Document jBmoV6MQMj2zjm6xk4jdN8wvp

FILE NAME: Texaco (TEX) DATE: 1953 DOC#: TEX011 DOCUMENT DESCRIPTION: API Meeting Minutes with Article by Dr. Heuper P AMERICAN PETROLEUM INSTITUTE 5 0 WEST BOTH STREET NEW YORK 20. N. Y. Of TECHNICAL AVICM rmooA. O.AICTOA March 13, 1953 To Members sod Associates Subcommittee os Carcenogenidty Kieffer Davis M.D. (Chairman) Marshall Clinton M.D. L. E. Curtis M.D. Robert E. Eckardt M.D. F. D. Gassovay M.D. C. E. Bine M.D. , E. K. Linder li.D.- M. H. Hevquist M.D. Jobss V. Osborn M.D. . B. B. Reeve, M.D. ' L M, R. C. L. C. B. C, B. M. B. M. L. C. B. D. Allan F. J, E. V. Henderson Cole Beard, Jr. Mithoff Shepardson Landen Burroughs Bent E, Dooley Sanders Adaas Gentlemen: At the request of Doctor Hevquist, ve enclose agenda and minutes of F ifth Meeting - BP (MC-1) Advisory Committee held January 16, 1993. Very tr u ly yours, DVS: Jb me: Members and Associates Medical Advisory Coaslttee Drs. A. Wesley Horton Robert A. Kehoe John J. Phalr / API 05567 Copy from D* Stroop for Information of Members and A ssociates of the Medical Advisory Committee . __________ ________________ 1-19-53 ESSO LABORATORIES Standard O il Development Company Medical Beeearch D ivision p. o. Box 51 Linden, H. J. January 15, 1953 Mr. D. V. Stroop Amrican Petroleum In stitu te 50 West 50th S treet Hew York 20, Hew York Dear Mr. Stroop; ' I am attaching a reprint o f an a r tic le r ecen tly .. written by Dr. Eusper. I think that th is a r tic le should he brought to the atten tion o f a l l o f the members and associates of the Medical Advisory Committee o f the API. Very tru ly yours, - / * / B. X. Eekard% R. E. ECKAKDT, M. D. BEEsilk Enel. - Environmental Cancers: A Review by Dr. V. C. Hueper Reprinted from CABCER RESEARCH. Vol. 12., Ho. 10, pp. 691-97< October 1958. API 05554 JAM 015529 Reprinted for private circulation from CANCER RESEARCH VoL 12, No. 10, pp. 691-97, October 1932 Copyright 1932 by Cancer Reieareh, Inc. M M H B til t i l Environmental Cancers: A Review W. C. H veper (Varimaf Canrr IntHtutt, Vniltd AM Btalik 8tnic*, Ftdtnl Ssevrty Afmty, M U , Ui.) Although the knowledge of an environmental diverse chemical and physical agents. I t has been causation of human cancer is much older than th at of the exogenous origin of infectious diseases, there exists a striking, if not alarming, contrast between for the same reason th at the rather diffuse etiologic concepts of physiologic aging and heredity have enjoyed a much greater and m uch more lasting the extent to which this information has been put appeal than the much m ore definite and reliable to scientific and practical use in the study and observations on the diverse exogenous causes of a control of these two important groups of disease. considerable variety of hum an cancers. In the attack on the infectious diseases the mam efforts wereexpended on the discovery of the specif . Bxaxsrrr ic causative agents and on their subsequent elimi Since, in a recent discussion of th e age aspects of nation from the external and internal human environmental and occupational cancers (Iff) the environment by appropriate preventive, prophy fundam ental fallacy of this concept as to the lactic, and therapeutic measures. Interest in the endogenous properties of the host, as represented by heredity, constitution, aging processes, race, u ri sex, in determining the development and course of infectious diseases did not, as a ru le ,. assume a dominating character. These factors were recognised as having mainly a modifying, b u t not m ajority of human cancers was discussed in detail, it remains to point out th a t a sim ilar situation seems to prevail as to the validity of the heredity theory. Conclusions drawn from selectively inbred strains of mice, a notorious biologic artifact with out parallel in nature, have been instrum ental in giving to hereditary factors an exaggerated and caustl role, by exerting a certain influence on individual susceptibility to the pathogenic micro organisms and on the course of the disease. The investigation of the anatomic and biologic proper1 ties on the various reaction products, particularly . those of chronic granulomatous nature, remained usually a less important side issue in devising effective control measures. The investigations directed against human cancer, on the other hand, paid relatively little attention to the factual evidence of its established environmental causation, but concentrated first on the various morphological aspects ofcancer and cascer cells and, more recently, on the biochemical : and biophysical properties of cancer tissue. Canj *** was, and still is, considered by many invest!ga1tors a