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FILE NAME Brakes BRK DATE 1961 Mar DOC BRK016 DOCUMENT DESCRIPTION Journal Article - Carcinogens in the Human Environment - Pathology re gt ra cn my $$ A one OR C 22/22//8322/832/2/83 No. byAAC iy 135 a ade a wo Sods PATHOLOGY # a? a PATHOLOGY pea ayeCRS me : Ly PH SeRUELES 99 be 1. PT a PacesSRS * -tetartBaca wee "> it OFFICIAL ORGAN PERICANPERICAN SOCIETY 2 EXPERIMENTAL PATHOLOGY Carcinogens in the Human Environment To Be Concluded W. C. Hueper 237 Production of Arteriosclerosis in the Rat H. Gold 268 Zinc Protection Against Cadmium Injury to Rat Testis me oND mess dee: dn au ese a venr sae egtoe K fren ae Tt TEIVE* NT , TSee nt S. A. Gunn et al Fluorescence Microscopy in Exfoliative Cytology hey 23 alt Bi ix l39 abebebasa W. Liu toyte I. General Considerations Ce Bagi A II Application to Gynecologic Cytology 7 petry Typing of Bronchogenic Carcinoma W. Umiker Diphenylthiocarbazone Blindness in Dogs J. M. Budinger Prevention of Bone Marrow Heterografting C. C. Congdon and D. B. Duda Adrenal Hypoplasia P. G. Winquist Intraglomerular Mitosis in Rat Nephritis R. B. Jennings and M. H. Haber 330 me n# + ony 8 -~@ ae jen perry Sapa ae aak Ur ns es ET 44) Congenital Adrenal Hypoplasia N. Kerenyi 336 oe, EE oo Cystic Lymphangiectasis of the Spleen J. A. Harshman et al Ah EIEN 344 1 cel Human Plasma Cohn Fractions and Mouse Tumor SARI a P. A. Herbut et al 349 Pie LAAT 354 progre 4 atf; con 2% automation ety VOLUME 71 NUMBER 3 @ deinemane, a4 pee & the <1 > ea a= ate ivy ee vag ve tee Se AMERICAN AMERICAN MEDIC MEDIC e sections The haracteristics Carcinogens cylin Made from . Sf really ee blue off ffusion Full bodied ais >> in the W. C. HUEPER M.D. BETHESDA MD staining from slide > Human Environment deat 2.25 4 A , al ; ready 1 of our own prepa- orms to use 2.25 . nh 3.00 Lx . modification in modification of 4 . ious work involved 4 liffusion into other 4 ies 2.65 ee 7Despite the fact that the existence of # environmental carcinogens has been known luce brilliant differe : a for about 175 years professional interest hols od ey . 1.50 y and appreciation of these pathogenic prod- ky Invaluable Invaluable single saoleu agents icture No aware aware ter soluble sf ucts of the modern industrial economy and the their increasingly important role as causal of human cancers have remained at speciale rather low level Only during the last section vad! decade has the general public been made of the presence of carcinogens in the 25 3 human environment through the widespread oi publicity which radioactive fallout and ciga- all countries will be based to an increasing degree on the growth and diversification of industrial activities and the greater use of industrial products undesirable and danger- ous carcinogenic health hazards from such sources will assume considerable stature as public health problems which will demand comprehensive organized study and extensive preventive control measures I. Significance of Environmental Cancer Hazards ' Frette smoking have received as potential - Environmental carcinogens i.e. physical avsa environmental cancer hazards The general chemical and parasitic agents being constit- _ Hateaeg population has been alerted also to such * 1igUSEEE possible dangers to health from industryrelated sources and products by the atten- uents of the human environment are practically the only recognized causes of cancer in man 58 , New York H.Y tion which lately has been given in the H.Y H.Y public press to carcinogenic hazards from a A few of these agents have been for ages constituents of the natural environ- ~ arsed ate a@ oR air pollutants and food additives and con- ment such as ultraviolet radiation of sun- ao ry ee: * ee eg taminants Since the modern economy of 4 *Submitted for publication May 5 1960 SOLUTION National Cancer Institute eer a8 This article will be concluded in the April ~ light especially active in areas with dry and sunny climate and causing skin cancer radioactive contaminants of the air water and foodstuffs from natural sources par- ticularly in restricted areas with highly radioactive soil and rocks such as a certain 15/237 oeet ie, eenL?ens ar. mraintina tL) ee: 2 sat Sues ; % Shaze So a pesnem: 57 reed ix? 1 Ty RE nie a 3 tay eet 4 BP ai xe: . haya g & Riraees te sag sess: [ak ;1: ft OO oes + baa a Pati om etdLa rhs Fu*dey i Te ae * it i i 4 : : a : ; - Tyre ys a: < bhies : cS j i , 3 a3 | a a] f y 4 uy ; : % * : a ^' M 4 Be j : 3% - ig & eH : : Gg rH a 3: : Pa Paa te H iq bd Ps Mie g i > Lg ~ B i} NI Bs. * Fa * " a ot : ae SNS ' * & i: Gi z 2 ; gfe y [fi ge 3 es ; Es f Ba 4& aay : a . q 4 ag : a Jo : . af e" PATH23O53 LOGY ARCHIVES OF PATHOLOGY CARCIN region in Germany " region in the Ore MountaiMonuntsains Germany where the population is said to have a increased incidence incidence generally senical increased cancer drinking incidence drinking ar- senical pollutants of drinking water ob- tained arsenic containing soil tained from containing soil or rocks such as a region near Cordoba Argentina endemic arsenic where an endemic type of arsenic cancer of the skin skin exists exists and infections infections infections with with Schis- Schis- tosoma hematobium such as those observed in in South EEgyptgypt Iraq Iraq and ing there an endemic AfriAfcricaa and caus- caus-caus- occurrence of cancer of the bladder . b carcinogens a a part yearsyears environmental A second group group of environmental environmental environmetal second environmental carcinogens man and has been the is made environment of thethe human human environment for mamanny y of human soot containing Exposure Exposure to aromatic soot containincgancecr-ancer- producing aromatic hydrocarbons has doubt- existed lessly existed as long as man has used containing containing living matter for cooking heating heating his his his living quarters and for cooking his food or for smoking foodstuffs habits purposes Age habits for preservative chewing such as chewing betelnut quids or khaini quids indulged in by inhabitants of certain oriental population smoking groups or smoking tobacco products also espe- affecting affecting have created cancer hazards affecting espe- cially the oral cavity and respiratory tract for many generations c AAnotn her othAnother er group of of made mma an de environ environ eee = however environ mental carcinogens of recent tional date 312 is constituted rapidly workers constituted of increasing is rapidly increasing increasing a num- * Popul Popul Gr . num- variety chemical ber and variety of chemical and physical mei which agents which are the products of the oy, physical 3 mod- = Y arahe cotton pl - farmers farmers _ mod- manufact ern industrial development These agents = workers environ fy are by by far the largest number of environ known mental carcinogens of the known QP : Cf workers re oil refine . hair fact environmental carcinogenic spectrum These bait mak - cigigg new industry industry carcinogens carcinogens are we in in eng part highly potent agents They are in countered in a considerable considerable numbnue mberr of of rotograv * _ rotograv Re arsenical = } occupational activities ingredients or ocupational activities ingredients ingredients are oXri 5* contaminants of consumer goods food- S53 7 cosmetics sanitary * KEG sanitary stuffs goods sanitary cosmetics household 233 : medicines etc. goods medicines and are ae : pollutants goods 5 2% air soil of the general air water and soil iinndduuss pesticides radio- trial residues pesticides ~ trial residues of radio- wastes " active these activvee faflloautlfallloou utt Human HuHmumaann exposure to to : ' fallout environmental Human exposure oc- recognized environmental carcinogens curs curs thus from from various sources sources sources and at oc- nu-nu- various to merous opportunities All these contacts to specific carcinogens as well as to all carci add nogens nogens to thethe total ccarcinogenicarccarcinoigenic nogenicarccinogenic load aa ay - to whiwhcichh persons and persons and population population 2 groups become subjected to different degrees and . y ? for various reasons Table ) TABLE Recognized Human Carcinogens Their Origin and Distribution in the > Human Environment and Cancer Caused by Them * we _ Arsenic ~ Sites of Arsenic Recognized Skin Lung Liver Suspected Mouth Esophagus . Larynx Bladder Exposure Dermatosis Neuritis Arteritis Laryngitis Perforated Nasal Septum Bronchitis Anemia Gastroenteritis Liver Cirrhosis . ; Compounds of Economic Importance tri- and pentavalent metal and alloys ores of silver gold copper tin lead cobalt nickel antimony iron pyrite realgar orpiment arsenic acid arsenions arsenic trioxide arsenic pentoxide sodium arsenite calcium arsenate - copper arsenate lead arsenate cupric acetoarsenite Paris Green cupric arsenite Scheele's . Green Schweinfurt Green London purple Wolman's salt arsine Arseniuretted Hydrogen . _ arsanilic acid cacolytates arsplenamines lewisite etc. tryparsamide carbursone arcetarsone Stovarsol - * Operations and Products with Contact to Irsenic for Producers Processers Users Consumers Residents alloy lead shot dust fumes mist vapors in and around metal ore smelters and refineries dust and water draining off slag heaps of mines and smelters water from containing rock pigments in paints ink glazes glass soap and dyes of textiles ; and paper decolorizer of glass mordant preservative of wood pelts furs hides dehairing agent of pelts herbicide pesticide cattle and sheep dip grasshopper and mosquito bait in- ; secticide of potato beetle Japanese beetle cotton boll weevil codling moth gypsy moth algicide rodenticide gas purification by Thylox process war gases lewisite etc. hair lotion animal feed additive pharmaceuticals tonics antianemic preparations Fowler's solution Dono-van's pills Asiatic pills cacodylates arsplienamines caustic ointments etc. * Table 1 continued thru page 27/249 16/238 f 8 E Crocide Tremo i i taining | ioe ad Magne Alumin 3 Calcin _ qt Iron i. Silica co a: ae - 7 rae wants 7 environ Aue 47h . date =. wae. S45 Population Groups with Occupational and Environmental Exposure to Occupational Groups Airplane pilots arsenic roasters artificial flower makers book binders bronze workers cannery workers peeling fruit treated with insecticides citrus fruit orchard workers cotton plantation workers glass workers dyers dyestuff makers electroplaters enamelers ture the mod faege agents Suet. Skat environ% known at known 2 knownSE knownThese it~ These m My re ie Se a ' A. farmers fur handlers and pr^'parersgalvanizers gardeners glass mixers glass workers glue manufacturers gold refiners ink manufacturers insecticide makers insecticide sprayers and dusters japan makers jewelers lead factory workers lead shot workers linoleinu color workers lithographers miners of arsenic copper zinc silver lead ores oil cloth manufacturers oil refinery workers paper colored makers paper glazers paper hangers paper printers pelt and poison pharmaceutical pencil hair hair factory workers pencil colored makers pharmaceutical workers photographers poison printers pyrites bait bait ' makers pottery decorators pottery plant glaze dip ers dippers and mixers mixers printers pyrites burners rotogravure workers tire manufacturers rangers rubber compounders mordant mixers rubber pressers rubber sealing wax makers seamstresses handling fabrics dyed or treated with bie Fechce. arsenicals sheep dip manufacturers smelter workers sulfur burners sheep wool cutters sulfuric sulfuric mber ofizsae! lients or food40 acid workers stevedores tannery workers taxidermists textile printers timmers tobacco processers velvet makers vinery workers vineyard workers war gas manufacturers weavers of yarns dyed with arsenical pigments weed killer producers wire drawers wool preservers wax goods manufacturers zine mixers zine smelter chargers felt hat carroters ferrosilicon workers sanitary 4 Nonoccupational Groups Residents in vicinity of metal smelters and of orchards fields and woods dusted and sprayed with arsenical pesticides persons consuming drinking water and Rete 1 indus . foodstuffs contaminated with arsenical algicide and insecticide residues persons smoking tobacco ~ with arsenical residue and inhaling arsenical air pollutants from burnt coal veterans with war- S. radio- to these gas poisoning patients given prolonged treatments with arsenical preparations anemia psoriasis syphilis trypanosomiasis etc. ; inhabitants of rooms with containing wall paint gens oc-oc- ad at nu- or wallpaper . Asbestos to ntacts ee: - ill i carci Sites of Asbestos Recognized Lung Exposure Stigmata fibrosing pneumonia involving asbestos bodies in sputum asbestos warts of skin fingers first lower lobes asbestosis groups 1 tye groups < : and rees : f wg Dat yl Peis ssigee Compounds of Economic Importance Chrysotile Chrysotile eas, Amphibole <>: SongAmosite Estas Crocidolite ao Tremolite con- ae taining %. Magnesium Aluminum era 3 neon en;a7 at etee me, aiecer wele's gen 4 Pa , Calcium Iron Silica be 7 Operations and Products with Contact to Asbestos for Producers Processers Users Consumers Residents Asbestos rock mining loading shipping crushing milling asbestos spinning weaving mixing cutting pressing molding plastering cementing clothes cloths sheets blankets curtains brake linings yarns cords ropes twines ribbons artificial snow filler in rubber goods plasties and roof coatings filter cloths filter pads filter paper artificial wood tiles shingles card boards wall boards partitions panels paper clutch facings clapboard pipe coverings pipes insulation blocks insulation jackets gaskets pump packings electric wire insulation structural heat insulation facings of acoustical building materials catalyst supports in sulfuric acid production putties Population Groups with Occupational and Environmental Exposure to Asbestos Occupational Groups Asbestos rock miners miners loaders truckers crushers millers asbestos spinners teaters electrical appliance and wire manufacturers masons carpenters heating equipment workers rubber workers shingle and tile manufacturers building material manufacturers filtering material manufacturers molders of asbestos products asasphalt makers putty manufacturers asbestos cement makers asbestos paper cardboard and fining producers asbestos felt insulation workers asbestos sound insulation worker asbestos insu- lator pipe coverer asbestos mbe wrapper asbestos cork insulation worker Nonoceupational Groups: Residents in vicinity of asbestos processing and textile mills inhaling plant effluents polluted with asbestos dust Hueper . 17/239 * CE Re a oo Ma tese eaL rth wt re Sele peas Eger bas 27, Fatt rena aw Pee : = es ver oe ae a Fe . ey oe tet we te ? : vien andl toe 4 del pe | Sines.yasSLT a =e Ot soe carted * oo withFSS. ee Thy State seeee yeaE s, oka eo G3 ay20b tnherterdf tel i Don te *. piantree ndWOE ined A asBGSY enath pli ae dey LPM7 SyE~szte: {arty a , 4 a %. es TOoT d icyCORR aS.op A, EPS SSG POS att ESTE Vf , oeePeset.e en.Veh rE Smerer hy Pj aa Pay on fa ey te, te b 3 : 4, ay ad id Wn ony aN cs ck RT PERI eae? WOR in EER TIMEAS EM Mc; YS Partpet gm NEE WERTVeS eine Yat x ARCHIVES OF PATHOLOGY Chromium Sites of Chromium Recognized lung nasal cavity Suspected stomach Exposure Dermatitis cutaneous chrome holes ulcerated and perforated nasal i septum laryngitis tracheitis bronchitis chronic fibrosing pneumonia chronic gastritis indolent intestinal ulcer chromium- Compounds of Economic Importance Di- Tri- and Hexavalent ore chromium- chromium- metal chromium alloys iron nickel cobalt chromium oxide chromium trioxide chromous chloride chromic chloride chromyl chloride chromic nitrate chromium oxychloride chromium boride chromium carbide ammonium chromate sodium chromate potassium chromate strontium ei Matte chromate calcium chromate barium chromate lead chromate zinc chromate sodium dichromate aa potassium dichromate chrome sulfate chrome alumi ammonium chrome alum potassium chrome : = ei : e Nickel ~ | te Ni Metallic . [ alum stearate chromium chloride chromium acetate chromic acid ammonium dichromate Alloys L copper chromate chrome hydroxide chrome phosphate chromite ore roast chromate roast leached residue stearatochromic chloride Operations and Products with Contact to Chromium for Producers Processers Users Con- -4 sumers Residents grinding mixing chromate manufacture electrometallurgical chrome | 5 production stainless steel manufacturing and processing industries production of chromium Iron Chr ae: i Nickel C Nickel St 2 i compounds for tanning photographie paint ink textile shingle rubber plastic glass petroleum pyrotechnical pottery printing wood preserving industries electroplating plants aviation- railroad- shipbuilding industries dye manufacturing industry chemical and pharmaceutical imdustries manufacturing plants match manufacturers wax and product indus- tries oil and fat industry Fiberglas manufacturers and processers cement industry blue print industry metal wares and machinery electrical appliances corrosive and antirusting agent polymerization catalyst oil cracking catalyst anticorrosive primer paint pigment pigment in paints inks glass plastics rubber shingles linoleum glazes enamels etc glass and pottery frosting and etching agent chemical cleaning fluid textile mordant oxidizing agent in dye production bleaching agent for fats and oils leather tannery and finishing chemicals dry 4 battery chemicals wood preservative and staining agents Fiberglas coupling agent corrosion retarder in refrigeration brines in air washers in cooling water of diesel engines locomotives automobiles boilers ingredient of match explosives cements repellent for fabrics felt hats glass fiber drapes paper hiss at ee 3ees% * BSR are & Nickel A Nickel C ; Population Groups with Occupational and Environmental Exposure to Chromium tional Groups abrasive makers abrasive workers and polishers airplane sprayers bleachers blue print makers colored candle makers cement manufacturers chemical workers chromate and chrome pigment producers chrome platers chrome manufacturers and processers chrome ore miners loaders shippers grinders and mixers chrome producers and proces RF So ee sers crayon makers dye manufacturers dock workers electroplaters electrometallurgical os aie workers enamelers enamel makers explosive manufacturers FiberglasFiberglas producers and proces- sers furniture polishers glass and pottery frosters ink makers linoleum workers lithographers match producers mordanters paint manufacturers painters metal cutters and welders oil re- 274 ay finery workers pyrotechnical workers printers paper dryers paper waterproofers photo-* engravers photographic workers pottery glaze makers pottery glazers refractory refractory brick makers a and masons railroad engineers rubber workers plastic manufacturers soap makers stainless - steel producers processers buffers and polishers pyrotechnical workers shingle manufacturers - leather finishers tannery workers textile printers and mordanters textile waterproofers wax ornament workers welders wood stainers and preservers boiler scalers dry battery makers colored glass producers fat bleachers Nonoccupational Groups Residents in vicinity of chromate plants airplane manufacturing ior and maintenance establishments railroad yards shipping building plants scrap metal smelters oil 3: refineries home users of paints containing chrome pigments and of containing anti- rusting agents in steam heating plants consumers of drinking water containing industrial wastes . polluted with chromates and of fats bleached with sodium dichromate toe : a A toeht 18/240 Vol 71 Mar. 1961 Nickel 5 Sites of Nickel Recognized nasal cavity paranasal sinuses lung +, >.