Document LKpJaG3Xy8qGVm4mE8OM0LqqQ

FILE NAME: Z< DATE: DOC#: Z< DOCUMENT DESCRIPTION W,dDZZEZ DZZZZZKZ^ Public Health Technical Monograph No. 1 A MethodolofJ for Environmental and Occupational Cancer Surveys By W. C. Hueper, M. D. Chief, Cancerigenic Studies Section, National Cancer Institute of the National Institutes of Health, Public Health Service, Federal Security Agency INTRODUCTION Environmental cancers are ma.lignant tumors which are usually caused by prolonged exposure to exogenous agents of various types. In a few instances, th~sc (mVirOlll1lClltttl clLncel'"pl'odncillg factors aro well-defined physical 01' chemical agents; in olhers they (lre variable and uudeterminec\ mixtures of chemicnls; while in a thil'd group tho cancerigenic exposure is represented by contncts or conditions of a rather vague nature. '1'he differcnt environmental carcinogens which IOl'ln a parL of our natural 01' artificial environmcnt are Pl'llC- Licll,lly tho only known causes 0r cancer in mltn fit the present time, and for this roason hllve COllsiuel'n.ble genoml significance. Exposure to these factors is related to occupational activities, llwdicincs, diets, cosmetics, building material, hn.hils, customs, climate, iamm, contnminants of drinldllg waLeI', almospheric nil' and :foodstuffs, mul procerIm'es 01 warfare. Since prevention of cnncer depends fllndamentlllly on adeqnnte information as to its cLiology, the study of environmental cancers, which may bring vastly incl'cnseu knowledge as io Lhe catlses of all types of ClUlcel's) is one of thc most important approaches to n futuro cont.rol of cancel'. Envhonmentnl cancel' surveys which are direclecl a.t this goIII rcpreseni, thcreIore, a lmsic stop in the development and institution of preventive cancer control meaSures. A. THE NATURE OF THE PROBLEM Invcstiglttion into the epidemiology, etiology, and control of ell" vil'omnenial cancer depends upon the applicution 0: knowledge and approachos peculiar to this special type of huzard. Oltcn thesG fnctors mny not be adequately considel'ocl in the uS1.Utl studies of Loxic industrial health hazards and differ in some respects irom those used in epidemiologic investigations ol inlcctions tliscases. For example, some of the onvironmental carcinogens, snch as betanaphthylamine and bonzidine, scarcely over CUllse toxic manifestations. In most instances, the oarcinogenic process olicitod by theso arolUatic amines in the bladder is symptomntimdly silent during a IntenL period that lasts :trom 5 to 25 years. Industrinl health surveys limited to the demonsiration of acuLe or chronic toxic reactions and disregarding the peculiar nature of these carcinogenic hazards would lllil to disclose the serions danger to exposed pel'sons. Other environmcntal carcinogens, such ltS benzol, ionizing radia4 Hons (X-rays or rays from radioactive substances), will produce 1 or severe degenerntive and necrotizing reactiens in the tissues as the result brief but intense exposure. This more striking effect can obscure the fact that less severe but more prolonged exposure may produce cancerOllS responSes in the same type of tissne aftel' R long latent period. 'When these two different types of rel1ction urc seen in members or a surveyed occupational gl'OUP, thcir etiologic kinship may not be apparent. Moreover, the long latent period clutractel'lstic of environmental cancer fOl'mation tends to l1illder the recognition of causal relations between the exposure io carcinogenic agents and the subsequent de- velopment ef cancer. This outcome may well appear when the affected individual hus long since left the employment in which the effective exposure occul'red. One purpose of environmental cancer surveys is to collect daLa on or the oCCllrrence, incidence, types, and cnuses of these malignant turnors Rnd their precancerous mrmiIestations, on the routes and types exposurG to the carcinogenic agents involved in their production, and on tllE~ physiochemica1 states and properties of these agents. Only through such information is it possible to establish the principles upon which effective measures for the prevention and control of e11- viromnental cancers must be based. Another purpose of occupationn1 cancel' surveys is to determine which pel'SOIlS may be effectively exposed to environmental Cal'ChlOgens and thus become potentia] victims of environmental cancer. Since the develo})ment of such cancers depends on a number of associated factors, environmental cancer st1l'veys mnst obtain reliable dala ior an adequate number of cases on age, sex ancll'uce, as well as the degree, nature and duration or exposure, and the length of Intent period. Information 011 the approximate mh11mal effective exposure to any particular environmental cal'cinogen und on the expected latent period is essential in establishing standards for precaulienary and pl'eventive meaSlll'('S. A final objective of occupational cancer sllI'veys is the celleetion of specific technical information needed for the institution of adequate centrol measures. These datu CUll benefit industry by aicling in the design rmc1 introduction of effective technical measures IOl' protection oi their personnel The evidence acquired through such surveys should also provide a sound ttnc1 approprinte basis .for drafting pl'oper allcll1niform industrial disease cedes, food and dl'ug legislation, and wOl'kmen's compensation laws covering the v[l}'ied and complex reatUl'es of envirenmental and occupational cancer hazards. 1. Occupational Carcinogens orOccupational ca.rcinogens, known or suspected, cover a wldo range inanimate and animate agents. This spectrum, summarized in tabl0 1, incluc1cs a great variety of organic chemicals, both aromatic and aliphatic, several inorganic chemjcals, various types of physical mdintion, and the parasite, Sohi8to8oma lwmatobi'Ulln, the only gcnel'ally recognized animate cfl.l'cinogell, which nUacks outdoor WOl'kers in Egypt tmd other tl'opicn.l countries, inducing u form of bladder canCer. Table 1. Recogl1-j,zeel find stlSpected occupational carCi1togem 1. Chemlclll Cl1l'clnogenFl: (a) Ol'gflnic ciwrnlcnls: (1) .al'omu tic chemiC'als: Betnnaph thylnmtnc, bonzldllHJ, anllme (?), benzol, tm'l nItel1 , USIJll1lIt, Boots (domestlc, industl'ial, ana commel'cIal), shulc DU, Cl'lHle }ltl1'affin 011, cl'lHle flntllracenC! oli, crcosote, lubl'lcnUng fllHl fll~L oils uua gl'QIISCS, SYIlthetic cstl'ogcns (?). (2) AUpllllt.ic chcmlcflls: Is()propyl 011 (1). (b) IllOl'ganic cllemicnls: Al'senlcnls, chl'omntes, nickel cllt'bollyl (7), nsi)C!slos (?), bCl'ylllul1l (1). 2, Pliyslcnl cm'cillogcUS: NonJonl~lnS' l'ullinU(lll-ultl'll violeL rayS, iOIlI:61ng l'atlintollS-COl'pnSClllal' rllcHntlolls (ulplHl nn<l b(lln l'ays) uncI electl'onic l'udlntlons (gamma and X-l'l\ya). 8. Pfll'llsltic carcinogens: SolltistmlOma lW1iUttobiztm, It must bo pointed onL that the variolls ol1vil'ollmontal carcinogolls differ considerably :ill the.ir potency not only from each othm' but also among members of the same typo, Tho carcinogenic potency of different types 01 tal' vH,l'ies gI'eaUy, gas-houso ll11d coko-ovell tal' being the most poLent. Similar val'ju.tiol1s seem LO exisL rogarding tho curcinogenicity OI the various types of soot und tho difforont kinds of nu,tul'al and processed potl'olollms, mttny of which a}'o nonc!.ll'cino~ genic. Beta-naphthylamino appea.l's to he much moi'O carcinogenic than benzidine. 'rIlO data on OCCUl'l'onco ftlld incidcl1co 01 occupational cnneal's, as they Ilppen,r in published reports, are very inadequate. Tho adUltl 1111mber of cancers which a1'C occnpaLiol1al in origin is undoubtedly mnch hjghel' than is apparent 11'Olll the recorded observations, Sillco it is oftOll difficult to establish tho oCCUptttiollnl causation of cancel' l'e~ suIting from exposuro to known carcinogens (often mnny years pl'e~ vious]y), and because the medical pl'oiession is to a certain extent insufficiently aWRl'O of the existence 01 occllpat.iOl1al cancers, even cancers pl'oduced by recognized occupational clll'cinogolls ofton escape l'ecognition as such. Furthel'more, it seems highly probable that many occupational carcinogens Ill'e still unknown, and, in viow of the fnct thut new industria} eompollnds are boing synthesized and mlum~ factlll'ed every year, tIle SpccLl'um of indusLrial cal'cinogens may be growing oven widor. 3 2. Nonoccupational Carcinogens Occupational cancers belong to the larger group of environmental cancers produced by contact with exogonous agents. Contact with carcinogens may also be reltttod to habits, hobbies, diet, mcdicinal agents and devices, and other nonoccnpational environmental factors. The known nonoccupational carcinogens are summal'izerl in table 2. They include many agents peculiar to certain cultm'al and geographic groups not found in the United States (such as the kangri and okutta) as well as such almost universal agents as solar radiation, soot, nnd arsenic. As in lnblo 1, the fact is indicated that many of these carcinogens are not yet proved but are only suspected on the basis of limited evidence. Collection of additional ovidence in these fields may not only point out hazardous habits or llsages, but may also reveal hitherto unsuspected occupational carcinogens. Data plovided by occupational cancel' surveys are the only SOUl'CC of roliable iniormation on the minimum cdl'ective exposure, maximnm and minimum lengths of latent period as related to degree of exposure, and on other important aspects of environmental carcinogenesis. Table 2. RecoglJized and suspected sO/trees of 1l0otlOCcupational environmmtat cancer 1Iltlhod ofapruure all d CQr(jllOi/eJI Potential 'Ilea 0/ canC<'!r HABITS: Smoking (tar) (1) or chewing of tobacco (khaini). Betel ntlt-lilUc~tobMcO quid chewing~ _____ ~_ Chewing of tar, paraffin, cto. (1) ____________ Lip, tongue, oral cl\,vity, larynx, lung. Lip, tongue, oro.