Carcinogens in the W. C. HtTEKX. bcthesda, md. Human Environment* CH. Sources of Potential Environmental Cancer Hazards to tile General Population Many of the cancer hazards affecting the general population may have their origin in me or several industrially produced conumer goods or environmental industrial mllutanta The irregular and variable epiienriologic scatter pattern of cancers of 'afferent types among members of different opulation groups and in various geograph: regions is at least in part a reflection of te influence of significant local fluctuations a the qualitative and quantitative composion of the environmental carcinogenic specinn upon the cancer panorama. Among ie consumer goods which may be involved 1 this respect, the following groups detrve critical analysis for the presence of irrinogenic agents (Table 7), * This article is continued from page 269 of the CJ ^ . Lw>j CO . , . •t * • to*5 The abundant opportunities for intense and prolonged contact of the general popu­ lation in many parts of the world with actually or potentially carcinogenic agents of diverse nature are not restricted to the. increasingly widespread use of consumer goods but, recently, assume considerable proportions through the introduction of re­ lated occupational cancer hazards into the home through various hobbies, particularly those connected with the do-it-yourself movement (Hnepert,. The adherence to suitable and ade* precautionary meas­ ures which migfit provide protection against hazardous liquids, as well as gases, vapors, fogs, mists, sprays, fumes, and dusts gen­ erated during such activities is often totally.lacking, especially if contact with such agents does not elicit immediate and serious THIS DOCUMENT PPG INDUSTRIES, INC. DID NOT COTH.FROM IT'S FILES. AND CANiOT BE AUTHENTICATED BY PPG INDUSTRIES, INC. “Ker h“rd’ “ NOTft^S W5fU¥ENI.ffl(! NOT GCsv-t i-«yiyi r ^ HUS ARCHIVES OF PATHOLOGY Taiu 7.—Environmental Polhttantt and Ctmsnmer . gpqygit or reduce the inhalation of the ac* Goode ae Potential Sourcee of Environmental ^ tive ingredients of these preparations as Cancer Haearde -T ■ • . I ( k - «±- ? O O g ur Oif < “ o o-ii i~ ’2 Ul O 'jJ £E O X ■- £ g^' o _ ui ■ivpfei -ur— ij— .t----- r^si . t* :^'r 2 o co o o.- 2 s E z a 3& « e oy o °5e a. 0. Sow r -., Sly Lto ‘ .... ’ •■■■-'■. eini's? l Dtmary acnataaocfcaa: (a) toad kUIIUtm and iwntamlnama tnrtndlac tbri.iktrtkfly poilntad dilnldsf war. parricmp matoriafc, and rliiailrali ®) naturally pmwu tagradlaati lad pollutant* (alka­ loid*, aiaanimla, aalanlnm, cadwcttra mbamnnaa) (t) rbmlreU (nomad rtnrtnt mrtain praeaailm pro. eaduraa (baat, radiation) of toodatufla tad dnilaf tba pnparmtton of food* trooj natural and arttfl. dal maradiaoo.iV toodmnffi frnarflnr tmtktag, prokorvrad aod rapantad hmflnfc frUlina orar to opmi Ora, Mo.) (f) diaoir daflctwwiaa aod tmbalaooaa Intartorinc tad orcanfe Inaction and tba aparatlnu of BittboUs BWbll&ilBV (VltlBlO B ooraplar dadoMociaa, lion daOctanry, protala dafidaocr, India* dabdaney, ate.) H. Honmhnlil (ood*. mob aa mnltary pxKU, «»■ lha roualtr drool.'boma-madia* noaorni* polouoi,. poadddaa, rtontnt aaanta, poUabm, aatiroattof *(ani*, paint* and paint rataorata. datarpoita, aolaantt, dry ctautn* amot*, dyaa, harttetdm. oomraotpu-aa, aoinatlni. ato. HL Dnmoanc and taooral air pdlntnnu. mcb aa kranatlo »od alipharta bydrooartMm tonnad tnm tba ineomplau eombnmton of ewbooacooua fuola, ftoollna, dloaal dl and oonl (antonwbUa whanat, dam from twrad aod aa* pbaltad raaili, aoot), ebnimata aaroaols tnm tie oondluonlas aqulpoMnt and **—— baatinf plant*, pamidda •praya (miao aod topi) laoaratad (him doomtie