distinct disease entity and is not regarded as an atomic reaction product to a large m tm h r of B n m d (or pvMkatjoo Jane S3, IMS. distorted significance as im mediate causes of human cancer. While it m ay be conceded th a t them exist a few rare cancers which display hereditary tendencies, a t least one of them (cancer of the skin in xeroderma pigmentosum) depends in its causation on the prim ary action of an exoge nous agent. Although xeroderma pigmentosum is due to an inherited hypersensitivity to solar radia tion prevalent among some inbred family groups, this fact would scarcely justify the conclusion th at the ordinary type of solar cancer of the skin is pri m arily an inherited m anifestation of the host organism which is activated by an exposure to solar rays. Such an inversion or perversion of normal reasoning would have to disregard the fundam ental fact th a t w ithout solar radiation there is no cancer, irrespective of the constitution of the individual. The allegation th a t hereditary factors based on 691 API 05555 JAM 015530 692 Cancer Research prolonged- inbreeding play an important causal role in the production of the lung cancers among miners of. radioactive ore in Schneeberg and Joachimsthal (Vesin {38]; Macklin (27); Lorens [26]) represents another example of the rather loose speculations which have been advanced to bolster the cause of the heredity theory. Apart from the fact that none of the various proponents has offered any concrete evidence in support of such a claim, any significant degree of inbreeding in a community of about 10,000 inhabitants (Schneeberg) having a railroad station for many years would indeed represent a most remarkable biologic and sociologic fe at This speculation ad vanced by investigators remote from these opera tions has no basis in fact according to German in vestigators.1 The occasional occurrence of lung cancers in several members of the same family working in these mines certainly cannot be regarded as proof of a hereditary liability. Similar observations of a familial appearance of sldn (scrotal) cancers were reported from England during the past century in families of chimney sweeps. Such familial cancers were obviously caused by an occupational or en vironmental exposure to soot by several members of such families without necessitating the assump tion of a common hereditary susceptibility. The high rates of attack of several environmen tal cancers rather clearly indicate th at heredity evidently plays a relatively insignificant role in their production (cancer of the lung in 73 per cent of miners employed in radioactive mines--Baader [8]; Hueper [16]; cancer of the bladder in almost 100 per cent of dye workers following highly exces sive and prolonged exposure to certain aromatic amines--Goldblatt [11]; Mueller [82]; Gross [12]; Hueper [17]; cancer of the skin in 100 per cent of workers with contact with pitch for more than 40 years--Sladden [83]). ' I t is likely, however, th at such an almost com plete obliteration of individual inherited or_ ac quired constitutional differences in susceptibility to exogenous carcinogens occurs only in the pres ence of an overwhelming, high intensity exposure. Whenever groups of individuals become exposed to carcinogens of low potency or sustain exposures of ' low intensity and duration, there appears evidence indicating variations in the speed and character of the individual responses to the environmental carcinogen. A constitutional influence evidently 1Non of Um diumtou*Gsnuaa workers mention! in their pspen ths oecumoes of inbreeding in tbe mining population of tbe Engebiige end LtniW h in answer to a recent inquiry stated that nothing is known among German scientists in Ibis respect. controls the susceptibility of different races solar cancer of the skin, to which light-pigment, individuals are much more liable than dar pigmented individuals. The effect of this raci difference in reactivity to th carcinogenic acti, of the ultraviolet radiation from solar sources reflected not only in a lower incidence of sk dancer in Negroes than in whites, but also in different topographical distribution of the sk cancers observe in the two racial groups. Wh skin cancers in whites are mainly located in t skin of the exposed parts of the head, neck, upper extremities, those observed in Negroes a predominantly situated in tbe usually cover parts of the body and the lower extremities (8] Since arsenical cancers not infrequently invol the unexposed parts of the skin, it is reasonable conclude from the above evidence that the vari tiona in the topographical distribution of sk cancers in whites and Negroes are, in part, due