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FILE NAME: Kent (KNT) DATE: 1956 Nov DOC#: KNT147 DOCUMENT DESCRIPTION: Journal Article - Environmental Causes of Cancer of the Lung Other than Tobacco Smoke - Diseases of the Chest o! ' - r i ! -e; X V-. ! f.Am f-S Nj O ,, o-n \/> "z: it .......... ^ T i nt er im Session --Seattle, W a s h i n g t o n November 25-26, 1956 VOLUME XXX NUMBER 2 .... n i i -v^> a ilfei* <, * F T -l - 1 - , - > 'it ; - " ' 0 > rih a 34'td:'xr. 'XX W <HT] r n 6 r " j 7 t _!/ - 5 . /'I OFFICIAI. PUBLICATION A GUST 1.358 PUBLICATION OFFICE, CHICAGO, ILLINOIS EXECUTIVE OFFICE, 112 EAST CHESTNUT STIC ET, CHICAGO l , ILLINOIS E n tered o s S econd C lass Idg.Cor a t th e P o stciiice a t C h icag o , Illinois C op y rig h t, li)56, by to ...merican College of C hest P hysicians : ;; i : Environmental Causes of Cancer of the Lung Other Than Tobacco Smoke W. C. H U E P E R , M.D. Bethesda, Maryland The recognized or strongly suspected environmental causes of cancer of the respiratory system form an important segment of the environmental carcinogenic spectrum. 1. With one exception all so far known exogenous respiratory carcinogens wore discovered during the last 25 years (Table I), that is, during the period in which a remarkable and progressive rise in the number and frequency of cancers of the lung was observed in most industrialized countries (Fig. 1). 2. The various respiratory carcinogens are more or less well defined chemical or physical agents and/or are associated with distinct occupa tional activities engaged in by circumscribed workers groups (Table If). 3. The clinical, epidemiologic, pathologic and experimental observations related to these agents all of which act through the respiratory route TABLE I OCCUPATIONAL RESPIRATORY CARCINOGENS AND CANCERS RECORDED DURING PA S T 75 Y E A R S; T H E I R CAUSES, S IT E S AND N U M BERS Agent Arsenic Asbestos Chromates Nickel Coal Tar Petroleum Oils Isopropyl Oil Radioactive Chemicals o k e of Cancer bung Lung Lung' Lung Notes and Nasal Sinus Lung Lung and Larynx Lung Larynx Nasal Sinus Lung Nasal Sinus TOTAL Discovered 1930 193d 1932 1932 1936 1936 1946 1879 1931 Num'iiT of i'cv-onled Cases Cthor U.K.A. Cou alivies Total 7 :l 6 23 20 92 112 75 (5 140 0 84 84 0 51 51 0 53 53 7 33 40 1 0 4 0 6 0 0 625 3 0 123 1,019 1 4 6 625 3 1,142 National Cancer Institute; National Institutes of Health; Public Health Service; IT. S. D epartm ent of Health, Education and Welfare. Presented at a Symposium, 21st Annual Meeting, American College of Chest Phy sicians, Atlantic City, New .Jersey, Ju n e 2, 1955.  ; 142 W. C. H E P E E August, ion*; i ri'oresen or cancel sw-Tie occ pu'.m-ana carcinoji pdotren D c-spi on reco: observe' cvidcnc- .C TiVde I' x wl'S TABLE II--SPECIFIC Alien !. Arumm C hrominm Nickel _ Iron Radioactive Substances Isopropyl Oil Coal T a r Fuine;. Pen oiw m OH .s WORKER GROUPS WITH SPECIFIC RESPIRATORY CANCER HAZARDS ______________ W o r k e r G r o u p s Manufacturers, handlers, and users of arsenical insecticides; arsenic smelter workers; taxidermists; sheep dip worker- ; copper smelter workers Chromate m a nufa cture rs including p la : maintenance workers; chrome pigment handlers Nickel-coppor matte refinery workers Iron ore (hematite) miners ? Radioactive ore (pitchblende) miners; miners of nonradioactive ores working in radioactive mines Isopropyl alcohol manufacturers Coke oven operators; gas house retort workers Paralbn presses; male wo. sers and drill..' ; : me ; metal lathe Arsenic Asbesti Frylli .;;- v n in Nickel -.re ri Radio; Sub Isoprt oil Polve Hydr soo Petn Deri- oil Caso Diesi Ex h; C asc Eoo voi. x x x ENVIRONMENTAL CAUSES OF CANCER 143 represent the only reliable factual evidence available on the causation of cancers in different parts of f l u respiratory tract (Table III). Although some occupational, medicinal and experimental observations suggest that pnimonary carcinogenesis may ensue after a non-respiratory contact with carcinogens, there exists no valid evidence incriminating hereditary or endogenous factors as primary causal agents of Iranian lung1cancer. Despite the fact that the total number of occupational pulmonary cancers on record is relatively small, the comparatively