\ Cl\vlty, cheel{. Ornl oavity. CUSTOMS: Cal'rying of special beating devIces benenth clothing ncal' abdominal skin (kniro, kangri) J or sleeping on hot stoves (lmng) J causing burns and exposure to tar !.tnd soot. Smoldng of oigars with lighted end in mouth (chutta) (tnr and buru injury). Sldn. Oral cavity. HOBBIES AND HOME ACTIVI'l'IES: Gardening with oxposure to solar mys, and 1l.racnicru nod othcr cllcmioal pcsticidcs (soot, otc.). Sailing, fishing, golfing and other ionns of outdoor SPOl'~s with exposure to solar radiation. Home--engineering with contact with mineral oil delivativc8 (?). Use of pnints and paint removcrs containing benzol, chrome pigments, asphalts, carbon blacks (1). Skin, Internal organs. Skin. Do. Lcukernial lungl skin. 4 Table 2. Recog11ized and SI/spocted SOIJrces of tJ0110CCllpatiotJal tJtlvJron. me/lial Ctltlcel'-Continucd Mefllorl 01 apo8ure and cateilllJ(lelI Potenllal alles oj cancer HOBBIES AND HOME AC'l'IVI'l'IES-CoIl. UBO of chlorinated aliphatie hydrocarbolls in cleaning fluids with hepatotoxio proporties modifying metauolism of endogellolll~ nnd oxogenons carcinogens (?). r~ivor, int~rnal organs. MEDICINES AND MEDICAL DEVICES: ArscnicaIs ______________________________ _ Tal', impure vll.sclino and mineral oiL ~ _____ ~ IIepatotoxlc {lhcmicals (chlorinated nliphnti{l llydrocal'bons, oinchophon, oto.) (?). Hemntotoxic chemicals (bOllzol, su1follnmidcs (1) al'omatic organic chomioals) (?). Ultmviolet radill..tion _____ ~ ______ ~ _____ 4 __ _ X-rays________ ~ __________________ ~ ______ Radioaotive chomicals (ionbing l'ndiatiolls) _ _ Sldn, int{ll'nal organs. Do. Liver. Lcukcmia. Skin. Skin, bono, loulcomia. (?). Sldu , bono, lung (1) loulccmin (?) 1iVOl' (?). DIETARY FACTORS: Dietnry iodine cle!l.cleuey _______________ .. __ Dietary protoin lLnd vitamin B <lOlnplox doficionoy. Dietary vitamin n oomplox doficicnoy_______ Arsenical contamlllo.nts in food, drinldng water, ail'. noatod mineral oil aB fat substitute in bakocl goods (?). 'l'hyl'oid. Liver. Lnryngopharynx, Sldu, iuternal organ!!. Internal organs, COSME'l'IC FAC'rORS: XMl'adintion for dcpilntioll ________________ _ UlLl'avio)ct lamp OXPOBltl'C fCI' tttllnjng (?)~ __ _ Arsenicala ill hail' lotions and tonics (1) _____ _ Lamp black in oycbrow pcnoila (tat) (?) ____ _ Impurc vtl.sclinc and mineral oils in ointments, oreams, etc, Estrogons in sldn creams (1) ______________ _ Impure anilinc dyos in lipsticks, otc., contnIning dye illtormodintes (7). Skin. Do, Do. Do. Do. Drcflst, Dladdor. OTHER BNVIUONMENTAL FACTORS: Tal' and soot in atmosphcl'io all' (?)_~ ______ ~ Dry and sunny cUmnto with oX{lcF.lslvo solar irradiation. Pnrasitio infootions (sohlstosomiasis) _______ ~ Ionlz.ing rad1ntion in water and ail' in l'ogiona wJtb l'fldioaotiv6 orcs (?). Lung, sldn (?). SkIn. Bladdcl', liver/ intestiM. Lung, bono/ homatopoictio tissue. 5 3. Industrial and Public Health Hazards At the present time, environmental cnncer appears pl'imariJ, industrial problem! although it extends into many nonindustri~ pations. Fully 90 pel'Cellt of the known environmelltn,l card nevcr existed in dangcrous concentrations until the developn industrial Pl'occsses which brought workers into fl'eque.nt nn contact with them. As Ule injurious agents have made their I ance with the growth of variolls industries, cancers have de' among exposed workers. Perhaps one of the most striking e~ or this pattern is the nppeal'unce of bladder cancers among dye 1 subsequent to the establishment of aniline dye il1dustries in countries. Observations in many industries indicate that,. j known occupationul carcinogen and the proper conditions of e~ the appcarance or oecupationa] cancers becomes merely a qllel time, i. e., of sufficient latent period since the start of tIle op Clearly such hazards constitute an industrial problem den intensive study and control efforts. Such industrial carcinogens not only provide n serious hID the exposed workers but may possibly also affect tha heuJtl general population through various routes of contact. Carci agents pl'Oduced or handled in industrial operations) WOrkBh( labol'lltories may enter the air, watcr supply, or soil after blZ charged as waste. Persons living or working in the fume ( disposnl area may thus come into effective contact with the gons. Contaminated clothing worn by workers in carcinogen] tions may also create a hazard when luundel'ed without precautions in the factory, home, or commel'c1al laundry. possible extension of industrial hazards to the general popn the incol'porution of cal'cinogells into goods 101' general cons either ns essential parts or as contaminants. Of course) t or similar extrinsic carcinogens which appear as industrial mny also be part of the generul artificial or nntl1l'al environm indepeudent of any industrial operations, Information and conclusions dl'awn from occupationnl ca vcys, therefore, will have applications that are not re8trict~ industrial 01' occupational HeM, but may have relevance to t1 problem as a whole. Since environmentu.1 cancers represent majority of those cancers whose eti010gy IS ]mown, <>bservatj, ill relation to these tmnol'S have positive and immediate vah: study and possible future control of the many types of 11UlTIt whose cnuses al'e still unknown. cS B. TYPES OF ENVIRONMENTAL CANCER SURVEY To attain the objectives discussed above, oovernl approaches may be 1.1sed in environmental cancer surveys. The first mothod suggested, analysis of death c81'tifioates, provides a preliminary 01' exploratory approach which may give valuable clues and point to fruitful fields for further investigalion. The second approach, occupational history studies of cancel' deaths, involves tracking down possible occupational .factors in tho etiology of individual eall~er cases, The lhird approach, the plUllt survey, is essential 01' determining precisely which workers come into dangerous contact with carcinogens) bow many may be affected, through which route the exposure takes place, what organ or Ql'gans develop cancerous responses, and othell important n.spects of occupational carcinogenesis. For the organization of un occupational cancel' snrvey on a State level, it is essential thnt closo cooperation be established between various State agencies (dapartmollt of health with its divisions of canoer control, inc1ustl'in.l hygiene, a11d vital statislics, and department of Iabor) and that contacts bl! made with the Stnte medical society (committees on ClUlCCl', industrial madicine, public mlatiolls), local tllmo)' l'egistries, and, whoro neCl!ssal'y and desirnblCl, the State association or clinical pathologists and pub1ic health nurses association, The over-Rll direction of such a survey should bo provided by the depariment or health and the work should be cnrriCld out by either the di vision o cancer control 01' the division or industrial hygiene> dcpending upon which ono of these two agencies appears best suited and equipped for the work. Since occupational cancer is mainly It biological phenomenon, it appears reasonablc to place ill chal'ge oJ: the project, It physician experiencecl in cancer, industrial medicine, or both. 1. Analysis of Death Certificates V\Torldng on the premise that cert.ain occupational activities or coniact with various occupational or environmental ngents result in all abnol'mal1y high incidence of iotal crtncel' denths, as well as ill an abnormal distribution of cancer as to $ites, the nffects o such factors on local cancer mortality might be d(lmonSll'aled through tl cl'iti('nl analysis of data recorded in death certificates. If such environmental carcinogenic innuenn~s aro sufficiently pronounced and specific in a certain area, and the worlmr population is relatively stable, it might be profitable to plot the 10cRI distribution of cancel' deaths as to total number and ns to sites. Comparison 01 these data with dntu. from an area having u diifcl'cnt environmental and, particularly, occnpa.. tionul carcinogenic spectrum should reveal suggestive relations bet wean these Lt\ctOl'S and caneer illcidence. Dy comparing the l'ela- 890678-60-2 7 tiv~ frequency of cnncer cases for various sites in the region under study against tile nOl'mully expected frequency, it may be possible to locate regional foci of carcinogenic cxposm'e-plants, industries or occupations which deserve further investigation and in which protecti ve and preventive measures are needed, To establish such correlations, not only the l'esidence but also th~ place of elnployment must be noted and evaluo.ted, For the purpose ot such analysis, the map of the survey area mny be ilivided into regions with more or less well-defined onvironmental pnttel'ns-industrial, agrioulture, ul'ban~commercial, maritime. ,\Vithin the jndustriall'egions, establishments should be noted which provide known or suspected carcinogenic hazards. Such industries may include tar, pitch, asphalt, and creosote producers and consumCl'S; organic chemical, dye, and pllarmacentical manufacturers; l'ubber producers Imd processors; paint manufacturers; distillers and refinars of peh'olellm products; smoltel's, refiners, and uSers of nonfel'rous metals snch ns copper, nickel, zinc, silver, and chromium; producers and Uael'S of radioactive substances; glass and pottery manufactUl'el's; makers nnd users of metallic abrnsives; textile makers and dyers; and othel's, Appendix A. provides a more extcnsive, although by no means complete, listing of OCCUl)utions in which carcinogenic inflnences may be suspected. In addition to name, l'esidcllce} ngc, sex, cause of death, and place of death, information on individual cancel' C!u~es 'which may be ob~ tnhled from death certificates will include occupation, industry 01' business in which tIle deceased Wns employed, and social security Humbel'. Tllese data nppear ns items 1 to 16 on the Occnpational Callcer Record blnnk given as appendix B. For purposes of analysis, it will be nccessnty to code this in:fol'mntion and tral1sfer it to punch cards. ,\VhclleVel' the natlll'e of the informntion makes this possible, itcm 11 (industry or business) should be coded in three wnys: (a) By oceupntion, according to the Alplmbetical Index ror 00cupations and Industl'ies~ 16th Census of the United States, 104.0, Bl11'eau of the Census, (b) By specific OCCupu,tiollal carcillogenio hnzard, according to t110 Occupational Hazard Code, a.ppendix C. (0) By plnee (community or region) of occupational activity. Since infol'mntion rccol-ded in death certifioates :is known to be oi-ten unreliable, and because death certificates do 110t give any dntn on lengl h of r~sidence, length of employment in last occnpation, 01' pl'evious ocollpntional employments, nny oonclusiDns drawn :from a fltnt.istioal analysis of this natul'e must be merely 8uggestivo. In some instnnccs, they may eYen prove misleading, nnd any report based on suel), all analysis should emphasize ih~ limitations of ihe technique. 8 If proper consideration is given lo these limitations, llOwevor, bio- statistical studies of this type may yield vahmblo clues that can be 101l0wed up by olher types 01 epidemiologic investigations, as) for example, those described bolow. 