> Exposure Dermatitis nasal polyps chemotoxic pneumonia stritis indolent ae .taegeee , Co'mpounds of vEconomic s, Importance Operations and Products with Contact to Nickel for Producers Processers Population Groups with Occupational & Environmental Exposure to Nickel divalent 4- See uni- tri- i ride ; chromous tetravalent chromium ride ESSE Copper mate strontium 4-4 Ris " Nickel Matte Nickel Ore um dichromate dat, "pee fi, Nickel tassium chrome Metallic chrome dichromatef : . Alloys Copper un dichromatef lisa chromate roast ask *) Users Con Chromium " tx Iron Chromium iz. Nickel Oxide Bu, Nickel Sulfate rs Users Con Bare: llurgical chrome ,e Nickel Sulfide * Nickel Nitrate | = chromium iaisieg * of "t Nickel Hydroxide lass petroleum, ! Nickel Chloride ants aviation -hAeARAY Nickel Ammonium pharmaceuticalRt <S=ulfate Nickel -product indus ett! Carbonyl Nickel stry blue tirusting apgreinntt pigment > i! Formate Nickel |,ceeeee Acetate Nickel in ent Carbonate Carbonate Nickel iNaphthenate . Users Consumers Residents Nickel ore mining shipping load- Occupational Groups Acrylic plas- ing grinding smelting refining nickel carbonyl production metallic nickel production Monel metal and stainless steel manufacture and tic producers abrasive manufacturers aluminum anodizers ceramic glaze makers and glazers coin makers electroplaters electronic processing nickel alloy production and processing nickel plating powder metallurgy anodizing alumi- num acrylic plastic production appliance workers Back transformers dipolar antennae enamelers painters paint manufac- turers German silver manufactur- hydrogenation of vegetable oils ers and silversmiths hydrogen hydrogenation catalysis in chemical manufacturers Monel metal pro- | industry and synthetic coal oil pro- ducers and processers margarine duction enamel and glaze produc- tion and = application ceramic industry glass production electronic industry electrotype manu- manufacturers glass producers metal flash cont operators nickel alloy copper producers and silver aluminum processers nickel- facture German silver production chrome alloy workers nickel ex- electric appliance industry alkaline storage battery production flash- coating of metal surfaces textile tractors nickel ore miners loaders shippers grinders and mixers nickel smelter and refinery work- ies locomotiv2e-5s5 fabrics lent for at AS 43% oo rm aA N+ ickel Carbamate mordant for stabilizing metallized dyes nickel soaps as additives to crankcase oils sealing agent for anodizing aluminum ers nickel polishers and buffers stainless steel workers and processers nickel carbonyl manufactur- ers powder metallurgy workers Occupa- 23 ,, Shais e en . Fs yers bleachers wac8 - . ae rkers chromate and ; processers hears: oil refinery workers storage battery manufacturers textile lyers and workers tale manufacturers Nonoccupational Groups Users of containing kitchen utensils : trometallurgical 2.20 ers and proces- SR RE s lithographers welders oil re+- 2. (QAeRas oa: and tableware a Aromatic Amines > . , Sites of Aromatic Amino CancersRecognized bladder ureter renal pelvis suspected in- roofers photo- 7stae ta ry brick makers a Bt nat Likers stainless ay Beets manufacturers 42: rproofers wax = lattery makers 2:. testine lung liver prostate . fe Exposure Excretion of aromatic amino compounds and their metabolites in urine hematuria often no symptoms of prodromal character Compounds of Economic naphthylamine naphthylamine benzidine xenyla- mine auramine magenta phenetidine chloronitroanilines nitroliphenyl tolidine diphenyla- mine naphthylamine aldehyde condensate naphthylamine xenylamine antioxidant manufacturing . tal smelters oil * yellow AB yellow OB naphthylamine thiourea naphthalene etc. naphthol pitch naphthylamine still coke aminostilbenes coal tar petroleum fuel additives oxidation inhibitors containing anti- Industrial wastes Operations and Products with Contact to Aromatic Production handling loading processing using of these amines cleaning of stills handling of tars of stills their use in lacquer production repair and maintenance activities on equipment emptying and disposal of barrels and containers use in production of dyes and rubber antioxidants production of rubber rodenticides pharmaceuticals lipsticks colored margarine butter baked goods cheese crackers etc. dyeing and use of textiles and leathergoods with dyes with carcinogenic aromatic amine > ingredients or impurities red sky writing rat catching production and handling of security paper use as reagents in tests for chlorine and other inorganic ions and metals for separation 19/241 ate . orate ve er} pee e a oa s a Se en LA a reEDIRC ae4 ow ageAS rtete oo Parart)he s= a et Perfeteed ae) 3 Ay sci ef : dete + ' e ume . Seg eles he :ayes tien ryeiin > ea 6 lyagaeat i? TOSI Sa wee d pe Ake: Tee elem ae gn Fe See rere? p23 RES Pal [sed tye Bebe ye. ar i Re he % - ee ee odeke Re wei am Pe ~~ ue y les Rte Ae te Staak AaTaTt 2FED2 ks abe reUnaene PRAEGR eT L ^' ri rt 4 1 ; Ve A catsea te be ee on PeteheStk iRfied EL. E RE oe al eesy, 3He Fa, coed Sot ESOC TIO heer cen PAgl wal Sy = eee Ei MY oat *, ? Artes aa < : Prtea ti N . soe eae : A * . * Leta > Tage PATHOLOGY beet wy a #38 . . ARCHIVES ca aan OF woke dyes di- of phenol mixtures laboratory use in tests for occult blood and for folliculinization in biologic patent stains in quantitative and qualitative analysis for various metals handling of coal tar fuel and crude anthracene stabilizer of carotenes industrial chemical and triphenylmethane dyes etc. molding antioxidants compositions lacquers /: whiteners manufacturers of detergent manufacturers using ie gasoline and aviation fuel gasoline dyes Sudan IV yellow butter json butter butter Population Groups with Occupational and Environmental Exposure to Aromatic esis Amines- 35 eels < wae welders, Occupational Groups Producers of dye and antioxidant intermediates and of dyes and antioxi >: 220 oteating Norn dtearntmsarpghaarrmianceeubtaikceadls rodenticides industrial and biologie laboratory reagents cosmetics but 72 eM een Temovers _ in fume goods repair and maintenance men truckers yard men workers employed <j " zone of aromatic amine operations rubber manufacturers rat catchers textile fag an plastic chinaware dyers and printers laboratory technicians security paper manufacturers and sers airplane pilots chemical workers coal tar patent fuel and crude authracene produceprrs oces 2 and ~sio4 handlers painters pharmaceutical workers chemical workers leather dyers citrus fruit 3: dyers fur dyers and furriers marmalade jelly and candy makers soft drink manufacturers ink makers photographic chemical manufacturers pharmaceutical manufacturers colored wax goods cy tetonew as + makers lithographers , hsdethie Nonxrupational Groups Residents in vicinity of aromatic amine prosuction and oun consumption plants rubber factories users of foxxlstuffs and cosmetics dyed with colors containing . 2 ya % carcino- "sky genic aromatic unine impurities patients treated with carcinogenic amino compounds : re tet * pyridium tolidin fuschin auramine light Green SF brilliant Blue etc. users of rubber goods tenge come taining carcinogenic antioxidants users of detergents with carcinogenic whitening agents of } aromatic amine nature of polishes with colored ingredients users of brightening and ta whitening agents in household detergents of aminostilbene nature consumers of the sweetener -phenetylurea and of bladder chloride : ; - ; Benzol : Sites of Benzol Recognized forming tissues leukemias lymphosarcomas . allergic cytoEsxipsoslueruekeS moitd irg eacmtia onsta hypelrepulkaosipaeniaandaplmaastiuaraotfiobnonaerrmesatrrio n wboenreythrocytosis leuko 7 agranulocytosis of containing drugs purpura ' marrow allergi.c-2 : Compounds of Economic Importance benzol derivatives with i" or producing allergenic dyscrasias of the forming tissues drugshematotoxice pry operties : Be Z .: Operations and Products with Contact t:o Benzol for Producers Processers Users Con sumers Residents tar production and refining petroleum processing paraffin extraction extraction exe 4 2; and refining production of rubber and rubber goods production and Ar tiny re- " movers lacquers rubber cements bronzing silvering and gilding use of paints paint aay 4 343 : leather resins styrene cleaning fluids leather enamel liquids artificial 355 gue Kore: Sains aviation fuel industrial solvents plastics extractiownatoefrpbroonoefs fafbartiscsanldinooillesum cmleoatnoirnganodf Fras - " machinery degreasing; manufacture of chlorinated sulfonated nitrated oxidated alkylated i hydrogenated and dehydrogenated benzol derivatives production of explosives pharmaceuticals 77issuy aonpteirkantoicokn cpheetmroicchaelmsicadleteprrgoednutcstiopnhotographic chemicals rotogruture printing coke oven Tn . mami- . - 0. ove Peay Occupational Groups Coke oven worke.s worke.s coal tar refiners and users petrochemical facturers service personnel of automobil --~4 airplanes solvent ..-9s Be Ea. paint remover producers painters degreasers iters rubber manufacturers paint and aT dry cleaners linoleum and plastic manufacturers makers of workers rubber comenters 5 T pharma- sake ceuticals detergents rotogruture printers organic chemicals explosives ; manufacturers paraffin and wax refiners oi- l aga fat and be extraction workers airplane dope workers alcohol workers aniline workers art- Sage glass workers asbestos impregnators dry battery inakers beauty parlor operators eee belt see scourers benzol purifiers brake lining makers bronzers burnishers rubber gasket makers and - *pady scalers in can industry carbolic acid makers chemists chlorodiphenyl workers cyclohexan- maleic anhydrid- ethylbenzol- aniline- nylon- styrene- ates isopropylbenzol turers clutch impregnators coal tar still cleaners mordanters nitrobenzol manufac ^' nitro cellulose workers pencil makers perfume makers pharmaceutical workers ee ^' a photographic chemical manufacturers picric acid makers plastic tweoxtrikleermsakpheernsol poplriosdhucers - pro- ducers polishers pottery decorators putty makers cobblers compositors dye makers enamelers =-: ey engravers flavoring extract makers glue manufacturers ink makers lithographers metal BAS Bs 20/242 Vol 71 Mar. 1961 SP as a e Pr a -1 ' woes we S ., Mes En Mess af Bhs CARCINOGENS IN HUMAN ENVIRONMENT t washers silverers plastic ion in biologic tarpatent coal patent ap ; dyes facturebrsuutstinegr ohreyoii and lan IV ue butter millinery workers mirror pyroxylin makers rubber buffers cement oe2= mixers compounders and dippers rubberized asbestos board manufacturers rubber pressroom cm 3FaSt:workers rubber reclaimers and treaders shade cloth workers shellackers shellac makers shoe iteeEy ^f'actory makers shoe finishers wooden shoe heel coverers smokeless powder makers tar pitch oil tank cleaners textile fullers tobacco seedling treaters trinitrotoluol makers type a43;, cleaners varnishers varnish makers war gas makers waterproof fabric makers wax makers natic welders wire insulators window shade makers Amines tes : antios woe a lacquer es and antios Sp at cosmetics bo removers but2 x a dry rkers employed tyr Nonoccupational Groups Home users of paints of paint cleaning fluids rubber cements hematotoxic drugs s cs Isopropyl Oil and varnish polishes removers spot ; : . mt Sites of Isopropyl Oil Recognized paranasal sinuses larynx lung textileplastic can. pee ers proces ae andbs producers Products eS rus fruit Tepiteeee}. ~~ Exposure Stigmatu Compounds of Operations and with Population with Population Groups with dyersae ufacturers ink ored wax - goods #i portance hah $28 a See = ef. Economic f,: fiom ta Im- Contact to Isopropyl Oil for Producers Processers Users Consumers and Residents ; Occupational and Environmental - Exposure to Isopropyl Oil . nmadincionngscuomnpstiuomnptT*im3o5naaea i tats Crude cohol isopropyl liquor al- Production of isopropyl alcohol : ' Occupational groups producers of isopropyl alcohol | pyridium unds 2 her goods con- ; ning agents cohol bronchiectases anod f34h and Rey ng Oe y brightening f the sweetener Environmental ate Occupational Exposure en 5 fe monohydro- ras se Mustard Gas Bis Chloroethyl Sulfide Sites of Mustard Gas Recognized lung larynx Exposure Stigmata chemical bronchitis pneumonia Population Groups with and Compounds of . Operations Products with emphysema chemical to Mustard Gas ' Population Groups with monohydro- oe 2 sem) Economic Im- | Contact to Mustard Gas for Occupational and Environmental Sti ) 2 ocytosis leuko- Economic | a i at, * portance sO 2 dichlorodi- s ethyl sulfide or Producers Processers Users : Consumers and Residents Production of sulfur- and nitrogen- mustards filling of gas ammuni- Exposure to Mustard Gas Occupational Groups producers loaders and shippers of mustard Barrow allergic toxic propertics = ; 58 + Yperite or Lost a and related nitrogen : _ mustards = tris chloroethyl tion transportation of ammunition handling of gas munition : gas am- gas and gas ammunition users and recipients of gas ammunition especially military personnel also med ical personnel physicians nurses rs Users Con-- = ralfin extraction- 5 raints paint re- rtificial leather 2595 +75 um motor and C. Is cleaning of| Beoi. is clated alkylated pharmaceutical7s:ce FF: ay ing cokeoven Pe fa IT ae schemical manu- 3. an an ss etc. Nonoccupational Groups civilians a Lote 7 of areas exposed to war gas . Anthracene ; Sites of Anthracene Recognized skin of hands forearms scrotum Exposure Stigmata dermatitis photosensitivity comedones melanoderma with greenish tint hyperkeratoses warts Compounds of Operations and Products with . Population Groups with Economic Im- . Contact to Anthracene for Occupational Exposure . portance a Producers Processers Users Consumers and Residen.s to Anthracene . . irers paint and cementers dry ,,y . losives pharma- 24336. Paranaphthalene oh -_ Anthracene Oil a , Green Oil > ax refiners oil .-ySeqgtbs~ Carbolineum ne workers art- 1/034 Sturt ; = ue ir operators beit 4p . shet makers and \*(SP5g#O So: rs cyclohexan- ae of oye . : shenyl manufac re Coke oven and gas house of / tar distillation manufacture of alizarin . dyes and anthraquinone purification of anthracene oil anti acene -. cake grease manufacture wood + preservative briquette making -. lubricant of wire rope diesc fuel paint lubricant of clay molds for . brick making waterproofing of Occupational Groups anthracene plant workers brick manufacturers dye workers grease factory workers lumber picklers diesel engineers mechanics chemical workers workers nitro- henol producers + .ers polish pro- fae ne Ae a oe 1 = . wert en lumber stabilizer of gasoline in, secticide fungicide protective coating against ultraviolet radiation ikers enamelers graphers metal ahr: fi: manufacture of synthetic tanning agents ingredient of printing inks 7 . a * 71 Mar. 1961 _ .. 21/243 a ca a EVAL Dy ist lini coe ea . A) . ett af se ce : z te we ape iS 8 i: ; 74 Re Bae ees pa kas oF bunts ; * 2. eet en 7 ; if iF Bary 4 : : i : ay is Pad : i te a ies as te < ery, oer2:5. searpn Drtpabriyt at 9 Pe ved*ate Genny, tal she 4 ay ss Gee ahers ; 5 d Sre ne re ae et ey GO Pe NT? x . sani , + tal Ea Wop A rae ELF te a SES pe ST hc 9 a Re Bebe ahs EC 4 Pat teres a] asetwar es 0 *, Wiad fk aitAy w 12 chtebad ~a eets MFA NeTie A ii 4 38fi! 3 iy wy gts Li Aa fey .! ES 4 Ths By nity tt + - Coal Tar and Pitch RRC CARCIN = Sites of Cout Tur Cancers.