high cancer attack rates observed among the different worker groups studied provide weighty evidence in favor of actual causal associations between an exposure to the specific agents and the subsequent development of respiratory cancers (Table IV). The reported number oil cases of occupational respiratory cancers doubtlessly represent only a fraction of the total number which TABLE III ENVIRONMENTAL LUNG CANCER SCORE BOARD Arsenic Asbestos Beryllium Chromni m Nickel i ron Radioactive Substances Isoproi: vl oil Poiyoyulic Kyuroc arbons coal t a r , binii, pitch Petroleum Derivatives oil mist Gasoline Diesel engine Exhaust Gasoline Epoxides Site of Cancer c - UiJ tv C 1 H a U 3 X b .S 'H. Is PZ o Skin X X X Population Affected Type of Evidence B e ! _i 5 a li l 3 ^U oS oS u5 1 o X ?X X ?X ? X X ?X (J ? 11 1 li X M X X ? X X X X X X X Skin X X Bor e X X X Hem at. tissue Conn, tissue XX X X X XX XX X Skin Skin X ?X ,, X X X ? ? X ? Experimental Evidence e Other organs Bone Bone Conn, tissue Bone C o n n , tissue Bon <3 Conn, tissue Hemal, tissue, etc. Skin Conn, tissue, etc. Sk, n Conn, tissue Skin Skin 144 W. C. H U E P E R August, 1956 TABLE IV RESPIRATORY CANCER ATTACK RATES BY ENVIRONMENTAL CARCINOGENS Affents Aromatic hydrocarbons: Coal ta r iuraes Petroleum oils Carbon and silicon poly mors: Isopropyl oil Asbestos Metals : Arsenic Chromates Nickel Ionizing- radiation : Radioactive area Sites of Cancers Lung' Lung; Paranasal sinuses Larynx Lung incidence in Poymiation at Risk 500:100,000 2000:100,000 10:100 ............ Lung Lung Marcs ) 1'n r a u a s a l sinuses Lung yJf. ............ 329:100,000 574:100,000 Lung' ............ Attack Rates Percent Morbidity Mortality of All Rate Rate C a n c e r --------------------------------------------- Deaths P e r 100,000 45% 55% 134.5 ........ (normal 6.5) ......................... ........ 13.2-20% asbes- t(o0s.i8s-2.a4u%topsied normal) ......................... (42x normal) (2 On ........ normal) 145.7 males (10.9 normal) 146-338 ........ ........ (50-80% of all deaths) occurred. Some of the lung cancers were certainly mistaken for tubercu losis, pulmonary abscesses, silicosis, asbestosis, siderosis or other forms of chronic pulmonary disease. Another portion of these tumors was recog nized as of occupational origin but not made a matter of public record, while a third fraction developed in workers many years after they had left the hazardous occupation and when the causal relations to their previously sustained exposum,-! had been obscured by the passage of time (Table V. Page 156). The almost exclusive occurrence of occupational king cancers in male TABLE VI LATENT PERIODS OF ENVIRONMENTAL RESPIRATORY CANCERS Agent Asbestos Chrom sites Nickel Tar fumes Isopropyl oil Ionizing radio Lon Average Latent Period Lunff 18 15 22 16 .... 25 - 35 Ranjre of Latent Period 15 - 48 ,5-47 6-30 9-23 .... 7 - 50 Nares & Naiad Sinuses Average Latent .Period Rantu of Latent Period .... .... .... ii 3-26 .... 10 6-16 25 19 - 32 jlKik ri* > M*j f 'f A S A A 8!lfIL:k'frM: ,,C i  '* sw __ ,r' ?;-v i i fitos ' *r *>-'-1 , ' * ' * `~ ` siiV. voi. x x x ENVIRONMENTAL CAUSES OF CANCER 145 workers is in good agreement with the fact th at males are predominantly employed in occupations having lung cancer hazards. One oi; the known exceptions in this respect are the lung cancers found in female ashes n workers. The male-female ratio of lung cancers among workers who bestosis cancer of the lung is for this reason at the low level of 2.3:1, indicating that with an equalization of the degree of exposure there FIGURE 2 (Reproduced by permission of the British Empire Cancer Campaign.) | rK g p i-T -w " 1. W. C. H U E P E Aujrusl, 19r,i; HISTOLOGIC TYPE TARLI!I VII OF O CC UPATIONAL RE SPI IIA T 0 R Y CANCERS Agent T:u' Fumes Nickel Chromium Asbestos Radioactive Gases & Dust Nickel Radioactive iases & Dust Isopropyl ttn Organ Lung Lung Luna1 iamg au na Nwes and Nasal Sinus Xaves and Nasal Sinus iSares and Nasal Sinus Squamous Col Carcinoma With or Without. C o r n i . i'.co' i o n 'flou ml Cull o r A n a p l a s t i c or Cat Cell P olym orphic Cardncwia Carcinoma Adeno carcinoma o 2 4 3 2 11 3 2 6 14 !) 