Document Z4b8O2ZvadrZRJwNLXkmKr8VZ

FILE NAME: ALCOA (ALC) DATE: 1959 Sept DOC#: ALC085 DOCUMENT DESCRIPTION: Published Article in Medical Journal The Ohio State Medical Journal PStuabtleishMeeddiucnadl eArsstohceiadtiiroenc,tiaonscoiefnTtihfiec Csoocuientcyi,l nfoorn-parnodfitbyorgthaenimzaetmiobne,rws iothf TahdeefOinhiitoe membership, for scientific and educational purposes. Voi. 55 September, 1959 No. 9 P erry R. Ayres, M .D., Editor CharleMsanSa. gNineglsEodni,tor -- Bus. Mgr. R .AGssotrdMonanMagoionrge,Editor Occupational Cancer T. M. FRASER, M.B., Ch. B., B. D. DINMAN, M.D., and W. F. ASHE, M.D. Historical ^UR KNOWLEDGE of cancer of occupa tional origin dates from 1775. In that year, when this country was occupied winitwhomrdosrethcaotgebnetlomngaettdertso, PaermciovraellelPeogtatndtegsecnriebread tion a disease peculiar to chimney sweeps, which, as he put it, "always makes its first attack on, and its first appearance in, the inferior part of the ascnrdotumme,mwbrhaenrees . o. f. tihtepesrcvraodtuems ,thaendskisne,izdeasrttohse, testicle which it inlarges, hardens, and renders truly and thoroughly distempered; from whence it makes its way up the spermatic process into the abdomen, most frequently indurating, and spoiling the inguinal glands; when arrived within the abdomen, it affects some of the viscera, and tthheesne swooorndsb,ePcoomtt,eswhpoasinefunlalmy edhesatsrubceteivne.p"reseWrviethd more vividly in the orthopedic fields, described the first recorded instance of occupational cancer, of a10typpeerwcheicnht oinf tthhee 1c9a2s0es's osftillscprrootdalucceadncneerarilny England. In 1794 came the next step when Benjamin Bell observed that scrotal cancer from soot could develop in persons who were not chimney sweeps; and in 1882, a further occupation was in vboeelvnedcownfhiremnedP,arinisc,riimninfainteddingarssetnhiact ahsatvhee nceauvseer of skin cancer in the copper smelting and tin refining industry. In 1875, scrotal carcinoma from a different AAnpPnrriuelsae2ln1M-t2e-ed1e,tibn1e9gf5o9or,ef ththeeOSheioctiSotnateonMeIdnidcualstArisaslocMiaetidoinc,inCeolautmbthues for September, 1959 The Authors Dr. Fraser, Columbus, is an officer of the RRoesyiadlenCt ainnadAiavniatiAonir MFeodricceinea,ndDepparertsmenetnlyt oaf sPirteyveCnotlilveegeMoefdMiciendei,ciTneh.e Ohio State Univer sor,DDr.eDpainrtmmaenn,t CoofluPmrebvues,ntiisveAsMsoecdiaicteinPe,roTfehse Ohio State University College of Medicine. m anDor.f AthseheD, eCpoalrutmmebnuts,oifsPPrreovfeensstiovreaMndedCichianier, The Ohio State University College of Medicine. source was observed by Volkmann in Germany, gwahgoeddienscsreibpeadratitnhgrepearcaaffsiens fraommoncgoalwdoirskteilrlsatioenn, and four years later a new clinical field was en tered when Harting and Hesse reported the contro versial Schneeberg cancer of the lung, the symp toms of which had perhaps been described by Paracelsus 350 years previously (1531). cupBaytiotnhael ctuanrncerosfhatdhebeceenntduersycrsibeevderoarl soptehceurlatoecd upon. Unna, in 1894, suggested that the hyperkeratotic and malignant skin lesions of saiiors were due to excessive exposure to the sun, and in d1e8r95cacnacmere tihne tfhierstddyeescirnidputisotnry.by XR-erhany owfasblaidn criminated early in its development when Frieben described resulting skin cancer in 1906, and the wefhfeecnts Mofaiiotlnainzdingforuanddiatbioonnewesraercaogmaaisn riencorgandiizuemd dial painters in 1929. 1217 Still other industries began to be involved, chromates, for examples, being suggested as a cause of lung cancer by Pfeil in 1911 and con firmed by Machle years later, while in 1932 Grenfell found lung and sinus cancer in certain nickel workers, and three years later Lynch and Smith reported a high incidence in asbestos work ers. Further, as a puzzling entity, Weil reported p1a9r5a2n.asal sinus cancer from isopropyl alcohol in These are by no means all of the cancers whose origin has been attributed to occupation. Legal files are filled with allegations of cancer produced by a single trauma. It has been suggested that exposure to carbon tetrachloride in the dry cleaning industry leads to cirrhosis with a high incidence of hepatoma. Leukemia has been blamed on benzene and on x-ray exposure. Rub ber has been suggested as a cause of brain