- Recognized skin scrotum, lip larynx lung suspected bladder Q Exposure Stigmata dermatitis melanoderma photosensitivity loss of melanoderma hyperkeratoses warts papillomas smell awel ter Compounds of Economic Importance Importance tar pitch refined foe tar coke oven tar blast furnace tar coal tars topped tar gas house careycor bases pitch coke Bergius oil far coal tar natpahrthgarleeansees coal tar light oil coal tar acid oil tar "> Operations and Products with Contact to Coal Tar and Users Consumers and Residents. PitchPitch for Producers Processers coke ovens blast Production of tar and pitch in illuminating gas manufacture oil and furnaces tur distillation enamel and coatings of iron and steel gas pipes slips docks locks water pipes tanks pilings etc. industrial surfaces mold and core binders target pitch for clay pigeons carbon electrode fuel foundry es | a proofing tars and pitches roofs decks reservoirs bridges pitch roofing and water +) : ing walls laminated felt and fabric impregnation 2 cal conduits and drainage coal of paper conduits and fiber pipes for electri- purposes boats rubber softener tar paint impregnation of fish nets caulking material for 238 reclaimer and medicinal ointments cosmetic products compounding materials pitch coke roofing paper boxes manufacture of tiles soaps hair lotions manufacture of chemicals ~~ battery , eae Ke disinfectants pesticides ore linoleum flotation printing inks rubber composition varnishes solvents agents of engines and machinery reagents cresylic acid heavy cleaners degreasing chemicals drugs explosives parts quinoline manufacture of resins plasticizers synthetic tanning hydroxyquinolines production of phthalic acids dye derivatives pickling inhibitors ~~ sprays carbide intermediates chlorinated naphthalenes vehicle for insecticide 2 insulation tape production animal dips patent fuel briquettes cork stone manufacture = Impx : : Black B 3 Lamp Bl Black It 7 Population Groups with Occupational and Environmental Exposure to Coal Tar and Occupational Groups Artificial stone markers asbestos goods workers battery dry workers brick layers corkstone makers carpenters brush asphaltasphalt workers plastic coke oven workers chimney sweepers coal tar makersmakers cement makers workers electrode makers workers and refiners cordage factory electrometallurgical and gas house workers insulators painters workers fishermen boat builders flue cleaners pavers pitch workers lens grinders road repairers roofers roofing paper and shingle makers tope makers shipyard workers conduit manufacturers insulation board soap makers paper preservers electrical makers still coal tar cleaners water proofers wood picklers rubber equipment manufacturers electrician cobblers brickyard workers wood workers pipe manufacturers and layers briquette and stokers smokeless fuel producers chemical patent fuel makers facturers blowers breakers workers -wheelers impregnated felt makers tar paint manu- hostlers briquette tippers railroad stokers -shovellers -pilers -grinders fuel stowers manufacturers and weather stone makers proof concrete users electricians electric appliance and cable manufacturers paper conduit manufacturers cosmetic workers insecticide bomb manufacturers farmers Nonoccupational Groups Residents living near tarred roads steel ; read yards power houses using coal fuel users of insecticide plants gas houses rail- - naphthalenes made from coal bombs containing methylated tar cosmetics medicines 3 Black N ts > Peas Furnace Creosote an Se s SusSpietcetseodf Clruenogsote Reco:gnized : skin hands forearms scrotum face neck penis " Loo papEulxepsoshuyrpeerS kertatiosgesmwa arl tsateldaenrgmiaetcittaissesof hands forearms face and neck melanodermaa ,. e Compounds of Economic Importance Operations and Products with - Contact with Creosote for Population Groups with ~*~ < Producers Processers Users ; 3 Occupational and Environmental Exposure to Creosote . Consumers and Residents Wood and Peat Creosote Coal Creosote 238 Creosote Oil electrical vie Carbolineum farmers 22/244 Distillation of wood peat and coal fractionation of blast furnace coke oven and gas retort coal tar cre- osoting lumber poles pilings boards blocks shingles railroad Doe ea Occupational Groups Distillers wood peat coal tar creosoters of 1 lumber telephone and o.aee line workers railroad track work crs carpenters miners farmers . ae Ae Vol 71 Mar. 1901 #2Sie) 3 # HOLOGY CARCINOGENS IN HUMAN ENVIRONMENT Middle Oil Heavy Oil ties mine props diesel engine and industrial furnace fuels lubri- brick tile and pipe pressers furnace men diesel engine engineers cant of brick molds tile and pipe molds sheep dip Lysol manufacture skin and hair lotions expectorants tonics emetics germicides riveters roofers Lysol manufac- turers Nomoccupational Groups Consumers of medicinal preparations containing creosote users of cos- ' rocessers os R nufacture and water Wyse ns 7 retainDate bs} metic preparations with creosote Industrial Commercial and Domestic Soots Sites of Soot CancersRecognized skin scrotum lung Exposure Stigmala dermatitis comedones hyperkeratoses warts papillomas bi- ' tuminosis anthracosis of lung 4" 'Compounds of #: >"), Economic _ Operations and Products with Contact with Soots for Population Groups with Occupational and Environmental Producers Processers Users ' fi * 3-4 Soot Carbon battery Borgie+ te: solvents +75 re legreasing legreasing Sa bee legreasing $2kstty St ~ tanning ' tanning tanning LO ARS | inhibitors insecticide Black Bone Black 2_, Lamp Black Oil ' Black Incomplete EES 3 = Combustion ? - Combustion Prod- uct of all kinds of carbonaceous mat- Consumers and Residents Industrial and domestic furnaces and power plants ships carbon black plants oil field and oil refinery flares smudge pots coffee roasting plants automobile and diesel engine exhausts rubber manufacture plastic- paint- ink- black ter Acetylene paper carbon paper and therinal Black Furnace :: dry cell manufacture absorbent workers si Hi 77.3 Ric makers 7 AF34 Black Oil Furnace |= Black Natural Ga Furnace Black explosive phonograph record shoe polish confectionery linoleum leather coating fertilizer pesticide |, " cleaners S2Ar: . repairers > rs paper ers wood : . Channel Black rs wood er 1 make,:r+s a' it manu- 33: oe stowers Sy colored concrete and grinding aid in cement industry cosmetics soot from railroad engines incinerators smoking and roasting of foodstuffs meats fish coffee etc. dust from abraded automobile tires coke ovens smudge pots curing of tobacco charcoal broiling of meats and fish printing metal foundry soot burning charring of liquor casks cosmetics charcoal and tur- pentine making lacquer Exposure to Soots Occupational Groups Chimney sweeps cooks meat and fish smok- ers coffee roasters coke oven workers oil field and refinery workers carbon black and other black manufacturers soot burners furnace men garage employees diesel truck drivers bus drivers taxi drivers painters ink and paint manufacturers printers rubher compounders foundry workers orchardists and farmers using smudge pots burning used crank case oil and old rubber tires etc. tobacco farmers railroad engineers and train personnel roundhouse workers eyebrow pencil manufacturers plastic and explosive workers carbon paper makers lacquer and varnish manufacturers farmers using diesel tractors shoe polish manufacturers linoleum and leather processers liquid oxygen explosive makers plastic manifacturers concreters plastic makers Nonoccupational Groups Residents in areas near carbon black plants railroad yards harbors oil refin- eries power plants along roads with heavy truck and automobile traffic exhaust rubber tire dust roasting coffee or smoking and con- suming smoked foodstuffs drink- ing hard liquor aged in charred wooden caskets or eating charcoal broiled and often burned meats or ty ses- 4 nmen0 t (iisaSel ars ote ' Poa en pice EES se . kis electrical 372% k workSP- or farmers farmers Jar +, fish using eyebrow pencils contain- ing carbon black operating home incinerators smoking tobacco prod- ucts especially those cured by fuel oil smoking and holding burning end of cigars in the mouth chutta production of soot and tar in acci- dental burns of skin or in burns associated with use of kangri kairo or kang 7 23/245 ee, ane eee ee Rath Tawra5 Vine ens ot etm, whe wy ean AoPnOnDeri Ae yates tae ae oerismerne ae '^'e d Sat aOTT he aa] meg Fig te astyes TF fel m 38 aha Ta20ig BeFre e B 2 >a ares Naewt, : 3 eye fark gly ty]gblyts 4, pce . or Tae erat gkat aera 3fat:, Letheit eg! ple Se ti) aerate Ree a - 1} i Neti LD A a 4 at uy * - ara tS 3 : I - ea = ey qk :a : 2 Ry | m i in 4 u he i m. di. . ae on { ; re ve , : : \ } ' i t { 1 t i Mineral Oils Archives of patiioloGY Petroleum- Shale- and Lignite Oils Greases and Solvents ff > Sites of Recognized skin scrotum suspected larynx lung Exposure Stigmata dermatitis comedones hyperkeratoses warts papillomas Bergius Compounds of Economic Importance petroicum oils shale oils lignite oils Eok hydrogenated coal oils Tropsch hydrogenated coal oils crude cracked oils whe crude cracked oils catalytically cracked oils residual oils industrial fuel oils Bunker C iS we fuel oils home fuel oils diesel oils lubricating oils and greases cooling and cutting oils - kerosene light lubricating oils gasoline naphtha gas oil petroleum spirits engine distillate &, green oil blue oil polymerized and oxidized aliphatic and aromatic hydrocarbons and epox- "; ides from volatilized gasoline exposed to ozonides distilled and cracked native asphalts Operations and Products with Contact with Mineral Oils and Greases for Producers *<' Processers Users Consumers and Production work in oil refineries 3 lignite oil--, -. shale oil- Bergius oil- and Tropsch production plants and their 5 maintenance- .% repair and yard operations including pumping stations of pipe lines and trucking ase furnaces of industrial and domestic oil power and heating plants textile cotton wool silk synthetic |..* fiber asbestos and metallurgical factories greasing and oiling of machinery degreasing .*) of metal parts servicing of automobiles and trucks and railroad cars and airplanes repair detergents petro- work on such velicles production of rubber ink paint carbon black Z chemicals plastics linoleum oiling of roads paving and repairing of roads printing oiling A ! of water surfaces in antimosquito work spray painting nebulizing and spraying of , cutting i oils and of pesticides with an oil or kerosene base curing of tobacco leaves and servicing of smudge pots production of medicinal and cosmetic preparations eet Oils.- Population Groups with Occupational and Emironmental Exposure to Mineral Oils.- Occupational Groups Workers in oil refineries lignite oil and shale oil plants truckers tanker employees workers in oil storage facilities oilers garage men automobile service ie station employees painters printers insecticide sprayers textile workers rubber workers metallurgical workers machinists mechanics gunsmiths optical lens grinders greasers oil = *. EMSS oil 373: furnace attendants railroad engineers and roundhouse workers ink and paint manufac- pots turers road workers carbon black producers farmers and orchardists using smudge tobacco farmers repair and maintenance men in oil refineries textile metallurgical and . other plants airplane pilots spraying insecticides or oil on water surfaces detergent manu- facturers makers of medicines and cosmetics containing mineral oils Ps oy Foots User User seg: 7 ts" Nonoccupational Groups Residents of areas sprayed with insecticide mists users of 28 APE eas medicines laxatives ointments sprays and cosmetics hair lotions creams etc. containing mineral oils consumers of drinking water polluted with mineral oil naturally or artificially ~ Rica or of foodstuffs from insecticide sprays ship fuel oil dumped into bodies of water home Rees use 7 of insecticide bombs paint bonibs etc. urban population inhaling automobile and diesel engine exhaust containing noncombusted gasoline and oil as 1 awaef. fumi fruit fruit perks. of p Petroleum Asphalt Bitumen Tar Coke Pitch Carbon Lignite Tar Shale Oil Tar . linin Synthetic Hydrogenated Coal Bergius Oil Tars a he Sites of Petroleum Asphalt Recognized skin scrotum suspected lung larynx > oe Exposure Stigmata dermatitis melanoderma hyperkeratoses warts papillomata 27: Compounds of Economical Importance distillation and cracking products lignite ~ and oil shale retorting products hydrogenated coal Bergius oil distillation products bitumen Sse petroleum coke petroleum carbon petroleum pitch blown asphalt residual asphalt sludge . t& asphalt . te: Operations and Products with Contact to Petroleum Asphalt and Petroleum- LigniteShale Tars Coke and Petroleum refinery shale oil refinery lignite retorting plant Fry cand i linir 5 pee deic o iy pres : Beets mea 3 ioe a : ; Bergius oil manufacturing plant production and handling of asphalt paint enamel mastic resisting and proofing coatings vanishes acoustical compositions acoustical and * building and paving blocks adhesives compositions for roofing armature carbons and windings fabrics asbestos filler artificial lumber asbestos panels asbestos felt calking com- pound chewing gum tiles shingles rubber fuel lacquers disinfectants floor coverings medicine paints ointments ornaments pavements pipe impregnating agents paper impregnation ; preserva> tives scaling wax stair treads tree surgery compounds vases proofing agents so, river eetr bank protective coatings battery boxes brick sidings road construction roofing mbes materials 1:ge et pacen. AE casting molds caving protectives cement cork composition like and ditch protec Saint ston : Saas Suey tives depilatory erosion preventive fibrous roof coatings pavement filler carboids concrete 24/246 ae 1 . 71 Vol Mar. 1961 hk o ~ i z . } as IOLOGY iyi es ats eee wee Fae CARCINOGENS IN HUMAN ENVIRONMENT Sart W3u5 leather composition mirror hacking mortar putty pipes planks felt impregnation table E- * tops brake lining clutch facings cords undercoating of automobile and railroad cars insulating board stucco ropes tubes wall board wrapping cloth carpets antifouling paint briquette _ binder foundry cores electrodes rubber ingredients pipe conting expansion joints macadam material japans cattle sprays burial vaults dust laying material phonograph records friction elements electrical appliances knobs insoles pipe dips plastics rotogravure ink shoe fillers ~ washers frothing oils linoleun tars electrical insulation material ws Population Groups with Occupational and Environmental Exposure to Petroleum Asphalt and , Petroleum- Lignite and Shale Tars Coke and Occupational Groups ea halts 225. electrical workers Producers 7 Xa P, etroleum- lignite- and shale refinery workers truckers painters masons carpenters : we chemical workers electrometallurgical workers road construction workers Producemirtse oilbA-oriesAZheiNSs mite oil- > mite oil- Vy roofers dike . a 4 LFS levee- revetment- c. onstruction workers paper shingle and tile manufacturers concrete workers paper conduit conduit manufacturers pipe pipe dip ers dippers rubber workers tenance oe V% ie foundry workers building material producers blocks felt acoustical composition wall boards runs panels fillers calking compounds cork furnace attendants tree surgeons battery box manu- } facturers artificial leather makers automobile and railroad maintenance workers garage at- tage: ey , atnenddaunstesrs pbhraarmkaeceliuntiincgalmamnaunfuafcatcutruerrsers*. cosmetL ic manufacturers farmers briquette. makers - ~" 9 oiling 5 Nonoccupational Groups Users of asphalt depilatories shale oil tar ointments residents - near asphalted roads and traffic highways with dust from abraded rubber tires and petroleum tar oil coating near oil refineries with effluents from catalytic cracking towers 3 ~ . on . - - - as . Paraffin and Petroleum Waxes a Sites of Paraffin or War Recognized : skin suspected lung stomach Exposure Stigmata dermatitis wax boils folliculitis comedones scleroderma melanoderma papules warts hyperkeratoses : ntaining ficially ce ome use E: I engine - ste bitume..n2 sludge >" mildewproofing ointments * _ Compounds of Economic Importance Importance crude semirefined fully refined micro- '> crystalling waxes slop wax slack wax sweat wax scale wax bottom wax black wax Foots oil petrolatum solid jelly liquid synthetic Tropsch hydrogenated coal waxes Operations and Products with Contact to Paraffins and Waxes for Producers Processers Users Consumers and Residents Wax pressing extracting and refining wax blending oil refining adhesive for laminating paper filler of meshed fabrics saturant of cotton braid and jute coating of wires and cables water- and proofing of textiles tarpaulins polish for shoes furniture automobiles floors etc waterproofing of brick walls luster cleaner coating of fruit and vegetable preserves waterproofing of cellophane impregnation of wrapping and building paper rayon fiber lubricant impregnation of cartridges desensitizer of explosives histologic impregnation material absorbent of neutrons oiling of wool yarns of eggs and of plastic beads ethyl cellulose coating of metal in Cottrell precipitrons artificial fruits and flowers barrel lining beater size for various paper stocks belting impregnation beer can lining binding agents blasting supplies bottle cap liner coatings Brewers pitch composition candles capsules carbon paper cheese coatings chewing gum ingredient collapsible tube lining cosmetic creams hair dressings cosmetic baths crayons dehydrated food packages "_ deicing compound dental waxes dressings for mechanical belts drinking impregnation egg preservatives electrical insulation field ration packages sealing compounds lipsticks meat coating metal drum lining ordnance packing paperixard cartons and drums paper milk bottles fruit and vegetable coatings printing inks ingredient radio parts rain clothing rubber compositions rust preventatives sealing and luting com- 1 pounds ship launching grease leather stuffings depilating wax feather remover of fowl : dielectric paper transfer and photographic papers lithographic papers nonabsorbent creped cellulose impregnation for sanitary napkins waterproofing of insulating boards molls for photoengraving and electrotyping roofing paper shrouds for goods and machinery mulch t paper soda straws sound records stop for glass etching tank tar treatment for wine peas: rs, 7: etc. galvanized iron conting glass fabric impregnation grease typewriter ribbon wax acid #-<.,, bottles wax emulsions and sizings wax figures and toys match sticks manufacture of chlo- reserva- tie: river s WBE . rinated paraffins potting compounds cosmetic surgical material cutting and cooling ous lining preparations Jat terials Me | *i laxative soy Population horticultural wax with of acid pipelines terials -siidestieg te he A Oc upational Environmental 0. Population Groups with Occupational and Environmental Exposure to Paraffins Paraffins and W'axes W'axes > protec waa Rage ate Sy Oc upational OccupOcupaational tional Groups Wax pressers petroleum Ae, Groups proces- : refinery workers producers producers users proces- proces- i! uncrete Gates: sers of the various products listed lignite and oil distillation ~ shale at Aty r ' 1961 orets 6S ESB Sf *~ wr 25/247 eymek weinesh poe thn, 4 Srysat>e t tebe hapetehCre pantapne > 7 FS eTaaee OENina es %i or eee.tep'et6 we tae t oun Bmaoma & aeLary de,Swat,cerbor yee SS attanone eaS edrelied Ht oes Feeal : TO Ge 0 VEREeed ~ te g Eat BA he ny ENEick mae eyRSanamvac Mn ais ve pan 78 os | + a eye reset pared Ps Leeow etchhes roe s.3Chak ae 7; wee. S I oe smn aak t wath SenoA m3 S &o| f tne mabejyae weve < iar Ry etLe -%, a Ve: eaere oer iy ed A Sernees as bok,nary 4 1: eree Rone eS i PH.Pee RadOrgwal. Oeyas vay San3e3, TN125 phes i. ae . a AsLte EP Ka er ray Hoabe ^' Deretesigeat anaSort:irspee % meOR te a : 44, . 