7 1 3 6 1 OO IsJ 4 VP. XXX o; cryp etio'ogx Occui like othi The rei ;rg und a niultic asbestos PCmon with sid '0 canee tional . ir. m utui s; ] s.arre tu have- an JCVV C.t n-p'-' a s 't develops a tendency toward an equalization of liability to lung cancer. w, -, ia< Several types of industrial lung cancers, such as those caused by radio iT-Ooiain ; active substances, chrome pigments, and coal ta r fumes, show a definite Since lb shift into younger age groups than those observed in cancers of the lung bn ' sno o r a s i , whit* m i s s , m v m m t s , 19m ( eowafo a. lew] 4 M jxuteA fiath Sates par 100,000, ISiifcs 8*1 Pepatati Whiff oo OQ o ( U? <[ Uoi s [1 sc FIGURE 3 Voi. XXX ENVIRONM ENT A i.. CA U SE S OF CAN CER 147 of cryptogenetic origin, but characteristic of cancers of occupational etiology. Occupational respiratory cancers moreover have long latent periods litre other cancers of known industrial or environmental origin (Table V I). The relatively massive exposure to carcinogens not infrequently prevail ing under occupational conditions may perhaps account for the fact that a multicentric genesis of several types of occupational lung cancer, i.e. a/oestosis cancer and radioactive cancer, is not infrequently observed. Pulmonary fibrosis associated with silicosis in radioactive ore minces or mih siderosis in hematite miners seems to decrease the individual liability m cancerous developments in the lungs thus affected. While many occupa. onal lung cancers are of .squamous cell type, many others display an ir,mature cr round cell type or exhibit glandular structures. In fact, several different histologic types of cancers may occasionally occur in the same tumor mass (Table V II). Thus, no special histologic type seems to have any fixed relation to any specific causal factor. Occupational respira tory cancers critically studied exhibit a general symptomatic pattern common to and characteristic of environmental cancers. 4. Many of the agents incriminated in occupational respiratory carcino genesis, such as arsenicals, radioactive substances, coal tar and petroleum oils, had previously been known as important causes of occupational and medicinal cancers of the skin developing usually upon cutaneous exposure. Since the mucosa of the respiratory tract may be considered as an inverted, but specialized entodermal extension of the ectodermal outer lining of the RESPIRATORY SYSTEM CANCER DEATH RATES BY AGE AND SEX White Population,Urban States and Rural States,'United States, 1349 Sic.tr s with less than 4 0 % urban papulation colled rural, and states with mere then 0% urbe;- popihation called urban. Rural state* V t > i\ SO, Mi$5nAr^N.G^5.G,W.Vu.1Ky. Urban stater: R.l, M ass,NX, N.J.,Calif,D.C. S O U R C E 1V it a l Sta tistics of the Um'cd S t a le s , 194; STATISTICAL RESEARCH S Z G T m 19 5 0 Popuiotion Censu3 of the United States AMERICAN CANCER 9*53 FIGURE 4 148 W. C. H U E P E R August, TABLE Vili THE TIME TABLE OF DISCOVERIES OF OCCUPATIONAL CANCERS N am e of Aironi Dnto Discoveror Organs yviTootod Nature of Exposure Chemicals: Organic Soot 1775 Pott Skin (Scrotum) Occupational Coal T ar (Lignite) 1.87(j Volkmann Skin Occupational Con: T ar (Bituminous) 1892 Dutlin Skin Occupational Coal T ar (Anthracite) 1910 Zweig Skin Occupational Coal Tar (Fumes) IffilG ICaushata Lung Occupational Creosote Oil 1920 O'Donovan Skin Occupational Anthracene Oil 1908 Oliver SlU;l Occupational Paraffin Oil Bell Skin (Shale Oil) 1870 Occupational Petroleum Still Coke 1890 Derville and Skin G uermongrez Occupational Petroleum Paraffin Oil 1910 Sehamhorg Skin Occupational Ptrole u)a i a.:1uie: tia g Oil Heller litio Skin Occupational Shale Lubricating Oil 1910 Wiisbn Sim Occupational Benzol 1928 Deimv and Borgmano Blood Form ing Tissues Occupational Aromatic Amines (live Intermediates) Rohn. 1895 Bladder, Ureter Kidney Occupational Isopropyl Oil Mustard (las Chemicals : Inorganic Arsenic Asbestos Chromates Nickel Physical Agents : Ultraviolet Radiation Roentgen-Radiation Radioactive Substances 1940 1953 Haie and ITueper Yamaha, Hirose & Miyanrishi Nasal Sinuses, Larynx Lung Lung Occupational Occupational 1822 1887 1900 1935 1935 1 932 Paris Hutchinson Saupe Lynch & Smith Pfeil Grer.feil Skin Skin Lung Lung Lung Nasal Cavity & Sinuses, Lung Occupational Medicinal Occupational Occupational Occupational Occupational 1894 Unna 1902 1906 .1911 1922 1879 1923 1928 Frieden Wyes Von Jagic, Scinvartz & von Siebenrock Beck Haerting & Hesse MeNcal, Ward & Willis Loewy 1931 M ar 'and Sk ;n Skin Skin. Blood Form ing Tissues Bone Lung Skin Blood Forming; Tissues Bone Occupational Environmental Occupational Medicinal Occupational Medicinal Occupational Occupational Occupational Occupational Vf'. XXX LI b or] y, .or y cmopg oyoy a "on or sin y 'oup : wie hove s fo r di refii ho we .ons fact b iny v, prodi) Ita The ating V,:!. XXX ENVIRONMENTAL CAUSES OF CANCER. 