tumors, etc. However, these latter suggestions would appear to have been based more on a dubiously founded theory of proximate cause, than on a critical and adequate review of the data. Nevertheless it is evident that occupational cancer exists, and before we can prevent it or protect vagaraiientisets itt,heirte baereh,ootvoesobusesrvteo wlehaerrne thhoewy omccaunry, and to define the etiology as precisely as possible. Eckhardt's recent book Industrial Carcinogens states that of the cancers proved to be of occupa tional origin, 75 per cent involve the skin, 15 per cent occur in the bladder and 10 per cent occur in lung, bone, paranasal sinuses and larynx. Skin volOvifngthethe75skpinerEcceknhtarodft osctactuepsattihoantal60capnecrerceinnt comes from exposure to coal tars and 36 per cent froHmyderxopcoasrubroentso: shTahlee oeial.rly studies in England presented a confusing picture because scrotal can cer occurred in apparently unrelated occupational groups: Chimney-sweeps, mule spinners in cotton mills, the coal gas industry and Scottish shale pitTs.o complicate the problem of correlation of these apparently unconnected occutrences numer ous other factors were found to enter the picture, such as: a. The susceptibility to the development of skin cancer appeared to vary from individual to individual; b, The'tim e of exposure required for its de velopment appeared to vary from as little as four months in the case of bituminous shales to as much as 50 years in the case of British lubricating oils; tit skicn. canIcner wsoomueld innodtivmidaunailfsestthiteselafpupneatirlanlocneg of after exposure ceased. As a further complication it was discovered that the carcinogenicity of these substances ap peared to vary with their geographical source, the European, Middle and Far Eastern oils and tars being more carcinogenic than the American, and tthhean StchoettoisthhershEauleropoeialsn.being more carcinogenic Consequently inquiries carried out in the earlier days in Europe and the U. S. A. on the basis of the English reports showed a relatively low in cidence of skin cancer from these substances. Thus, because of the interplay of many different factors it took some little time before the common factors were observed in soot, pitch, tar, mineral oil, and various petroleum tar distillates. in WJaiptahnthine 1d9i1sc5ovtherayt cbaynYcearmcaoguilwd abeanpdrodIcuhciekdawina animals by prolonged inunction with coal tar, a great step forward was made; and in 1928, Twort and Ing published the results of their investiga tion into the carcinogenicity of various lubricating oils, showing that while sperm oils were harmless, petroleum oils possessed some carcinogenicity and Scottish shale oil was twelve times as dangerous as the petroleum oils. They also observed that tbhoeilihnagzaprdoinotf othf ethpeetfrroalcetuimon,oitlhsevahriigehderwbitohilitnhge series being greater than the low. The greatest advance, however, came in the 1930's when Shear and Andervont,18 while in vestigating the polycyclic hydrocarbons, discovered that the synthetic substance 1, 2, 5, 6-dibenzan thracene was carcinogenic, while Cook, Hewett, aconadl tHartetgheerrweleantetdosnubtsotaniscoelsat3e, f4r-obmenzcpayrrceinnoeg, eannidc mbeethcyalrcchinoolagnenthicra, cetnhee wfohrimcherthbeyeinaglsocosnhsoiwdeerdabltoy more potent than the dibenzanthracene. Kennacwaracyin,oginenEicngalacntidv,itywewnatsonnotto rdeesmtriocntesdtratteo ththaet pboylyontuhcelrearsuabrsotmanacteics hsyudcrhocaarsbotnhse bbuetnwzaacsrisdhianreesd, benzocarbazoles, the aminostilbenes, the aminophenyls and numerous other compounds. The carcinogenic subclasses of polynuclear hy drocarbons can, however, be clearly related to their parent substance phenanthrene. The evidence in dicates that the carcinogens so developed may com bine with cellular substrates in the body and lead ceeitrhtaeirn dkireeyctlpyrootreininsdiorer ctelnyzytometh-peroetleiimnsinaetsisoenntioafl in Hthoewretghuelnatidoon wofe nfoarrme atol dgaryowinth.t8he occurrence . of occupational skin cancer from oil or tars ? It The Ohio State Medical Journal is, of course, relatively more common in England and Europe than in the United States, Heller10 showing in a study he carried out for the Rocke feller Foundation that the incidence here is rare. Cases, however, continue