2. Occupational History Study of Cancer Deaths Using as a basis tho information obtained :Crom death cmtiIiclLtcs, it is possible to study the occnpntional histories: of selectod cancol' cascs in order to discover possible causa1 factors. The available evidence indicates t,hat ai least some of the ClmCBl'S involving certain ol'gans (skin, lung, nasal sinuses, bladderj bone, bono mnl'l'OW) 111'0 caused by occnpational 01' onvironment!ll cfl.1'cinogens. Less conclusive evidenee, such us geographical, topographic[ll, age, and sex c1istl'ibntion, implicat('s environmental and possibly oc~ cupational factors in tho proullc6on of enncer in oth~r Ql'gall sysLom5 (gastrointestinnJ, nervo11s). By tracing back the. ollvil'onmenta1 and occupational histories~ and, whor~ pOfisible, discovcring other oxogenOllS agents to which the callcer pnLient WitS exposod, it may be possible to substalltiate flll'tller t11e80 fiudings, tiiscoYol' hitherto unknowll carcinogens> and determino tl10 incidence of varions types of cuncor in different occupations and industries. In planning such a study, pl'Opel' consideration must bo given io tho faet tbat thesc tumOl'S usually l'C8u1t from oxtcllc1ed exposurc and n.ppeUl' only u.iter long latont pOl'iods, tho latter ranging ordinurily from I) to 25 years. It lS nccessltrYt therofore, to ascel'tain the oceuN pationnJ and nonoccnpational CxpOSUl'es 101' as long as possible a pe1'iod preceding death. SUell information should include, in ud~ dition to the nmnes nnd locatiolls of ihe variolls omployers, dctu,iled information ns to tho type or typps of operations in which tho in(livicliml was employed) tho physical 01' ohcmicttl n.gmlis io whieh tho individual was cxposed, and tho length of omployuumt in the vnriolls occupations, Whenever possible, information on. injuries ltucl diseases sustained dUl'ing the survey p~riod should also he co11ected, as tJ1CSO lllay indicato specitic. precancerous 01' pm'iClwccn'Ol1S l'Gn.CLiOllS. (Sce 0-2,) The typc of iuformation required appoars 011 Uw Occnpational Cancer Record (appondix B) ItS items 17 to 30. Data on tho employment history of the a(lcensou. mny he obtaiued from n Humbcr of sonrces, including the lusi H.Lt.onding pllysicialt; hospital records; cmployors all<l their inSUl'UllC(l cur1'iors; institutions such as hOllles for tho a.ged, sanitarimns, mental institutions, illfil'~ mal'ies, ete.,in which the deceasod may havo beon an inmate. After thc places of employmont havo thus beon aseEIltninod from ono m" more 01 the..tlo sources, it is necomml'Y to oblftin detailed ill:forma.. tion as to the type 01 work performed and the types of occupationnl and nonoccupational agents with which tJ10 deceased oame in contact, 9 wlleUBVO\' avn.ilahlo inr01'mntion suggest,g the possibility of Clll'cinogenic expOSllre. Data on the duration, intensity, und typo of ex poslll'e should complete the informRtion l'eqnil'ec1. From u. crHical evaluation of the inlOl'mntioll CD] lectcd for each case~ -it is usually possible to appraise whetlun' 01' not one 01' several occnpatiOllu,l inctol's migllt have plnyec1 Rn essential role in the production of .a particular cn.ncer. (See C-3.) l'hrough this npproach it is possible to ascertain not only the extent of ]mown occllpatiollal cancer llllZal'ds in a given area but to lillCOVel' n,lso ne\Y industrin.1 carcinogenic agents and foci. The pre3" once of tIle lattel' will be indicated hy tlie pl'edominnnc.e of cei'tail1 types of cancers among individuals either engaged in ft specific opel'a~ tion or cOJD.ing in contact ffith somo pal'tieuhll.' ngollt present in and common to different operations. 3. Industrial Plant Surveys The indiYichlfll plant survey is necessary to determine precisely the location and nature of suspected cal'cinogcnic exposLU'es, In order to discover whether such haznl'ds ncbmlly exist in a particular plant, their nature RmI mode of opm'atlon, nnclllow they may be controlled, it is neeessary to ImO'\v as accurutely us possiblo the number at persons who lmve been exposed and the number showing effects, the nature of thcse effects and the type of the contact. For thB pilicient p10nnlng and conduct of such plu.nt surveys, it is desirnble to start by oblnining some basic information 011 the jnd-ividnul industl'ial cstllbJishment~ withhl the study area. These data sl:konld :inc)l1de phmt location; c1nrntion of opel'ntion; tYPfl of medical service; names of plant mnnagel', plant, physician~ and lmUll'anee car del'i mtmbel' of employees; raw materials used and goodR pl'odnc~c1; and nlly evide.nce of snspected or estnblishec1 carcinogenic hazards, The Plant SUl'vey Record form, given as ap}Jendix D, shows these dat!l as items 1 to 11. This 'preHminnry Sltl'V~y need only be approximate and is hltflnc1ed mel'ely to ascertain whethel' n detailed sllfvey is indicated, how many investigntors will be needed, the length of time to be l'Gqui1'Bd for tho study~ the type and degl't:e of assistance and coope],(Ltion nvn.iltthle from the management, and the availability of employment, medical, l.111d insllrnnce rccords. Since several years of contact with the carcinogenic agent are usually required fm' eft'ectiye exposure and Slnce the late11t pel'iod is seldom shorter than .5 years and sometimes more than 25 years, cancel' records of industrial operations shottld be obtn.ined 101' as 10ng a pCl'iocl as possible, up to 30 years or more. OccupatiOlHtl cancer surveys 111'6 novel' spot surveys bnt. always time sUl'veys. Howover, the biological nl1d e])idemiologic behaviol' of ()CcuplLtionn] 10 cancers makes its advisahle to survey estahlishmclllS that have been in opol'a..tion for tlS litLle HR ~3 Y('Ul'S, 1Vol'lml's in SHch plants may hnvo already developed pl'ccnl1Cel'OllS nl\d pcricnnccrons lesions, especinl1y if j 110 carcinogenic hnzlu,c18 aired th~ skin, bladder, Done, 01' hcmn,tOl10ictic tissu(}. It is uu]ikely that within s1Ich a shod pet'lod, cancel' aUl'ilmlablo to occupational exposure will OCClII' iu statistically signifiCfLllt numbcl's, bill tho timely l'ecognition of these nonmalignant le. sions may SU1've as It warning signal and hasten the inLl'odllction of adcquate Pl'CClllli.iowu'y mOnSlll'CS, fOl'e~tllllil1g the appearance of un epidmnic of occnpl1t Iona) CIIIWCl' nL SO!lIC Inler date. In surveys of thiH type, the chief eil'ol'l flh{)uld be expm1C1ed 011 discovuring und analyzlllg pCl'Bonncl clll'l'elllly m' 10l'mCl'ly om1110yed ill opel'nlions wil h apl)]'c0iltble l'oeogni~(>d 01' suspected carcinogon.ic ha.znl'ds. ThC'F]o IJlll'scms 1\1'0 Lhe ItClllltl tcst subjects wInch may delllOl1shHt.~ tho lJ'pc :md dC.gl'CC of ]Ul1.Ul'U through significa.lltly elevaiN] CunCeL' illcidmlCCl mtes. Only when llwse sludies demonsLrate tho exislcncc of an o('cllpnliolllLl carcinogen is it advisable to extend tlw invcf:lj iglllio!l lo gl'OUpS of workers exposed lo n les801' dcgl'(](~ so ftS to d<'iel'lllino f.bc widol' scope I1ml I'lUni:HC!ltiOl1S of the hazard. Iniol'1lmLion on the hl'll1th 1tl1<1 on other occupational exposures of Lhoso persons nmy be obl!dll(~d thl'Ough the occnpntionnl history RLmlics of canccl' deaths, 118 described above j plant omployment l'OC~ Ol'ds; plrmt mediclll l'(!COl'tlH; ins\ll'ltl1CO compnnies j hospitals; physi~ Clans; insLilut,i(HlS; u,nd soein1 H('cl1l'Hy l'CCOl'us. an To obtnin l'cliublo incidence Iiglll'l.!S, the pl'cscni, health sLatus 01' enw;o ol denth should Le doLermincd whenever fensible for wol'l{ers cU1'l'ontly 01' formerly mnployacl fm' l1.n ndeqllltte p~riod in operations wHh cnreinogeHlc hm-ml'ds. Since occllpnti01Hd UllnCOl'H hl1vn It lllUmt p~l'iod thltt is tlsual1y moro than f) YC!!u's, if tho pln.lIL has a fllhly rapid labol' turn-over, it may bo round t1111L no wo1'1wl'!; ill 1l1'pn,l'CllLly clll'einogellic opcrnliolls {t1'S sldrl!l'ing from mmCBr or oven from Pl'CCIUlCQ)'OllR l(~si()lls, Indeed, tho medicnll'ocol'c1s of the plant 01' ils imnn'm' may sbow no occupaLiOlllll cnncer lhl'onghonj llw CHt.i 1'0 poriocl 0 l' npOl'tl,Llon. IloWGVCl', it mn.y bo discovel'cd, by following np fOl'm~l' employees, that soma persolls hn.vo doveloped occlIpaUolltll cnncOl'S possibly aLLributftblo to the clU'cinogcuic ngonL to which Lhay wore exposed from 2 to 30 ycurs earlior. La/bar tl1l'lt-OY01' may, thol'Ofol'Cl totally oblitOl'ato any ovidoncD of Ull.llCOl'Ol1S rcactions in POl'SOllS exposed unless adequute follow-up sLudies of fOl'mol' Cllnployees aro mndo over n. p~riod of sufficiollL longth, BI~y lIS to 30 ye[Ll's. ConsidortttioIl must bo given~ moreovor, to the fact that mnployees with OCCuIHltionn,l cl1.ncor or wiLh therapentically controlled occnpatiollnJ Oll.ncor aro, ill gonoml, 110L continncd in operations with cll.l'cinogonio hnzal'ds. In soma establishmonts, howover, this practico is not 11 followed as it is held (Jut!, removal from the haz{tl'dollS occupation doos not improve the ultimate prognosis, n,nd by continuing tIw O1nployee in the occupaLion the aLsolute number or persons so exposed is held aL a minimnm. This practice) 011 the oLher hand, tonds to incl'ease primary cancer incidenco UffiOllg exposod wOl'kel't:l. It is usually round that various om}lloyeo groups aro oxpo8cd in widely differing degl'cos to any caL'cinogellic agent or ngents that may bo present. Office workers, for eXllmple, aro not as 11 rule significantly exposed to inclllsLrial mtrcinogens unless the admiuistrn,t.ive qun.rters form au integl'ul or closely related part OT the production zono, thereby estublishing direct contact; or unlesB the disposal of carcin.ogenic wltsLes, such as rumcs, dust, v[t,lJors, ga~cs, mist, reprcsents all environ~ mental hnzal'd in the office area. Not inil'eqnently it is found that only lelutively small gronps of workers hnve effective contact with carcinogens. In some industries, howGvel', such as chromate opel'a~ tions, pl'actically nIl production workel's arc exposcrl to carcinogenic Itgcnts to some degree. 