149 LUNG \B LE IX CANCER DEATH R t f ' PER 1,000 D EATH S OF ALL FOR SEVEN (7) INDUSTRIAL GROUPS IN OHIO, 1947 AMONG 5,-309 MALE CANCER DEATH S (MANCUSO) CAUSES Industry Iron and steel Transportation Agriculture Rubber and plastics Stone, clay, glass Non-ferrous metal Mining and quarrying TOTAL Respiratory Cancer 2.18 2.91 0.82 2.34 0.63 3.22 1.53 1.76 body, the development of cancers from these structures following a respira tory contact with the mentioned exogenous carcinogens appears to be a phenomenon in line with previous experience (Table V III). 5. Although the existing factual data on occupational respiratory car cinogens are at present limited to relatively restricted worker groups and apply to a comparatively small number of cancers of the respiratory organs, a considerable amount of circumstantial evidence suggests that identical or similar respiratory cancer hazards may prevail for much larger worker groups having occupational contacts with the known carcinogens. Epidemi ologic studies on lung cancer death rates made in this country and Europe rave shown the existence of marked variations in the liability to lung cancer for different large occupational groups (Tunic I X ) . Some of them revealed - definitely excessive frequency of pulmonary cancer (Table X, XI, and XII) as well as of cutaneous cancer. The possible significance of these observa tions in perms of occupational lung cancer hazards is evident from the fact that there are over 5,000,000 employed in American industries sustain ing various degrees of exposure to combustion, distillation a n d cracking products of coal, petroleum and other carbonaceous matter (soot, carbon (Continued on, , ' .79) TABLE X LUNG CANCER FREQUENCY AMONG OPERATING AND NO N-O PERATiXG RAILROAD W ORKERS Railroad A B Period 1940 - 1950 1939 - 1949 Total No. Lung Cancers 29 104 Lun g ' C hikumv Oporaljnp; HR Workers No. Per Cent 24 83 59 57 Lunc; Cancers N o n - O p e r a tin}? RR Workers No. Per Cent 5 17 15 14 X-uofc C a n c e r s Undetermined RR Workers No. Per Cent 30 29 There were four timer as many non-operating RR workers in one company as oper ating ones, who represented train personnel, round house and track workers. 150 W. C. H U E P E R August, J.95C TABLE XI OCCUPATIONAL GROUPS W ITH AN EXCESSIVE LUNG CANCER INCIDENCE Occupational Group M( tal workers, welders, nders and polishers, . i e makers, tool a F die foundry vu i'uvrK, in- al moulders, lathe workers, etc. (;igar run mrfacturers an c! iolneeonir is Engineers, mechanics, machinists, plumbers, etc. Painters, and decorators Tar workers, road workers, asphalters, paviours, stokers, patent fuel workers, furnace men, foundry laborers, rollers, etc. Potential Kespiratory Carcinogens Investigator Metal dust, lubricating oil mist Borst; Kennaway and Kennaway; Turner and Grace; Mueller; Dublin and Vane, Wynder and Graham; McLaughlin; Brealow et al. Tobacco dust, insecticides, soot S ey farth ; Borst; Kenna- way; Engcr; Veraiuya, L rinkmarm Metal dust, soot, lubricating oil BECC* 1944 & 1952: Gillespie; Turner and Grace; Mueller; Wynder and Graham Meta! pigments, coal ta r dyes, carbon black, asphalt paints, solvents, vehicles (lacquers, resins synthetic phr sics) BECC 1944; Mueller; Dublin and Vane; Fulton; Wynder and Graham Tar and pilch fumes and dust, soot Kennaway and Kennaway; F u lto n ; BECC 1952 Regis- trar-General (1938) ; McLaughlin *Report of the British Empire Cancer Campaign. TABLE XII LUNG CANCER MORTALITY IN SEVERAL COUNTIES OP .MONTANA 1947-1948 (LULL AND WALLACE) County and Total Population 11)40 Major Industry Deer Lodge Copper 13,627 Smelting Silver Bow Copper 58,207 Mining Cascade 41,499 Copper Mining Smelting Gallatin 18,269 Agriculture Number Lung Cancers Male Female 21 0 .... .... 