5S. } a an CaP ; Cal's i Ve " ru wy,, dh * 4, 5 ae di]: a Rr a a1 we! Ss ; 13 r Spd ihe | ca 4 ates Tee Sew a PR Sei ; erent WETY } BuseRe ( : ail Ady epi Ht j SONATA ke } tyi aS ; i cic q eeby i sey PEP 8 a5 | BEMIS le ; ' FNS a on Ey Ke co iat ae Q % r . SSE as aid 3 yo? : : 5 F ~ Sema Mil: : # ? NaF B . : ay}! . ff ; , A ie ^' 2 B 13 3 i : es 4 ;- if 4 2 Ss | z 3 es 2 i i] 2 ah An | z cBUal ao tregste | : TASTES : as ~ * 4 % tay . hoe pe ret, ann . hes ARCHIVES of pathoLOGY x . Nonoccupational Groups Persons . with paraflin and parenterally injected for medical or waxes habitual users of paraffin oil laxatives cosmetics cosmetic reasons and waxes of impure grade consumers of foodstuffs containing paraffins packaged in paraffinized coated with parallins or waxes and containers users of chewing gum containing waxes etc. bones Sites of IonizIionngiziRnagdiaRtaidoinations Radiation a- ^ -Radiations hematopoietic tissues lung Recognized skin subcutaneous tissue liver larynx thyroid kidney suspected breast uterus 3 Exposure Exposure Stigmata radiation dermatitis radiation ulcer of skin melanoderma leukoderma atrophic foci hyperkeratoses chronic telangiectases loss of hair periostitis leukopenia and hyperleukocytosis Importance Devices and Compounds of Economic Importance radiation from earth crust and in water of ponds springs etc. due radiation Ionizing radiation natural radioactive elements and their to presence of radioactive compounds series artificial compounds of uranium- thorium and actinouranium- radioactive substances radioactive isotopes cathode tubes oteflevision tubes radar tubes radio tubes electron synchrotrons and roentgen particles ; : related accelerators Operations and Products with Contact to Users Consumers and Ionizing Radiations for Producers Processers Residents diffraction apparatus production and and ray tube and apparatus manufacture ray radiology atomic use of television and radar equipment roentgenology industrially used energy production and laboratory operations radiophysics operation of ray and cobalt bomb photographie equipment sterilization of and surgical dressings with ionizing radiations electrostatic foods drugs paint on dials watches etc. diagnostic and eliminators fluoroscopes luminescent depilation ionization devices resistance therapeutic use of ionizing radiation cosmetic uring devices weighing devices radionetidveevitcheisckndeeslsay devices identification devices are meas- paintings chicken eggs and gauges radiography of castings forgings use for chemical welds medical and industrial use of radioisotopes ionizing reactions ( polymerization polymerization etc. Mining of radioactive energy present in radioactively contaminated ores or other minerals refineries ores coal cobalt etc. uranium ore smelters and . Population Groups with Occupational and Environmental . Occupational Groups Atomic Exposure to Ionizing Radiation. such devices as well as energy fission plant and laboratory workers military personnel handling and fusion bombs biologists chemists chemical gas . mantle manufacturers laboratory technicians and attendants workers persons handling laboratory wastes luminous dial including cleaning personnel and with luminous paint repair personnel of such devicpeasinatnedrs handlers and shippers of scrap metal pharmaceutical handling workers using radioactive isotopes and them nurses tracer physicists morti ians operators of electrostatic substances Ee physicians pathologists devices are used ( eliminators and persons working in rooms where such aie printing . radium refinery workers plants radiologists radium laboratory . workers haar research workers using radioactive material roentgen and cathode tube manufacturers television and radar tube makers and * beau- ticians shoe salesmen uranium dye workers ceramic operators roentgenologists 4 manufacturers glazers uranium ore miners miners in radioactive mines urawnoirukmerpsaignltasmsakers tile . reasNoonnsocpceurpsaotnisonal Groups Patients receiving ionizing radiation for diagnostic or therapeutic therapeutic foodstuffs exposed to rays for removal of hair or for fitting shoes contaminated with radioactive fallout or inhaling such materiaplersons consuming Rae < skin contact persons bathing in radioactive water or or having 453 plants - drinking such water residents . near radioactive icy Sites of Ultraviolet Radiation Ultraviolet Radiation ca.; suspected melanocarcinoma Recognized skin basal radioactive hwo Se? papEilxlpoomsausre Stigmata actinic dermatitis melanoderma Sources of Economic Importance Sunlight Radiation from Welding Arc Mercury Are & 26/248 Operations and Products with Contact to Ultraviolet Radiation for Proxlucers Processers Users Consumers Residents Outdoor occupations especially in dry sunny altitude 18 climates and at high on large bodies of : ro] Occupa- Population Groups with Occupa- 27 tional and Environmental . Exposure to Ultraviolet Radiation 0 1 Occupational Groups Agricultural laborers boatmen cattle men construction workers oil operators a mY . ya, ye. CARCI fe . ef - i. Car ery : trai yeF . Ee resa - oon cee % Z : ^' % i : : : . . 3 : os # # . i fo 2 . * 4 ! . t .. * ee . SEP > or - ot i CARCINOGENS IN HUMAN ENVIRONMENT Set yC-arbon Arc Ul> traviolet Lamps ity Flame Fluorescent Lamps et x a : wouter reflecting solar ultraviolet radiation welding administration of ultraviolet radiation for cos- | pharmaceutical manufacturers of vitamin D preparations railroad engineers cowboys drivers of metic and medicinal purposes ex- posure to intense radiation from = fluorescent lamps trucks and buses farmers fisher- MEN gardeners herders house painters lunibermen miners of sur- face mines masons nurserymen . oA oilfield workers railroad track workers ranchers road workers . rural mail carriers suilors sports- men stockmen vineyard workers welders barbers beauty op- <u tubes th elerators a : : oe Loa a fe . me - a : yO: - ~ tes , . mo _ oss a - 1 drugs + aS ninescent at's RS. ~. cosmetitce Rye - re 3 critical analysis distribution A critical analysis of the distribution of #iXq~ these established human carcinogens in the _ general environment of man demonstrates meio: a widespread exposure to such agents 4 rs and 1 77S 39: While for most of these agents a conclusive handling wieq. liation SF | =" ( proof of their producing action and thus the existence of an actual cancer haz- Aurs gas eeGhag ard from contact with these agents is lim- ited to occupational exposures general we aceutical ap ok oiea we hologists Ag vre such ee experience with carcinogenic agents indi- 1 cates that without any doubt many of the nonoccupational exposures to the modern workers RIES industrial carcinogens by the general popu- cathode Rees lation As glazersglazers oe glazers beau- * must constitute a cancer hazard at = present quantitatively undetermined which in some persons causes or contributes to - re erapeutic Lbs the causation of cancers suming 1eranteesge: The evidence on hand when critically and ing skin dioactive PR aos SCENE competently Sgr af [ evaluated in fact strongly sug- # gests that the majority of cancers affecting i the following organs are attributable to ~ exposures to environmental carcinogens ; skin mouth paranasal sinuses larynx lung 3 esophagus stomach intestine liver blood- :. forming organs bone bladder kidney and are thyroid The probable existence of similar relations Y <4f. causal relations can be suspected moreover pi^'egy: for at least a part of the cancers affecting . Agricultal ttle men Sse wAaer the brain breast we a important The important eA agents evidently ayia ry evidently agents ee ee ; Hueper ae , . and uterus which role which in play in the environmental environmental production productionproduction of erators lifeguards policemen . Nonoccupational Groups Resi- _ dents of sunny regions of mountainous areas of ocean shore areas golfers sunbathers water sportsmen tennis players persons : receiving ultraviolet radiation treat- ments for cosmetic or medical : : reasons skin diseases tuberculosis rickets rickets etc. . > . cancers receives receives additional weighty weighty additional support from the following facts a Striking quantitative and qualitative differences which cannot be attributed to racial factors exist in the epidemiologie cancer panorama in different parts of the world The general cancer panorama as to different organs affected and to incidence rates for various sites involved among in- habitants of countries of the Western fundamentally World for instance differs from that present among natives of Africa b Cancer incidence rates for males and females in different parts of the world show = marked fluctuations which in part can be traced to the influence of definite environ- mental factors active in only some but not all regions and population groups to different degrees upon the members of the 2 _ sexes c The recent changes in the incidence rates of several cancers especially lung cancer cannot be attributed to alterations in the biologic composition of the human population i.c. endogenous factors but must be related in changes in to rather recent quantitative quantitative the quantitative and and important qualitative qualitative qualitative composition of the carcinogenic spectrum in most industrialized countries d Similar Similar Similar causal higher factors must of the observed higher frequency of underlie underlie cancers _, 27/249 . Te er tret aEFo. xrP Reet *. Ny ig aktii Pee : a2 paree , oe . den re,7 aap? apaes! 7 <a ; x <be y be ny ok es Se oh ~ ot as " ayy et sh y epede e SF sep BakeDaw ar44,a te od dad aoe Sian Lea p1g it rw heral ' ia 7 pales ee pa. - rake iy Beast Ea | anes ence ase SE erat wag std a td 7 dPgsi cy | i: . 4: Brdter's^'AEE* is eee 3 iA ae aAges Zz TEA $5 ciara Serer ee SANs me we Ri * ae Ls eee IEE epromSnoei Sasae oe te Ne Se. e Aa? pe eae eae mteg : eee vy Raedhs 4 oh RRUNAwCihS Sp Ott i ale of various organs among inhabitants of urban areas over of rural ones that found among those Educated guesses concerning the possible or probable causes of some of these observations are justified by applying the evidence existing on recognized human carcinogens to these developments How- ever in most instances such tentative conclusions prove to be either insufficient or totally inadequate for providing satisfactory explanations for all aspects of the epidemio- gree Archives of ge pathology & wy NAN: logic phenomena cited It quite ORT becomes quitequitequite obvious that additional environmental causal factors of unknown nature fon must be active in the production of human cancers and their epidemiologic fluctuations in dif- ferent population groups and during various satay periods It is likely that some such factors may be represented by the numerous chemi cal agents which were found capable of pro- ducing cancers in experimental animals and Table which have become an integralintegral part of the human economy 2. TABLE Potential Human Carcinogens Their Origin and : Human the Human Environment and the Cancers Caused by Siles Aliphatic and Aromatic Epoxides of Epoxide Suspected : skin lung forming Distribution in Them . -*:* : tissues Compounds of Economic Im- portance - Operations and Products with Contact to Aliphatic and Aromatic Epoxides for Producers Processers Users Consumers l'opulation Groups with Occupa |: wee tional and Environmental Exposure to Aliphatic & Aromatic Epoxides ee ube TIMES BESOIN Aliphatic and aromatic epoxide monomers and polymers Vinycyclohexene dioxide Ethylene oxide Propylene oxide - and Residents ~A Production of aliphatic and aromat- ic epoxides and epoxide resins plastics and polymers atmospheric oxidation proxlucts of aliphatic and aromatic constituents of volatilize gasoline by ozone and ozonides sterilization of instruments and dressings food preservative fumi- gant polymerization products of ethylene oxide and propylene oxide used as lubricants vehicles sol- vents binders intermediates in production of rubber and in food . - Occupational Groups Worker < abso groups producing processing using - nt 1aitura handling the various items listed 33 ay eeyy Nomoccupational Groups Residents s Fe i3 x of urban areas inhaling volatilized } gasoline oxidized and polymerized by ozone and ozonides formed by | * 3 photochemical action of intense *..i37 solar radiation users of consumer tt goals containing epoxides mono- : mers or polymers + pharmaceutical cosmetic agricul tural textile paper petroleumn and - other industries: ointment bases for ee open dressings vehicles in supposi- Pine tories carriers of drugs antibiotics sulfonamides cosmetic creams lipsticks hair dressings assistants in rayon spinning dis- persants of dyes and lakes sizing and finishing components of tex- tiles demulsifier of crude petroleum oil emulsions selective solvents for aromatic fractions additives to tin- and plating baths solutions OBS, for electropolishing aluminum in- gredients of buffing compounds im- - me Res 7 . ; pregnation of electrical contacts ee. ; film former on silver conductors intermediates of plastic and resin 14 rarer production solubilizing and spread- ing agents in agricultural sprays 2 continued * Table binders in detergent thru page 37/259 soaps inter- 28/250 Vol 71 Mar. ' Amt eee pen = a oes ATHOLOGY ATHOLOGY 28. CARCINOGENS IN HUMAN ENVIRONMENT : comes quite ae mental causal Pex bet ure must i me Pag . . - ; - agents mediates in antistaling of bread and stabilizers of ice cream intermediates softeners of leather of household detergents and dis- vos! Bye sok re , : persants of household cleaners coatings of drums barrels cans structural plastics for castings lamination of glass encapsulation ' Lf of electrical parts aircraft parts pro ablpre o animals animals ne ae tt tanks pipes solder vo { ie 7# i Us = oAcee Ue : wR) i sie: { is : aa . animals and and Propiolactone Sites of Propiolactone Suspected skin connective tissue part of the 4 > Compounds of >" Operations and Products with Population Groups with Occupa- Economic Contact to Propiolactone tional and Environmental Exposure , Importance v3 for Producers Processers Users to Propiolactone Consumers Residents a Hydracrylic acid " - Production from formaldehyde and Occupational Groups Producers a . lactone hydrolyses under formation of =.polymeric acrylic ketene acrylic polymerization agent chemical intermediate for propionic = compounds virucide for biologic and industrial users of propiolactone producers of virus vaccines poliomyelitis hydrophobia and ester acids' - - products air disinfectant of human tissue implants plasma . plastic manufacturers Nonoccupational Groups Recip- ae ih ahs { ayes \ i pate eee I Vy ag - AR Wee eens 1 Arey cy 24 cf ients of biologic preparations steri- lized with propiolactone persons " listed SEK ei 1-: atl Residents : eo a SVC font inhaling air sterilized with this virucide Carbamates . Sites of Carbamate Suspected lung hematopoietic organs Exposure Leukopenia transplacental penetration with effect on fetus 7 Compounds of Operations and Products with Population Groups with Occupa- Economic Importance Contact to Carbamates for Producers Processers Users tional and Environmental ExposurEe xposure to Carbamates Consumers and Residents Urethan Ethyl Carbamate Urethan aldehyde _ ' condensate Thiourethans phenyl "" =: carbamates Isopropyl Production of urea from ammoni- um carbamate production of carbamates and polyurethan plastics fungicides weed killers insecticides insecticide repellents snailicides sedative for fish rubber vulcanizers accelerators plastic stabilizers antioxidants diesel fuel additives corrosion inhibitors se- lective solvent of chemicals and drugs surface active agents resins plastics adhesives rubber solid and foam resistant textile bristles fibers casting and potting compounds coating materials for wire glass wood metals etc. plasticisers hypnotic sedative an- Occupational Groups Producers of carbamates and urea farmers railroad track workers employees of fish nurseries road workers pharmaceutical manufacturers rubher and plastic manufacturers dye workers cosmetic workers Nonoccupational Groups Persons treated with carbamate medicinal preparations and possibly the offspring of pregnant women given such preparations residents of areas in which carbamate pesticides are dusted or sprayed users of cosmetics containing urethan consumers of foodstuffs containing carlxmates as latent flavor devel- esthetic antispasmodic anticonvul- opers sive antileukemic antipyretic diuretic antiseptic anthelmintic enzyme inhibitor miotic trypano- cidal ingredient of quinine scleros- Mar. 1961 % y 4 A 1g wig See ing agent ingredient of cosmetic astringent latent flavor developer in packaged food dye intermediate ingredient of nonluminous candles Pan age Wits rare 2S. ersten: poe baat x ae en ACI ve TER A CF CS pee Ste AErs oayhse Fe 1 ay eget Norerenenee \ eet oe a FS . . ARCHIVES OF PATHOLOGiY" Chlorinated Hydrocarbons Carbon Tetrachloride Chloroform DDT ee Aramite Chlorinated Naphthalenes . i Veh dichlorodi- Sites of Chlorinated Hydrocarbon Suspected liver lung skin Exposure Jaundice liver degeneration and cirrhosis dermatitis Compounds of Operations and Products with Population Groups with - Economic Contact to Chlorinated Hydro- Occupational and Environ- Importance carbons for Producers Processers mental Exposure to Users Consumers and Residents Chlorinated Hydrocarbons Carbon tetra- Carbon Tetrachloride Occupational Groups tae eae! Workers Reig tc ee chloride Manufacture of chlorinated hydro- producing processing using and 74a . chlormethane carbons of benzophenone and car- handling the various items listed 4 Chloroform bon disulfide dry cleaning agent chlormethane spot remover mint remover de- Nonoccupational Groups Persons : DDT greasing agent organic solvent ex- using carbon tetrachloride and - chloroform as cleaners or as fire- phenyltrichloro- tractant of fats and oils fat . . ethane waste essential oils extinguishing fluids at home or as alkaloids solvent for paint removers persons consum- Aramite gums resins waxes ing foodstuffs containing DDT .. 24 butylphenoxy . isopropyl flufiudmigparnotductfiiroen chloroethyl sulfite refrigerants Chlorinated preparations Naphthalenes Halowaxes _ . and rubber ex- tinguisher of refrigerants Freon hair shampoo anthelmintics anes- thetic pharmaceuticals Aramite Insecticide cide livestock dip moth repellent for woolens and furs soil poisoner Chlorinated Naphthalenes Sol- Aramite as residues or inhaling =, such materials following spraying or dusting of these agents for rea- sons of personal sanitation or of ie pest control persons using chlorin ated naphthalenes around the house or around the farm as greases of machinery or as impreg- nation agent of lumber vents plasticizers crankcase oil additive upper cylinder oil cutting oil ingredients contact insecticide ovicide soil poisoner wood impreg- nating agent for shuttles in weav- ing impregnating of paper capacitors wood preservative seal- ~ . 