uaa of bomba or daUawad tram airplaoo*. radloactira sub. mam of loaal or (moral auaoapbarte poOution. todoMrtal mid dotnaatlo oflloanti. Watar pdlutonta from ibdMmda* Mlaat, ioot.'aotomobOa arhanat, tndaatnat atBomta, ranofl ad«nu a< tau Md ttpoUs and mMMr («) dumrin *t p«wid«* toniMd dnrlnc tatmidaliaa (») «m«a <«) >T<>I«W dUBUOn X Naomi and frnlbaUs martin***, Uikkam*. aod ttiaX SjaUmla rmuncra X ITWlvtfc flarartn* ***nt* X SortMtanii (detwfant*. Immlnf t**n(i) 7. HuSKtant* LPtwoi lUraa and elwnal wartifaim «*«nt» X Watar omdlUouan (ludUa, Aoocldm) IX lLSattmteltBM* iXStatatM IX M. IX Food madlflan and Umnomi (oat Uod«U«r», ate.) M. OH and la* mlttKau* and fl*u* and paUabaa <* cudy darlTad ftm panataiim IT. OopW aatoma and aa »»Wdaa at am* addltlTaa IX HtItmhh* «H» and Ma (ooocalnlno aaamtad. tottMd a( Urn bM&tMkr iapoataat rniaatmaaad. latty add* aad. pmrtbtr atatal aa a eonumiaant). IX JBL tBsiMfln ib4 joMiflss tt. Odiiw a—ta B.F«4 XFauetdaH (a) » npUmdcMt* «r> C/3 «> (0) (WaUaau X xutlapowinnc aad rattr—firrmoa s< ad traits aad XlnsaetrapaHanta 4, HttBMii X asubaotlca (M ta food Umaia aad addad ta (oodsatls) XAsuoymua 7. Emma* X FaaaOawa (ifilnaaf) - X Pan gaawa (sdnval o4h) IX Wstar r-'i"**"*- anal In and silx paBcbam tan. IX CbmrtaU MrtlMn* Madia IX Wiauptnc and mtUf natartaN (pmffla. IXIaat adlmot ta taaatad products IX Homtaold datmaotf and ttrtr baoadartandm) CM> IX t'm InHtlnt radiation CnltianotaO IXIstitec ndMtm (ndtnaattanl to than la tha tarn at rad Inantra taftanx IX Watar aanpantlan tatardasu carbons, which are extensively used as sol­ vents. paint removers, degreasing agents, aning fluids, anesthetics, and more t 4f recently particularly as pesticides and herbi rides and found for this reason as residues L in many foodstuffs. The existence of such £ relationships between exposures to carri- v nogens displaying additive effects must properly be appreciated whenever it should become necessary to establish a maximal permissible dose of a particular agent in specified types of products, if the same or similarly acting agents are present in many other products lo which persons become exposed for occupational or other environ­ mental reasons. 1. Food Additives and Contaminants.— The potential magnitude of the needed environmental carcinogenic sanitation pro­ gram can be envisioned by establishing the scope of one segment of this problem re­ lated to food additives and contaminants only. The following groups of chemicals deserve consideration in such an under­ taking (Table 8). The extent to which foodstyffs contain additives and contaminants is evident from the facts that there is a list compiled by American (Food and Drug Administration; Food Protection Committee) and English investigators of some 800-1,000 food addi­ tives and that many foods daily consumed by the general public are contaminated with feed additives (estrogens, arsenical*) and • pesticide residues of some type, such as arsenical* or chlorinated hydrocarbons (DDT, etc). Only very fragmentary in­ formation is available as to the potential carcinogenic properties of a considerable number of these agents (Hueper). The following tables and discussions briefly summarize the evidence available on established and potential human carcino­ gens' used as food additives or present in foodstuffs as contaminants or generated in them by processing procedures in the United States (U.S.) and/or other countries (O.C) I. Intentional Food Additives: A. Food and cosmetic dyes. There exists some hu T”g g man, and a great deal of experimental evidence concerning the carcinogenicity of" an appreciable number of synthetic dyes^ (Hecht; Symposium) (Table 9) former'v THIS DOCUMENT VVAo notla record of PPG INDUSTRIES, INC, DID NOT COME FROM IT'S FILES AND CANNOT EE AUTHENTICAtED r.rjas.iai^i *mTF NOTt. > ■ \.,i:;. „,:., . ; JVJQT Q j;.';C \ : ■ 33 ARCHIVES OF PATHOLOGY ■“■ ‘ Tails 9.