differences in causal agents active in the prode tion of these cancers. I t is unwise, however, to generalise or over phasise the role of racial factors in the causation environmental cancers. Although primary hepa cancer incidence is high among West Afric Negroes, their American descendants do not d play any such tendency (Berman [3]), indicati thereby th at not racial or hereditary factors t environmental factors are underlying the Afric experience. Likewise, it can be considered established th at the absence of penile can, among Jews and the high liability of Chinese this type of malignant tumor do not depend up race-conditioned constitutional differences, but i mainly the result of differences in personal 1 pene, especially the circumcision practiced a t early age by the Jews. There thus exist not oi "environmental familial cancers," b u t also " vironmental racial cancers," which have no n tion to heredity. Sax Differences in the sex distribution of cancers feeting several organs (lip, m outh, larynx, brow skin, and bladder) have given rise to the cono of a sex-conditioned susceptibility to ce rt cancers. Observations on environmental cane lend no substantial support to such a thee Cancer of the lung of unknown origin has a m< female sex ratio of from 4:1 to 24:1, accordine various investigators (18). Asbestosis cancer of lung, on the other hand, displays a male-female ratio of 2.4:1, indicating th at with an equalizat of exposure to a carcinogenic agent there occ also an equalisation of the incidence rates of b API 05556 JAM 015531 Hueper--Environm ental Cancers: A Review m to it| lark. **i*| CtOft *S 1 skin BXq *Vbile a the and at ; veitd <)., ivolv* able to vari*. f kin due to iroduc. vereng tion of lepatie Vfrican iot dij. .Jesting jw s but ^A frican d autcer nese to id upon but art n a lb y . d a t an iot only Uo " en no rela* ncersafbronchi, concept certain l cancers theorysanale' d in g to cero f the iemale sex jalization re occur* es of tuoi , . he two sexes (Merewether (80}). Like* *"** * most improbable th at the male-female wise* it.15 . ; , j (or Mexican men and women set and Edmondson [87]) living in Los ,'5 teiner. ' ^ .,, u t e d factors. It is note- Ang**.". . ,, ,^ 1 that the entrance of female worthy i -a n the English textile plants was fol- mulej Pft*r a suitable latent period by the appear- ,0 o f cancers of the vulva in some of these nC* which fact thereby demonstrates th at f^lm u lesp in n ersacq u ire the anatomic equiva* u l of the scrotal cancer of their male counter* (18). While oral cancer is rare in white P*" ,, this tumor is rather frequent in Indian chewing betel quids (Bashford (4)). This iwvo cancer of the oral cavity represents W per t of all cancers among Filipino women. For this **000 the sex ratio of oral cancer among Fdi- is inverse to that found among white people Pk.M tini the temperate tones, where the male- 3 1 sex ratio 3 : 1 (Maxwell (*]; Vedder [88]). These and other similar observations indicate iw t the differences in the sex ratio of certain dicer* of unknown origin are apparently not dueT in the main, to hormonal factors but rather reflect variations in the types and intensity of exposure U>environmental carcinogens affecting members of t],e two sexes to a different degree for reasons of occupations, habits, customs, clothing, hobbies, u d general living conditions. Ennmaouxnc PtTrxax derived from the demonstration of a centrifugal spread and scatter pattern of occupational cancer hazards from the focus of original production of carcinogens in basic industries through processing and consumer industries to the ultimate handler and general consumer of the finished products. This pattern becomes apparent in the occurrence of skin and lung cancer among the producers of tar and pitch in gas plants and coke ovens, the appearance of similar cancers among tar refinery workers, roofers, road construction workers, cork brick manufacturers, and other members of sec ondary industries and trades handling and using tar and pitch. An identical chain of environmental cancers among successively exposed population groups exists in regard to arsenicals, which have TABLE 1 Chronologic and Gaooaannc airarancs op Bladder Cancer among Dye workers in Ddteeent Countries (it) Canto? Germany Mntrwr neartad IBM Switserlaad Great Britain Rustia Austria United Ststss Italy Japan Frano ISOS 1018 ISM IMS 1M4 IMS 1040 ISM Total at. Aatksr dad m i lis i Bahn Appretti, matdy SM Schedler IM Boss SM Rosenbaum and Gott&sb TI Schneller (1) Ferguson ri at. EM ai Maio _ M Nagtro and Kinoaita * w BDuard-Ducfcaaat 1 Hie type of the epidemiologic pattern of en* vironmental cancers