7 ing compounds coatings ingredients of retarding paints ; Estrogens Natural and Synthetic - blSaidleds eorf Estrogen Sus, pected uterus breast prostate forming tissues . Exposure Glandular endometrial toms in the male cirrhosis of liver hyperplasia gynecomastia feminizing symp Compounds of Economic Importance mt Estradiol - Estrone Estriol Equilin d- Equilin Di- - ethylstilbestrol Hexestrol etc. . . . Operations and Products with Contact to Estrogens for Producers Processers Users Consumers and Residents Production of estrogenic chemicals manufacture of estrogenic preparations for medicinal cos- metic and agricultural uscs handling of estrogenic animal feed and implantation of estrogenic pellets into fowl cosmetic lotions and creams aes Population Groups with Occupa- * } tional and Environmental Exposure to Estrogens te og oy Occupational Groups Chemical and pharmaceutical manufacturers - ; of estrogens producers of estro- .: genic cosmetic preparations farm- ers using estrogens in feeds for 4 the chemical caponization for fowl es and for the artificial induction of lactation in dairy stock and for + stimulation _. production of . eggs for Aa In- Nonoccupational Groups ate we Nonocupational 30/252 fants and adults receiving estro- atv: gts menopausal 7708 genic treatment for 3 great See variety of ailments vee Vol 71 Mar 1961 Sirens eee Reta te Si GS A NE SRLS ete Cittet Ae ree ixins ' Workers ee Workers pe a ' ORG ng and Sh e ike a _ rm - ste ae, symptoms hypogenitalism dysmenorrhea arrest of lactation arteriosclerosis carcinoma of the prostate and breast gonorrhea of vagina in infants etc users of estrogenic cosmetic preparations consumers of meat from animals given estrogenic feed or estrogen implants . Diethylene Glycol Sites of Diethylene Compounds of Economic Importance Glycol Suspected: bladder Operations and Products with Contact to Diethylene Glycol for Producers Processers Users Consumers Residents Population Groups with Occupational and Environmental Exposure to Diethylene Glycol Diglycol 2,2'oxydiethanol Production of diethylene glycol and of derivatives ethers antifreeze plasticizer of polyvinyl alcohol solvent of phenolic resins dyestuffs and in toluene manu. facture textile fiber sizing and finishing agent hygroscopic con- Occupational Groups Producers processers users of the various items listed Nonoccupational Groups Smokers of cigarette tobacco treated with diethylene glycol humectant ditioner of synthetic fibers conp- ling agent in lubrication soaking knitting and similar textile opera- tions humectant of tobacco in cigarettes leak preventive ap- plied to jute packing of gas mains dehydrating and desulfurizing desulfurizing agent of natural gas softener of glue plasticizer of cork resin binders book binding adhesives solvent in alkyd resins in steam- set inks inhibitor in magnesium fountry sand mold mixes addi- tive of oils used for metal cut- ting agricultural polishes diluent of sprays and brake fluids ' Hydroxyquinoline ey fowl Woe Ga} or fowl tion . etic > of wee . for nd fi." anne. = en =: 3: Silas of Hydroxyquinoline Suspected : uterus rectum brain bladder Compounds of Operations and Products with Population Groups with Occu- Economic Contact to Hydroxyquinoline pational and Environmental Ex- Importance for Producers Processers. Users Consumers Residents posure to Hydroxyquinoline . oxyquinoline quinolinol its copper and zinc chelate Production from quinolines in coal tar its use in chemical analyses as a precipitant of metal ions chelate former as a stabilizer of hy- Occupational Groups Manufacturers and industrial users of the various products gardeners military personnel pharmaceutical complex its benzoate and \ drogen peroxide employed as a bleaching agent in cosmetics as a manufacturers cosmictic manufac- turers tobacco growers food proc- sulfate and its iolochloro iolochloro - rocket propellant as an anti- essers chemical workers and : catalyst in chemical reactions as chemists fluorescent screen manu- and diiodo a fungicide in ointments and pow- facturers adhesive proxlucers compounds ; ders athlete's foot Dutch Elm chemists mercury- disease textiles paints in ad- Nonoccupational Groups Users of hydroxyquino- hesive of paraffinized milk con- cosmetics rectal suppositories con- line tainers in fluoroscopic screens traceptives fungicidal powders and J x 31/253 iw cy BeeRilatiey dyTO es terend ak nedgheteetab 58, Fares Leta ware ta Ww tee ta2 ay: Sot Poet are Aer apecae yi as pde8 s ee rat Nagy ur veery ee Fa eeats HfYY Uviee ia # Eyre ' 7 Stynea4aestes a { a Sevr 7 Ee wel incebw rw a . 74 ay ze i Soran REDE: oe AGG ITE PSS ANG ZASONCR a al ARCHIVES OF PATHOLOGY in baby powders as an amebacide ointments amebacidal drugs baby antiseptic antiperspirant deolor- powders processed foods contain- ant bactericidal agent in rectal ing additives with hydroxy- suppositories and spermicidal agent quinoline or packaged in containers . in contraceptives food preserva- using this chemical in adhesive tive fungicide for tobacco leaves smokers of tobacco treated with emulsion paints separation reagent it of beryllium from aluminum Detergents . Sites of Surfactant Suspected skin lung alimentary tract bladder Compounds of Economic Importance Operations and Products with Contact to Surfactants for Producers Processers Users Consumers Residents . Population Population tional Groups with Environmental Occupa- tional and Environmental Exposure to Surfactants 4efi Thiour 2 ; Doxiecylbenzol derivatives Production of dodecylbenzol pctroleum or petroleum products Occupational Groups Worker groups producing processing us- Polyoxyalkylene kerosene production of deter- ing and handling the various items < sorbitant alkylates gents household and industrial listed . petrochemical workers de- Tweens Tween from the basic chemicals packag- . tergent manufacturers handlers. Tris ing and shipping and subsequent and - shippers manufacturers of polyoxyethylene handling of detergent powders and soaps dentrifices lubricating oils sorbitan mono- laurate liquids for production of soap sub- stitutes soap additives dentrifices rubber latex ore flotation ma-.: terials electroplaters garage men 1; Tween Tris polyoxyethylene - sorbitan mono- additives to lubricating oils drycleaning liquids ore flotation agents rubber latex fabrication as 4 bak- silk and wool manufacturers "jos * ers processed food manufacturers , dry cleaners , .? cleate Polyoxyethylene 8 stearate cleaners of metal surfaces elcctroplating degunuming of silk and scouring of wool as car washes additive to foodstuffs Nonoccupational Groups Users _ of certain household detergents and 5 dinnerware contaminated with de- tergent residues consumers of . foodstuffs containing certain emul- sifiers fat substitutes stabilizers - or dentrifices with such additives 3 Tannic Acid Sites of Tannic Acid Suspected liver ' Exposure Stigmata liver necroses Compounds of Operations and Products with Economic Contact to Tannic Acid for . ae Population Groups With Of Occupational and Environmental Importance - Producers Processers Users Consumers Residents Exposure to Tannic Acid Tannic acid Tannin Producers of tannic acid and tannin from vegetable products tree bark nut shells leather tanning slime depressant in ore flotation agent cotton and rayon dye mordant thinner of drilling mud pro- Occupational Groups producing processing handling and + using the various items listed < Nonoccupational Groups Patients with degree cutaneous burns. tein fiber curing agent antioxidant ea sO, containing containing Yea. - solutizer process for removal of mercaptans from gasoline manufacture of repellent fabrics weighting x% preparations for intestinal disorders 2% with or without ulcerations con< sumers of tannic containing ,,pyrogallol manufacture weighting .. foodstuffs of silk fur dye clarification agent : ~~ +: eat containing containing teed containing s 4 Sh 46 Sic , of fruit juices precipitanotf . gelatin cosmetic astringent as- tringent of mucous membranes in- testine in diarrhea cutaneous burn remedy ingredient of rel wine tea nuts fruits hop etc. -Pit yac-Pihtch 4 ail 32/254 . . Vol 71 Mar. 1961 3 Seog Mae a nel Py ae 4 , F ra ivP e e:eee oe caaasss CARCINOGENS IN HUMAN ENVIRONMENT .- : . mae) sari; Th,iourea Thiouracil Thioacetamide Acetamide and Derivatives 333 en Sites of Thiourea etc. Suspected liver thyroid ntainers rie foes Aber Exposure Stigmata Hypothyroidism with Population adhesive ioe aba oe - Compounds of ed with Sites wee "4 Economic ag bE Qe : Importance sen aa 4, Operations and Products with Contact to Thiourea Thiouracil Thioacetamide Acetamide for Producers Processers Users Population Groups with Occupational and Environmental Exposure to Thioura Thiouracil Thioacetamide Acetamide , . Consumers Residents Ste : Thiourea of Thio- Thiourea Inhibitor of thyroid Occupational Groups Producers PEA, as ce *.. carbamide 2* Thiouracil - - function medicinal antithyroid - agent fungicide accelerator of processers and users of these com- pounds in the different industries Gees Methyl +, . sprouting in dormant tubers pesti- , Stee ints ngs 2 wo s uracil a ~ cide flame proofing agent of nylon a RS e.). Propyl Worker cs >. thiouracil Thioacetamide weighting agent of silk dye bath adjuvant of textiles gold or sepia sing ku See a . Thioacetamide toning agent in photography urea - xus items erat, Acetamide or substitute in formaldehyde kers de scat + oO Ethanamide .- handlers ct ooe Aer + ot ws, vs resins pickling inhibitor and in- gredient in cleaning and plating of irers- -fof ase oils oleses ting a A io ; metals preparation of nonglare - mirrors synthesis of sulfathiazole Thiouracil Antithyroid agent _ and occupations = Nonoccupational Groups Con- sumers of fooxistuffs contaminated with these substances persons receiving thiourea and thiouracil | preparations for medical reasons . -_ ; ; ers bakSe ae Bes facturerese eee | iy facturers verges i Thioacetamide Organic solvent leather in- in textile and paper dustries accelerator of _ vulcanizing of Buna rubber stabilizer of motor ; Users fuel containing tetraethyl lead com- bined with mercury a mordant of seed grain solubilizer of riboflavin Acetamide Solvent of organic and inorganic chemicals soldering tabilizers , tabilize+rs additives additives ache eS ei > ares ~ flux dye solvent in textile industry ingredient ingredient molding ingredient of urea molding com- activator in bleaching pound activator in bleaching liquor wetting agent accelerator in dye- ing raw product for pharmaceuti- ca cal manufacture nutrient for mold . * ig et Se growth humectant for paper antiacid in lacquer explosives and a Chen Cas ;* aoa. cosmetics plasticizer in leather cloths films and coatings iq 1: - ants a: i4 * enPPEr. ig ey mise es 2 5 : is : ms, a -6 a4 _ Rae mrs i :> Us a ve Baviny oy ial ns ety peeks) pn ae ans aa me - sg 28, Re hs ae 23515 Fa Si flea SB;Bd - Thermic and Oxidation Products of Oils and Fats of Vegetable and a hes i . oe . Animal Derivation Waxes and Greases . Hee if Patients is burns ON prepara- +r f=As nnic acid (2A, Sites of Vegetable Compounds of Economic _ Importance . and Animal Fat Suspected lung alimentary system bladder Operations and Products with Contact to Processed Oils and . Population Groups with Occupational and Environmental Fats to Producers Processers Exposure to Processed Vegetable ' isHey mia i are u abn Lisers Consumers and Residents and Animal Fats and Oils . od Me Lard Vegetable Dairy products margarine salad Occupational Groups Deep a Oils and Fats Shortenings dressing shortenings coatings paint ingredients varnishes lino- frying cooks restaurants ready to cat food industry margarine aii was Candle Pitch team inks soaps detergents sur- manufacturers processers and re- 7 Bone Pitch Rubber Pitch face active agents agents emulsifiers degreasing lubricants finers of oils varnish ink- and fats linoleum- soap- paint- leas eS Bors Margarine Emulsi- plasticizers refining and render- detergent manufacturers makers Pen fier Glycerin Pitch Wool Fat Sperm Oil Fish . ing of oils and fats hydrogenation of shortenings and salad dressings of oils and fats deep frying = Nonoccupational Groups Domes- of fish meat baked goods resin tic cooks consumers of poly- eh - Mi pee ty AS Hueper oe 33/255 eT Tera STfente ANS en att mer,mae $, OVrEnRS CLEC on eteeea! hackae LPIA oe te ee EO STte " SE at oo Oe 2 Soh RAT de, o$ PL Cec reaPeleDaas Te re ~~Le $4 Te RN tent Cs aoeee 2 on x Oils Polymerized & oxidized fatty acid emulsifiers and contaminants of heated fats & oils or of chronictreated fats and oils bleached production core binders japans production of candle and sonp stocks refining of vegetable oils with alkalies refining of refuse greases packing house grease bone grease garbage and sewage greases woolen mill wastes lacquers lubricant for borings : merized and oxidized fatty OAL acid acid ~ aa CARCINOGEN 277aereee = BLT: * eh from products from fat frying iE or deep frying t as emulsifiers in margarine and Meg 88 Soluble i sb a. Pen! Be eSgoluble salad dressings or shortenings Sites Poly consumers of breads and rolls pre- areasareas pared with the emulsifier polycellulose Compounds oxyethylene 8 stearic acid 8 amI an of tL organs auxi he ae v 5 cellulose Fi glycola.l: . polyoxyethylene 8 stearic acid Insoluble Carbon and Silicon Macromolecular Polymers Cellophane -.. .' Polyethylene Polyvinyl Chloride Polyacrylic Plastics Polystyrene , Polyamides Formaldehyde Plastics Polysilicones . _ Polytetrafluoromethylene Sites of Polymer Suspected site of implantation and mucosal contact Compounds of Economic Importance Operations and Products with Contact to the Various Hydrophobic Carbon and Silicon Polymers for Producers Processers Users Consumers and Population Groups with at Occupational and Environmental ' Exposure to Hydrophobic Carbon | and Silicon Macromolecular : Polymers Residents Processers Procesers =Su= btosan Kollic | ProcessersOperations . Processers Use packin : Kadhesive deterg y Chold | detergenit,s drilling fluids i : see creamingrubber a et emulsions ws f nylon Pl Pi Dextran mud ' hin =mudPolyvinyl I Monomers and polymers of the various polymers listed as well as their different copolymers and related polymers Methyl and phenylchloro- silicones and their polymers Carbon Polymers Production processing use and consumption films packaging materials impregnation of containers including foral containers bottles tubes flasks boxes for foodstuffs medicines cosmetics chemicals lining of cans barrels etc. coating of textiles paper etc. sheets plates rods tubing pipes structural material glass substitute water proofing textiles yarn thread optical goods furniture household and garden supplies wax blends electric ap- pliances leather substitute rubber substitute bristics surgical prosthe- ses materials sprays for mothball- ing of machinery and ships etc. sausage skins textile finishes den- Occupational Groups Workers engaged in production processing| use and consumption of items listed Nonoccupational Groups Users of medical and dental protheses of cosmetic surgical implants of cosmetic sanitary and medicinal preparations containing these polymers as ingredients persons using consumer and household goods containing these polymers a =( .Polyvinyl rae ice -# "SN medium adlies es Spee felt and straw toeasyes ' stencil screens fF semipermeable Zoe screen printing . ake and acoustical met De bonding mater oedefects 4 ad . Population BREE Polymers e303 ous ous items list tal prostheses cosmetic surgical implants . Polysiloxanes Water repellent lubricants anticaking and anti- taininpgolymersthese t=ainingtainingtainingtaining these LAS, usi = PS foaming agents grease and oil re- - pellents polishes rubber- metal- and plastic agents slippage cast releasing improvers for textiles hydraulic fluids water- proofing agents for leather ma- - sonry impregnation agent stopcock . x Exposure Exposure liaterials gr 3" Compounds - Compounds a0 grease filler for voltage con- , 34/256 ductor in aircraft moisture sealing compounds resins rubber foam rubber hand lotion ingredi-- ent antifoam mist in treatment of pneumonia and pulmonary edema ingredient of antibiotic paste sur- gical prostheses =. all 141.67 ae beryllium copper ae = of 141.67 141.67 ; EC magnesium 3 i aquamarine emera aquamarine + + teee beryllium beryllium cl Rv THOLOGY oe THOLOGY Ri 1 fatty fatty acid acid eee acid my a, adh . ips with 2H ee : : hobic Carbon5 - ee ee nL nT Oe eT a | :< ~ ARCINOGENSIN Human Environment Fo ~ ARCINOGENS ae : ,:_. Soluble Soe Carbon Macromolecular Polymers Sodium Carboxymethyl Cellulose Dextran Polyvinyl Pyrrolidone Polyvinyl Alcohol Sites of Polymer Suspected soft tissues around implants lung inucosal contact areas organs and tissue of retention and deposition Compounds of Economic Importance carboxymethyl cellulose NaCMC cellulose Bi < cellulose glycolate CMC dextran polyvinyl pyrrolidone Periston Plasmosan Plasdone ; 2: Subtosan Kollidon polyvinyl alcohol iodine polyvinyl pyrrolidone 43 FIX. Operations and Products with Contact to Hydrophilic Carbon Polymers Production a= Processers Users Consumers and Residents and processing of for Producers monomers and a* s. polymers packing and shipping industrial use and application sodium carboxymethyl cellulose 4} a =, adhesive detergent additive soil antiredeposition agent whitener retention agent in household detergents filtration reducing agent in drilling mud emulsifier of oils in water base drilling fluids ingredient of printing paste for textiles emulsion agent for paints ceramies VY. creaming rubber latex antistick compound preparation of grease paper size of paper st and textiles filtration agent of uranium ores paint thickener thickener of polyvinyl acetate = emulsions nylon sizing emulsifier and stabilizer of ice cream cheese thickener of foodstuffs - Dextran Plasma expander size of paper and textile thickener adjunct to oil well drilling : S Glaeaeae ee Bag Polyvinyl Pyrrolidone Hydrogen peroxide stabilizer germicide for topical oral and intravenous use plasma expander adsorbent of toxins and dyes hair lacquer drug dispersant ' C retardant of drugs suspending agent of cosmetics and foodstuffs clearing agent of beer > and fruit juices copolymer of plastics film former substitute for shellae and other natural of items listed <> gums in lithography and printing processes redeposition of soil preventive for household ups Users of . protheses of plants of cos- nd medicinal poly- ng these persons using yt sehold goods | .mers an . : detergents - a ( Polyvinyl Alcohol Ingredient of cosmetics emulsifier and gelatin substitute in foodstuffs 22 PK ipew ice cream coating of candies and confectionery medicated films incterial culture medium adhesive pharmaceutical preparations sutures dressings sausage casings size for oh oie felt and straws improver of ceramic clays coating of paper size of nylon cotton fabrics ie ss stencil screens tape boiler scale inhibitor release agent of molds of plastic compounds :semipermeable membranes polarizing films gaskets belts ingredient of ink photographic and ..screen printing emulsions gasoline hose resistant gloves heat coatings electrical and acoustical insulation additive to paraffin aluminum salt waterproofing compound _ bonding material of synthetic nonwoven fabrics surgical prosthetic material for filling tissue . defects oe . . Population Groups with Occupational and Environmental Exposure to Hydrophilic Carbon : Occupational Group:s Producers processers users and consumers of the vari- ous items listed . Nonoccupational Groups Users of hair sprays cosmetic preparations and foodstuffs con- > taining these polymers recipients of medicinal preparations by various routes containing these 2 polymers users of household detergents inhaling dust or mist ' ms. . oe - 71 Mar. 1961 : : Beryllium "a oo 4. Sites of Beryllium Suspected lung bones et Exposure Stigmatu and chronic berylliosis demonstration of berryllium in biologic i ao materials granulonias of skin and other tissues Sx ps Pea: a oe 3 Plo e , Compounds of Economic Importance Glucinium bery beryllium alloys of copper aluminum magnesium nickel steel emerald aquamarine beryllium chloride pie Hucper Operations and Products with Contact to Beryllium for Producers Processers Users - Consumers Residents Ore mining and milling production and processing of alloys for cylin- der heads of motors springs metal parts in precision instruments watches cog wheels ball bearings screws electrodes for welding electrical contacts surgical instru- 'ments and needles tempera- . Population Groups with Occupational and Environmental Exposure to Beryllium | Occupational Gorups Workers producing and processing the various items listed and becoming exposed lung skin etc. to berylcontaining dust fumes frag- . ments = Nonoccupational Groups Exposure to phosphors from broken fluo- 