to occur throughout the wwoitrhldc, utthtienghiogihlseswthionsceidceonncsetitaureisnitns,g nianmewlyorkaenris mal, vegetable, and mineral oil with added agents, vary widely accordingly to use. The active agents in cutting oils of mineral origin, nevertheless, have been shown to be the now familiar 3, 4-benzypyrene, and 9, 10-dimethyl-l, 2-benzanthracene, and consequently a degree of hazard continues to exist that warrants a continuing drive to have such oils replaced by inert materials.8 unIcnomtmheoncoianl gthaiss icnoduunsttrryy,, awnhdichin ftohretunshaatelelyoiisl industry, nearly 4,000 cases had been reported in England by the middle of this century, and of those cases of occupational skin cancer that have occurred in this country approximately 70 per cent have been associated with the handling of gas works tar and pitch. In the petroleum industry, however, a greater wdaanxgeesr" tahriastesr--emthaiant afrfotemr ththeepr"oscoe-scsailnlegd"of"pslaarcak ffin wax, in wax or paraffin presses. These have been shown to contain some unsaturated aromatic hanyddrooncaorbcocanssiown hhiacvhe gciavnenberisheitgohlayclcinariccainlolgeesinoinc., In addition, some of the aromatic components of high-boiling fractions of petroleum have been shown to be carcinogenic, as have some of the tars prepared from petroleum by catalytic crack ginegnipcritoyceosfseths.e laFtotertruinsabteylyn,otmheeadnesgaresegroefatcaarsctihnoat of a high temperature coal tar. Eckhardt20 states that 60 per cent of occupa ttiaorsn,alansdkin36capnecrecrencotmfreosmfreoxmposeuxrpeostuoreshtaole cooial.l Today, knowing much about the where, when and wtiohny ios fnothwespeososcibculep.ational skin cancers, preven Arsenic: We know far less about the other 4 per cent of occupational skin cancer. Arsenic was incriminated as a carcinogen in 1887 by Jonathan Hutchison whose opinion has been confirmed to gaairidmediteads aexctaennctebr-yauoxtehtiecr,s.i. eA. rasesnuibcstaisncneowwhirceh provokes changes in epithelial cells predisposing ctoinwoamrdas caassnocceiraotuesd cwhainthge.expTohseuroecctuorreanrcseenoicf chaars been observed particularly in the manufacture and use of sheep dip, where a squamous cell car cinoma may be produced after many years of exposure. It has in addition been noted after prolonged medicinal treatment and has been for September, 1959 shown in Europe to occur from the constant presence of arsenical dust on the skin. Fortunately, as with other occupational skin cancers, prompt ebxycissciorunpuislouussuaalltyteneftifoecntivteo, athned pcaenrsobnealprhevyegnietende of workers so exposed. areNcitornacteersn:edAthsefanritarsatoetshehraivneorbgeaennic rceopmorptoeudndins Chile as a source of occupational skin cancer by Prunes15 who describes a hyperkeratosis which after 10 to 30 years may undergo carcinomatous change. However, since only 17 cases have oc curred among 30,000 workers over a 9 to 10 year period in Chile, further evaluation of this agent as a carcinogenic material is indicated. agePnhtysiimcapllicAagteedntsin: cTarhceinobgeesntickitnyowisn ipohnyisziicnagl radiation. The effects and dangers of radiant energy from x-ray and radioactive compounds are well known. It should be remembered that in addition to the therapeutic use of such agents, with consequent exposure of both patient and ther apist, there is an increasing use of powerful radio active sources in industry for such purposes as inspection of manufactured parts, tagging of com pounds with radioactive isotopes, manufacture of luminous paints, oil surveys, etc. Thus there is an increasing risk of exposure which, if prolonged, miIgnhtthgieveearrislye idnayssomoef ciansveessttoigmatiaolnignianntot cthhaengeef. fects of radiation numerous instances of malig nant change developed in the skin following vdeelrompamtietinst oorf uolscteeoragteionnic, swairtchomoaccfaosilolonwalilnygtheexpdoes umroeretocoinmgmesotendeifnfetectrsnaolfeemxcitetsesrisveinexapdodsiutiroen. Btoutthaes the hazards were slowly recognized die subsequent precautions which were devised slowly reduced tHhoewinecviedre,ntcheeofdamnagleigrnsatnilclyetxoisatsn,eagnlidgibinle tahmeopuenrt. haps less rigidly controlled industrial situation theBpoothtenhtieaaltdaanngder ubletcroavmieosleatllltihgehtgrehaatveer. been blamed for