depends less on certain constitutional factors of the population studied (heredity, race, sex, age) than on the composition, as well as the type, intensity, and duration of action of the agents constituting the envitonmental carcinogenic spectrum to which they have been exposed. The physical and chemical carcinogens exert their disease-producing effect, ju st like the pathogenic micro-organism, whenever and wher* ever they operate under proper conditions of exposure and irrespective of the special, type of con* tact (occupational, medicinal, dietary, habitual, environmental, etc.) present ^ The general soundness of this concept is attested by the following observations. The appearuce of occupational cancers in the various industrialized countries has closely followed the spread of certain industries. This sequence of events is **11illustrated by the chronologic and geographic oppeamnee of bladder cancer among dye workers is different countries following the establishm ent ofaniline dye industries (Table 1). Additional support for the concept proposed is elicited cancers among miners of arsenic-containing ores, sm elter workers, manufacturers of ar> senical insecticides, users and consumers of foodstuffs and drinking water contaminated with such arsenicals, as well as individuals receiving arseni* cals for medicinal reasons (Hueper [16]; Neubauer [88]; Arhelger and Kremen [S]; Butzengeiger [8]; Hill and Faning [14]; Arguelk), Tello, Macola, and Mansano [1]). Occupational can e hazards also display a cancer distribution pattern which shows the highest attack rates among the population groups employed within the immediate vicinity of the carcinogenic industrial foci and gradually decreas* ing attack rates among population groups increasingly remote from it and thus less intensely and frequently in contact with carcinogenic agents. A good illustration of this concentric distribution pattern of occupational cancers is offered by the arom atic amine bladder cancers. The bladder cancer incidence rate, according to past experience, was highest among interm ittently b ut intensely exposed m aintenance and repair men who were followed in decreasing order by operators regularly `i ****? m Cancer Research employed in the manufacture of beta-napbthyla- mine and benzidine, these by truck drivers, yard men, chemists, engineers, and supervisors who have irregular and mitigated exposures. Whether or not "neighborhood cases" of aromatic amine cancers actually occurred among the population residing or working within the fume and waste dis posal zone of aromatic amine operations is still doubtful and controversial (Mueller (88), Hueper [17], and Gross [18]). Since, according to Gehr mann, Foulger, and Fleming (10), workers em ployed in a building formerly used for the produc tion of beta-naphthylamine have an occupational bladder cancer hazard from contact with the minute amounts of the chemical volatilized from impregnated building m aterial, neighborhood cases of this occupational cancer may conceivably occur among persons living near aniline dye plants with defective loading, shipping, and waste dis posal arrangements for beta-naphthylaxnine and benzidine. Another major factor determining the char acter of the epidemiologic pattern of occupational cancers is represented by their latent period, which in turn depends upon the relative potency of a particular carcinogen, its physicochemical proper ties (solubility, dispersion, chemical reactivity Or*aa Skia Lun* Bladder TABUS Latent Pb u o m o r Entoonm xntal H it) OCCUPATIONAL C A N O Amaic! medicinal occupational Tar Craosote oil M iam i oil Cruds paraffin oil Solar radiation X-radiation At_._lia-Uj ot BtfiN (resra) IS ts SO-M SS SO-M 15-18 SO-SO 7 S u f i 1U* tam essM (rssn) S-40 4-4 1-S0 14-40 4-7 Mi 15-40 -IS c;ggp - Un 1 t s - t i . - Tar fumes 10 -ts Ionising radiation 15-M T-S0 Aromatic amines IM S S-40 and affinity, etc.), the physicochemical and carcinogenic or enticarcinogenic properties of ft vehicle or its associated Agents, tjbe route of con tact, the intensity of th e mdivjduqJ exposures, the'- rhytbim.fcfi&tbfc total duration tit ave a distinct influenc^ upoh f cAocer* aniong e ~ exert a denpiteinf lent period, W fth decrfcasiUg in ire theredccufs incidence oz cancers and a lengthening of their, latent period. Apart from individual differences,iJ susceptibility, these Regularities'in the intenliU of exposure to environmental carcinogens main]), account for the wide range of latent periods corded for environmental cancers (Table 8). The target organ of environmental carcinogen depends on various factors. Special tissue admit of benzene to the fat tissue