35/257 . Bets > yes y Kye git sem ey tabadsria Fcaraen asltfe ist; vatteen * el 3k. 34 ae 2 sf eon ghee fe we Be i re Cre : |4 pag , a& : pane Fl i tis AD ae i PL inet iPNc:e bys I ig i : i P43 wis if rat athe i ; Beach RY 4 phe D> pea eedaie th Le EGET PaaS, +i is ek Mati te rere: Sry wg a Sask a8 st ns Pag a] ikPeds 5%) : t PC 2 z y - fi Po } ge ue ry + i i u 4 fa i et i aj gi Bl: x: 7 ype 4y it wen 5 a] eerp = : F 5 AS ; ear * : E BSCE of Eo N it Ne A Bibs 53 oe Abed dente Rta \ heryllium oxide, sodium beryllium oxide sodium nitrate, beryllium fluoride beryllium nitrate beryllium bromide beryllium beryllium borocarbide beryllium sulfate beryllium silicate stearate ture membranes, paris af pumps; membranes parts of pumps rescent windows beryllium glass windows beryllium crucibles refractories refractories fluorescent tubes fluorescent light tubes glazes cements , ceramic temperature resistance tools and temperature glass cosmetic enrmedical powders artificial artificial en- shielding shielding atomic energy are operations mantles electric arc carbons grinding agents soldering welding archives pathology pathology vane rescent tubes residents of of light tubes smelters and aii beryllium smelters os Cobalt Cobalt Sites of Cabalt Suspected car Consumers Population human Sites Cobalt conective connective tissue lung so Compounds of Suspected Suspected connective tissue Operations Operations and Products with Environmentat Since Since 4 . Economic Contact Users Producers Occupational Environmentat Environmentat animals animals animals by the: Importance oo Users . Users - Exposure Cobalt Cobalt o by ' ore, cobalt Mining and Occupationa tone 2 Occupationa Occupationa + Cohalt cobalt smelting of cobalt ore Mining smelting gum formation in Occupational Groups processing ay gaged production production en- ST Occupationa Occupationa can s : that under alloys cobaltous these agent acetate cobaltous deactivator convection loop formation nu- products products processing users agent ~. organ Noncupational : carbonate carbonate cobalt- gasoline reactors clear reactors carbide and their users cermiets Nonoccupational Groups ---- -- - other Tropsch ---- -- -44 seen seen ous carbonyl catalyst pigment and syn- sumers vitamin vitamin Ba f ois that baltous chloride colors in glazes , |. Be 2 it among cobaltous nitrate thesis paints enamels plating alglass paints various eet ; ER that among seen: . Emental cobaltous oxide types of steel * EmaenrtaleWear which cobaltous cobaltous speed die and valve tool which - car cobaltous cobaltous high dye ingredient of vitamin - reason this phosphate phosphate : wool accelerator of drying of paints and varnishes must reason | be los baltous sulfate potentia ; potentia potentia lo dence to ~ Selenium Sites Sites Selenium Suspected especially Sites Suspected liver thyroid Stigmata articl Compounds of liver jaundice Compounds Operations and Products =. consumptio Economic - Contact with consumptio consumptio Importance Contact Selenium for Producers Processers Users aanae Occupational Environmental Environmental Exposure to + Selenium ' saniti { , consumptio consumptio objectionab objectionab cancer Copper Copper cancer sulfuric sulfuric possible present sludge seliniferous ~ plants plants alloys therefore The copper stainless steel, cadmium selenium selenium evidence selenium selenium chloride fact diethyldithio- additive diethyldithio- diverse diverse carbamate carbamate carbamate greenhouses diverse The selenate selenate Oe: nattionhalliy isn sul sulfoselenide Consumers Residents Copper refining sulfuric selenium duction both selenium giving vulcanizing ac- proxluet rubber glass paint celerator pigment brown amber elec plastie plastie rectifier photoelectric cell tronic rectifier photoelectric leather pigment pigment ceramic decolorizer decolorizer printing stainless stainless additive soil additive insect repelling and poisoning poisoning greenhouses citrus fruit chemical chemical oxidizing catalyst toner toner photography film toner xerographic plates for electro- workers Exposure to Occupational Ocupational in :; 2 gaged production processing processing and use of items Persons Nonoccupational Nonoccupational Nonocupational Nonoccupational Groups Persons possible possible zr avaaes b : selenium containing naturally x 5 evidence metics evidence not foodstuffs sel- ne: contaminated contaminated ss c selenifer- selenium gens plants eniferous grown meat from eee enougesnsfact u - ous grain and such car tes ae food food animals eating meat plants food animals eating such plants) . eats foll | of - nationally Sake port tt : At Ga port port Fol photographic photographic printing cosmetic medicinal agent lotion against dandruff dandruff Chair lotion against > dandruff : ext Fol * thology thology it 2 : . 36/258 Lig EIA ; Cerys phar hey > Na se Tee ee CARCINOGENS ENVIRONMENT CARCINOGENS ae IN HUMAN ENVIRONMENT 4 . ai a { ore Iron . Sites of Iron Suspected lung liver ' Exposure of the lung siderocirrhosis of the liver ' Compounds of Operations and Products with Population Groups with +s rf URES ee Chr Rake +) a oe tae: _ ., Economic | Importance | te Hematite iron * Contact to Iron and Iron Oxide Dust to Producers Processers Users Consumers Residents Hematite Mining iron ore trans- 9 Occupational and Environmental Exposure to Iron and Iron Oxide . Occupational Groups Hematite a : a bod Rint iy. PN metal iron oxide id = sar pigment y2 HFrite a >. wre tat esary pata. ta t xP tate ve ty. NE Soe RES LAR Hiv Sa i we tt : eae <n. ae . portation and shipping iron and steel production grinding and polishing of iron casts in foundries polishing of glass mirfors optical glass metal parts diamonds production diamonds production watches and use of iron pigment oxide as in paints iron work ship hulls etc. rub- berber lilnoilenumoleum paper ceramics miners foundry workers makers mirror polishers manufacturers painters witch paint experiences Since the with experimental animals 4 by the administration of known practically Sweden " think it is the most urgent problem to investigate in finest de- od atheerothts huhemesaren scientificpaalrltyicularly important beginning eed wiitteaeEmental experi- 76 ote 4 oesEBamdTsueehssenpteiccmustrieally time + with A: carcinogens those of tails the exogenous causes of cancer This occupational type have amply demonstrated problem seems to me to be easier and more SF that under proper experimental conditions fruitful than the researches on cellular ' ig agents elicit cancers of the same or !. changes in cancer of course very a organs in one or several animal spe ) too May 9 1955 it seems sound to assume Austin M. Brues Director Division eyeam that { among thecarinogelns arge number of . of Biological and Medical Research Ar- carcinogens some will be found gonne National Laboratory Lemont Ill which are carcinogenic also to man For yr & # this reason all experimental carcinogens be looked upon the being potential human carcinogens until evi- to the contrary becomes available is presence in consumer goods such as _ foodstuffs cosmetics home rem- But if thereis an increase in lung cancer and if thisis due to an extrinsic factor then something in our environment has been per- mitted to go well above the allowable level according to the criteria used in our probably regulated business . . . The question of environmental carcinogenesis is 4g edies sanitary goods household goods and other articles of general and uncontrolled quite properly attracting increasing attention and one foresee that it is likely to ironmental enium 7 ' consumption and exposure appears to be becomea source of financial importance in objectionable since these agents may create cancer research Presidential address workers.en- cancer hazards which are difficult or im- 46th Annual Meeting of the American . processing ' iar possible to demonstrate with the at- Association for Cancer Research 1955 listed 5 Persons mming . cos is naturally nium sel- ( available epidemiologic methods and therefore may escape discovery . 3 The available factual and circumstantial evidence on environmental human carcino- Once an adequate amount of reliable and valid causal data on environmental carci- nogens becomes available the control of many human cancers by recognized and in selenifer- gens and cancers thus indicates that exog- proven public health methods of a preven- meat from wch plants . enous factors may account for many and tive nature should offer the same prospects diverse diverse cancers afflicting mankind as those successfully applied in the past for "4 The following statements of two inter- the control of infectious diseases because nationally prominent medical scientists sup- of the existence of many similarities in the port this interpretation of the evidence behavior of the causal agents of these 2 . a Folke Henschen Professor of Pa- classes of pathogens and of the disease thology Karolinska Institutet Stockholm manifestations elicited by them Table 3 37/259 % 2 a4 3 3 Es sy 5 os RTE o4 t R Redt Lo St : 0. : jTomwesdeTjeroa ety te . te 7 SIN Aea,re tke ee weEI. or ome a PSC geee ere Se mes as TB .~ rary 7h LY, Th Bibs wR Pe ~~ MS gdeiy tars Set epg re? TE ; UN Te . 3. or mewSr Eyee te va REL waepes vs or x pore NETO Ye an earnso,n i ie BU OM SIGH we ? NPY GALeaTaoe . omroont DIS SERLDAY ABloipplnednee ty g oer repey: ARS fevshtamtatty parva . AT TY Sed EPO TAO o ey ere Ser GTN TRS ii SSA ct TAS tt Rat 2 rtehe ome TABLE Similarities in Epidemiologic and Symptomatic Patterns of Environmental Cancers and Infectious Discases 1. Carcinogenic spectrum is as wide and varied as pathogenic spectrum of infectious diseases allinities of introduction 2. Shift in main target organ dependent on route of causal agent occurs in both groups of diseases 3. Carcinogens like Infectious pathogens may display tissue and organ definita : 4. Minor changes in chemical structure of carcinogens may cause change in target organ similar to that seen sometimes with different strains of organismus 5. Carcinogens vary among each other as do as infectious pathogens In virulencemarkedly in potency 6. Differences in individual susceptibility to the action of causal agents are found in cancerous as well as infectious 7. Curcinogens are as diseases 8. Successive specific as infectious pathogens changes in the reaction status of the host and in the character of the renction products cimructerize the cancerization not only process but also some chronic infectious conditions 9. Cancers and Infectious diseases have pattern centrifugal distribution distribution II Characteristics of Environmental Carcinogens 1. Definition.While Definition.While there is no entirely scientifically satisfactory definition of car- cinogens the following definition may be adequate for all practical purposes A car- cinogen is a chemical physical or parasitic agent which when coming in contact with and introduced into animals including man under proper conditions elicits cancerous reactions in one or several organs and tis- sues regardless of the route of exposure and the dose or physical state of the agent used Carcinogens are capable as a rule of producing cancers in one or several species but not in all species and in one or several tissues but not in all tissues The target organ of the carcinogen may moreover vary with the species The carcinomatous reaction moreover may appear in an organ or tissue which is remote from the site of primary contact " It follows from these statements that a carcinogen which is capable of producing cancers in experimental animals may or may not exert the same action in man or not at the same site For this reason every effort should be made to obtain evidence on members of popu- lation groups which become exposed to any agent capable of causing cancers in animals The population groups most suitable for 38/260 ge . ARCHIVES Of pathologY pathologY sag such purposes are usually industrial pro ducers or users of such agents As long as fent human evidence is not on hand experi demonstrati mental carcinogens remain merely suspect for a partic . of exerting a cancerous action on man ie recognized c they remain potential human carcinogens recognized cinogenesis Any restrictive and viewpo precautionary viewpo ! measure fical which may be applied as a matter of com mon sense to such agents for the probable ca protection ~ of the + . agent until 7 population therefore cannot be ca based on conclusive scientific facts but Sh incriminating circumstantial evidence It would indeed be foolish and irresponsible ; mental cane : tba e on the other hand to lightly dispose of such adopted .. dirresponsibl potential cancer hazards as being calar lated risks which must be tolerated as plannedplanned plannedplanned Gill unavoidable products of normal living in an industrial economy en fore ge The acceptability of a chemical or physi cal agent as a noncarcinogen depends on the adequacy of the test procedures ie dose routes of introduction frequency 2#e%ththeey length intensity and duration of exposure of observation time number and specioefs animals and type of vehicle including . sol vent and dispersing agent Unless chemi- fore as shoul experi should scientific cally variable and defined mixtures are < be tested the agent investigated should chemically identified and pure and the in struments vehicles etc. used in the test procedures should be free from other cards nogenic agents including contaminations from carcinogenic air pollutants w | fensive a Che fensive list prepared b ranged on acteristics physical Likewise final recognition of a coal Sones and chemical agent as a carcinogen 5% shouldshould ze not be granted on the basis of observations 2 reported by one investigator or group of investigators only This acceptance should depend on the reproducibility of the results 3% ys TABLE Dose Variations for Different Carcinogens at a 50 Tumor Yield Level for Treated Animals* 323 cae Carcinogen 2 3 - Dibenzanthracene Methylcholanthene 3 Benzpyrene Dimethylaminostilbene -Dimethylaminoazobenzene R. Boyland 83888 83888 83888 83888 83888 71 Vol 71 Mar. . . . an 1962 ) ) a aes ates ik 21 - HIweper, ~~ ae et ~ SRE La Seer w.7 t WAL. - x PATHOLOGY CARCINOGENS HUMAN OF S34 CARINOGES rn industrial prpro-o- y industrial' pro- 57 ENVIRONMENT ENVIRONMENT 4: eek by at least two better even more independ cannot - be released by the metabolic forces . gentsAslong as ent parties of investigators However the of the body from its inactive state the car- on hand merely in ction experi- suspect demonstration of carcinogenic properties for a particular agent by investigators of recognized competence in experimental car- cinogenic component remains carcinogenically ineffective Thus most of the various food dyes which contain naphthylamine cinogenesis should be regarded from a prac- or naphthylamine in their molecules have tical viewpoint as adequate evidence of the been carcinogenically inactive when tested probable carcinogenic qualities of such an for the protection agent until this conclusion is either sub- evicdaennncote ribe irresponsible efore Istantiated or refuted by the results of atific facts - buton investigations by other competent experi- tial ... : Imental cancerologists This attitude should irresponsible and be adopted to guard against any loose and ee Eirresponsible ly disposeof such Eiresponsible positive or negative claims as beingcalcuwhich might be advanced on the basis of calcu be tolerated; # and incompetently interpreted planned of xf.results of experiments by insufficiently ex- normal living $ physi ros Poso=ad a s perienced investiigators nvestigators or planted by parties chemical or = qf, withspecial interests Reports on the ingen depends - on fa alleged carcinogenicity of chemicals there- t procedures i.e44 ' fore should contain detailed information on on rats although 2 have shown carcinogenic properties for mice Orange SS Oil Yellow HA Experiences made with various chromates differing in the degree of their water solubility have been of similar nature The highly soluble and corrosive chroinates as well as the almost insoluble chromates have proved when tested on _ rats and mice to be carcinogenically little- or ineffective while chromates of medium. solubility have proved to be highly potent carcinogens It is likely that similar differences in solubility or biologic availability of certain inorganic and organic arsenic frequency action 's : the experimental procedures used before compounds may account for the contrasting | f exposure length they er and species of sol icle including * should be given serious consideration as scientifically acceptable evidence i 2. Classification of Carcinogens statements made concerning the occurrence of arsenic cancers among members of pop- ulation groups exposed to various arseni- it Unless chemi- cinogens may be classified according to sev cals . ned mixtures are eral principles j - b Target Organ Classification Carci- be gated- should a Chemical Classification In the ex- ; 4 pure and thein- tensive listing of experimental carcinogens nogens have been classified according to the specific organ or tissue in which they elicit used in the test 3 from other carci * contaminationMs24 physical llutants tion of a physical 24 prepared by Hartwell carcinogens are arranged on the basis of their chemical characteristics This grouping is useful for demonstrating the distinct scatter pattern of carcinogens upon numerous classes of cancers i.e. skin lung liver bladder etc. This classification has some practical merit if one is interested to know the various car- cinogens which have been shown to clicit cancers in a certain organ or tissue regard- carcinogen 24 is of observations ? ator or should group of oe chemicals and our present lack of definite . factual knowledge concerning the special chemical characteristics which convey car less of the route of administration However in many instances the site of the target organ depends upon the route of introduc- acceptance should ?24 5% ility of the results results cinogenic properties to some but as a rule not most of the member compounds of any particular class The concept of chemical tion and for this reason may change when the route of introductionis altered It may be mentioned moreover that minor chemi- ons Different ee 4 group carcinogens thus has only restricted Tumor Yield Animals * : ee 2S: applicability and is ~e si ; FH, _ent for only two 3 generally valid at pres- carcinogens classes of carcinogens. ASgoe chemicalspossess- . * . Pah. . radioactive chemicals and 9 882 882 arsstseg . ing estrogenic propertics Ne ing aa contain Evenin chemicals which may contain in- cal changes in some members of the hepatocarcinogenic dye group shift the target organ from the liver to the bladder The following 4 classes may be estab lished on this principle used in a modified form 100 ~2:g54 . tramolecularly the active carcinogenic com- I. Cancers at the site of primary contact ar- ponent . 