skin cancer, but in neither instance has there ever been proof that the incidence of skin malignancy among employees with such exposure exceeds that in the general population relatively free of such exposures. Local trauma of a con tinuing nature, such as the rubbing of a basket or hod on a particular part certainly predisposes to or causes cancer at the site in a very limited segment of the world's population. Bladder The history of occupational carcinoma of the bladder dates back to the origin of the German synthetic dye industry in the latter part of the 1219 last century, when the accidental discovery of the dye, magenta, led to the development of the vast complex that constitutes the present-day chemical industry. The condition was first observed by Rehn in 1895, who demonstrated to his skeptical colleagues the occurrence of bladder carcinoma in asidseerrieeds otof dbyee wanoirlkineer,s. a Tvhieewcatuhsaatl wagaesnthheledcofonr cmoanncylusyievaerlsy, sahltohwonugthhamt opruererecaenniltilnye itinhaitsseblfeein noncardncgenic, although it may in an apparently mpuarteeriasltsa.te be contaminated with carcinogenic For some time after the initial discovery the re ports of these tumors were confined to Germany, but with the expansion of the British synthetic dye industry during W orld W ar I cases began to ap pear in England in the 1920's, and by 1931 what would appear to be the first American case was reported. Despite stringent precautions in the in' dustry, tumors continued to occur, and in 1954, Case and his colleagues in a remarkable statistical study of mortality in England and Wales during the period 1921-1950 showed that the overall risk of death from bladder carcinoma in workers en gaged in the manufacture of dyestuffs was 30 times that of the general population.0'6 However, along with the development of the dye industry, research into the causal agent was proceeding in Germany, England and the XJ. S. A. amnadticbecfoomrepoluonndgs itwewraes theotssaebirisehspeodnstihbalte.theNuarmo erous compounds were incriminated, including aniline, toluidine, xylidine, benzidine, the naphthylamines, etc., but of recent years it has become accepted that although other carcinogenic agents exist in the dye industry the naphthylamines, particularly the beta isomer, are the primary culOprcictsu.pational carcinoma was first attributed to the naphthylamines in 1898, but after World War I beta-naphthylamine became accepted as the cause on epidemiological grounds, some 10 years before bladder tumors were produced by it in dogs by Hueper and W olfe. Both the alpha and beta isomers are common dye intermediates, de veloped during synthesis of the various dyes, and beta-naphthylamine, at least, has been shown to be carcinogenic to animals. Some controversy ex ists over the carcinogenic properties of the alpha isomer which can be separated in its pure state from the beta only with considerable dif ficulty, but it is generally believed that any re sulting carcinogenicity arises from associated betanaphthylamine which may contaminate it up to 5 per cent. The discovery of diazotization by Griess in 1220 1858 led to the development of the azo dyes for which new aromatic bases, including the naphthylamines were required. Benzidine, chemi cally related to the azo dyes, and incriminated as a cause for many years by Maguigan, is known to be carcinogenic to rats and dogs, and has been conclusively shown in the statistical study of Case and his colleagues in England to produce a high incTidheencaezoofdybelsadthdeemr steulvmeos,r ailnthmouagnh. evincing no evidence of carcinogenicity in man, have been shown experimentally to be carcinogenic to animals--oaminoazotoluene, and 4-dimethylaminoazobenzene r(abtusttaenrd ymeilcloe,wa)ndprboldadudceinrgtumlivoerrs inneodpolgass.msThine aniline dyestuffs, auramine and magenta do not appear to be carcinogenic per se.18 comThpeoutnudms oinr wmhainchis doefverelolaptsivefrlyomlowthegraadroem, aantidc its development is influenced to some extent by the age at which exposure begins, there being a slightly increased susceptibility in older men. It generally develops in those susceptible some 4 to 18 years (average--16 years) after initial ex posure, the required duration of the latter being approximately one year. As far