contained in liemat poietic organs thus seems to account for its exciu tive teukemogenic action. The intensity of en| TABLE 9 Site or Canceb and Bouts or exfosube mtact CuUm - C xriMglul IfM t Arsenic Coal Ur, pitch, soot, asphalt Creosote e, m uucsm oil Pctfokum inkslL cokt. Iif Petroleum ode (high boOiu) Sbsk o il crude penffin off Usait* oil sod paraffin oil Ultraviolet ndiotioo X-radiation, radioactive SH* st ( Hematopoietic t* sues Respira tor Arsenic duet Chromium eompound dust adfussos ` Nickel dust ood vapor* AsheitUst 'Bet^ssphthrlitiiiae, b o u dins dust osd vapor* Coal Ur fumas Petroleum oil aiist Isopropyl oil vapors* RldSoMtfo Bit ggJCffi Lung Lung Lung,nasale*vit; LuamndV.tinuse* Bidder j fjw ir Lung Nasal sinuses, hr pus, and lung Lung Inge*. tiou Arronlc Radium, moothorium Skis Boas t--pn wrt Hla Us a* Messr frsa v iie t lu ,n , u i l UsbtaS hr dbtiUaUoa (40). posure to some environmental carcinogens al seems to determine the distributory mechanism the resulting cancers. The relatively high f quency of heterotopic m ultiple primary cane observed among dye workers with cancers of i urogenous tract as well as other organs (lu stomach, intestine, prostate--Mueller [88]; H per [18]) teems to be due to an unusual hemal enous spread of the carcinogenic hydrocarb ordinarily mainly excreted through the w (Bonser [7]). The principal reason for the app since of cancers in various organs, however represented by the route of exposure (Table 8 Epidemiologic and demographic studies car out during the past two decades have den strated the existence of marked and signifii variations b the total incidence of cancer as wi in the organ, sex, age, and race d istrib u te cancers in different countries, regions and po] API 05558 JAM 015533 lifferencea in the intensity .ogens mainly at periods re. able 2). il carcinogens tissue affinity id in bem&to. : for its excluensity of ex. xfoscre SHt ol ( u w Ua ffematopoietic tisSUM Jug junf. nasalcavity, and sinuses , Lung f Bladder isial anuses, Jarynx, and lung Lug Skin Bo m spropsaol laohtiiatd reinogens also *mechanism of vely Isigh frerimary cancers cancers of the organa (lung, dler [82]; Hueisual hematog hydrocarbons sgh the urine for the appearis, however, is (Table 8). studies carried i hare demonand significant x n cer as well as distribution of xas and popula- HuepeR--Environm ental Concert: A Review 695 , _ , ups, While a part of such variations is due a carcinogenic hazard, figures on incidence must ^ .jg ^ iie e s in the age distribution of the various be calculated for this group only, and not for the filia tio n groups surveyed as well as in the qual- total plant population, since the latter procedure P"of medical care and of medical recording of results in an undue dilution of positive evidence jUcase*, there remains for many of these discrep- and thereby in distorted epidemiology informa InAes in rates of regional cancer incidence no other tion. The limited occurrence of bladder cancer to fusible explanation than the differences in ex relatively small and restricted groups of dye work posure to environmental carc"inogen!ic *fac*tors ers (10), the excessive liability to scrotal cancer (Table 4) limited to workers employed in paraffin pressing The striking differences in the lung cancer operations in oil refineries (84), and the increased morbidity rates in metropolitan centers located in liability' to lung cancer among persons with fu- be same part of the country m ilitate against the b e s j^ jij^ d not among all persons employed`in ^ocept that such local discrepancies can justly be asbestos .operations--provide pertinent illustra- attributed to variations in medical care and r e - ..tid u o f u is point- cordiogor differences in the biologic composi- TABLE 4 jjjju gad hereditary properties of the populations concerned, or to the predominant action of a single Long Cancer M oasinm Rate, its? and im t. r a t tiologic environmental factor, especially cigarette Residents op Eight Meibopoutak Centers jffpl-iny (Wynder and Graham [41]). The local per 100,000 Population* variations as well as the consistent increase of C m IMT m t IMT IMT Ti u l is t IMT lung cancer morbidity rates m ust be ascribed to a Atlanta s.o 18.4 1.0 5.0 0 3.0 combination of exogenous factors affecting, to New Orleans 13.1 33.1 t . s 4. 7.5 30.0 differing degrees, the various population groups as Dallas . E8.0 0.8 0.4 5.1 17. B in isib u i well ai the two sexes surveyed. Since the known | D n w . 4.3 13.3 (.1 1. t .l 5.0 4.3 0.1 S.S 11.0 5.0 14.8 environmental lung cancers have a latent period' San Francisco 15. 34.3 8. 