27 2 .... .... 20 5 .... 1 0 .... Tot.il 21 29 25 t Total Cancer deaths 98 Per Cent Lung Cancer Male Female 80.8 0.0 259 22.6 1.5 .... 299 12.7 3.5 Annual Lung Cancer Death . K ate p er 100,000 Male Female 145.7 0 * -- .... 48.6 3.9 .... .... 46.3 12.3 8! 3.0 0.0 5.2 0 .... .... The estimated crude death r..:e for lung cancer among white males in the entire United Ctalcs in 1947 is 10.9 per 100,000 population. The workers employed in copper ore mining' and smelting inhale dust and fumes of arsenic contained in the are and released as a by- and waste-product during the smelting nrocess. , ., Vo!. XXX LUNG Ci CAN! Type G"oa ..oun Othe Terri S-VNDA ( (IMA ' Gado **Mctr< ,;:i'* U r b a * `S:::* R u r a vol. x x x ENVIRONMENTAL CAUSES OF CANCER loi TABLE XIII LUNG CANCER M O RTA LITY E N N I S IN A U ST R IA P E R 1,000 D E A T H S (J. H E E B IC H AND R. NEUBO LD ) Community Vienna C ' s 60,000 - 1,000,000 ( m s N ,000 - 60,000 Rest of Austria Total .32.7 18.2 18.4 10.3 Males 59.0 31.6 32.3 17.3 FcmicIoB 7.8 5.0 3.9 3.7 TABLE XIV CANCER OF THE LUNG AND LARYNX, ENGLAND AND WALES 1946 - 1949 (K E N N A W A Y AND K E N N A W A Y ) u 5 j g-s u l fcll d *c- o! 1 T y n e of C o m m u n ity Greater London County Borough Other Urban Districts Rural Districts Lunf? Cancer P a t i o - N u m b e r of `P e r s o n s Producing One Death Male Female 100 100 129 137 160 156 233 185;:'- Mole 100 125 148 170 rer Persons Death 0 Female 100 55 60 42 TABLE XV STANDARDIZED MORTALITY RATIOS* FOR LUNG CANCER MORTALITY OF SELECTED SITES IN URBAN AND RURAL COUNTIES OF OHIO, W H IT E MALES, 25-64 YEARS (MANCUSO, Th. F., MacF A E L A N E , E. M. AND P O R T E R F I E L D , J. D.) Cancer Si--- uS Years Included Riirhl Metropolitan Seven Other Counties** Urbanized Counties*** "Rural Counties**** Lung, 1947-1951 122.9 81.8 68.6 s - Ratio-- Observed Deaths Ci ------------------------- x 100 * Expected Deaths "" Metropolitan County: Counties with cities of 100,000 or more in 1950 (91 per cent urban). Urban County: Counties with cities with populations between 50,000 and 100,000 in 1950 (66.2 per cent urban). Rural County: Counties with communities with populations below 50,000 in 1950 (41.4 per cent u rb a n ), comprising 73 counties. Ci W. c. H U E P E R August , 90 LUNG GANGER TABLE XVI D E A T H R A T E S I N 25 S T A T E S O F T H E IN 1940 AND 194S CRUDE DEATH RA T E S PER 100,000 UNITED STATES INDUSTRIALIZED STATES Stillo IMli .1948 Connecticut 8.5 li.i RI ino is 8.1 8.? Marybtno 6.5 8.4 Massari inset ; 10.1 10.2 bile :b o'OO 5.7 7.1 Mew Hampshire 7.4 10.1 New Jersey 9.7 9.7 New York 10.3 11.9 Ohio 6,0 7.3 Pennsylvania 6.7 8.4 Rhode Island 8.7 7.4 STATES WITH REGIONAL INDUS?!; UVTJZATION St aU> fi.m; 1948 Florida 6.8 7.4 Louisiana 6.5 8.5 Missouri 7.3 9.4 Montana 10.0 8.8 Nebraska 5.7 8.0 AGRICU LTU RAL STATE :i Stato L0 4 6 1948 Alabama 4.0 5.1 Arkansas 3.6 5.4 New Mexico 2.6 .3.0 North Carolina 3.1 4.0 North Dakota 5.6 4.1 Oregon 4.1 4.4 South Carolina 3.6 3.7 Washington 5.1 4.2 IVyo rin g 4.9 3.9 The death rates for the year 1946 were taken from "r|,he American Cancer Society. Inc., 1949, Cancer Death Ratos for oach State in the L o b ro States by Site" (3) ; those For the year 1941; wore pet breed by the National Office of Vital Statistics. Vo'. XXX LUNG AC a;-. MO Fri mury C 11 - w toss Aliarla Xew i ^I;;I . .. > 4 ..-over .ban F r Chicane F itts ",u Detroit Larynx AiU at; irmin Den vex San E- Chicag 'bo -or sit vBiom< .T-MKbv : 1 .A/: : : . " -M ' . C " V#b W W uu . I 0'P'i 3N V.,'. \ K X E N V IR O N M E N T A L CA U SES OP1 CANCER 153 TABLE NVII LUNG CANCER MORTALITY AND POPULATION ENGLAND DENSITY (STOCKS) Groups of adjacent towns with over 200,000 occupied dwellings: London and Suburban A re a ..................................................... 156 Birmingham and Suburban A re a .......................................... 134 Manchester and Suburban A re a ............................................ 159 Liverpool and Suburban A re a ................................................. 162 Leeds and Suburban A re a ......................................................... 