as the mode of action on the genito urinary system is concerned, the compounds dis cussed above, although established carcinogens, do not appear to make their attack in the form in which they are absorbed. The action occurs wnoitthvinia ththee bbllaododder,strreeanma,l apnedlvias,ppoerarsuretoterb,eaanfd fected by metabolites of the substances concerned. The effective carcinogens are probably hydroxy derivatives of the amines, to which man is highly susceptible. Since this susceptibility is not shared with the common experimental animals there is considerable difficulty in producing the tumor in uthreinalaryborparteocruyr.sorTsheoref itshesomoretheyv-hidyednrocexyt-haamtinthes are the glucuronic acid conjugates.7 Boyland has linked this ortho-hydroxy theory with the metabolism of tryptophan, and has shown that one of the metabolites of tryptophan, 3-hydroxy-anthranilic acid, which is greatly increased in bladder carcinoma, is itself highly carcinogenic, and suggests that this is the active causal agent in Tthhee ocdcyuepaitniodunsatlryc,archionwomevaero,f itshenboltadtdheer. only source of carcinogenic aromatic amines. In 1954, Walpole and others10 in England showed that the compound 4-aminodiphenyl, used in the manu fpaoctteunrte caorfcinaogreunb,baenrdasnhtoiorxtliydatnhte,rewafatesr aMehliigchkl1y4 and his colleagues in the United States showed that a high incidence of workers where this com The Ohio Slate Medical Journal pound was made from 1935 to 1955 developed bladder carcinoma, although the rubber antioxi dant produced from it does not appear to be car cinogenic. In addition, another compound, 2acetoaminofluoride, used as a commercial insec ticide has been shown to be carcinogenic. Respiratory Tract When considering occupational cancer of the respiratory system, which in this context includes the tract from the nose and paranasal sinuses to the alveoli, it is pertinent to observe that there has been a considerable overall increase in the incidence of lung cancer during the past 25 years. How much of this is due to improved diagnosis and greater frequency of autopsy and how much to atmospheric pollution, increased exposure to occupational carcinogens, and other as yet unknown factors can only be a matter of opinion. And, because of a paucity of experi mental evidence that points conclusively to any specific compound, it has become more and more necessary in analyzing the occupational factor to rely on the results of the long-term controlled statistical study. However, much can be gained in this type of study and several compounds will cbieateddiscwusitsheda tshiagtnihfiacvaentlbyeeinncrsehaoswedn intocidbeencaession cancer among those exposed to their hazards. beeCnhrkonmoiwunm:to Cprhordoumcieumchcroonmicpouulncdesrahtiaovne, ldoenrg matitis, and caustic effects, giving rise to the well known "chrome holes" (perforation of the nasal septum), chrome dermatitis, and chrome bums. Tchhaensge,e haonwd eivtewr,asaroerigniontalflyolltohwouedghtbythnateocphlraosmtic ium had no carcinogenic properties. In 1936, however, some 25 cases of pulmonary carcinoma were recognized in Germany in men who produced cinhrothmoasteeswhfroomusecdhrcohmroemaotreess ianndtanrneisnidgu, eps,latainndg and similar procedures. of Ucansteisl o1u0tsoirde15Geyremarasnayg,obuthteirne 1w9e4r8e Mfeawchrleepoarntds his colleagues14 published a study of incidence in the five chromate-producing companies of the UrenspitierdatoSrytatceasncsherowiningthtehacthrtohme adteeatihndurastteryfrwoams s1h6owtiemdesthahtigthheerintchiadnenceexpoefctneda.sal Tirhreityatiofunrthdeidr nthoatt ptahrealilneclidtheneciencoifdelnucnegocfarlcuinnogmcaarvcainrioemdafraonmd psilmaniltart.o pInlavnetstiingaptionpgulfautriothnesr tthhaety wcoenrecluodtheedrwthisaet the difference in incidence lay in the nature of the compounds handled and consequently suggested that the monochromates may be the compounds for September, 1959 hreasnpdo,nKsiobvleenfeotral.c,asrucgingoegsetnthesaits.acidO-snolubthlee, woattheerrinsoluble compounds in chromate ore are the etiologic agents. At this time one may conclude that the specific etiologic agent is not known. In Britain also, the incidence appeared to be negligible until 1955, when Bidstrup and Case1 showed in a statistical study that the incidence