0.1 0.0 M .S sually from 10-tO 25 years; it may be Chicago Pittsburgh 18.3 88.5 3.7 8.1 4.5 7.0 4.0 5.5 8.0 18.0 7.3 13.0 c_o.___ - that .the losing trend of lung caacep -Beppllsdbr MowstrlcsSsctbo, NatisaalCaacsrlastitaW. is sf^ibfitlhle to cHahges in the environmental carcinogenic specthm which started around the a te a n a iy iilp ^ ^ turo 6 the ^ t^ d D d '.tB h h 'ff^ s6 fv c h ifih isi^ e - include not onl,,y workers presently e m S ^ T ^ ^ I coming increasingly evident .(H jieper fl|]). Sup- sufficie..n..t.l.y., long'perio>dd, so as to cover the minimal poH_iif,,c -th--i-s--fc--o-n--cerpt is the fact tiiat the sm jority of latent .perifhd---o-f--theavaevrage occupational cancer eh' tii*nSfTfifRlffltKffJfIacIl*' 4Abd bTm m dn acncSulTp. national cancers jdISiLg- (/ 5H years},-,bL,uaAt,ablIsbob aU b II Mformerly.employed workers covered during the last 25 years involve canceraju dead or alive Who'left the mdustry;rplant,-dpeti^ the respiratory, trac t (cancers .produced by tiqn, or ,1 fulfilling this, condition. The mium compounds, nickelrarmnicalSy^bestos,1 inclusii ^sh o rt-term employee!' taji betroleiim.qiis, isopropyl oil, radioactive sub- with- srn l^ tw iS d m l^ ih e stfi<$i5 (fci/88). ,, surveyed ices i senous-ciliUWb ' 'In the conduct of epidemiologic studies oc en factor^: vironmental cancers certain im portant precautions "'*or InebhclUiiVii'fc- have to be observed, if misleading, incorrect, or in Ice'the occurrence of environmental cancers conclusive results are to be avoided (Hueper [17]; rarely has the character of an epidemic, but as a Downing [0]). I t is essential to survey as far as rule appears as an endemic, it is necessary to con practicable the total effectively exposed popula duct epidemiologic studies as long-term investiga tion, and to exclude from membership in the tions, which means the analysis of data covering actually exposed population group all those indi periods of a t least 5 years. Negative results ob viduals who have merely an "adm inistrative" ad tained from short-term investigations comprising herence to it. In a survey of environmental can periods of 1 or 2 y ean give, a t best, inconclusive cers among oil refinery workers, for instance, it is results if not incorrect ones (6). scientifically not permissible to include office per In view of the long latent period of environmen sonnel, sales people, and other white-collar work tal cancers it is necessary to restrict occupational ers, unless they sustain real contact within the cancer surveys to plants which have been in refinery area to suspected or recognized carcino operation for a t least 10 years, unless a large por genic agents for occupational reasons. Similarly, tion of the workers in their employ has previously whenever, within an industrial population to be been employed in similar operations elsewhere. surveyed, only a restricted group is shows to have The absence of published reports on the occur- API 05559 JAM 015534 696 Cancer Research rence of occupational cancer in an industry hav ing known or suspected cancer hazards is no assur ance th at a serious occupational cancer problem in these establishments is nonexistent Perhaps the most notorious example that can be cited as an illustration of such occurrences is represented by the long delayed discovery of the lung cancers among uranium miners of Joachimsthal. Although the existence of a high lung cancer incidence among the Schneeberg miners was established in 1876, despite repeated inquiries made by German investigators with the various governmental au thorities under whose jurisdiction the uranium mines in Joachhnstha! located nearby on the southern slope of the Erzgebirge were operated, it was not until some 60 years later th at the high frequency of lung cancers among this group of similarly exposed workers was recognised. Until th at time (1026), the century-old practice of mis taking Tungcancers of the Joachimsthal miners for pulmonary silicosis or tuberculosis was continued. Likewise, associated pathologic conditions some times may operate in .obscuring the co-existence of an occupational cancer. This danger exists, for instance, for absestosis cancer of the lung, unless a thorough necropsy study is made. Gtscxxoaaffw ' An analysis of the action mechanism of the vari ous recognized, suspected, or potential human carcinogens supports the viewpoint th at the ma jority of cancers develop a t sites where, for some reason, the most intense or most prolonged ex posure to the carcinogen takes place. The follow ing types of mechanisms determining the distribu tion of environmental cancers m ay be distin guished. a) Cancer developing at sites of p` rimary contact. --To this group belong the cancers