132 Sheffield with 124,000 occupied dwellings............................................. ......... 135 Newcastle and Gateshead with 87,000 occupied dwellings.................. -..... 114 A ggregate of 6 towns with 50,000 to85,000 occupied dwellings............ 113 A " g r t e of 3 towns w ith 40,000 to50,000 occupied dwelling's............ 107 A.ggnwate of 12 towns with 30,000 to40,000 occupied dwellings............ 104 Aggregate of 13 towns w ith 20,000 to30,000 occupied dwellings............ 100 Aggregate of 29 towns with less than 20,000 occupied dwellings............ 89 TABLE XVIII IN C ID E N C E OF R E S P IR A T O R Y CANCER, 1937 AND 947 MORBIDITY RATES FOR NINE METROPOLITAN CENTERS, BY SEX P E R 100,000 POPULATION* Primary Site arid City Bronchus and bang A iUinta Orleans J.i-.11idS Birmingham Denver San j >co ' bjr _ i*mini' s'h Detroit Males Pernales Total 1937 1947 Per cent Increase PM7 j ? Per cent Increase jpMV Per cent j947 Incvonsc 5.0 13.4 : os 1.0 5.3 400 2.3 207 :i 3.1 39.1 198 2.8 4.2 50 7.0 20.8 174 5.9 29.0 392 0.5 0.4 1180 8.1 j b',2 ahn 4.5 IS.9 320 2.1 3.9 86 3.3 11.0 ! 0.1 21.9 1.41 4.2 8.1 93 U.b 14.8 j 5.6 34.3 120 3.9 8.1 10c 5.1 29.S i j.2 13.3 29.3 .122 4.8 7.0 . 63 8.8 13.0 105 9.7 26.j 169 4.9 5.5 12 7.8 15.6 114 12.6 32.0 154. 2.3 5.7 148 7.6 19.0 I 1 o ! j t-- 3!j' L r V .y n x 1 .du; i 1.4 4.0 .SO 0.3 0.3 0.9 1 02 X O !ns 11.3 14.9 32 0.4 1.0 150 A .i) .Ci 36 Dallas 3.2 5.3 66 1.5 0.4 73 2.3 2.7 17 Birmingham 1.4 4.0 186 0.0 1.3 0.7 2.6 271 Denver 2.0 4.1 105 0.0 0.0 ..... 0.9 2.0 122 San Francisco 4.5 8.8 96 0.2 0.8 300 2.4 4.6 92 Chicago 6.7 7.0 4 0.4 0.6 50 3.5 3.7 6 Pittsburgh 4.4 8.0 82 0.4 0.8 100 2.4 4.4 83 Detroit 3.5 6.4 83 0.4 0.3 -- 25 2.0 3.4 70 '"Biometries Section, National Cancer Institute. 1 v 1 'NS5 *c; w. c.. H U E P K R August , 10" X X A ROM. AS) ) o.yo bbtCOS. .'Aid Cli co ntact inhnbn, as ar.se 0. Si been fc 0 '0:n ; sustain .srens. V corcma tOS is i elbuent special '. '.sor c in soot industr ' ' . V ' V)() }; .v . , ; ;.a c A 't h uncos i mut voi. x x x ENVIRONMENTAL CAUSES OF CANCER 155 TABLE XIX AROMATIC HYDROCARBON ESTIMATED IN ONE-MINUTE SAMPLES OF DIESEL EXHAUST WITH VARYING LOAD AND ENGINE REVOLUTION SPEED WITH FUEL INJECTION INEFFICIENCY (P. KOTIN) RPM LeaI 1000 0 3 /A i/2 8/4 4/4 1200 0 1/4 1/2 3/4 4/4 1400 0 1/4 3/2 3/4 4/1 Quantities Expressed in U gm ./M inute Conciiiion Compression Release Pyrene CPD. X pByerennze 137 22 146 Compression Release 267 76 465 Compression Release 536 175 772 Compression Release 3.300 640 1320 Compression Release 2500 639 876 Compression Release 208 0 9 Compression Release 257 0 47 Compression Release 448 278 437 , Compression Release 888 488 432 Compression Release 1912 614 1706 Compression Release 188 0 80 Compression Release 177 56 78 Compression Release 220 76 1372 Compression Release 734 837 892 Compression Release 822 346 1687 BenzFerylene 22 42 124 610 3.265 79 10 171 930 976 0 0 368 1071 944 aAntnhtrho-no . 0 43 223 472 469 4.3 24 197 320 944 20 " 16 69 577 656 b:acks, t a r f umes and dust, pitch and asphalt dust and fun ms, lubricating and ng oil mists and fogs, engine exhausts) ; over 2,000,000 with com acl i;j metal fumes, vapors ancl dusts; and many thousands of others imuding for occupational reasons other occupational carcinogens, such as si'senicais; asbestos and radioact ive materials. I. Since some of the recogni.A'd occupational respiratory agents have a.'.aii found among the local ami 'or general air pollutants particularly of c l a n and industrialized areas, people living and working in such regions ain beyond any doubt an attenuated form of exposure to ibese careino- g ; While inhalation contact with chromium compounds (chromite ore, chsomates, chrome pigments), beryllium compounds, arsenicais and asbes- to- is usually of local character and depends upon the release of specific effluents by certain industrial plants or the use of certain chemicals for special purposes (pesticides, antirusting agents), respiratory exposure to other carcinogens air pollutants, such as polycyclic hydrocarbons contained in soot, exhaust fumes of gasoline and diesel engines and fumes from industrial furnaces, oxidized unsaturated aliphatic hydOcarbons from evaporated or non-corubusted