of lung carcinoma in chromate workers in the pre vious six years was four times greater than expected. As with other occupational cancers, the latent or induction period may be very prolonged, often as much as 20 to 30 years, and in some instances the tumor has appeared long after exposure ceased. Nickel: Nickel, which is known for its ten dalesnocybetoen pirnocdruimceinaatesdensaistizaatiopnotednetrmcaatrictiins,ogheans. A significantly higher incidence of respiratory carcinoma has been shown to occur in workers in the nickel industry, the carcinoma chiefly affect ing the mucous membranes of the nose and air sinuses, although sometimes found as a bronchial carcinoma. Several theories have been propounded to explain the occurrence of these tumors, all of them handicapped until recently by lack of ex perimental confirmation.' The original theory that the responsible agent was a metallic arsenide fcoarrmdeedd lfarrogmelyasbseoccaiuasteedocfoma ptooutanldsabhsaesncbeeeonf dainsy other evidence Of arsenical poisoning. The favored theory relates the occurrence to the Mond process of nickel preparation in which nickel carbonyl is heated to drive off the carbon monoxide and allow the deposit of finely divided nickel. It is suggested that thereafter the nickel carbonyl, which hydrolizes in water to nickel and carbon monoxide, or finely divided esuleimtabenletalfonrictkheel, pisroidnuhcatlieodn aonfd tdheepotusimteodrsa.t siAtels though previously it has not been found possible to produce tumors in animals from nickel except fboyupnadresnutperpaolrtadfmroimnistHrautieopne,r1t1hiws hthoeomryaniange1d95t8o produce adenocarcinoma in animals exposed to fine nickel dust. at Athsisbetismtoes:to Tsuhgegreestisthnaot aesxbepsetroismiesnctaalrceinvoidgeennciec in any form. It has been shown statistically in England, however, that there is a high incidence soufffleurningg cfarnocmercionncausrbreesnttosaswbeosrtkoesirss, kDnoolwl nint1o95b5e noting in a study of men who had worked 20 years or more in the asbestos industry that the incidence of lung carcinoma was 10 times that expected, while in the official statistics of the Chief Inspector of Factories and Workshops in 1221 1955, 22 per cent of 222 men and 12 per cent of 143 women showed combined asbestosis and car cinoma.8 The induction period appears to be very long and the tumor is highly malignant. Although claimed by some that any tumor fhraosmbeaesnbeosbtosservisedthbeyrBesounlsteor,f Fsaiumlpdlse ainrdritSattieowna, rti2t that in the exposure of both the asbestos worker and the iron ore miner, in each of which a high incidence of pulmonary carcinoma is noted, there is a common factor of silica-induced fibrosis which in each case precedes tumor formation. They suggest that in the one situation fibrous asbestos, and in the other iron oxide, modify the action of silica such that the silica acts more as a carcinogen and less as a fibrosing agent. Dissenting voices however still refuse to ac cept asbestos as a carcinogen, and in a recent article Braun and Truan4 report an epideminological study of asbestos workers in Canada, showing that the incidence compares favorably with that in other workers. It should be noted, however, that the asbestos exposed to these particular min ers was obtained from chrysolite, while that asso ciated with lung cancer is usually derived from hoIrnrobnle:ndeA. s mentioned in connection with as sbiedsetoross, isanandaspsouclmiatoionnaryhacsarcbieneonmas,hsotwatnistibcestwfreoemn Germany and England indicating that the in cidence of carcinoma in hematite or iron ore workers is approximately two and one-half times eavs efrr,eiqnuevnietwasofinthtehefregqeuneenracly poofputhlaetisoind.erosHisowof wcaerlcdienrosmoantae waroenndoertssweehnyimn otrheiscagsreosuopf opfulwmoornkaerrys if the foregoing reports are true. Beryllium: Of perhaps more immediate local interest is the metal beryllium, noted for its wide cdoomsapglee.xityAltohfoutgoxhicit ehffaesctbeinen ekxntroewmnelyformisnoumtee time that osteogenic sarcoma could be produced by injection of beryllium it has not been possible until recently to demonstrate any carcinogenic ef fect by experimental exposure analogous with that of normal occupational use. However, recently Vorwald17 has shown that, under certain circum