4-10 11-20 21-30 31040 41 and above Years 10 18 | 12 1 German 15 years 10 22 N 2 American 16.6 The total number of observed case of chromate cancer of the hung from both the United States and Germany is DOW well above 100. since additional CRAEL have been discovered after the above figures were reportesi 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- man 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 bichromates 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 were made by various investigators Grenfell Cooper 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 1924 Merewether The average age at death was 51.0 years for the nasal cancer cases range 86.0 to 66.0 years and 53.0 years for the lung cancer cases trange 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 invoived the nasopharynx The four pulmonary cancers that were studied histologically were of small round cell or squamous cell types The inhalation experiments conducted br 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 ewai ewe Nevd awen eweit idl 2, if f useiA arr i ay of be Boers FETS pte yg hairs Agate re 4 Fhiay BatyPg ZSes 1 - 4 Re ab ae OA t err as dF : Sp wy etai ran ieee AN ds Pe a STEN ed owe RESO ot wry ah ALD ee Page 60 INDUSTRIAL MEDICINE sustained by the workers in the nickel since the copper matte refineries Canada and used in England manufactured in ute contains only min- amounts of arsenic The origin of the ar- senic according to Amor is not from the but from the sulfuric acid matte used AND SURGERY February 1951 Since cancers of the to continue to respiratory tract seem workers there occur in English nickel refinery is sufficient indication to investi- gate thoroughly their causal demiologic and aspects by epi- tical as experimental methods for prac- well as scientific reasons Definite in- formation should be obtained whether cancers are of arsenical these : i ae by Amor causation as claimed = . add a! or are attributable to the inhalation of nickel carbonyl vapors and thus represent a separate type of metal cancer A study of the Fig 9 respiratory cancer incidence in Highly anaplastic carcinoma in a Schneeberg miner in nickel plating manufacture workers engaged showing meny grotesque cells which are commonly pigments and alloys and and use of nickel in the polishing of seen but not specific for an irradiated mucosal lining nickel may aid in clarifying the presently con- and the air in the mine ducts contains troversial curring etiologie aspects of the cancers OC- active gases and dust radio- among the nickel refinery prolonged prolonged strongly indicates that a workers exposure to these agents is causally related to the occurring pulmonary malignancies PHYSICAL the AGENTS Kil large number of radiation Despite Weber Uhlig Thiele Rostoski Saupe and Schmorl Thiele Stocklasa and Penkava persons have been subjected to intensive whose lungs Stocklasa Schmorl Scheffler Rustoski Rajewski rays for medicinal reasons irradiation by cancer of the Saupe Rostoski Saupe and Schmorl Neitzel Ludewig and Lorensen Lorenz andi breast or lung there is not a singie case of medicinal ray of demann Lange Koelsch Hueck Lin- cancer the lungs on record Hopmann Beyreuther Chronic radiation pneumonitis on the other Beyreuther Agricola Aucke Arnstein Baa- hand has been of relatively frequent der Bauer Epstein Henckel H^/rtung and occurrence Hesse Apart from the extensive hyalinizing and Fischer Wasels Teleky Doubrow Pel- ing changes characterizing this fibros- Ier Saupe Behounek and Fort Czechoslovakian process there occurred swelling and transformation of the al- Commission Ziel Woldrich Tscheinitz Sickl Behounek Pirchan and Sicki veolar epithelium cells and cellular into cuboidal and columnar ries Beutel and Woldrich L^wy Humph- tion giant cell monstrosities and stratifica- Work in radium Fig 9 laboratories formation and squamous cell may represent metaplasia of the bronchial epithelium Bauer an additional source of occupational cancer of and Schaer Warren and Spencer Warren and the lung through inhalation of radioactive gases Gates Widmann McIntosh and Spitz Leach Farrow and Foote Jacobsen Freid and and dust Three cases of this type have been observed in chemists Neitzel L^wy Mart berg Bauer Engelstad Gold- land moreover reported the produced similar re- actions in the pulmonary parenchyma and bron- carcinoma in painter who occurrence of a a nasal sinus in a luminous dial sustained a similar chial epithelium of rabbits without obtaining cancerous is apparent from the exposure It responses Warren and Gates reported Goodman that discussion of Evans and corresponding acute lesions in rats a similar respiratory hazard may The development of a squamous cell exist for employees of mesothorium refineries of the larynx on the basis of a chronic cancer and thorium mantle factories who inhale thoron ray in- jury produced by 86 ray treatments since the degree of atmospheric radioactivity in given for a skin disease of the neck was reported by von such plants was found to be in quantitative agreement with the Eicken and experiences in Schneeberg b Radiation of Radioactive Substances Joachimsthal mines 40 to 600 x 10-11 There are only two cases on record in curies of thoron per liter of air in thorium which x prolonged inhalation of radioactive gases and ations against 40 to oper- 10.1 10.1 11 curies in Schneeberg mines and 30 to 560 x 10-11 dust by a laboratory technician and a chemist Joachimsthal curies in engaged in the production of medicinal mines Since Bryan and Silver- preparations or in the manufacture radium man recently pointed out that electrostatic of luminous paint respectively Tonges and Kalbfleisch eeiltihmeirnatora covered with a gold film containing Kalbfleisch Belt Doenecker caused fatal fibro- polonium or radium present an industrial sis of the lungs The high incidence of inhalation hazard by contamination of the air pul- monary cancer among miners in with fine particles containing radinactive Schneeberg Joachimsthal where radioactive ores are minaendd terial the possible development of ma-- pulmonary cancers in workers engaged in operations where - soe Vo"" ' hate 