500 : J. carcinogenic activity depends upon _ scuic asbestos chromium nickel soot tar the biologic availability of this component : petroleum oils rays etc skin lung nasal ae Ito the tissues of contact If the component : sinuses bone leukemia 11996611 l'ol 71 Mar. es 3 *f oe 39/261 nahihee etNote - fy Gg BOsoNeU$s, 3 ie wageas 2 + A HeNES tat s Xd ee grea. theamare nies erie eearfaa . ~ wh?re an inoSmStey 3 ql care aessger 3 ae 3 fap ry > 4 3 Pons a Teta :. 4: i: BNE Ge CETE TS ata Ay By SO et ty SRSBS Wert STAR Gage i FatAE -. * le Esp vepeT NI OY i. RENary 1 : \" . a. a i :, Ste BREE PS ke pag SE: : =F = t eity FS 2 B : #3) 2 5SSH + : a" nae ji eninge omens Gaba san LER Fdcehan ICH ne on PHELAN den eee vo men AN II III bladder Cancers at the site of excretion aromatic amines arsenic skin Cancers at the site of secondary retention radium and storage radium benzol arsenic arsenic tho- rium X azo dyes etc bone bone marrow liver skin etc. IV Cancers at the site of special affinity hor- thyroid mones organotropic chemicals liver genital organs forming organs organs estrogenic chemicals goitrogenic chemicals hepatotoxins myelotoxins c Human Carcinogenicity Classification or Species Specificity Classification Carci- nogens may be grouped according to their specific activity i.e. according to the various species in which any particular , carcinogen may be capable of eliciting cancers Of main importance in this respect is a classification in which the relative significance of carcinogens concerning their carcinogenicity to man represents the guid- ing principle The following groups may be established when this principle is applied 1. Recognized human carcinogens mainly oc- cupational carcinogens and a few environ- mental . ones radiation solar radiation ionizing = radiation from natural sources arsenicals arsenicals } soot schistosomiasis 11. Suspected human carcinogens for which the total available evidence experimental and . human is not completely conclusive as to III _ tthoebiarcccoarecxitnroagcetniivceisty to man estrogens iron Potential Potential available available carcinogens human carcinogens for for which which the evidence is restricted evidence is restricted to observa- tions on experimental animals and which represent constituents of the human econ- omy i.e. with which man has frequent and intimate contact in the form of consumer goods industrial activities industrial or industry environmental pollutants IV Experimental carcinogens which are chemi- cals shown to cause cancers iin n experiexperimental mental animals but which are not constituents of any part of environment human the and economy human economy economy or which therefore are en- significance tirely at present of scientific Carcinogenic Carcinogenic d Carcinogenic Potency Classification Clas ification Classification An attempt has recently been made to dis- tinguish between strong and weak carci nogens and to use such distinctions for the establishment of screening methods of food additives and contaminants for carcinogenic properties and potency Table 3.4 In and Table Boyland Berenblum Fieser Bryan and Shimkin 40/262 i . , y ' : . ARCHIVES OF PATHOLOGY practice the establishment of such a , classifica tion is bound to encounter distinct difficultidi experience for Existing experience several several reraesasoonnss Existing Existing experience experience large with a number of carcinogenic ; test Similar performed on numerous carcinogens stricctalrycisntoagnendsardihzaed shown that even when standardized Homogenic Cr Similar defic Similar * r in e gens re test conditionsconditions rating marc poten rating any are particular empemlplooyeyd ed particular the carcinogen Homogenic poten marc marc marc for particular marc considerably carcinogen vary with the different strain of the same species with the sex as well as with different species The potency rating is marc 4: Experimen aromatic hyd of subject is also subject to marked fluctuations fluctuations de de suggest that pending upon the particular type of test when these conditions used i.c. the route of introduc tion the type of vehicle the use of single form form especi or repeated administrations the length of hydrocarbon hydrocarbon the observation period mortality rate from hydrocarbon other causes among animals in test series etc. Quite apart from the considerable difficulties encountered in defining in gen when when form 335 vt especi especi ; . 4, general erally acceptable terms local and tumor yield length oflatent period metastat ie spread growth rate and accurately what common qu are the criteria of a strong carcinogen in in contrast to a carcinogen there weak exists present no reliable method for at measuring in absolute terms carcinogenic potency 5 . of potency ra absorapbsorpttion ion preparation preparation preparation a chemical for any particular species much 2325 ence critic - less for several or all species ' introduction The discrepancies distribution The genic genic marked " potency discrepancies between discrepancies different in in different species between different species potency for a particular carcinogen are well illustrated carcinogen by observations made on several highly doubtlessly carcinogen amines Benzidine is carcino- carcino: species for aromatic distribution : f All system : carcinogen * : polycyclic| carcinogenic for man but seems to be weakly took has rather weawkelaykly carcinogenic carcinogenic since carcinogenic forfor dogsdogs it it ee took ae demonstratisnignce some 7 years for the ef s been aromatic a ne metalsmetals metals pres- for ence of bladderbladder in tumors in 2 of 6 el ( : , dogs fed benzidine for many years Spitz et Similar e Cla : : al pleteness observations Similar observations exist exist for acetylami potent nofluorene acetylami nogenesis nonfoflluuoroenreene nofluorene whwhiicchh iiss evidenetlvy identlyevidently a which potent nultista evidently carcincogen arcinogcaercninogen for in the many organs in rraattss causing this species this species most most cancers cancers on aes < iaIxlyaa geaeas the only Dogs the other hand reacted after 7 to 8 nogenesis 7 nultista i. gand years of exposure to relatively massive doses of this chemical with the development of blad Graffi 18.67 der cancers et al 7 Morris produce ing these 18.67 The almost universal inability to produ;ce prgoumiosthib cancers of the lung in experimental animals by the inhalation of carcinogens which 6S ung carcinoge - oe 18.67 : . OT i eee id be i ed doubtedly Jia lifficulties ey at least part are responsible for cancers of the human lung is one example xperience BS enic tests ' has Similar gens pogens ndardized shortcomings for the existing methodologic oe deficiencies exist for many carci- in regard to determining their car- cinogenic potency to parts of the alimentary psotternacins Experiments DETARpata nt es "3, with carcinogenic polycyclic bine initiating and = promoting properties It is remarkable however that under certain circumstances even carcinogens of the initiating as well as of the promoting type may elicit tumors without the coaction of the other complementary carcinogenic factor i.e. that they behave like complete carcinogens Among the known initiators gt KO ne is well strains hydrocarbons adsorbed to the sur- aromatic cy ratin suggest tions testa : of face of carbon particles soot carbon black dens that the carcinogenic potency of these carcinogenic compounds is reduced when these agents are administeredin this introduc single single form of single " are sisinnglegle especially when the carbon particles of of very smallsmall size becausebecause thethe adasdosrobrebded length ate are not readily eluted and this is true of urethan triethylenemelamine and propiolactone while among promoters this has been observed for croton oil phenol and Tween 60 and may be present also for dodecanol Poel because of these findings and his own observations with the " cocarcinogenic or promoting basic fraction of creosote oil proposed that all promoting | SYiy ree . Bie pas 3 =. ai wicca es > froSmage hydrocarbons . st series released for action from such by carcinogens were in fact weak carcinogens siderable have particles ; in substances of the host organism i.e. they siderable become unavailable i.e. they exert an effect synergistic with that produced by the carcinogens tested biologically belonging 1 gene When Whenusing f carcinogens to- Set^/l^/the other hand has recently chemical classes thereis often no stated that in his opinion all promoting *: = tely different 242 common quantitative denominator between * agents exerted a purely nonspecific cell- te E common an, Ks he + nogen vin was the ofcomparativecomparaticve omparative proliferation hyperplasia -stimulating ac- etd them for establishment nogen poiency they constitute re exist rates Likewise tion tion and and tthuhs us t did did not not constitute a ae eaaae specific e Beasuring absorption or removal rates of carcinogenic factor essential for carcinogenesis . * tency preparations ie o tes much subcutaneously injected influence critically tumor yield at the site of Saffiotti and Shubik in contrast have argued from their observations on the ef- 4i All classify ort introduction as well as the ap appearp ance earance and carcino- : of cancers in remote carcinoO-f distribution organs ecies for systems to or grade proposed llustrated =za carcinogens on the basis of presumptive aromatic carcinogenic potency have been applied to v aromatic Little this highlyBap polycyclic hydrocarbons 4 aromatic compounds aromatic amino- amino- and none fects of low concentrations of carcinocagrcinogensens given in single doses alone or followed by carcinogen repeated doses of the same carcinogen or of croton oil that a clear distinction can be made between an additive action of carcino- genic effects and a promoting action of a cocarcinogen on a carcinogenically sensi- tized tissue It is also certain that not all Pe i atet ~ ae ee idee ay the pres- *; for metals or radiations proliferation agents act as dogs fedom et al cetylami : st potent 409 cers 1. on the rae c Classification by Carcinogenic Com- Recent observations on cocarci pleteness have given rise to the concept of nogenesis a multistage mechanismin the cancerization process i.c. the separate action of initiat" Fing andpromoting factors in the proc- cocarcinogens or are weak carcinogens On the other hand experiences with certain hyperplasia chemicals administered in combination with complete carcinogens indicate that such effects upon certain organs may be essential for promoting cancer development in organs esses of cancerization and cancerigenesis which would not occur if the carcinogen 6 Berenblum Shubik Foulds Set^/l^/ would be administered alone Carcinomas a Graffi Salaman etc. Walpole in analyz- of the thyroid for instance result in rats 3p By promoting carcinogens carcinogens distin- ing these data recently proposed to guish between * initiating and complete " i.e. carcinogens which com- ; by the combined administration of a goitro- thiouracil thiouracil with acetylaminofluorene gen thiouracil with acetylaminofluorene which when given alone does not cause cancers of the thyroid Cancers of the es itd ane ti Lee > ateote PeFr 41/263 4 a? sy Teed 4) eta cad a> oDnabs meCaATRBIALIFSitsSAREPaIAiRiUtOEhEacLEEneceeen whichZe graphic Saar ARCHIVES OF PATHOLOGI CARCIN Pa ***** Os breasts in mice are observed when methyl- The amount of available information ***** cholanthrene administrations are combined c conditional carcinogens is very scanty and come int i with that of estrogens Jull Estrogenic little understood as to the actual role generate oe A treatments in combination with administra- complementary factors play in such types * deve i * ah STZ tions of acetylaminofluorene are ineffective of carcinogenesis It is moreover obvious graphic in rats for increasing the incidence of that with a few Factors . breast tumors while this effect is obtained exceptions carcinogens of den 7 ith } when in the experimental are complete carcinogens which need neither which 1 Ag tan management es- cocarcinogens nor complementary factors E trogens are replaced by progesterone Can- for the production of cancers It is felt Ber My . tarow Stasney and Paschkis therefore that at least at the present time Ss te It remains an open question whether or the available data on complementary of Te not the various properties promoting hy- conditional carcinogenesis do not lend them te perplastic carcinogenic or tumorigenic selves to the development of a useful and s a TA Sme ascribed to promoting agents are in all cases scientifically sound classification of card- Spe identical and thus perhaps different phase nogens LT effects of the same property or represent 3. Action Mechanism of Carcinogens Bar possibly separate biologic qualities inherent The carcinogenic effects of chemicals sas ror] ee in the same chemical At any rate in view - cells and tissues differ in one fundameunptoanl of the highly fragmentary and controversial - aspect from their toxic effects While cells REE Sh evidence available on these interesting and and tissues will recover anatomically and provocative aspects of carcinogenesis there functionally from toxic effects unless they seam TW appears to be at present insufficient evidence are killed by them and at times PO on hand for the development of a useful acquire after recovery maany increased even te and rational classification of carcinogens on re sistance to a repeated toxic action of the principle of initiating promoting and a particular chemical the biologic effects of Sass wre complete carcinogens as proposed by Wal- i carcinogens are definitely lasting if ts . . pole There exists apparently a second group eae af . of possibly incomplete carcinogens These tNtat % are agents which need to become active the action of some endogenous or hereditary factor or of some exogenous factor or factors of exogenous dietary nature which are totally unrelated to the chemical cocarcinogens Urethan for instance will elicit pulmonary tumors in certain heredi- not permanent and for this reason makes once carcinogenically exposed cells more susceptible to repeated exposures on on chemicals i ng the carcinogenic effect of = cells more readily understood one may com pare the action of carcinogens on cells with that exerted by light rays upon the ling instances emulsion ling of a photographic film In both A instances the activating agents act upon certain spe cific elements present in the exposed mes at TE nerbeesedpectivbe e23; Sh o SS carpcroi-noies Cit change/s aoe TUT Ba SACS 334 Fonte tarily predisposed strains of mice or will dium This action does not to a " cause the development of skin tumors when continuous or prolonged it may rather PAS the - its intraperitoneal introduction is combined brief or intermittent The degree of with cutaneous applications of croton biologic and photochemical effects produced A number of oil tissues emulsion on the tissues and the emulsion respective produced Ag a 6lm A azo dyes of the butter yellow ly has a direct relation to the total + dose \3 dimethylaminoazobenzene type are most of the activating agent administered - prone to cause the development of liver cancers in rats if these animals receive While right from the start the diet deficient in riboflavin a genic as well as photochemical effects Such carcino- duced are indelible and permanent and it gens appear to be conditional carcinogens result in additive and cumulative whic whic Safe which need the complementary action of in the exposed medium be another factor for realizing their carcino upon repeated expo sures they are initially not demonstrable in genic properties either medium unless additional - factors 42/264 Vol 71 Mar. 1961 aeaeel ee ta oa ecte TM te te a 1? 8 pe a OF PATHOLOGY S wees LMen be $ CARCINOGENS IN HUMAN ENVIRONMENT . q we able information on is very scanty 1 and he actual role which " play such 4 types ' moreover obvious P come into play i.e. factors which are either generated in the host organism or applied as developers and fixatives to the photographic film Under the influence of such factors there occurs a gradual development exposed to the carcinogenic action of coal tar as well as in the mucosa of the urinary bladder in dye workers having occupational contact with carcinogenic aromatic amines Such phenomena are known as false posi carcinogens of demonstrable and visible alterations which need neither tives in industrial medicine In fact this plementary which factors represent the cancerous growth or course of events is the rule for the histo- cancers It is felt 4 the 4 photographic image respectively The logically cancerous lesions of the skin in it the present time length of time required for visualizing the monkeys appearing after repeated paintings 4 product of the interaction between complementary or 3 with coal tar because these reactions tend 34 s do not lend them- the activating carcinogenic or actinic agent to regress and heal despite continu^'dappli- = it of a useful and and the medium i.e. the host organism and cations of the cancerous material carci- ification of carci- ry the photographic emulsion depends upon the intensity of exposure as well as on the The permanence or irreversibility of a ok cancerous response thus depends upon the of + relative reactivity of the exposed medium action of some biologic fixating mecha- Carcinogens.- of chemicals ie the relative degree of constitutional or nism probably provided by the host upon 1 one fundamental acquired sensitivity and susceptibility of theism theism theism organ- Ifects While cells person and the degree of sensitivity of 4. Safe Dose is technically possible the emulsion respectively The develop- to determine a minimal effective dose of mental period in the cancerization process a defined is known as latent period . carcinogen under specific experimental conditions applied to experi- It may vary depending upon the specific . mental animals of an established strain exposure conditions prevailing and the re- activity of the host organism between 6 months and 50 years according to experis ences made in man with occupational car- osed cells more cinogens If the action of a carcinogen is osures *s For mak- weak and the resistance of the host organ- of chemicals on ism is high the development of the cancer- ciess xl one may com- ous response in the tissues may be so slow . that it never reaches a manifest dur- ens on cells with 5 stage pon the aS ing the lifetime of such a person but re- einmsutlasncieosn 1 both , 4 mains in some intermediary precancerous stage Under corresponding circumstances 94 the photographic image may not be visual- ized at all by the application of developing chemicals or only a faint and indistinct , image appears on the film For making a photographic image on a film permanent fixatives have to be em- { ployed because without their action even belonging to a certain species Such information has obviously more scientific than practical value in assessing even crudely the relative degree of cancer hazard to human beings from contact with such agents because of the known specificity in the qualitative and quantitative reactivity of different species to environmental cheinical and physical carcinogens The limited value which this type of information pos- sesses under the prevailing circumstances is even more restricted by the fact that in the great majority of experiments the num- ber of animals used is insufficient for ad- judging the presence of weak carcinogenic effects among members of the species used For obtaining any information possibly applicable and valuable to the human prob- lem many hundreds of animals would have <7 4 art the carcino- oF cal effects pro- + a developed image will ultimately fade and disappear Somewhat similar phenom- ena have been observed in human and ex- perimental cancerous reactions Lesions lative changes 389 which were clinically and histologically repeated expo- -/3 cancers have regressed spontaneously i.c. Jemonstrable in itional factors at: seep biologically cancers they were not Erevrsible Erreversible cancerous reactions found for instance in the skin Such have been of workers . 