'rhe invesLigll,tions should bo extended not only to individuals regu~ Jurg1y employed in hazardous opel'll,tiolls or constnntly in contact with carclllogenic agen Ls, but also to those e11tering the hazardous area 01' coming into contact with carcinogens at irregular int~rvals. Int()r~ miLtent, irregular, or rhythmic exposures of varying intensity may be sllstained by such WOl'kOl'S as watchmen, repail'men, packers, shippers, tl'llckol'S, supel'visol's, clel'ks, control chemists, guards, and yardmoll. COllsidemtion should also be given to workers clun'ged with the dis~ posal of wastes and emptied containers of carcinogenic matel'ials 8S well as to those workers who mn,y become exposed to au appl'eciable de~ gree through work ill noncarcinogcnic op~rations located near the hazal'dous one) and thereby llossib1y hecoming exposed t'o cUl'cinogcmic gnsC!s, vapol's, fumes, dusts, etc., ol'iginltLil1g from tbe latter. Through investigat.iOllS within the plant, exact. information should be obtained ns Lo the nature or the suspected carcinogenic agents; type and ronte of contact to which employees are exposed; and the tJ'pe and intensity of snch hazards and their possillle vUl'in,tions during different periods of opol'lttion 01 the plant due to changes ill manufactnrh1g methods and ill l'ltW materials used. 1{ol'eoVCl') record should bo made or any diif(}l'onces in the degree and Lype of GXpOSlll'e (skin contact, inhnlati<m, ingostion) and the phy"ico~ chemic11.1 stutus or the agents (dusL, fumes, mist, spray, vapol', gas) in different parts 01 the snme operation and in difiol'ent parts of the plant. Special ntLention should he paid to ascertaining the pnrticle size 01 dust, .fumes, mist, etc., as this factor determines to Ucertain degree the severity O.l exposure to l'espiratory cancel' hnzfl.l'ds. Suoh distinctiollS arc indicated 101' chemiciLl as well as physica.l carcinogenic agents. Differences in this .fncLor nffoct not only the incidence I'ate of occupa~ 12 tional cancers among various gl'OUpS or worknrs hut may also be ol distinct influence in determining the site of resulting cancel's. '1'0 assay cancel' huzards in industry, the plant mnst be surveyed by a trained observer a.s ouly such a person cuu detect the potonLial uanger )Joints. In carrying ouL such plant unnlysBB) it may bG wiso to follow these suggestions. (a) The investigalor should he thol'ougllly fall1i1inr with the pl'O~ duction methods und with the materia.ls hundled and man.ufactured in the pllmt. lIe should be able to note any irregulurities or exceptions from usual procedures l1.11d readily dote.ct areas ill which carcinogenlc hazards may exist. (0) Studies shonld be maue when the plant is in OPOl'ittion. Conditions of exposure and observance of precautionary measul'es by wOl'Imrs and lll:l.nagcment can be properly studicd only under working conditions. :Moreovel', there is an opportunity to study tllo physicnl appearance of 'Workel's and, with permission of the mann.gemcnt, muko pm'sonal inquiries of fOl'emen and workers in. regal'd to suspected hazards. (0) Sinco visHs 01 this sorL may be announced well beforehund, thero is nu opportunity for cleaning up any operation. Such a procedure mlLy result, unintentionally, in the obliteration of important evidence, It is, thcl'crore, aclvisable that the illspector look closely at the condition of windows, corners, 1100ks, ledges, sUl'races and joints or of pipes and U.UCLS, an.d ol,her mn.chinel'Y ror evidence of pOOl' housow keeping. Arrangement. and effectivencss exhaust ven Liln.tion should be tested. (d) Any survey should include the yard and adjacent buildings, packing and shipping iacilities, and disposal of wastes and emptied or containers. Finally, the study should hn extended to the neighbor- hood the plant, noting unnsual effects on eo10r RJul SUl'laces of houses, vegetation and animals, and condition 01 drinking water in order to discovel' any possible e.Erects on the environment of cnl'cino~ gcnic agents hll.udled 01' produced wilhin the phmt, 1Vhol'o evhlence indicates the cllvil'omnontal BpJ'cad Ol an occllpnLiona1 cancol' hazard (0 persons living near the plant, Ule survey shou1rl bo extended to the population Hving or working in the vicinity 01 the plant and Illny, if .foasible, include an epidemiologic study of cancel' among wHd and domcsticfLLed animals :in the al'ca, (0) Contact should always be made with iho plant physician and orinformation obtained as to the type 01 mec1ical supervision, tho typo mediealfaeilities availablo, and the omployment IlUU mec1imtl policy observed in conncction with worlmrs who havn developecl precanccrous ott Cu.nOOltOU9 la9ions. (I) Through cfLrelul qnestioning the :invcstignlol' should discover allY ehanges made in pl'oducti011, h~ndling, aud l)l'ectlutionaJ.'Y mcus~ ,13 m'es employed during the period of plant operation. Such changes may hnve a iuvorubJe 01' ad vel'S(l e1f8ct on the conditions of expoSllre. The direction of this influenro lUny sometimes be rather unexpected. For eXllmple, improved production methods alld precautionary measUl'es which may rednce the concelltl'ution of cUl'ciuogenic dust in the ntmosphel'e lUny also inCl'GIlSe l'ltthel' than c1imimsh the degree or exposure. In ol'der to obtnin better yields ill production, the cal'~ cinogen may have been m01'e finely powdm'ed, thcl'eby causing fl dust ,vhich reaches the deeper regiulls of the bronchiul tree. The COllsequent intensification of the cHl'cinogenic cUect callses an incl'eased incidence and a shortened latent period 01 the rmmltnnt callcer of the lung. A corresponding resnlt may follow when a mlst huzard is converted lnto R vapor huznnl, 01' dust hazard into a fume or vupor hazard. Changes in the physico-cllemical status of the Cltl'Clnogcn mny result, moreover, in a shift of the sile of lbe ensuIng CUllCel'S. (See C-l.) Althongh it is not likely that fl ca1'cinogen present in mist form may reach tho BUSEd sinuses (unless these have become 1tbnol'll1uIly uccesM siblo through opol'utive procedures, such as It1'O pel'fOl'mcd for the l'elief of chronic sinusitis), C!U1CCl'Ol1S reuctiol1s of the sinus lining lUay be Itnticipated if the cnrcinogen appeal's in the form of a VUp01' Cl' gas tlmt can entor the sinuses and be trapped, condensed, and l'ctuined ill the cRvity. In investigating the effects of such changes in proullction methods, the bwcstigntol' must constnlltly benr in mind that, as a rule, effects do not become evid~nt until a ]Ilg period of nt lcnst 5 YClll'S) cOlTeBpoml~ ing to the usual Intent period for the type of cltncer, has elapsed. Detailed informution should be obtained on the pt'cventive, Pl'OphyM lnctic, sanitary, and medicnl measures taken by plant mnllllgemCllt for reducing 01' elimillttting the CllllC{'l' h~tZn,lJd and of the llntes upon which such measnres were introdllceu. The type find extont of precautionary measnres ta.ken; extent of medicfil supel'vif)ion; nlH.l follow-up of former workers nnu of workers shifted from hazlll'dons to nonhnzludous opOl'ations, Special attention should be pnid Lo the methods employed in the (lispoSIlI of carcinogenic induRLrial wastos, since inn.dequate meltsnrcs of waste dispoStll mny lelLd to a perpetuation or reintl'od uctIon 01 cancer hazards iJl to operaLiOllS whieh mfiy have Lecn mn.de sde fl'om the stundpoint of prodnction. C. SPECIAL ASPECTS 'l'he conduct 01 occuplltionnl flllnCGr 9U,."eyg prosonts n sories of specia1 pl'oLlcms which mnsl be taken into pl'O})Hl' considel'nLion to assure results tllnt are relinble, significant and valuable for the con 14 cluct of cancel' research and fot, the illtl'odu~tioll or proventivo Il1eaSlll'es, 1. Contact-Site Relations of Carcinogens Observations in the field of onvil'omnentu.l carcinogonesis have ~hown thnt t.he route of contact with these agents, fiS well fiS the rouLe n,nd nature of tbe metabolism and excretion. 01' t.he sHe of thoir dcposibon plays a defiuite 1'0113 in determining the siLe of the enslling cnncer, rl'hose observations are SUlIlll1ttl'ized in table 3, which indicates the tYl)C 01 COlllfiC~ (direct and primary, depository, oxrret.ol'Y) for various ca"rcil1ogens and the sito of resultant cancer. Table 3. COiltact-site j'olatiolzs of cal'cillogem Site of cancor 'J'ype of contact Caroinogen Dh'ceL, prirnn,l'Y contn.ct_ Ski n ______________ Dcpository contactw _____ Excretory contnct______ . Dh'oct, primary contn.ct __ T~u ng, I.n.l'ym:, nnsal floinuscB. EXCl'ctory contncL - - - __ DI adder, Ul'cter, kidnoy. Bone and uone luarrow. EXOl'ctory contact_ ~ w - __ repOSitOl'Y (onlt _ -- Dil'cct primnry cOlltn.oL_ Ultl'aviolClL radiaMoll, X-mdla.tiOll l'udionotivo enorgy, tlW, pitch, 800t, pl'ocessed minoral oils. p;roascs, o.rsonicals. Al'sonioals, - A1'scnicals. Hndionctivn AUfIOS ",nd dusLs, flllHOS, (ht!>I.!;, mists, VfI,pors of tnt', pitoh, processed minorfl,l oils, chl'omatcs, niolcol Onl'bollYI (?), arsonIc, D.BhIlSLoB ('!), isopl'opyl oil (1). - - - Radioo.ctivc gnscs. Arolllatio mnhtOIlJ 1,1\1' (1), fl,rflcmlc (1), Jouilling l'arlill.LiollA (l'll.diOl~ctl"o snbfltauucs), bon~ol, ueryl- 1ium (?). Xwmdiation, Despite the fact thnL the tisslles 01 the n,limentn.ry find nervous systoms are directly or indil'ocUy oxposed to a gL'oaL llmnbm' of ellvil'Ollm.auLal agents-some, such as tar, peLl'o]omn del'ivn.LivGs, Il.l'scnic a.nd benzol) having definite cn.l'Ginogenie 1l1'OporLicH-!Llld althollgh canccl'S of the n,limentary trac!' exhibit. topogrnphicu'] fOltLul'oS iurlicnLing tho causa] action of exogenous carcinogons, thero oxiflt SllO ddinitc evidence Lhnt specific eXog'enons and envil'onmentallwtol'S aro involved in their genesis. Since cancers of the nlimental'Y Rystml1 cOllstitute a1most or one-half of all cancers observed in males find since canc~r of this orgall Hysi-mn, as well as those the contra] nervons syslem, usually havo a p001~ prognosis, it may be hopod that cmvil'onmenw.l en11001' stll'veys will 8-00678-.'10-8 15 provide data indicating the cansation of at least somo of tho CltllCers affecting these two organ syst~ms, and th~reby hell) open tho way to their ultimate control. 2. Environmental Cancer Pattern III studying tho medical histories 01' symptoms of wOl'lwl'H ~xposed to occupational carcinogens, attontioll should bo givml Hot only to cancers, but also to pl'OCanCel'ous lesions (prolil'omtive conditions which arc sometimes observed preccding and not inll'cqnonLly lending to cancer), and pel'icancOl'ous lesions (conditions dno to cILl'cinogenic exposure, but are ullrelated to the cn,rcinogollic procoss, yo~ serving as stigmata o:f previollsly sustained sPGcific clll'cinogmlic OXpOSlll'OS). Proper attention should be givon to tho impOl'tullL facL tlllL~ oxogenOllS carcinogens not only elicit hypm'plnstic and bonign nooplnstic eellular proliferations prcceding, prepnl'lttory to, or simulLltllBonsly with, cancerous reactions. Depending 011 tho <jUl1lltitfLLivo nnd qunlitntivo conditions of oxposure, thoso carcinogolls may also cnllf)O clegollOl.'u.tive, necrotizing and, in fact, anti-cancorous e:iTectH. Sunh lunbivltlont responses to oxogenoW:i carcinogons uppeuI' in many iormH and aro not infrequently prescnt ill individuals with ollvironmontal prOCltl1Ce1'OllS and cancerous lesions. In :flLeL, whonevor such an ollvironmental callcer pattern, including both nplnsiogonic Rnd hypol'plusiogollic Hmnifescntiolls, can he demonstrated ill t.ho samo individual or a group of individuals ~xposed to the samo ag~nt, it serves as vltlllnblo cvi<lonco in support of an exogenous causllLion oC the cancOl'OlU; 1'09P0l180S ohsOl'ved in the population group. Among the exogcnons carcinogens which produce. theso Itmhivu.lonL effects aro al'senicals, benzel, ionizing l'udiationl:J il'om raclioacLivo chemicals and X-ray tubes, estl'ogens, 1ll'ot1ml1o, amI cm'Lttin nitrogoll mustal'ds. Theh anti-cancerous acLion is nt.ilizec1 in the thOl'lLVY 01 malignant tumers, while thcir carcinogonic acf.iol1 hnR rGRulLed oCM casionully ill the production of cancers whon thoy lmvo hnc'.H tlso(lmeH diclllaIly in the treatment of nonmaHgmlnL conditions. These ambivalent precancerOllS and pericnncol'ol1s l'mtdiollA to onvironmental carcinogens aro summarized in tlLhlo;1. As llltty he noted, they urc found 111 tho ontire rango of Lho carcinogenic Hpect,rmn nnd aft'ect t11e skin, nasal passages, hladdOl', bono marl'OW, lungs, Itud breasts, A characteristic envh'onmcntll.l cuncol' pattOl'll may 1>0 prm~olltocl by ~he changes in tl1e blood and hemlttopoioLic tisslles following oxposure to benzol 01' ionizing l'adiations. At 0110 oxtl'omo of (,he ReaIo, hOlwy exposuro is found to bring degenerutive, nocroLlzing and I1trophio ohanges, such as aplastic anemia, loukopenia, t,hl'ombocytoplmin, mac~ l'ocytic all(~min, n.nd sevoro u.tl'ophy of Lhe hClTIltlopoiotic tlssues. On the opposite end of the reactivo rango thoro occur loucooytotic, bypor... 