20 No. 2 INDUSTRIAL MEDICINE AND SURGERY Page 61 these devices are used textile paper might all be kept in mind Most of the recent instigators of the Schneeberg and Joachimsthal ung cancers agree that their radioactive can- sation can be considered as almost definitely - established ACE DISTRIBUTION OF LUNG CANCERS IN " RADIOACTIVE ORE MINERS 2R.23 1831 44 50-69 64-49 70 and over Total < 21 21 21 xy > 17 rr " e a I 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 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 Joachims- thai 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 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 in this group there were 44 different names Duplications existed seven times iplication fegree of and quadruplication repetition of names once is not each This 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 environmental 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 appears 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 eek - v4rt Z ore 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 Warschwaski 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 because cancerigenic 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 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 respiratory 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 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 MP lege * SE1 T hts 7 po. ae ch ata, e9 " ARA Cae Co nit i i LA's peked m Ke i eG+ =en easjeTee oy seat 4 gd vom 7 Le hoe aLwo. st Page 62 INDUSTRIAL MEDICINE AND SURGERY February 1951 of merely circumstantial evidence environmental that environmental factors play a role in the production of pulmonary laryngeal malignancies indicating significant nasal and 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 epidemiologic studies on this point are highly de- fective of occupational lung cancers mistaken for many years for tuberculosis or silicosis Future studies of environmental pulmonary cancerigenesis might well include proper consideration of local atmospheric conditions for air pollution with cancerigenic agents In view of the long latent period of environmental respiratory cancers which ranges from five to 40 years and because of the fact that these cancers may develop many years after Although all known environmental cancers have followed upon the inhalation of exogenous cancerigens present in the form of dust fume mist fog vapor or gas serious consideration should be given to the possibility that some or many cancers of the respiratory tract may be due to agents entering the organism through the alimentary or cutaneous route and being either excreted through the respiratory organs or having special metabolic or chemical atfini- ties to these tissues The past history of the discovery of environmental respiratory cancers has shown that the first indication of their existence is usually presented by the occurrence of a crowding of such tumors among members of restricted occupa- . tional groups Industrial physicians and specialists in pulmonary diseases might therefore make valuable contributions to the etiology and epidemiology of respiratory cancers by investi gating thoroughly the entire occupational history of their respiratory cancer patients for evidence of a previous exposure to an environ- mental cancerigen Special attention should also be given to all those patients who enter medical cessation of exposure to the cancerigenic exogenous agent it is essential that arrangements are made for the medical supervision and control of effectively exposed persons to extend be- yond the period of employment Likewise it is pertinent that detailed employment and exposure data in addition to name birth date and place and social security number are recorded and kept for all persons who had effective exposure to environmental respiratory cancerigens so as to ascertain in future investigations reliable and valid epidemiologic evidence on the existence and extent of cancers of the respiratory tract While such procedures will prove to be tedious and expensive they will amply repay all efforts by improving the health of our people not only through prevention of environmental cancerigenesis but through resultant fundamental contributions to the etiology of human cancer The experiences made in connection with en- vironmental respiratory cancers suggest that the regional variations in lung cancer among the general population may be attributable to locally restricted quantitative and qualitative differences in the environmental cancerigenic spec- trum care with the diagnosis of tuberculosis or silicosis or both and who have been employed in in- dustries where they became exposed to various cancerigenic metala such as arsenic uranium ores chromates nickel asbestos and bituminous substances The history of occupational res- piratory cancers offers several vivid examples ~ Likewise the evidence related to environmental lung cancers indicates that the increased fre- quency of these tumors observed during recent decades is apparently not caused by the appear- ance of one new environmental cancerigen related to occupation or habits but rather reflects the action of several or many cancerigens ^' le Sos cE e Pula Shes 4 ts dye br Shineron 4 ate ^' ~ He Says He Did It To Save Money LLINOIS Bureau Governor Stevenson on December 28 ordered the of Industrial Hygiene in the State Department of liquidation of the 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 ty no duplication of activities between separate state agencies existed in the competing activities of the bureau and the Industrial Hygiene Unit of the Department of cae Labor's Division of Factory Inspection The governor ordered ordered the bureau liqui- of dated by next June 30 the end of the present biennium The Bureau of Indus- trial Hygiene currently employs 16 persons and has a biennial appropriation of acre 133,735 The commission's report recommended and the governor directed that ey the facilities of the health department's central laboratory be made available to ys the Department of Labor to review findings made in the course course of its inspections es Le 8