gasoline acted upon by atmospheric oxidants, and radioactive matter, is of more or less generalized nature. Although the atmospheric concentrations of carcinogens encountered under these conditions are considerably below those prevailing with occu- 6 W. C. H IJ'EPER Ausrust, 95B ENVIRONMENTAL CANCER OF LUNG IN FORMER CHROM ATE WORKERS W.. XXX AR0MA1 GA SOL Tren d s in selected e n v ir o n m e n t a l fa c t o r s United States, 1900-1953 (1924-1926=100) F IG U R E 5A p at;on a] C-'G t11st t genicali In f;i of limy densely Some, y populat 'vere bt A si: rates n of Aus' Fiy. 2, States the siz therefc factors except: of air envi.ro rates, urban- the im dustry duetio 1. 1 dofne produ of cer O C Vo;, x x x ENVIRONMENTAL CAUSES OF CANCER 157 TABLE XX AROMATIC HYDROCARBONS ESTIMATED IN ONE-MINUTE SAMPLES OF GASOLINE EXHAUST WITH VARYING ENGINE REVOLUTION SPEEDS (P. KOTIN) IPM 500 1000 1500 2000 2500 8000 1500 Q u an tities IpNprc: sod i n U g m . a t 0 L e a d Pyrene CPU. X Benzpyrene Benzperlone A nthanthrenc 225 289 120 235 ; ;Y 439 325 61 177 102 507 266 33 60 36 oV4 142 40 73 27 346 127 25 70 31 121 25 13 85 J. 4 48 5 10 39 15 Rational exposures, numerous epidemiologic observations on the geographi cal distribution of lung cancer suggest that they are nevertheless carcinogenically effective. In fact, the first observations on an appreciable rise in the frequency of lung cancer were reported from the highly industrialized cities of densely populated Saxony during the first two decades of this century, dome years later it was found that high lung cancer rates existed for the population of the industrialized territory of the Ruhr valley, while they were below average for the agricultural region of the Main valley. A similarly irregular distribution pattern of lung cancer frequency rates was recently established for urban-inclustrialized and rural regions o' Austria, England and the United States (Table XIII, XIV, XV, XVI; big. 2, Fig. 3). There is moreover evidence from England and the United States showing that in general the lung cancer death rates incren.- c with the size of the community and the population density (YUnc X V II) and therefore display a certain amount of parallelism between these two factors and the presumptive degree of air pollution. However, definite exceptions to this rule have also been noted indicating that the quality of air pollutants may play a role and/or that additional, still unknown environmental factors may he active in controlling lung cancer attack rates, on a local level (Table W i l l ) . It is finally noteworthy that this urban-rural distribution pattern of lung cancer death rates conforms with the increased exposure of urban popidations to known environmental inriustry-reloi ed carcinogens and their progressively increased use and pro duction particularly in urban areas (Tables XIX, XX; Figs. 4, 5, 5A). CONCLUSIONS 1. The evidence presented definitely establishes the fact that some well defined exogenous physical and chemical agents are causally involved in the production of occupational cancers of the respiratory system of members of certain restricted worker groups. 2. Since epidemiologic studies of various large worker groups and of the 158 W. C. H U E P E R August, 1956 membership of special occupations have shown marked differences in their Jung cancer death rates and in view of the fact that excessive lung cancer death rates h a v e b een found in o ccu p a tio n a l g ro u p s w ith occupational exposure to known industrial respiratory carcinogens, it is likely that in dustry-related factors account for a much larger number of lung cancers than that on record. 3. The demonstration of recognized environmental respiratory carcino gens in the atmosphere especially of urban areas and of consistently and markedly higher lung cancer death rates for urban populations over rural populations strongly suggests that industry-related air pollutants may play a causal role in the causation of lung cancer and its recent consider able increase in frequency in practically all industrialized countries. 4. While occupational and indu-ary-related carcinogenic air pollutants seem to play an important role ir. the causation of lung cancer and its recent increase in frequency, it is obvious that 1'ey are not the only factors responsible for pulmonary carcinogenesis. 