16 leucocytotic and leukemoid reactions with the appearance of immature leucocytes, polyglobulia, leukemia associated with metaplastic eryth* ropoietic, myeloid and leukemic proliferations in internal Ol'gans, and myeloid and leukemic hyperplasia of the bone lllinrow. Table 4. Precancerolls arId periCatlCerollS reactions to environmental carcitlogem Reactions Etiologic Agents SKIN Alopccia~ Spotty less of hair____________________ _ Arsenio, ionizing radinLions ( r a d i 0 a 0 to i v 0 substances, X-radiation) Atrophy: Skin grossly thinned and gllstening in patohes, associated with keratotic arena, Pitoh, tar, asphalt, potralmUllt r a d ion. {) t i v 0 8ubsttLIHlC6t X-rndintion~ ultrn.violct l'ltdiatlon 1 BalM l'll.YS, Eczema: Dry sabOt'rhein patches on sldn __________ Arsenic, asphalt, pitch, scot, tnt'. Kcratosis: Flat, discrete, scaly 8J.'ea on akin with raised pearly bm'dol's, Usually on parts ef skin exposed to carcinogen. but may ocour in unexposed pm'ts, particularly about Bweat glands, wi th ai'senic. HYJ)el'kcl'atosis: Rough, fissured keratotio plaques with small, hard, wart-Uke 1101'118 usually cm hands and 801es, May become nodular and ltlcerate. Anthra.oene, IlI'senic, asphru t, creosoto, Cl'l1de minm'nl oil, parafBn, pitQh, soot, tlU', rndioaotivo aubstft.llCCS, ultl'lwlalot mdiationI X-l'ooiatien, Vel'l'ucae: Horn-like hypm'keratesiB ____ H _________ H Ulcol'ation: Breakdown of keratotic lcsIons__________ Araenicrus, Chrome holcs____ H ____ H _ H _ ___ __ ___ _ ___ Chl'omatcs, ohromio acid, Lcukoderma: Patches of subnormal melanin pigmonta- tion. Leuko-mclanoderma: Patehes showing inereased pigmentation and pntohes showing subnormal plgmcntntlon of skin. Most Gommon in areas of llighest pigmontation, and may involve oral mucosa, Melal1odm'ma: Patehas of inereased pigmentation ______ _ Alltlll'flOCne, al'flenic! asphaiL, crcosoto, ernde mlllcrnl oil, pn.raffin, pitch, tfLl', nOlliOlliv,- mg nnd ioniz.ing muln~ioll8 ( r a d loa c t; i v 0 rmbstanc6s) X-l'adiation, Ual'avlolot l'adlation, sclnl' radlaLioll), Scleroderma: Dl'Y. sealy. parehment..like skin, wit.1t enlarged porCSJ ft.Bf3oo1atcd with loukfl" melnnedorma. Cl'ude minorstl oil, pftl'nmn oH, loniz.lng radtntJolls (radlolloLlvo Bubstanoes, X-rays. ulkaviolot rays, solnt' )'ays). 17, Table 4, Pl'ecanceroltS mid pe1'lc(t1lce1'01tS reactlons to environmental ~a1'ciJlOgens-Continued Reactions Etiologie Agents . NASAL PASSAGES PnBillomas and 1}olYJ)s: l'owLhs ill nub'l\m, ethmoid GOlls and tUl'lJinntos, Nasal saptlllU pOl'fora-o tions, BLADDER - HemorrllRge, sllbmuoosal: Val'ying size, with tc}augicctns.is, I.oeatod lnninly in trigone and abo11t Ul'oteral orifices, Pll.~ilIOtnaB: OlYPOllS or viUous, pcdullc.uiatcd 01' sessile. Often multipie a.hOllt tl'lgone and 111'otornl orifl(l(~s, Isopropyl oil, niokel carbonyl, ohI"omatcs, aniCui cals. - Benzidine, bota"llnphthylmnino and derivatives. EYES paFillomas: cclunclllnted. Develop mainly on lidsJ oocasionally 011 eyeball, Arsonio, nspha}(" croosot.e, orude minerlll oil, pitch, tal'l ionizing l'ndiaUons, ultrllviolet rays. BONE Clll'onie poriostitis: Thlokaning of periostoal tiS:lllO, neOl'0l31a of banc, Ionir,ing l'adintions ~X"lt1YS, radioaoti ve snl1stanees , BONE MARROW IIYPOPLASIA DJ ood dyscl'aslRs: IIY}Jorplal!ia and motaplasill. IlplallLic anemia, thl'ombocytopenia,loulwpcnia, monooytosis, orythl'OCytosis, loucocytosis, leukemoid roactions. LUNGS Pnoumoconlosos and Rlloumonin: Asbestosis, uUpaid' rncmnOlJiR, chronic chemioal pncumon Il, Benzol llnd derivativcsl ioni;ll-ing I'll.diations (tadionctn)'o 8\11>stall ees, X-rays), ~ ... Asbcstoll, a1'senio, tar, soot, millM CI'nl oil mist, chl'ome salts, nickol oarbonyl. BREAs'r Painful; swollon bl'onsts: Glandular hypcrplasia, EsLl'ogol1ic ehomieals. InLorlUecliutG degl'ee.q of exposUl'e, whether continuolls or interlnittent, will produce mixed reactions. In genora.l it will be found that increasing exposure willl'esult in incl'easing effonLs of both the hYPGr" plastic and atrophic types up to a certu,in point. From that point, the increasing severity of exposure will cause a pl'Oponderantly nplasLio eiiect, overwhelming any hyperplastic reactions and leacling, us exposure increasGs, to death OT tl1e ol'ganism by destruction of tisSllGS, 'rhus, a primarily hYl)81'plustic phase may be followed by an aplastio pbase, 01' vice vers[\., c1epenoillg upon the degree and rhyt.hln 01 exposure. 18 tl'aet~ etc.), amollg persons living ill varions pn.rts of the SUl'vey aren.. Different types of exposure to t.he same cttl'cinogen, IlS wen as contact with different cltl'cinogens, have a direct inlluonco ou the incidence I'awe and locnlizntioI1s of cnncer within one pltl'ticulnl' Ol'g!lll system. For a conclusive demollstration of the occnpaLionnJ or environmental natul'e 01 M..llCel'S suspeoted on the bnsis of stutisticfll Itnd epidemiologic evidence, it is usually nnccs.':in,l'Y to l'c}Jl'odnce identical or cancers in oxperimm1tn.l n.nimals by meauS tlw snspecind agent. In Tact, it is held by many inveRtigntol's that tho lwtual canse of a particular occllpation1tl cnncel' is not proven nntil Qxpel'i.mental l'ew production Ims been flchievcd. Conversely, it iR 110t in [l'cqnenUy beM Beved that the demonstl'ati0l1 0 f cal'cinogenic r{!spOnSeB to aH exogeM nous agent in animals is evidence that i11is agent may exert a similar action 11'1 man. On tht\ basis of this assumption, chemicals produced and used in industl'Y und consumed by the general pUblic are screened and tested in expel'imentalanima1s for potenthtl eal'cinogenic pl'Op~ el'ties they may possess 101' mu,n. Howevm', cxifiUng rn,eta indicl1te that neitllel' a successful reproduction oi C1~ncel' 111 I\nimals nOl' the bionssay of chomicals fm' pot(\ntial CRl'Cl11ogenicity in man n1lfill eptil'ely the l'Gql1hements that must be plnced 011 811ch tests. For insta"nce, undCl' pl.'opel' cOllClitions 01 exposure betIL~naIJhthyl amine and benzidine elicit bladder onneel' in man. Sueh tmnQrs are pl'oc1nced in 100 percent of the jn{lividllals ailer suOidently intense and prolonged contact with theHo chemicals. Ago, Fmx, and heredity do not seem to have any aPP1'eciltble influence in thjs respect, The or experimental reproduction LhcBO bladdel' cancol'S was successfully achieved by feeding lDnle 01' fomnle clogs betltnaphthyh'unl.no, The1'c is controversy as to whether or not mbl>it.s l'cn.cf, simi1u.l'ly to the administration 01 beta~nl\phthyl1tn1inG; it is eshthHshed that l'nts nnd mice do not l'esponc1 with the development of bladdor cal1cel' when given this chelnicrtl by various routes, Itlthongh they readily show this response upon tIle inu:oc1\lction o{ 1,<,lttf.od aromatic nmines (2~MetylaminofluOl'el1e) llTIlI l\l'ollmLlo Ilzo-cmnponnds (O-nlUino~ o..zotoluene, o-toluidino), On the other hand, dogs led benzidine in high a.nd at times toxic doses fol' a 1lol'iorl or mo1'o Uum !5 yeu1's did not develop blltddol' tumol's; l'nls l'cceivillg t.he !'lttme il'on.LmcnL l'ospond with the pl'Oduction of cancers of the Cllstnolliull tube, hepaiocn.l'~ cinomus, and leukOlnia, 1'he t.wo al'omntic (lmines iound to bo carcinogenic to man cause species specific cu.nc()roua responses which in the rat are complicatecl by a sl1iit, o[ the ctLl'c\nogmlic shock ol'gan (i. e., the bln.ddel', in man) to Bevel'l~l OU1C1' tissuos (i. e.) liVOl', bono marl'OW and, pl'obnbly, eustachian t.ube) , The chemicnlannlysis of tho tU'inn.l'Y meiaboliles 0 f the two aro- matic o..millCs when givon to difforent species snggcsLs thn,t vltl'intlons 20 or in their metabolism chal'lcteristic for the species tested seem to be related to thB species specific carcinogenic properties observed. It thus was found that beta-naphthylumina is excreted by the dog a3 2-lmino-l-hydroxynuphthalene conjugated with aulfuric lcid, while l'ats, rabbits, and monkeys given injections of beta-naphthylamine in olive oil eliminate in the urine the base itself, its N-acetyl derivative, its N-acet.yl-6-bydroxy-dcl'ivative and an lmidentified dibydl'oxYllll11nonaphthnlene. After the ndmillist.l'ntiol1 of benzidine rabbits excret.e the free bnse and El. hydl'oxy~derivntive, white rats eliminate a hydl'oxylated compound and an acylate derivative, Workers exposed to chemicals containing benzidine excrete hydl'Oxy-derivatives, while acyl derivatives and free benzidine have not yet been demom~trated in mall. Various aromatic azo compounds produce cancel' of the liver in ruts but not in l'n,bbits. Observations sllggest that this species specificity is not entirely of [l, cOllstitutionalnatul'e, but depends in paTt. on exogenous dietary influences which, through impnirment of the nOl'Dlalliver iunction, cause an abnormal metabolism of the cal'cinogenic azocompounds. While n constitutional factor ,vhich causes a rapid excretion of butler yellow may account for the resistance rabbits and guinea pigs to the carcinogenic notion of butter yellow, the exogenons dietary iuctor that is essential for the carcinogenic action of the chemical in tbe rat is the riboflavin deficient diet, withont which liver oancel' does not develop. Recent experiments showed that rats Itept on all adequate diet and given 2,3 azotolnene excrete. 