stances of prolonged inhalation, experimental ani mthaulss acnooutlhderdehvaezlaorpd phuaslmboeneanryadcdaercdinotomaa,n anald ready highly toxic material. duAstspfrhoamlt,asCpohaalltGpaasv,edCorokaed:s haIsn boethener infcireilmdsi, nated as carcinogenic, and there was a suggestion 10 years or so ago from British investigators who examined the mortality statistics of pensioned gasworkers, that prolonged exposure to coal gas and 1222 coke predisposed to respiratory cancer; further studies, however, in 1956 could not confirm this, although it was suggested at the time that a change in processing of the coal gas could have altered the incidence. An interesting situation arises, too, among twhoerkWereslsihn ccooaall faienlddsghraapvheitseh.owInnvtehsatitgathtoerrse12isina significantly lower incidence in lung cancer in coal miners than in the general population, and that where massive fibrosis and cancer are found in the same lungs it is relatively unusual to find the two conditions in apposition to each other. This suggests that there is an antagonism be tween the carcinogenic process and the tuberculous process of progressive massive fibrosis. Atmospheric Pollution: Occupational expos ure to potential carcinogens is, however, only one factor in the etiology of lung cancer, and there are other fields requiring, and receiving, urgent exploration, notably that of general atmospheric pollution, and in particular, the smog pollution of Los Angeles, London, Pittsburgh, and the like. How much of the hazard so discovered will eventually be laid at the door of industry is as yet a matter of speculation. Conclusion Cancer of the skin, bladder, and respiratory tract under some circumstances are of occupational origin. In many instances the specific etiologic agent is known. When such is the case complete preTvheenrteionaries pmoasnsiybleareaansd mofusctobnefuasipopnliecdo.ncern ing the occupational origin of certain cancers. Lraitthigeartiothnaninclathriefiedcoutrhtes wofatelrasw. has muddied We are of the opinion that there are a number of cancers of occupational origin as yet unrecog nbeizeodthaenrsd. wTitho ardecvoagnnciizneg ttheecshen,oliotgyis thneerceeswsairlyl to have excellent epidemiological data on the incidence of cancers of all types, in all organs, jbuystagpeeran1d,00se0xhionspthitealgeandemraislsipoonp.ulaAtigoaninasnt dthnesoet data the critical industrial physician must plot the incidence in specific employee groups. These data will provide the clues necessary to initiate defini tbievetheresoenalrychb.asiSscfioenrtitfhice apprporoofvaol fofcaoucsceupsahtioounladl claims and can be the only effective basis for prevention. The hiding of evidence that can justify this proof is to be condemned and perhaps should be countered with strong legal measures. References in W1.orkmeBnidisntrBupic,hPro. mLa,teaPnrdodCuacsien,gRI.ndAu.stMry.:inCaGrcreinaotmBariotafinlu. ng The Ohio State Medical Journal Blit2. .J.BIonndsucsrt,riGal. MMe.di.,F1a3u:l2d6s0, , J1. 95S3.,. and Stewart, M. J.: Oc caMunipdnaetriosof.natlhAeCmaL.nucJne.rgCoilfnint.hAePsbaUethrsit.on, sa2ry5T:e1Bx2lt6ail,ded1eW9r5o5inr.keDrys,estaunffds OIropenraOtorres Aci3d., aBoCyalsrncidn,ogEen,, PanrodducWedatbsyon,EndGo.g: en3o-uhsydMroextyaboAlisnmth.ranNilaic tSutrued4,y. 1Bo77fr:a8uL3nu7,n,gD19.C5a6Cn;.c,eranind A,,Tsrbueasnto, sTi.n DM-:inAe nWEoprkideerms.ioloAgriccha.l TInudmu5os.tu.rCsHaysieng,,,WR1o7.r:A6k3s.4,PMo1.p9:5u8la.Ttihoens,ExpBercitte.dJ.FrIenqduuesntcriyal oMf eBdl.a, dd10e:r 1an4d46, .P1e9Ca5ra3ss.oen,, RJ.. A. TMu.m; ouHrsosokefr,theMU. riEn.a;ryMBclDadodnearldi,n DW. orBk., mmMeeedndia.,tEe1ns1g:ai7ng5e,dth1e9in5B4.rtihtieshMCahneumfaicctaulreIndoufstCrye.rtaiBnritD. yJe.stuInffduIsntrteiarl 18178:1,5G1G,ool1dl9db5bl8al.attt,t, M, M, W ,: W .: Occupational Occupational Cancer. Practitioner, Carcinogenesis. Brit. MAc.t9ioB.nu.Hll.a,Bdrd1iot4.w:3M,6.,AB.1:u95lCl8.,h. e1m4i:c7a9l. C19a5rc8i.nogens and Their Modes of To1x0ic. olH.,el1ie2r:,169I.,: 19O3c0c.upational Cancers. J. Indust. Hyg. & cEixn1po1og.seendeHsuitseo,pcPIrrX,oloWPngu.elmdCo.In:nahryEalxapLtieeorsinimoneosnftaiPlnowSRdtuaetdrseiedsanMdinetaGiMluicienteaNal icPCkieaglrs, ACor1ca2hl.. WPJoaamrthke.e,sr,s6W5W:6.i0t0hR.. P1Ln9.e5:u8m.PoricmonairoysiLs.ungBrCita.ncJe.r IinnduSsotruitahl WMaelde.s, 1S2ys:18t3e7.m, Mi1n9a5ct5hh.eis,UW. S.,. aCnhdroGmraetgeorPiurosd, uFc.i:ngCaInncdeurstorfy.thePuRbe.spHiraetaolrthy Re1p4.,. 