of the skin re sulting from cutaneous exposures to substances such as coal tar, petroleum oils, creosote oil, soot, and similar combustion and high tem perature dis tillation products of carbonaceous m atter, as well as to ultraviolet and ionizing radiations; moreover, the cancers of the nasal cavity, nasal sinuses, larynx, and lung elicited by the inhalation of arsenical, chromium, and nickel compounds, (beryllium?), asbestos, isopropyl oil, tarry m atter, and radioactive gases and dusts. The cancers of the connective, bony, and hematopoietic tissues following exposure to penetrating ionising radia tion may be included in this group of primary contact cancers. b) Concert developing at sites of elective deposi tion.--Arsenical cancers of the skin, osteogenic sarcomas following ingestion of radium and/or mesothorium, leukemia following contact with benzene, (thyroid carcinoma following radioactive iodine medication, leukemia subsequent to radio, active phosphorus medication, osteogenic sarcoma] following inhalation of beryllium compoundsfy may be included in this group. ' ) Concertdeveloping in organ with rpecialfunc tional or toxic affinityfor carcinogtnt.--Represent*, tivesof this group are almost exclusively caused by carcinogens of potential impqrtance as far as hu m ans are concerned and thus have been observed m ainly in experimental animals. Cancers of this type are the tumors of the liver developing follow, mg exposure to various azo dyes, aminofiuorens compounds, chlorinated hydrocarbons and so lenium, the cancers of the breast and uterus sub sequent to an excessive exposure to estrogens, and cancers of the thyroid following the prolonged ad m inistration of thiouracfl derivatives. d) Concert developing in organ of excretion <g carcinogen.--Cancers of the bladder, ureter, and kidney observed in individuals and experimental anim als having cutaneous, ingestive, and resptra tory contact with certain aromatic amines and.aac compounds due to the presence of carcinogens m aterial in the urine belong to this group. s) Concert developing on the hosts offunction! abnormalitiet due to certain dietary deficiencies ate representing a type of indirect or secondary environ mental carcinogenesis.--Cancers of the hypo pharynx and of the liver noted among populatio groups subjected to a diet deficient in vitamin 1 complex and protein as well as cancer of the live in rats kept on a choline-deficient dieta re membei of this group. f) Concert of A t young resulting from a tram placental penetration of carcinogens.--There exist so far only experimental evidence in support t such an exposure route in the dem anstratiom of tb development of pulmonary tumors in the of spring of pregnant mice given urethan near ten (Larsen (25]; Klein (24]). 'Whether or n ot a smrih mechanism may be active in the production congenital cancers or cancers developing during ii fancy and early childhood appears to be a worti while subject of investigation in view of th e findings. While it is not likely th at exogenous agents a the only factors responsible for human cancer th e increasing number and widening variety environmental carcinogenic agents suggest th. they seem to be operative in a much larg proportion of cancers than is recognised realized a t present. I t appears from the eviden available th a t the study of environmental cant hazards and cancers offers not only the me API 05560 JAM 015535 N .act with diotctiv to radio sarconig pounds?) dalJunepresenUmused by ar as hu. observed rs of this ig follow. loBuorene and se ems sub. gens, and ongedad. cretion of -eter, and erimental d respinsand u o cindgenic ip. functional enciet and y environhe hypo(opulation .-itamin B f the liver members n a (rantte n exists upport of tion of the i the oli near term t a similar luction of during in* e a worth of these agents are n cancers, variety of ggest that tch larger gnixed or e evidence ital cancer the most Hueper--Environmental Cancers: A Review 697 romising approach to the determination of the 69---------- Experimental Studie* in Metal Canceri|ene*b. Q. tion of human cancers, but is also the princiroute through which the primary prevention of Sneer may be achieved. Experimental Cranium Cancer* in Bat. X N at Cancer Inst (in p m ). 43. Imoauj, T. EL Incidence of Cancer in the Carbon Black Induitry. Arch. Ind. Hyg. fcOccup, Med, 1:559- 75,1050. r efer en c es <4. H unt, M. The TranapUcantal Effect of Lnthan on Lung Tumori|tneab in Mice. X Nat. Cancer lo st, 13M005-10, Asocsllo R. *t*! Tello, E. B.J Macola, B* A*: and 1051: SIaXUNO, L. Lo< cincer* cutineoe *n el amnkbmo 95. Lanamr, C. D. Pulmonary-Tumor Induction by Tran*, * i l :-- resional entkmfco en la provineia da CSrdoba, placental Expoeure to Urethane. X N at Cancer InetL 8: . r a. JUv. Fae. eien. mid. I'nhr. Citdoba, 8:409-31, 1950. 