5. Research on the etiology of lung cancer therefore should be conducted on a broad basis, including not only inhalants but also agents entering the body through noil-respiratory routes. EES Phi Eft 1. La evidencia quo se presenta definidamente asienta el hecho de que algunos agentes exogenos, fsicos y qumicos determinados, influyen causalmente en la produccin ele cnceres ocupaeionaffs del aparato respiratorio en ciertos grupos limitados de trabajadores. 2. Puesto que los estudios epidemiolgicos de varios grandes grupos de trabajadores han mostrado notables diferencias en la frecuencia de las muertes por canee]' del pulmn, en vista de que se han encontrado excesi vas proporciones de muertes por cncer del pulmn en grupos de trabaja dores que debido a sus ocupaciones sufren exposicin a substancias carcinognicas respiratorias industriales, es posible que los factores en rela cin con la industria tengan mucho mayor nmero de cnceres en su haber de lo que se concede. 3. La demostracin de la existencia de carcingenos respiratorios en la atmsfera especialmente de reas urbanas con mucho mayor proporcin de muertes por cncer que en las reas rurales, fuertemente sugiere que hay polucin de aire por las industrias que pue de desempear un papel causal en el cncer del pulmn y su aumento reciente en pirticamente todos los pases industrializados. 4. Si bien los agentes carcinognicos que polueionan el aire en los am bientes industriales profesionales parecen desempear un papel importante en la gnesis fiel cncer y en su reciente aumento de frecuencia, es obvio que no son los responsables nicos de la carcinogenesis pulmonar. 5. La investigacin sobre la etiologa del cncer del pulmn por tanto debe conducirse sobre una base amplia que incluya no slo los agentes inhalados sino tambin aqullos que ingresan en el organismo por otras vas adems de las respiratorias. Vo!. x c 1. F ragi Krfi Respi grup] 2. Beru: D ife enkrt keits: vulie mum Pbikt sino emop soldi W erI ge ge- im Z uvst kreb; alien . 4. Luft Zush r.ahn stanc 5. HU ' einsc ande V,,I. X X X ENVIRONMENTAL CAUSES OF CANCER 159 SCH L SSF OLGERU NGEN 1. Die vorgebrachten Belege stellen abschliessend die Tatsache ausser Drage, dass einige klar abgegrenzte exogene physikalische und chemische Krfte urschlich beteiligt sind bei der Entstehung des Berufskrebses des Respirationstraktes von Angehrigen bestimmter beschrnkter Berufs gruppen. 2. Nachdem epidemiologische Untersuchungen von verschiedengrossen Serufsgruppen und von Angehrigen spezieller Berufe ausgesprochene Differenzen ergeben haben hinsichtlich ihrer SterblichkeitsziiTor an Lung enkrebs, und im Hinblick auf die Tatsache, dass bermssige Sterblich keitsziffern an Lungenkrebs bei Berufsgruppen gefunden wurden mit be ruflicher Exposition auf bekannte industrielle carcinogene Stoffe der At mungsorgane, ist es wahrscheinlich, dass auf die Industrie zu beziehende Faktoren fr eine viel grssere Zahl von Lungenkrebsen verantwortlich sind als oie berliefert ist. . Der Nachweis von anerkannten, durch die Umgebung bedingten carcinogenoi Stoffen des Bespirationstraktes in der Atmosphre besonders in stdtischen Bereichen und von gleichmssig und ausgesprochen hheren uterbkichkeitsziffern an Lungenkrebs unter der stdtischen Bevlkerung gegenber der lndlichen Bevlkerung legt die Vermutung nahe, dass die im Zusammenhang mit der Industrie stehenden Luftverunreinigungen eine irschiiciie Rolle spielen knnten fr das Zustandekommen des Lungen krebses und seine krzliche betrchtliche Hufigkeitszunahme in praktisch allen industrialisierten Lndern. 4. Whrend berufsbedingte und auf die Industrie bezgliche carcinogene Luftverunreinigungen eine bedeutende Rolle ,zu spielen scheinen fr das Zustandekommen des Lungenkrebses und seine jngste Haufigkeitszunnhme, liegt es auf der Hand, dass dies nicht die einzigen, fr das Zu standekommen von LungenkrcV verantwortlichen Faktoren sind. 5. Forschungen ber die Aetiologie des Lungenkrebses mssen daher auf breiter Basis ausgefhrt worden und nicht nur inhalieruaro Stoffe einschliessen, sondern auch solche Bestandteile, die in den Krner auf anderem Wege als ber die Atmung eindringen.