6M3:e1l1ic1k4., 1W94.8.F. Escue, H, M,; Naryka, J. J.; Mczera, RBUl,raodAld.,.e,r74aT:n7ud6m0W,or1sh9e5De5lue. re, tEo. aP.:NeFwirsCt aRrceipnoorgteend -CXaesneysiaomf inHeu. maJn. Ind1u5.st.PHruyng.s,&LT.:oxCicaonlc,,er24o:f17N4i,tr1a9te42.Workers. Abstract in J. Ta1rs6. anSdheOari,ls.W.AJm.,. aJn. dCAanncdeer,rv2o8n:t3, 3H4,. 1B9.3:6.Skin Cancer from I1n9d:11u79c.e0d.V1bo9yr5wB9a.elrdy,lliAum. JC,,omanpdounRdese.vesA, MA.LA.:rcPha.thInodlougsitcriaCl hManegde.s, Am1i8n.esWnaslpCoalrec,inoAge.Lns., inanIndduWstriyll.iaBmrist,. MM..BuCl.l., H1.4::14A1r,o1m9a5t8ic, Tir1e9.CaWrcainlpoogelen.icAA.Lct.i;oWn iolflia4m-asm, iMno,-dHip,hCen.,ylanadndRo3b. e2r-tsd,imDe.thCyI:- 141-a2:m100i.n5o,Edc1ipk9hh5c4a.nrdytl,. British Robert J. Industrial Med., 9:255, 1952 and E.: Industrial Carcinogens. Modern MGrounnocgraanpdhsStirnattoInnd,u1s9tr5ia9l, pM. e4d.icine. New York and London, ALuRnegtrCosapneccetrivien SWtuodmyenof In a controlled, retrospective investigation of a1n5d8 wthoemeonnlwyitshtaptiusltmicoalnlayrysicganricfiincoamntase,fftehcetslarwgeerset aastisvoeciartiesdkswibthy simntoeknisnigtyhiostforcy.igaTrheettsecalueseof wreals gcirneoamtears fothranepifdoerrmadoeidnocaanrdcinuonmdaifsf.erenFtoiar teedpidcearr moid and undifferentiated carcinomas all the rela tive risks, with respect to smoking history and rate of cigarette use, differed significantly from unity at the 0.1 per cent level. thrTeeheotfhinedrisntgusdiaegsreoef sluubnsgtacnatniaclelryiwn iwthomtheonse. frTohme combined results of several investigations suggest that the characteristic excess lung-cancer mortality aamreonsgtudmieadle,s asilnmceostmdaisleappneoanrssmwohkeerns nhoanvsme ooknelrys slightly higher rates than female nonsmokers.-- NWaitlhliaanmMHaanetnezl,e!B, iMomicehtaryelBBr.anSchhi,mNkainti,oMna.lDC.,anacnedr Institute, Bethesda, Md.: J. Nat. Cancer Inst., 21: 825-842, 1958. ior September, 1959 SurgNicoadluMlaranGaogietmerenPtreosfeNntosntaoxic Controversial Problem in Wthee amreacnoangfermonetnetd owfitnhotnwtooxsicchonooldsuolafrthgoouitgehr.t (1) Thyroidectomy in all cases. (2) Selection noof dcualsaers. gToihteerrse sishoguelnderbael argermeeomveednt btehcaatusleargoef pisreaslssuoregensyemraplltyomagsreaenddthfaotr thceoshmiegthicinrceiadseonncse. oIft papillary and follicular cancer in asymptomatic nodular goiter in children under the age of 15 ytoemarys idnemnaondduslatrhygrooiitdeerctionmayd. uRltsouitnineantheynrodiedmecic goiter area, however, would lead to many unneces sary operations. easCe.anOcenrlyof.5th%e tohfyrdoeidathiss afroremlatiavlellycarnacreer dries sults from cancer of the thyroid. Furthermore, in this area about 2% of the male and 6% loafr thgeoifteerms.alTe hpeospeuloabtisoenrvhataivoensasfyamvoptromsealeticctionnodouf cases for operation based on the appearance of a solitary nodule, a rapid lobular increase in size of a goiter, hard irregular nodules, palpable cerv ical lymph nodes, and any other suspicious chaHnagveisngin dthiaegngolasnedd. thyroid cancer, there are again two schools of thought regarding the treat Rmoeunttinoef etnheblpoacpirlelasreyctiaonnd. (f2ol)licTuolatraltylopbese.cto(m1)y and removal of the involved lymph nodes with many variations depending upon the extent of tihseinlaedseioqnu.ateSinacseathraedisctaalndparordcedeunrebloofc rreemseocvtiinogn all local and regional lymphatics, its advocates itsenqduetostiaodnmabilte.thMatoistts tuhsyeroaisd asurroguetoinnes, phroocweedvuerre, uenset iatnwdhiennreexctuernrseinvtedriesgeiaosne.a--l mCeatralstWasc. sEabreerbparcehs, M.D., Milwaukee: Wisconsin M.J., 58:209, April, 1959. Ventricular Arrhythmias 4 Dae To Glucose It has been shown that an intravenous infusion of glucose will produce a drop in serum potas sium, This is apparently due to a shift of potas sium ions from extracellular fluid to intracellular fluid when glucose is assimilated by muscle cells under influence of insulin. W ith the drop in serum potassium cardiac arrhythmias have been reported. Patients who are receiving digitalis may show signs of toxicity when their serum potassium is reduced.--Fred H. Priebe, M. D., Indianapolis: }. Indiana M. A., 52:205, February, 1959. 1223