2,1 aminophenol ill the urine while l'ate given a riboflavin deficient diet i.n addition to the chemical eliminate al1iline in the urine and develop bladder tumOl'S. Another ~xn.mple 01 the species specific quality of cnrcinogens is offereel by tar. While it has been possible to elicit skin cancel'S readily by the npplicatioll of vaI'ious types of tar in man, mice, and rabbits and with some difficulty in l'ats and dogs, all attempts to obtain similru. rosIutltissinnomt ounnkloikyeslhyavtheaftaislepdec. ies specific factors ma.y be responsible for tho equivocal results obtained in experiments aimed at a repl'oduction of arsenic cancers in animnls. Since the average latent p0riod of ltrsel1ic cancel' oi the skin is relatively ahort wIle;l compared with the latent period for oil cancers, it is impl'obable that the species specific differences ill life SpUll play nn important role in preventing the carcinogenic action of arsonic to become manliest in uni.mals. It may b& possible that Ul~ generalized hall' growth in experimental animals creates l highor excretol'y potential o:f arsenic and thereby lowers its cn,l'cinogenic action. However, the strikingly apotty Rppenrance of [(rsenic cancel' in man points to tho nction of other mechilllisms, pl'Obn,bly of n.bnol'mal l1o,tul'e, that must be present before arsenic cnn 21 pl'oc1uco cancerous responses Gvml in mall, H ,i~ remnrlm~le in this connection that a high percentage of u.Il lllClChcllll~l lLl'SCl1lC C!tllCN'S have been observed in inclividnnls with psorinsis, Another eXUml)le or the groat impOl'Lnm:o or spcci(?~ speci~~ity is presented by the contil1uecl conil'oYol'sy n~ to tlw cn~'elllogolllclty of ostl'ogonic substnnces ill 1111,11. While them cn.n be heLlo tloubt that estl'ogens [ue essentially involvod in the dovelopmollL, o~ m~mmnl'y cuncel' of cel'tnin inbred slrrtins of mice 01 both sexes, It IH HLIll quosLionable ,,,hether estl'ogcns pu l'Licl}) 11,i 0 in the prodnctioll of snell LllmOl'S in mnn. Thero is little likolihood LlULl It d(lfilliLu dnlliHioll of this controversy win be obtained irom OllfJ(H'Yo.Liol1s U1ado on W()11lcm, HoweV61", recent observations mado ill mnll"s \ViLlI intellsivo n.tHl pl'oJonged medicilla] 01' occmpatiOIlft.l conLncL wiLll synthetio eALl'ogomi may soon pl'Ovidc the fin a] answet' to this CluesLion. Ull ilat m'nl or hillLt.nrnl l11n,mmary cancer 1mB beell fennu in several mnlcH who l'(~(!(\ivc<1 llwge amounts or st:ilbestl'ol io1' tho control of cancol' of tho prosLltie. Since normally lcss tha112 percent of al1 bl'onsl (:Rrciuomns OCCUI' in males, the conti.nued tl1erapeutic \lse 01 csLl'ogells in Lilo tr(mtmeni of pl'oflllllie or cancer may supply conclusive mduenco RA to tho c!U'dllogQllicity 01 ostl'ogens in man, The OCCllrronce or bypel'pln.Rin. Lhn breast in pharmnceutical WOl'lWl'S 111 EnglmlCl IUH] Lho TJnil(itl Eilu,(os engagod hl the mannfucture or sYllthot ic csLl'ogells nmy Vl'ovldo eonfil'mnlel'Y cvidence in this respect, if find when lnltmnml'y (~tmc{\l'S devolop in male wOl'ke]'s of this occl1patiollfil gronp. Brief 11lelltion may ba mllde h1 this connection of Lwo ndclitl011nl chemicals with potcntial 01' contl'oYCl'sin.l (,ltl'(linogoni('Hy to man Il,ml de.finilo or equivocal cRl'cinogonciLy to nnimnlH. HcnUcl'olloceupntionn] observations indict benzol us It 1(\111((.~mlogclli(\ ugOl\(, in Hum, lIow~ eVel', tho 8xlJOI'imelLUtl obsel'vatiolls mn(lt~ RO fILl' on{,lmly on mice are contradictory, BOl'yl1imn has been shown to ()li1~i LoHLcogmtio Slu'cOlUas iUl'abbits only by menns of lnil'tLveno118 11ljcotions, It is tu} opon quostion W11cthol' this obsol'yu,tion in<licRt.cf; tlmt t.his ~nl}Hlnnco mn,y eXCll't a similal' offset in wOl'lcers oxposec1 to iL by H, di.fTCll'ont routo, Spccios specific diffel'ences cxisl ttl~lo in Lho Hold of physicnl cnrcino gens and produce uncBl'tnilliios mul pl'ohlmm; thoro idonticn.l with those enconntered in" cOllllection wi Lh prinml'y cl1eluicnJ ctll'cinogens, Epidemiologic ovirlencn sLrong]y indimtlBH that H.1\ 6xCnFlHivG OXpOSlll'O to solar rays may result in cancol' of l,he oxpo~tHl skin nlUOl1g illClividun1s espeeil1l1y predisposed by Lhci l' light. COlHll1(\xioll. Obscl'vn~ tions mnc1e 011 mice nnd ruts subjecl(lc1 t.o intollHivG LJ'Olttl1loni with 11ltravjo]et rays seem to confirm thh; clLHsn.l rultttioll bGLW(lClll OXpOSl11'O to solar actiuic energy and Cflncm' deve1opmoni, lIowovor all nLtmnI)/."q to procllIce experImentally uliravio1ol CltnCOl' 01 tho ski'n in guinon. pigs nnd l'nbbits have Iailod, rrhus, ohsGl'vniions on Lwo species somn to negnte any relationship of solftl' il'l'ltc1in.tioll ttud Clll1CIll', Such (L 22 conclusion, however, is a frtl1acious one us far as man, mice anu ruts are concerned. The inability of ultraviolet mys to elicit skin Cll11cel'S in guinea pigs and rabbits mther may be dne to species speeific differonces in the pholochemical l'rlUcLions lLUd react.ion products pl'oJuced in these species. These species specific cliifel'<:-11ces in the response to ultrnviolet rays, by the wny, do not support tho \videly held COllcept that actinic energy elecits cancerous responses by causing pl'ilmtl'Y direct cellular muLu.tions, 'fhe available evidenoe fn,vors the idea. that physical carcinogenic agellts n,lso produce cancer through the mechanism of chemimtl deviations, or so far undetermined character. Evnluating the evidence on t.he species spceifidty of physical and ('ltelllicul carcinogens and its relation to occnpational carcinogenesis the following conclusiolls may be l'~nched: 1. Failnre to roproduce cancers of certain sitos in experimental animals, using agcntf! which seemingly pl'oduce such CallCel'S in man, does not disprove the carcinogenicity of the pal'liclllar agents for mun. 2. The employment of experimental animals in t.he screening of exogenolts agents for poteHtinl eUl'cinogenicity in mall, while being at present tho ouly availnblo and pract.ical method, is not Ull entirely roli able one. 3. III tho expel'iInentul study of carcinogens which affect humans the selection of a suitable species l'epl'esents thE) iundmmmtal pre- or requisite rOl' obtaining results thnt can be applied to mUll. '1'11e plunning, preparation and technical execution animlll experiments on OccuIJlttionul carcinogens present certain s11eeial aspeets und col1side1'lLions whieh may be WQ1'th mentioning since thoy may influenco decisively the outcome of the expel'im(lnt. Given a sllitublo Lost speeies, applied expel'imelltul occupational canCel' research mllst aim to tluplicu,te 01' at lenst closely approach in its experimental conditions the circumstances of oxposure t.hut Itl'O believed to lencl to tho developmont 01 cancel' in man. Expel'imelltal evidence obtni.ned in this way is most useful ill its direct practical application to tho cxiRLing occupational pl'ohlom, ox For installce, when designing (he eXl101'imeutnl conditions by which nn occupational hazard ellLniling the inhlLlation n. carcinogell is to 0., bo studied, it. is essential to nscel'tain first tho physioal siaLu8 o[ the corcinogen uncleI' the existing 'Working conditiolls; i. whether it is a gUSt vapor, mist, spl'ay, fume, dust, 01' a combination of soveral, lUld whut its pnl'ticle size is if it ocours in a dispe.rscd Iorm. n is ('specially important to asc~rtain the smallest pm-tide size Pl'CSOllt and its proportion in the dispersed matter. Industrial hygienisLs uro now pUyh1g marked attention to th~ determina.tion of the particle size, since this facior is oi ut.most im])01'tal1ce i 11 c1otel'lUillhlg thG depLh to which the inhaled particles l"e1letrats t118 rospiratory Lract., and thus in controlling the site a.nd degl'ee of exposure to the inhaled agent. Not infrequently tho sume agent llnderw goes several changes in its physical state when pnssing through various plant prOCCSSCH. For insta.1lce, chromite ores reaeh the fac- ortory conrsely gl'onu{1. The particles in this stuto may pass a sieve f) to 10 mesh. After t110 ore has been ground in steel ball mills to n. fine powder the pnl'ticl~ size is reduced so tho chromite 01'0 passes through n sieve of 100 mesh and half of it through a 250 mesh. '''hen this powdered material is processed in the pln.nt and dust is pror1uced~ it is obvious thnt tho smn.llel' dust particles will remain sLlspended in the nil' longer than the coarsm' ones and that the main exposure of the workors l'OBUltS from tho inhalation of the portion of chromite or chl'omuto compoUlHls huving the smaller pll.l'ticle size. When a.pplying such information to the experimcnt) it is necessary not only to select n, dust of propel' particle size but nlso I1n animal with respiratory passages that permit tho ponctration 01 the dust chosen illto tho bl'oncllinl tree. In view of the narrow respiratory passages or small anima.ls such as mice, it, is not likely that these species offcn' favol'uble unntomicnl conditions io1' nclministering cffective exposures to carcInogenic <lusts when the action 01 these dusts is dependent all direet contacL of the bronchial tissue to the carcinogenic ngent. When determining the dose o.f carcinogen Lo be administered, it is not unusual that data lls('(l havc beon collected and recorded by in- dustrial engineers and represent concentrations 01 the offending agent obtainod in a number of l'andom spot checks 01' are average values derived from tests of 10ngsr duration. Under practical working con- ditions, however, concentrations of inj m'ions and carcinogenic ngents may vary considerably during various phasos of the operation and especially at times 01 accidonts, during maint.onance work or during l'ep!til's. It is 101' these reasons that spacial occupational gl'OUpS om- ployed within a carcinogenic operation o!loll exhibit a. pal'ticnlu.rly high incidenco of occllpatiollaI canCOl' as they are exposed intermittently to highly incrcased concontrations of the carcinogenic agent. In the experimental nppl'on.chof) to occnpaliolln.l cancel' such observations deserve adeqnato cOllsidol'ations, as the uso of insufficiont doses calculated from ll,veragecl concentration figures may produce mislcad- ing negative results. Data on the concentration of radioactivity in tho Schneeberg mines, for instance, indicate t.hnt there arc not only appreciable variations in the dogree of avorago radioactivity in the different mine shafts, but that the content.B of radioactive gases within the snme mine vary considorably in difforent. piU'ts and nt. different times, tllel'eby cansing an exposnre to the miners that, as in,r as cm'- cinogellic conconirations are concerned, should bo measnred more in peak vnlues than in avornged values. Therefore, the propel' appli- 24 cation of observations Oll exposllre in tho field seCIns to bo nIl important part in experimental studios on occup:ltioual cal'cinogonesis. Since there is an almost complete laok of l'elinblo information itS to tho minimal effective closes for ll1:lU of the various occupa.tional curcinogel1s) and in view of the hct thnt the gl'ent. runjol'ily of exporilnental reproductions of OCC11putionn,l cancers havo beon clone with closes appreciably oxceeding those encounterod Ullder working C011- ditions in industry, it does not seem wise io ltttn.ch too much significance to negativo experimentall'cslllts when low doses wero used. 4. Age Factors in Occupational Cancel' A survey of environmtmLn..l cancer should include aU cases in the tll'ea, l'egardless of age, sex, race, or site. 