71 Mar. 1961 to be employed in such tests as apparent from the following considerations Observations made in occupational carcinogenesis in man and in experimental car- cinogenesis in animals have demonstrated that the degree of carcinogenic response ie the incidence rate of cancers among the population at risk decreases with the inten- sity and duration of exposure Carcinogens Es - . 43/265 ety AEten tte, ag aw wiePeeE Prey Th oS eS =};ask ra rk S28 bevet onan eS 35 ener scene Liespentear, oe a he3. ne Aes. ie to PY 4 . Le Ranial Pe aeie : ad =1 : sro bp AO # a TactFoon Gese abet e eadhlab ere PeS Wiens id Pr Su eL ed ae a 3)ea as At D feet } ,, a aof a eben are n os Tey, AR any an ry FS3 Fi aon Bit Ee ang hiAN where bent ie eh. + as ii 4 ona base EPSye x oor 2th $y ate vie i PRLAKS pew TORT Lovet 3-9.) ale PORTE feant ot o- rt: : Seas er AA. PF Sg To tied ite Soi Ge 7 ane etyBAe e5 PAI! STE ay By Wee ee be vee oe pee VRE Be ag bt, ser aha} sch ie Pee =t Sale i eaeoe AOS PATHOLOG PLE eal CARY eranGE oles ee aris cher Re Sire Ts a thus behave in regard to dose response like chemicals when tested for toxic and pharmacologic properties It may be mentioned ARCHIVES OF aL CAR the most potent human carcinogens have to be includedin the class of icals naphthylamine 3 4 wou = limit obser te a= D benzpyre SNe in this connection that the toxic and phar- which can safely be incorp expo = ORI arsenicals 2g a macologic responses of animals to chemicals ratedin foodstuffs Any chemical which sour + S E Sar 2SEn specific capable Kenvir Sad, Cees NtsCabo have SITAe ma ir a5" toxicologic . , goods chem rad are quantitatively as well as qualitatively as of producing cancers of any ty as those obtained with car- in any tissue or organ of any species whe Kasy _ cinogens The results of such tests have introduced by any route and in any degr , nevertheless generally been accepted and should be considered as a potential dos hum Freitt 7 ~ years 5 8! profitably been used for many | carcinogen until its innocuousness forma d : : eeitein science and industry despite their limi- has definitely been established Screening properties a tations concerning their direct applicability tests for carcinogenic of publ af ns man The available pharmacologic and cals entering consumer | are > BECO: chemica : methods make it relatively easy|ticularly indicated for those chemica the : : 249 to determinein animals minimal effective displaying some chemical and physical - toxic and pharmacologic doses which per- larities with known carcinogens Table cem mit the setting of rather reliable safety } standards for man The test methods avail- or producingin man or animals biologi effects often found with : inati s pracctiaccroacnliclvanyerocygivsenaonpgsleoutaagebnenldnecy sifduforiotr Oey te Torcmhetrste States cvaanlcuearble . year r1a,0t00 rCeEd ~ able for such a purpose in experimental suggesting therefore a possible 1 chemical carcinogenesis on the other handaction Table ) Hueper . S3:oh : are at present inadequate for this purpose The following calculation ffror a gen In an assessment of the potency of a eral impression concerning the - fey. carcinogen proper consideration must be given to the fact that marked variations range which must be exploredin screening operations for giving exist in the relative carcinogenic potency of information aan ene: chemical and physical carcinogens for dif- We havein the United a ferent species as well as for the same tissue or tissues in different species The target morbidity rate of about 5. living cance cases of all types and among 1,00 Scine organ or organs of different species for the carcinogenic action of an environmental persons per This same attack would be present in series of (can LENA excpaerrciimneongtaeln TEED The NRG IRAT potenacseeuc to entire star EST agent also may vary Under no circumstances should a carcinogen be considered safe for human consumption because it does not elicit any cancers when given by mouth to mice or rats while it produces cancers when introduced by some other route sub- animals exposed to one single zenongog if only one cancer would appear duriniggnGtned ars given year among 200 animals tested age carcinogen thus would display a equivalent to that exerted by the group of exogenous and : Re endogenous card ival cutaneous etc. some of cutaneouCshemical since establishpmoepnutlatisoanfsealfeyly TABLE and Physical Similarities ivtahle with Known Carcinogenic Chemicals Simlarites ~ eae Chemical 1 composition structure spatial SR configuration electronic density _a X _., leukem 2 Polymerizing and linking tendencies 3 Protein complex formation . / 4 Sulfhydryl binding or inactivation 3 Enzyme action inhibition or activation fermentative me- tabolism stimulation coenzyme I and catalase depres- ston etc. nogens active in the general is apparent that the of : sae et oes Carcinogenically TABLE Biologic Stigmata for Carcinogenically Suspect Chemicals - +: > REae : avav : Avh > 1 papiclellloumlaars hyperpllaesiuaskem pees for 2 pociasrocnisnostie 3 Anatomical reactions atypical oan 2 hyperplasias er j^"c j^"c perkeratoses carcinomatold sarcomatoid and pe renctions muenant polyps pre- liferations adenomas adenomatoid * +4 adenomatoid ieee Radiomimetic and mutagenic effects mitotic Hepatotoxic myelotoxic carcinolytic and _ Bess ee carcinost ^' A 3 = ma : effects L Ls 6 Potential carcinogenic metabolite formation particularly 4 Estrogenic effects h compounds having a hydroxyl and an amino group ortho each other in an aromatic system of 2 or more rings 7 Refractivity fluorescence Infrared and ultraviolet absorption spectrum 5 Sensitization phenomena chemoallergies " tion : 6 Congenital abnormalities in offspring after IntRraondeuyc Into pregnant maternal organisma a or 1 ae gree SPSS ma - 9 othe; = 44/266 pm pee e . : wea hal PATHOLOG t ee mf CARCINOGENS IN HUMAN ENVIRONMENT nogens would limits observations on observations the basis of such improper experimental observations would be improper because a the human population often becomes TABLE Tumor Yield from Graduated Doses of Benzpyrene Subcutaneously Injected into 57 Black Mice as Single Dose and as 12 Monthly Refracted Doses* Sources b it has contact with numerous environmental carcinogens which may exert a synergistic action and c it sustains a Sj any dose degree in 2 in , dose . of contact with these agents which tential humant neither can quantitatively or qualitatively ness man be determined nor can be controlled effec- d | Screening 334 Stively as long as it is present The recently published rather unrealistic and arbitrary + recommendations made on this subject by the Food Protection Committee Publication physical simi cember is Table 434 _ mals - og biologic 1959 are in need of critical exam- ination and modification before they are biologic cinogens biolgic a=nd suitable for practical adoption because they and do : iy not provide sufficient protection to the carcinogenic Ley ai S34, consuming public against cancer hazards . from food additives and contaminants S2ince a called safe dose of a carci- screening in screening ally valuable + ione eer 1- a ites cancer oad living cancer the existing methods wisdom and reason decrees that under such circumstances only 2 is a zero dose is a safe dose for all known suspected and potential human car- cinogens wherever such a level of exposure ' can rate be attained It obvious that the existence existence of a number of natural carci- nogens ultraviolet radiation in sunlight arsenical impurities in many environmental agents ionizing radiations etc. prevents such a goal from being attained in all in- A this is . the entire y geno , cu arsci- stances However this fact is scarcely a valid excuse for minimizing the additional opulation It ent of safety et fassad : arcinogenically cancer hazards which may be imposed upon the general population if such unavoidable exposures to carcinogens are reinforced by arcinogenically avoidable exposures to the same agents hyperplasins bydt: d and leukemoidleukemoid ulenomatoid pro- when incorporated indiscriminately and injudiciously into consumer goods arsenical pesticide and feed additive residues in > foodstuffs estrogen in meat radioactive materials in foods drinking water etc. medicinal preparations and environmental pollutants Such additional but avoidable exposures introduction after introductionintroduction may indeed increase the carcinogenic load ae PP>2 * especially in sensitized or hypersensitive metabolical y TI Shabeq metabolically abnormal persons to a level 71 -1961 16k 3; 71 Mar. -1961 oan RE 2534 ye -- --,-- i. No. of Tumors Within 18 Months Dose MB No. Mine After Single Dose 0.025 22222 6 0.03 22222 7 0.10 22222 10 0.25 22222 20 0.50 22222 22 17 Total number of tumors 65 After Refracted Dose 2 6 17 43 51 119 W. C. Hueper and Wm W. Payno at which the development of a cancer may ensue Practical industrial experiences with a certain highly potent occupational carci- nogen namely naphthylamine recently demonstrated as an impurity in 2 former food dyes and still permitted as cosmetic dyes yellow OB and yellow AB indicate that exposures- to a few micrograms per day are sufficient to create a definite bladder cancer hazard in man Daily contact with minute doses of certain carcinogens sustained over a long period of time thus may be sufficient for producing cancers in those persons of the total population at risk who are for constitutional or other reasons most susceptible Experimental information recently ob- tained on this aspect strengthens this view The total cancer yield of graduated doses of 3 benzpyrene administered subcuta- neously to series of mice either as a single dose or in 12 monthly refracted doses was studied It was found that the total cancer yield was much higher when certain amounts of benzpyrene were administered in 12 equal fractions than when the total amount was given by a single injection Table 6 Since almost all exposures of man to environmental carcinogens are of long duration and of the repeated type the cited experimental observations are of distinct significance in adjudging the seriousness of environmental cancer haz- ards even in the presence of contact with apparently small or minute amounts of carcinogens To Be Concluded - 45/267 . we . Tae132 Seehe 4 wy ea a% Pe3353 ThW439i, Respaet 29,a A en me paren enapvs v Seo ERes - wutoe pe : ah 2 atVio ie, a yh TR2 Ienee Re a atid! TES, hee a e t re an ee i JAN 1963 es? | CORRESPONDENCECORRESPONDENCE OO BRITISH 123 Congenital Defects and Thalidomide _ Due to read interested condition basal asbestosis stress its association not ~~ L^'cutier's _ only with malignant mesothelioma of t=he plepurlaebuur r a Sta Sta We We were to M. A. also of the peritoneum points rd : interested 1447 L^'cutier's Briefly the points following were 4 case report ecember 1 p 1447 of a baby with following Briefly the following made were ; : asbestosis multiple congenital deformities which were attributed to condition thalidomide Similar features were observed at a necropsy recently performed on a baby born in this asbestos hospital In this case however the date of prescription sharp asbestos of thalidomide has been checked from the original bodies produces pulmonary This prescription oe. - ete ee te prescription clinically usually overlooked prescription woman 29 was normally aged Case History delivered normally 1 There is a where the lesion is more bases presumably due to limited or basal asbestosis or less confined to the lung the downward movement of the - fibres before they become no signs or symptoms -. is not evident and is at It will be missed even microscopically . necropsy unlesz be of a 5 lb. 29 kg female infant at 41 weeks gestation She has one other live normal child aged 8. The mother was prescribed " triptizol amitriptyline 25 mg tds on September 14 1961 for depression and thalidomide ) " distaval was added on October 10 1961 25 mg daily One were prescribed She returned to her hundred tablets longer practitioner on January 11 1962 and reported that general sections are examined from the lung bases rE 2 While this basal asbestosis is unlike classical .. asbestosis in most particulars it appears to attain locally a carcinogenic concentration and as this lesion does not shorten the patient's life the carcinogenic action of asbestos can presumably act for period Indeed ~ this basal asbestosis may be found later to produce more was normatl hroughout November 26 1961 was Pregnancy Pregnancy was normal baby noted to malignant tumours than classical asbestosis = teaching upper limb deformities and an abnormaabnlormal have gross upper 3 In three years iin n the necropsy service ofmesothelioma a teaching <. - fattened face On the tenth day of life a systolic murmur hospital hospital six six cases of malignant mesothelioma were was heard for the first time Her general condition was encountered three pleural and three peritoneal and in otherwise good and she was discharged She returned to was demonstrated . The basal asbestosis the routine follow clinic aged 6 weeks in cardiac failure for Sick Children five of these the lung bases are only a few millimetres distant from the -~ of .. admitted and was to the Royal Hospital died on November 19 - peritoneum over the diaphragm and the occurrence whN ere e scheropsy was gross shortening of both forearms peritoneal mesothelioma in basal asbestosis is not not 7 - with absence of ulnar bones and flexural deformities of both wrists There were only four fusiform digits on both hands been amputated and a vestigial thumb had from the left heart was hand on September 19. The enlarged and showed truncus arteriosus and a high interventricular septal defect The lungs showed terminal congestion but were otherwise Tnhoermlaelft wawsas deficiency absence right diaphragm Thtiemes kidney absent and the kidneyone times There was normal gut The left kidney a apart from of left the absence of the kidney appendix times the right side - All other organs examined but found normal Lt other See ol : became pregnant unexpected the centres in 4 1961 in four nine examples of basal _. in in United found United States found ~.. asbestosis out of 15 cases of /~ pleural and peritoneal mesotheliomas in which adequate ~ lung was available for study In all but two of them the basal asbestosis had been overlooked -- ...-.- ocupational asbestos mentioned occupational significance unless 5 In of no patients very few of these cases exposure to asbestos direct or their relatives What was an industrial or + . , this is but this is _ are questions put to is more important is -* has that the world's annual consumption of asbestos in in this 2,400,000 tons It appears that this woman became pregnant whilst increased increased from 500,000 ' take pregnant in 1942 used tons wide such taking thalidomide and continued to for four to is and manufactured products that theoreticaly theoretical y that at 1961 five weeks after conception In a recent article in this - manufactured day that : . variety the number people products theoreticaly exposed 944 Drs journal October 13 C. Lutwak and the number number ofof asbestos people few ofmay thus rats suggest M. F. Hay working on that thalidomide is of to : work asbestos factories which designated designated exposed affects the preimplantation embryo in addition to the areare factories factories which designated asbestos factories toxic effect on limb buds The generalized abnormali- a article : factories ties in this baby are in keeping with this suggestion and . In 1963 will appear an articlein which I this case emphasizes the potential dangers of January to modern urban hazard . as prescribing any drugs to females of bearing age draw attention asbestos a and while . Asbestos is virtually indestructible strontium- whether pregnant not " has a of Ergate Bt te has life 28 years asbestos has a life permission to Farquhar grateful am to Dr. J. W. for | an infinity of years The article demonstrates on- reportgrateful report Tone ? ~ : evidence from necropsies that a large and increasing , - aElsm ie laegltics. Memorial . ANNE STEWART . percentage of the population are inhaling asbestos fibres Hospital Maternity Hospital As these tend to gravitate to the hung bases there will - ___ ~+5- _~ be a cumulative effect and one wonders if in 20 years ~ i Diffuse Pleural lung Exposure Exposure and Diffuse Exposure to Asbestos Dust and _ time asbestos mesotheliorna may not be common as cancer of the is day am etc. _ ~ Mesotheliomas ee ~ .P. J. G. THOMSON Department of Pathology _ STR The letters of Dr. W. J. Smithers and his University of Capetown Medical School - Observatory South Africa ee November 3 p 1194 and of Dr. W. E. _ mS colleagues REFERENCES McCaughey and his colleagues November 24 p 1397 . G. S. Afr med I. 1962 759 draw attention to the association between malignant | Thomson - Kaschula O. C. and MacDonald R. . - ibiidn mesothelioma of the pleura and exposure to asbestos press - it mentioned dust dust In the first letter it is mentioned that the degree of pulmonary pulmonary asbestosis in these cases of pleural meso- pulmonary A. theloma may be variable and in the second that the duration duration of the exposure to asbestos dust may be + intermittent It would appear that they have not noticed a recent article in which I describe a new pulmonary Risks of Primary Vaccination an - Professor G. W. Dick November 17 p 1275 . reprints a table I on Mortality per Million Primary *** Vaccinations which seems to me to mislead There is no mention of the number at risk in each separate age laeMindpagguapaveane huts Fee tsi ne anmer deaenb a ee beh comeuprnaocueeneoatbdhabighd > asithdeac B