55-70,10*7. iln ru ita , S. tV., and Knzaux, A. J. Anenkal Epi- 56. Loacrx, E. Radioactivity and Lang Cancer: A Critical * thjjtoir** of Medicinal Orifin. Surgeiy, 30:977-89, 1S51. . nw ota, E. W. Dec Lunjcnltrebe ab gewerbeinediti- Review of Lung Cancer in the Minera of Schnceberg and Joachimetbal. j . Nt. Canear b u t, 6:1-1X 1944. ' *' .(ebee Problem. VerbandL Deutseb. Groclbch, inn. Med., 97. Macxum, M. T,, and Mackuw, C. C. Dot* Chronic Irri- *7:311-31. 1951. totion Cauae Primary Tumor of the Human Lung? Arch. . uanroM, E. F. An Addiaae on Cancer is Mas asd Pathol., 10:994-46,1940. Animal*, lancet, 1:591-701; 1909. 98. Manccso, T. F., and H u m s, W. C. Occupational Can a --" C. Primary Carcinoma af tba Liver, pp. 1-19. cer and Other Health Hasaida in a Chromate Plant: A London: H. K. Uwb * Co.. 1951. Medical AppiabaL la d Mad. k Surg., 60:955-55. 1551. a Bmorner, F. L. Carcinoma of tba Lrttif in Chromata 99. Maxwuu, X L. Betel Chewing and Cancer. Brit. M. J.. Worker*. Brit. J. Iod Mad, 9:309-5,1951. 1:759, 1594, v Boxua, G. M.: Curaotr. D. B.j and J o u , J. W. As 50. M m v m n ,E B . Annual Bepert ofthe CbbfInspector ' Experimental Inanity into the Cause of Industrial Blad of Factoriee and Weriubope of the Year 1947, p. 15. Lon der Cancer. Lancet. 159:385-88, 1951. don: H.M. Stationery Office, 1947. a. Buta*ogei|*e K. B. Die ebronbeha Aneovergiftung dor Wiamr. ArnU. Wchmchf.. 4:555-55.1549. n^wacra. J. 0 . Cancerof Skin andOccupational Trauma. 51. Montpellier, X M., and Mueana-MonTmuxa, J. L'lpithllioma de la pean ches Is nonUfrieaia. Mane. Md, No. 309, 1950. JJtMJ.., lU :U } -n , IMS. 55. Mrw .rje, A. Ober Biaeen-und Niennacblldigaagtn in 10. Gssamamr. G. H.: Footom , X H.; and FtsaoNO, A. J. der Farfaatoffinduatria. HaiveC ebb. acta 16:1-41,1991. ' Occupational Turnon of tba BUdder. Proc. 9tb Internat 55. NnonAim. O. Anenieal Caneert A Beviaw. B rit J. Con|. Ind Med., London, pp. 475-75, 1945. Cancer, 1:199-444,1947. ' U, Goudblatt, M. W. Voeicai Tumour* Induced by Cbemieal S t Pam . R. C.; Hols, X P .i H n su cx s, N. V. Eckabot, Compound*. B rit X Ind. Med., 6:45-81, 1949. B. E.; Stamtok, C. L-: S u m , W. E.; SmmmAND, D. A.; It. Gnoen. E. Deo Careinom vom Standpunlct dee Gewerbe- . petbolefeo. Ante*. Cham., 63i398,1940.' 13. Hewer. S. A. Occupation! Cutaneour Cancer Attribut ebb to Certain Chemkab ia Indurtry. B rit Med. BntL, 4:555-401,1547. SuatDBA, K. Fleam s, H. G. M.; F w is r , W. Ear, L. T.; Wamum, G. G. R em en, X: Blamtomo, F. H.; and Kwo, W. H. Sympoeium on a Canear Control Pro gram for High-boQing CatalyticaSy Cracked 00*. Arch. Ind Hyg It Occup. M ed. 4:997-945,1551. 14. Bau, A. B., and Famrro, E. L. Studiee in the Incidence of 55. Slaodxh, A. F. Pitch Cancer. Rep. Intent. Cool. on Cancer in a Factory Handlint Inotfanic Compound! of Atacnfe. B rit X Ind. Mod, 6:9-6, 1945. Cancer. London, 1998, pp. 84-88. Brbtob John Wright fe Son*. L td 15. Hosrsn, W. C. Aging Aapccta of Environmental Cancan. S t S x m n irr, L. S., and Lom ann, O. M. Anecie and Can Pub. Health Rep., 97:775-79, 1959. car (Obatrvationi in the Metallurgical Induetry). Aroh. IX -- -- . Occupational Turnon and Allied Dbeaeea, pp. Hyg. It Ooeup. M ad, 4:199-905,1951. 43549. Springfield: C. C. Tbnmaa, 1949. 37. S n o w , P. E.; Burr, E. M.: and Edmommok, H. A. 17.------- Occupational Bladder Cancer. Trana. 9d N at Cancer Conference, Cincinnati, ISM (in preee). Pulmonar Carcinoma Revealed at Necropay: With Referenee to Inereeeing Incidence in the Loe Angele* County i t ------ . Environmental Lnnf Cancer. Ind. Mad. It Sun.. HoepitaL J. N at Canear Inat, 11:497-510, I960. 90:45-59,1951. S t V ssn a , E. B. The Incidence of Canear in Filipina*. 15. ---- A Methodology for Environmental and Occupa J.JLMJL, 86:1097-99,1999. tional Cancer Sumy*. Public Health Tech. Monograph 39. Vxanf, M. S. Canear puhnonabe provoqu par lee a..- No. 1. Fed. See. Ag* 1550. tiona radioactive*. A m m*L peol, 9:980,1049. . H em s, W. C. am Mamcoso, T. F. The Role of the 40. W sa,C.S.; Sim a. H .F .,Ja.; and Nairn, T.H.W.Qn*at State Health Department in the Control of Environ for a Surpeetcd Induatrial Carcinogen. Arch, la d Hyg. It mental Cancer. Pub. Health Hep., 97:044-51, 1051. II. Hosrsn, Vi. C. Esperimantal Studiee in Metal Caaeariieneeb. L NieM Canoen in Bata. Tasai Bap. BioL * Med.. 10:157-55,1956. Occup. MetL, 9:535-47, IMS. 41. Wthdu*. E. L , and Guamam, E. A. Tobceo Smoking a* a Poeeible Etiobfic Factor in Bronchiogenic J.A.M.A., 146:359-55, I960. SMM API 05561 JA M 015536