'l'he fina1 Rnalysis, however, should consider these factors sepllrutely and should make Ul(~ prOpel' adjl1stments for standardization) so as to obtain compal'nble. figures. Since occupational exposuro to cnl'cinogcnic agents does not sturt, as n, rule, before the a.gc 01 1G to 18 ycars, and inn.snmch as the a.vel'ugo lalent period for occupatioual CallC~l'S is 'from 5 lo 25 yeurs iL is advisable to restrict the evaluation of data in [1 study of occnpational cancel' to persons of the n.ge group above 26 yenrs. Although female workers oftcn leave indL1strial occupations ld, an early ugc, the extensive eInployment of fel1Ulle wOl'k~l's in certain illdm;tl'ios and professions with potential callcer haza],ds WHl'l'Il,nts their inclusion jn sllch surveys. Tllcse industries includa rubbel' goods manufll.ctul'e, luminous dial painting, spinning and weaving, X-ray and laboratory wOl'k Many envhonmeninl cal'cinog<mic factors, 0]1 the other hand, nct on the human organism at, a much eallicl' age thall the OCCUplllional orcarcinogens. Fm' instance) cpidomiological studios on the incidence penile cnneGl' ill circumcised and 1l0l1cil'cumcisccl popu1atioll groups i1Hlicate that the first 10 years of life are of definite impOl't[LllC(I in dotermining the OCCUl'l'Qnce 1\,ml agc of nppOfLl'!111Ce 01 penile cancel'. It is conceivable that eVCll pl'enaLul111atel'llal influonces, exel'ted 011 tJHl fetns by exogenolls factors pcnetrating the placental bUl'riel' may bQ , n.ctive in eliciting canccl' in the young. 'l'hus, there al'e no definite age l'nnge limitations hl gencl'nl CflllCel' SUl'\'eys. Detailed prcsentations of t.he prob1em of envil'omnentnl and occupntional en.neers and l'olu.tell\fiBOl'dul'S tlrc Ityn.ihlhle in the following publications by W. C. Hncpel': Occupationnl Tumol's and Allied Disonses) C. C. Thomas, Springfield, Illinois, 1042, p, 896. Environmental Rnd Occupalionn.l Cancer. Pub, IIenlLh Hep. Supp. 209,194.8. ThooG mo.y be useful 101' the intOl'pl'etnt,ion of t.he rcsu1ts obtaincd iu 13llvironmentaland occupational cn, nC()l' surveys. Al>PENDIX A Occupational and Nonoccupational Gtoups Suggested for Survey 1. Exposl1re to brn~ol 1lu<1 its <1el'ivntives. navhtbol, aromntic amil1cs, toluol, xylol (with poshlble mlntlon to leultemlll, lYlllIlhoSlll'COlllH, Ulla myelomn). All'vla ne-dope woI'lwl's, All'tliune hUll/rar employees. Atcolllll (CIC'lllltlll'l:.:<I) Workel's. Alllllne wOI'I((\1'8, Art-glass workel'S. Alil11~st():';'IJ\'Oducb; impregll atoI'll. Battery (dJ'y) mllkel'~. Bouuty Vitriol' o[Jerators. Brit SCOlII'crs. Hemwl lllll'illcl's, Bem~ol workcrs. Bl'ul(e lining makel's. BI'Oll1.el'S. Bmulshcrs. Cnn (rubher gaslmt) manufacturers. Uan (rubber gnsltet) 8enl~l's, Ual'bollc ueld maIHll's. Chemists, Chlol'Ulliphenyl maIcCI's. 0111 tclHllslr Imlll'egnn tors. Con1 tn r stlll cl callers. Coal tar wOl'Icers, Cohblel's. Color Illulcel's, Coke o\'en till' wOl'l{e1's. Compositors. Degl'ellsel's. D1slDfcctnnt makel's. Dry cleuners, Dye mnkct's, Dyers, EIcctroplnte1'8. F.Iecholliate Cl1sl BCl'llbbers. Elnamclel's. Enamel makers. Engravers. Elxploslve mnkers. Feather worlmrs. Il'mtlllzel' mn kel's, Flnyol'ing extrnct makerS, Gah'nnlzers. Gas house wOl'lcel's. Gm'lOlI ne blenders. Gllclel's. Glue mnIters. Ink makers. Lncquel'ers. La~ql1er malters. Leatllel' mnl{el'S (nl'tiflclal and patent). Linoleum wOlkers. Lttllogl'aphers. Motul washers. l\Ulllllery worlcers. Mlrl'Ol' sUverers. MorllnnLet's, NltJ'uhellzol lnnlWl'R, Nltl'ocl'I1l1losc WOl'iwl'S. Oil {'xtl'ltetora, Pn lilt I'Clllove!' lllllllufllctll1'el's. Palntel's, Pal'lI1fin mnlH~l'S, Pencil makerB, Pel'fumc lUlllters. PetrolCllln tJIsUllCl'Y and l'efinery worke1's, l'hRt'mRC(lutl<llll workers, Phenol mlll'N'R. PlloloPJlgl'aYel'fl. PhotographIc el1ellllcnl lllakcrs, Picric IlclrI IllUi(CI'S, Plastic le~l1Ie makers. Polish malcel's. PollshCl'S, Pottery de('orn tors, [11'111 tell's. Putty mnlwl's. P~')'oxyl\n )llnstl(! worlcel's. Rotogl'lI vU J'(~ workers. Hubhel' hnHcl'B, nuhbel' c('lllt'llleI'B, Hllbbcl' cement mixers, Hnllllel' compounders. H nuhe\' Lllpllel'EJ. lll1hhel' rll'I(>l'~, Ruhh!'I'lzerl f1RbQslos bORrel makel's. HuhllCl' mixers. Rnllhm' pl'eafll'OOm workers, Rllbbm' 1pc]nhn(,1'9. Hubbel' t.irr bnllders. Uulllll'l' ll'rarlers. Hllhllm' wOl'l<el's, Sllar1l' cloth worlccl's. SlwlIaelcCl's. Shellac mnlml'S. Shoe fInish et'S. Shoe factory wOl'kel's. Shoe-Ileel (wooeD coverers, SllIoi{cless powder makers. SOflP mnl{el's. Tm' dlsttl1el'Y worlwl's. _ Tu 1', pItch, oIl, etc" tanll: c1ennet'S. 't'extlle fullers. Tobacco seedllug tl'eatol'S. '.rrlIlllroto\uol makers. 'l'ype clennol's. Vllt'nlRIlCl's. Varnish makers. Vornish remover manufacturers. 26 Wnr gas mnlcers. Wnterproof tnbrlc mnlcers, Wns. lllAitel'a, IWeldm's, Wll'o insulntOl'R, Window shade Ulnltel's. 2, Exposnre to fll'Omatle mnlnes, flnlllllc dYGS and l'olntml aramntlc chemIcals (wIth possIble relation to cancers ot tile tJladuel', ureter and lddlley), (et) Occtlpntional exposure: (a) Occnrmtlonnl exposl1l'e-Con tinued AgL'leultul'ul Inbol'crs, Photogrnpltlc chemical WOl'lcel's. BluG pI'lnt mnkers, Candle makers, Candy (ca1ored) malcel's, COSlll(ltlC lnnllnfnl'tures (colored lfpstlck, powdcr, Cl'cam, eye bl'OW' pencil, skin tan lotions), Pl'lnters, nllbbcl' wOl'kers (El. ntoxidnnts : hetn-nnp11 thyln mine, plH!Ilyl- bctn-llnplltllylamlne, b II t y 1betn~nallhtl)ylnmJnc, etc.), Shoe mannfae! 1l1'el'B. Cltl'us fruit clyel's, Soft drlnl' (colored) mEllmfflC- Dye IlnnaIers, paclrcrs, mIxers. tUl'el's. Dye mnkers (anlline, naphtbYl~ Textne dyers. amIne, IlCllzldInc, xylWine, 'l'extlle p1'1n tel's. toluidIne, ct('.). Wax pencil llllllteI'S, Fm' dyers nnd workers, (b) NonoccnpatIonal exposul'e: On l'd0119rS (nromallc pesticides), Oonsumers of colol'ed foodstuffs, Ink Inll.lcera, Uscrs of colOl'ed cosll1ctlcs. Lcatller dycrs flud workers, Users ot dyed textiles nnd lenlh Lltllographers, m'goods that hleccl excC'ss dye MargArine (colorccl) makers, when coming in conbct with Marmalade and jelly (oolo1'e(l) swent and sebum. maJeE'l'fl. Users (frequent) of mcdical prep- Ol'C tlotntlon worlcel's (beta- nrntlons (!onln1nlng nromntlc naphthylnrnine, cresyllc aCid, nmino P;1'0111HI: antIIllRtamlnes- et<!,). nllCl'gles, }ul~'fcv(ll', etc:; nnnl- Palntcrs. geslcshendnche, nCl1l'algla, Pnlnt mflltCl'S, dysmollOI'l'hpR, nl'thrltlR, ml- Papal' dyers nnd manufactul'crs, ~rfllnc ; m(l<1ielnes (Uqulds. Plm l'm8.~Cltt1eHl wor1ccrs, tnhlets, cflpSulcRf olntmenls) Photographers, eolol'crl wItll nnlllne (lyes, 8. EXPOSUl'C to tAl', pitch, on, soot, asphnlt, creosotc, <'Ill'bon blflCI{s, IlIu'at11n. nntlll'acene (wlth possihIe relatlon to cancers of the slcln, lnllg, blndder, find lellkcmln) , Al'tlficlnlstonc makel's, Asbcstos go{)ds wOl'l(cl's. A.sphnlt workers, AnthmceRe monnfnctm'Cl'B. Battery (dry) wol'icCl'S, Bl'Ick ]nyel's, Dl'lekym'c] W'ol'itel's. Brlqnet mAlcers. Brush mnkel's. Cnhle mnlCC1'B ancl layers, Cnl'bon bIRC!)t mnlcel's nnd ltSCl'S. Chimncy BweepCI'S. Ooal cfll'bonlzntlon workers, Conltm' atm CleaMl'S, Coal~tar wnrlcel's. Colce..ovcl1 WOl'lCel's. Cor<1ngc-fnetol'Y WOl'ICel's. OOl'J{/~tonc makers nnd carpenters. CoItOEl. splnnel's, OreosotIng plant wOl'1cel'S. DIesel englnc nttendnnts, EIectl'lcnl eql1lpmellt Ulnnu:facll1rel's, Electl'ode mal(el's, lTInglneel's. FOt\fH1I'Y workers, Fishcrmen, li'llle cleaners. Fuel 011 8uppUers, ll'llC]{ drIvel'S, FUl'nnce WDlkm'S. Oas hOllse workers. Gas (Illnmlnutlng) worker.s. Genera tor slokm's, Oremm monlcers, Grease pit wOl'lcct's, Inlc makers, Inslllntol's, Lamp hlnclc makers amI users, Mach Inlsts. Mcchnnlcs. Metal wOl'b:ers, Oilers, 011 refinery wo ..leers. 011 weU WOrIWI'8. Optical lens gl'hlclE'l'B. Ol'e fiotntlon plnnt WOl'lrlllS, Pulnt slwnyers. Pnrllfl\n dlstlllC'l'Y wOl'lcer,s, Pa1'nffin plant worlcel's, Pavers, PlmnnaCleut[cal wOI'kers, Pltcb wOl'kel's. Plnatic cement WOl'ket's. P1'In tCl'S. Road repairers. 27 Roofel's, RooHng-pllppr WOl'lmrs. Itope makers, Rubber wOl'kers, Sanltnl'Y pipe nHlkcl's, Sblpyn I'd workers, Sonp ma](Cl'S, 811nl0 oil workel's. Stokel's, Tanl{ cleaners. ~'lU' pntnLers, Tnr llmnt mUllufucturers, 'I'lU' wOl'lml's, TcxLlle wOl'I{Cl's. Wutel'pl'oofm's, Water proof paper illnlwrs, Woocl plelders, Wood pl'(lservcl's. 4, Expos11l'c to chromium ana chl'omillm compounds (chromium metal dust, clu'omntes, clll'omlmu Ilih'll1ents, chromIe ncid, rhl'Ollllmu cnl'bollyl) (wlt11 poa~ slblC relation to CRllCel' of the lung antI nasal sinuses), (a) Occtlpa tloual expo!i\1l'e: (a) Orrupntional exposure-Continued Abl'Oslve malccrs. Abrasive wOl'I{ers and polishers, Asphnlt l'ctlnel'Y wOl'l{el's, Battery (dl'Y) mnlwl's. BJenchers, BlueprInt makers, Candle (eolol'ed) makers, Ooa) tl1l' worlmrs, Chromate, chromium pigments, :Mn tell-faetory workers. MOl'duntol's Pnlnt mnnufnclUl'el'E!. Painters. Pnl}cr dyers, Pflpet mnlrm's. Puper money mnlcel's, Paper watel'pl'oofel's. Photoengl'lIvel's. elll'omle aeill 0.11(1 It'ntlJel' tannlng compound mllllufnc- P1Hltogrnphlc worlwrB, PllologrnVUl'e wOl'kel's. tllL'el'S. Chromlum ore miners and millel's of othm' metal ores with clll'o- mlum admixtUl'es (cobalt). Orayon and peuell (130101'0(1) makel'S, Dock workcrs unloading elu'o- mtte orc. ElleetropJatcl's, Electrolytloal c111'0mll1m metlll manufaeturers, Ennmclm.'s, Enamel makers, POttCl'Y glaze makers, Pottcry makcL's. PrInters, RefrHcLory bl'ick mnlters nnd musons. Rubilol' vulcnni1.ers, Sonp mnlml's. Slt~illloSB steel wOl'ltel's, rl'nnncry WOl'lWl'B. Te~tllc dYel'fl. Textile printers. 'I'exllle wntcrpl'OOfel'S. Wax-ornament workers. Explosive m!lO\lfnctnrel's. FmnJtul'c llOllsllel's, GlRS8 and pottery fl'oatal's. Inlt makers, LinoJeum Worl(ers, Llthogl'uphel's, WOldCl'S, Wood stninel'El. (1.1) Nonocellplltionnl CXpOSl11'c: POl'SOIlH living or wOl'klng jn fUlUe lUlll dust zone of chromate plnnts. O. Illx,posm'c to nlekel fine1 nlcltcl compounds (n1rkel melnl dnst, nlClml cm'bonyl vnpors, nic}ce] oxh1c, nieltel Stl Iil<1e, llielteI alloys) (wllh possible relation to enncet' of the lung and nmm] sinuses), Abrasive mn nnfnctUl'(!l'S. CeramIc glnzol's. Ohemical wo1'lcers In opernllo11a using nlcl[el cntlll~1sls, CoIn makers. Elech'op] nters, Ennmelers. Eunmel mnkm's. Gel'man snvel' lllanllfnclllrel'R, German sllvel' SlnlU1S, Hyul'ogcn mllllufncl m'Cl'8, MOllol mctnl mnltm's. Nlclml filloy mnlwl's (coppm', sil-, vel', nlumimnn). Nlckel-cbl'ome alloy mnllufno- tm'Ol's, Nlcl{cl-ohl'Olne wll'c mnnllfll('~ tUl'ers, NtcJce1 extrnctors. Nickel Ol'e miners, NlclwJ Ol'e sme1ter and refinery workel's, NIckel poUShers, NicIml-steel WOl'ltel'S, 011 l'ctlnel'Y WOl'kCl'B, Storagc bnttcl'Y mnllufacturel'S, 1.'nlc mnnn1!uct\ll'el's. 28 6. Exposure to m'st'nic anti nfsenlell1s (nl'Hcnle mctn I, arsenious oxide. calcium al'SenR te. 80[11urn llrsenll te, loncl orsenate, CLllll'lc ncetonrscnlle, Purls green, London purplc, Scheel~'s gl'PCU, Schwclnflll't green, WO!lllnn snIls, l'cnlgm', ol'phumlt. lrowlel"a solutIon, Donovan's p11ls, nl'Spllenmllille, cacodylntea. Lewisite, AsiatIc pllls, etc,) (with possible relation to cancer of skin, lung, blaclc1al', livGl') , (a) OeCll[lntioll!l1 exposure: AI'sanlc roastcrs. Artificial ilower mnltel'S, Boole blndel's. Bl'om~e workel's, Cannery wOl'lters peeling fl'l1It tl'ellte1 with 111sceticides, CHl'uS fl'lllt Ol'chard WOl'ltel's, Cotton plantatIOn wOl'lwl's, Cnt-glass wOl'lccl's. Dyers, Dyestuff mnlters. Ell ec tl'olll aters, Enamelera. Fnl'mm's. Fclt ha t cnrroters. Feno-silicon WOl'km's. li'ttr I1nndlers nn(1 prcpnl'ers. Gl11vanlzers. <1l1l'denCl's, Glass mixers, Glass WOl'kcl's. Gluc manllfacturers. Gold l'efinel'S. Inle manufactnrers. InsectIchle mnnufnctUl'ers, Ins('ctlcid(~ spmyers ond dustcrs. Jnpan mnlccrs. Jewelers, Lcn(l factory workors. Leull shot makers. Linoleum colol.' worlters. Lithogrnvhel's. Minm's of arscnie, copper, zinc, silvcr, lend orcs. on cloth manufncturers. Oil l'efinery worke1's. :Paper (eolol'cd) makers, Paver glnzers. Pnpcr lumgcl's. Paper pl'lnicrs, (al OccupatIOnal cxposure-Continued Pell nnd llml' i!LCtOl'Y wOl'lu~rs. Pcmcll mu Itcrs (colorccl), l~llHl'lJ]UeeuUcul worl{el's. Photogl'llllhol'l:I PoIson llnlt makol's, I.loUery dCCOl'utol'S, P(Jtt(lry plnnt glal'.c (lIppcrs and mixel'S, PyrItes b11l'ucrs. HoiogrnVLll'e WOl'lCCl'S. Rllhl.J!'l' COIupolUHlm'R, Ullbucl' lllol'{lnut mixers. Unbbel' pl'caSOl-'s, RnbllOl' tirc workers, Scaling wax maltcrs, SE.'llmstl'cssca handling fabriC 1yed 01' tl'entccl w1th 8.l's(!Qicals. SIJ.(Jcp dip mllllufncturers. SmcUC'l's of al'senle, cO{l{\er, zinc. ail VCl', lcad orea, Sulfll\' b11l'Uel'B, S1.11fm1c acid \Vol'lcers. 'l'nnu(\l'Y wOl'lccl's (cHl'l'Iers). Ta.xl1c1'mists, Il'extllc llrinters, 'l'iunC!1'8. Velvet mnkers. Vinery wOl'h:ers. Vhl(>yard worlwrs, Wl1l' gas mnnufacttll'cl's. 'Vax ol'nament WOl'ltOl'S, 'Yefivers nsIng yarll dyed wltIl use of nl'sentenls. Weed 1<l11el' mnnufnetlll'Ol's. Wh'c tlrnwers. Woo(llll.'oSel'VG mnkOl'B. Wom} presetvors. Zinc mb::m's, ZInc smelter chnl'gCl'S, (b) Nonoccnpational eXIlOfmre: Users of arsenic containing drInIdllg wntol', especially nOllr Rl'!'lenlc 01'0 smelters and mines, of foodstuffs find 11q1101' contnminnted with arsenienIs. URers of nrsenic containing medicines (aL'spbcnmulllos, cncoclylntns, Fowler's solution, Asllltlo pills, Donovan's solution, arseniouB oxide in tonics, n.nUseptlcs, nutlllSOl'lasls 01' cnusLlc ointments, antlsllnSlUO(UCS), eosmetl('<! (hail' loLlona), Persons oxposed to inhalation of nrsenlcal dust spl'oud from arsenic Ol'(l smelters 01' by dusting nrsenicn.ls :trom nlrplnnos, 7. Elxposl1l'e to flRhf'Rtos (slllcntcs containIng calchlln, magnesium, h'on) lllclcol and copper) (witb possible l'clation to cancel' of tho lung). Al'tUlcHllwood nlnllUfaetlll'Crs, Asbesios1 mmlu tlOI\ workers. Asb('stos constrllcllon-mntcrlul WOl'lters Asbestos-mill workors '\'usbeL's, 111.101."- (mIll-bollrd, wal1boHl'(1. shIngle, tile, lzers. lllo1del's, cnrd~l's), In ol'tnl', ell)]l,el') . Asbestos mlncl's, 29 Asbestos Spill n<'I'8, Asbestostextile workers (Clotll, blanket, ClIl't11l1l, Sh.e~ts, rupes, cords, twine, th !'(llld), Asbestos wen"{'t'S, Bl'nk(\liIilng m!lnllfnctur~l's, Urll ke-\I 01 ng wOl'Iwrs, Cnl'pellt~I'S, Dye \VOl'km's (field find tlr~pl'oof) , Elect)'lc-wlre mnUtlfactlll'el'S, [i'llter-mntel'inl mnnuiactul'el's. GlIsi<ct milkers. InSlllfltlon wOl'lmt's (piDCS, bOilers), Plumbers, PUlUppacldng rneehnnlcs. Roofers. Hubbcl' Drodl1ei(on workers, 8, Exposllre to RolnI' rndlntion nuu to cnneer of tile skin), Agricultural lnbol'el's. BOfitm~n, Cnttielllen, COllstl'\l(>tion worlcel's. Cowboys. Drivel's. Fm'lucrs, l!'h;ll(lt'men. Gnl'denel's, IIerdelS, Ilollse pnintel's, Tlumbertuen, MlUel'~ wOl'ldng in surfnce Nm'SPl'ymell. OIlfield workers, mines, ultraviolet radiation (wlLh possible relation on oDcrntors. Phill'lllnceuticnl manufacturers of vitamm D, Rllill'Olld eng[ll~el'S, Ralirollc1 wOl'lcers. HflnciH'l'S. Hond workers. RlJ I'ut Ulull Cnrl.'iel'S, Suitors, SpOl'tsmen, stockmen. SUllbathers. \'Ine gl'OWel'S, WcldCl'S. 9. E:o<pmmre to l'Qelltg(l)H'a~'S and l'iHUOIlctlve cbemknls (wlth possible l'clnUon to cancel' of the skin, lung, bone, liver, anel hmltemla), (a) OCCllllllUonnl ('xposul'e ; AtoUllc mlPl'gy plant wo r}{Cl'S , ntologists, Chemists Gas mnntle mnnfncttll'el's, Lnhol'fltOl'Y t(lclmlclflllS anel ntten(lnnts. Lumhlous dinl l1ulutel's, hnnc1lars HmI Sillpp~l'S, nmtnl scrap IUllldlel's. Nlll'Ses, Plla1'1l1aceutlonl workers using racliollcUvc isotopes and maldug l'ndtofi('tiYC tl'UCCl' substances, PhYRielsts, Rnc1lO!.\rUye electl'OAlntic elilninntol' IUflmlfactnl'ers and operators of such devi{'es in texllle and Dapel' plants, RacUofoglc technicians. nn (lIoioglstFl. Rndlulll lnbol'ntol'Y WOl'lCel's. Rndlmn r(lfin(ll'Y wOl'l.<,)'s, Rt'Sf'fi)'cll wOI'lcers handling rmllonclh'e iBotopes una tt'fleer substances, nO(,JJtl~('n ancll'arllllm te('bnleians, nopnt~en mecilnllies. Ropnlgt'o-t1111(, lllil nufn('tlll'(lrS, Roen t,t!cllologlc;ts ()llC'cli('nl, eiecil'i(' lndlHltry. nvlnllon, metnllm'gl c, chentlcnl, tnxtll<', nrt ana jC'wl'lry, sho(> Finles, uC'anty pat'lOL'S, rcseul'ch), 8ho(' Ri1ICSlUm In j:JtOl'pg nsing fluotoscopcs fol' flttlng, Ul'nnlnm dye mltltm's. Urnlllum glass I11nlcms. Ul'nniullI glnze lllnl(('l's (tile), UI'anlum miners nu(l miners of rndtonetlve 01'CS (pitch blende, carnotite, etc,) , Ul'an Illm Ilaiut multGrs, (b) Nonoccullutlonlll eXl1oR\lI'e: Cur.rOll1m's of sllop 8tOl'es using lluOI'oliCOpefJ, Pntl~nt~ eonsumlng rnflionctlvc: wnter far medicinal pUl'pOFieS over long pel'lo(l~. PaU(>utR l'('('('lvlng large {lOReS of ionIzing l'urUatlon tOl' mer1irlunl purposes, People living In l'(>gions with l'n(lionctive 0\'('8 [lml dl'lnklng 01' bnU\lng III wntel' 01' l'n<1103<>tlve F.lPl'lngs, 01' rcsldlng In Lbe waste cliSllOElUi firea of l'ntUollctlve ODOl'a Hons. 30 APPENDIX B Occupational Cancer Record 1. Name 3. Residence: State 4. Social Security No. 1. Date of Birth 10. Occupation 12. Cause of Death 14. Name of Physician 2. Place of Death: City Hospital City Street t 5. Sex I 6. Color or Race Is, Age: Years Mos. Ill. Indu.stJ:y or Business Days I9. Date of Death 13. Method of Diagnosis: 1 Clinical ( ) Biopsy ( ) Autopsy ( ) Other ( ~ 15. Street 16. City 17. Clinica.L Diagnosis I 20. Date of First Symptoms 18. Pathologic Diagnosis: Microscopic ( ) Gross ( ) 19. Primary Site 21. Da~ of F"rrst Visit to PhYSi-/ 22. Date of First Diagnosis Cla.n 23. Stag.e of. Diesase at First DIagnoSIs I 24. History of Other Dlnesses of Site Affected 25. History of Injury to Site Affected ~ ~ 1:.1 26.. Occupational History: List occup3.tions in chronological order beginning with last o:r present one Dates From To Name ot Plant ..... . Location of Plant TypD of Business Or Product Mude Title of Job Type of Work PcrIQIDled --_. ---- --- I -- - - - I fll -- - - 27. Exposure: (Imoestiga.tor will name Mol'cinogenic stibstances to which employee has been exposed.) Name of Substance Name of PIlmt Date o! L3st Exposure I ., --~ - 28. Nsme any other important ma.teri2ls to which employee has been exposed. Jnent.) Duration of E:tposuro Yesrs Months Descnbe TYPB ()f E~osure and Estunate Peroont ()f' orkmg Time Exposed - - ----- (Hobbies; Ha.bits; Medicines; Cosnletics; Diets; Environ- 29. Additional Information Obtaina.ble at: PhysiciAnj Labora.tory; Hospital; Insurance Co.; Plant Medical Department; Clinic; Tumor Registry. etc. . Name Address 30. A:ny other information pertaining to tumor (Multiplicity, SitesJ etc.) Date NOTE: More bloeks should t-e added tmder Nos. 25, Zl and 29 on actual record form. Investigator J. Poisons-Continued *251 Soot Onmp blncl{, cnrbon blnclc, gas bln~]{, etc.). *252 Splnd1e 011. "253 Sterols. 254 Sulplmf chlol'idE'>, 225 Sulphur dIoxide, 2u6 S111plnl1'!~ttea hyll'ogon (hydrogen sulpbide), 257 Sulpll\l1'lc acid. *258 'rUl' and DItch i urtlficlal nf3p!mlt j bitumen-lignite. 250 Tclluthlln COll1DOlmd~, *200 Tell'ilChlol'ctlu1I\c (ncctyl(mc letl'llchlorl<1e). *261 Tcll'!lch}orethylf'nll (pel'chlol'cthylcne). 262 Teh'nethyl leal1. 203 rhnilinm. 284 Tin. 20(i Titanium oxide. *206 Trlchlol'ethylene, 267 Tl'lOl'lhocl'esyl phospht1tc. 208 Turpentine. *200 Urnnlum. 270 VanadIum. 271 Vinyl chlorIde. 272 Zinc i bl'OSS, melnl fumc fev~r. 278 StYl'ene. K. Trnuma (not covel'ed In nny of the nbo\,o) : Ohemical: 300 Clwmlcnl, acute. SOl Chemlctll, chronic. Physical: 802 Mechanicnl, acute. 303 Mechnnicnl, chroniC. *804 '.rhCl'l)1lc, acute (burl\). "'305 ', l1Cl'm le, chronic. Sent's, fistulas: It'ROa Sent's, fistulas, etc. It there fire present more thUll threo har.al'c1R, each of whlch Is fl'om u tlltrercnt major unzRrd group, code ill pl'cfcl'C1H'e nil follows: Q, 3", Ill, F, K, H, Il, 0, A, D. Cn.rctnogonlclty taQognl'l.(ld ot 8\tap~Qtc(1. APPENDIX D Plant Survey Record 1. CODlpany_____ - ___________ - ___- ___________- _____________ 2. Location______- ________________________________________ _ 11. Number of employees: I > s t e_______________________ _ 3. Plant manager___________________________________________ 4.. Plant physicia.n________________________________________ _ 5. Insurance carrler_______________________________________ _ 6. In operation sinoo_______________________________________ _ 7. _________________________________ _ ITodnms~ufarnruxedL 8. Known or suspected carcinogeDS__________________________ _ 9. ~edi~~oo_________________________________________ _ ~aIe_______ _________________ _ ~lt8________ -- _________ _ ~ol~_.______________ _ ~eIOale _____ ~ __ ~~ __ __ ____ __ _ ___________________ _ ~ite (Jo!o~ _________________ _ ~otal _________________________ _ ProduC;ion Office Total 10. Rate of labor turnover______________percent annually______ _ 12. Operation ~ . w/ I I I :!" co .. %~ 1 <. Operations involving known or suspected CQI'Cjnogen!c hazards- Number oI employees Type af e:qlOsure Male (J Female (J (Jonstant InterDlltten.t Ocessi- anal Inhalation Route of expostIl'e Skm Ingestwn Other Duration of e:tposure for '\l"0.kel' (years) Average Longest ~'" a. b. ...~ e ... I ...~'" E a 1"re- or pe.rl-c:a.ncereus e1fects noted ~a.Ilcers noted o :: Site Nnmber D:J.tes Site Number Dates ..'" i S. b. e. ---- ----- - - - - - - -- _._------_._- -_._- - -- ---.-- - I"J.) -..l