—Recognised or Suspected Carcinogenic Food Dyes Oryao Dre o <0.0 Ooaopot. Cat* Onl 1 <0.0 Taatalda.MiL ARCHIVES OP PATHOLOGY /. HOT COME i-n^!, Apart from the fact that almost ail of the - • :' f -«ct> -^'~ -v ’ fr^K w ‘ 3 : *. - . ---------- “ j^v---^,;::<--'4 i 'J?V; &?'■- ;'**»*«$§! -."^T ■ .v - V*', '«s*S3 * . f '- * B. Emulsifying agents and shortenings. 4!” v food, drug, and cosmetic dyes used in this An emulsifying agent prepared from a vege­ .'..\ and other countries have not adequately and table oil by the application of heat and ;. *. competently been studied for possible car- oxygen, containing highly oxidized and 5,;l.. dnogenic properties in experimental animals, highly polymerized aliphatic compounds, v>''. ■■J. no pertinent reliable and valid information and used for the processing of vegetable has ever been published concerning such pos- and animal fats,, was recently shown to , sibilities by surveying occupational groups produce sarcomas in rats at die site of ;l\ and- other’ specially exposed population subcutaneous introduction (Symposium). . . groups’ (gasoline handlers, dye manu- Distinct caution, therefore, is indicated in ■>•■ * facturers, textile and paper dyers, colored- the future concerning the incorporation of . smoke producers) for carcinogenic effects highly oxidized and polymerized oils, such " > . from these agents when present in a con- as those probably formed in deep-fat frying : ■ ■ * siderably more impure state than that re- processes, into products of human con­ ^ \ quired for food dyes. Such investigations, sumption or in consumer goods providing ~ however, are urgently needed because claims prolonged, and frequent cutaneous and re­ ” .'“"’have b«iradvanced, 1>ased on tlpidemiolbg-' spiratory ' exposures; Mention m*y- be- made i_ v.iodly deficient evidence, that the use of in this connection of observation* recently , ^butter yellow in Austria and in some oriental reported by Jardetzky et aL, who obtained ' countries. for coloring foodstuffs was re- hepatomas in 40% of mice fed a commonly ; ‘ . sponsible for an increased or excessive used shortening and in 63% f mice given death rate from primary liver cancer among orally a specific solvent fraction of this the populations consuming such foods foodstuff. / In recent experiments with several emulsi­ • (Zeitlhofer; Sta..Crag; Peller). Some of T the dyes listed as well as a few others fiers Fitzhugh, Bourke, Nelson, and Frawley I ■ (toluidine blue, pontamine sky blue, pyrid- noted that one of them, namely polyoxy­ i *■;. ium, Evans blue, trypan blue, fluorescein, ethylene (8) stearate, proposed for nse in > methylene blue, 10-tolidine)’ are.employed bread and rolls, produced when fed at a ' for medical purposes (Holoubek, Hendrick 25% level in the diet not only bladder and Hollis; Bickers; Weinberg et aL), or as stones in 25 out of 150 rats but in 13 of V’ insecticides (Phenothiazine, azobenzene) them also bladder tumors (9 paptQomaa ;< (DeEds, Wilson and Thomas) giving rise and 4 carcinomas). Despite this evidence -V’ - to allergic and photosensitizing reactions the Food Protection Committee of the Food . and/or cancerous reactions (Marshall; Gill- and Nutrition Board declared this food man; Simpson; Brown and Thorson; Brown additive as safe for human, consumption ° § (Publication 646) by arguing that the . and Noriind; Allen et aL; Spitz et al.). . The evidence on hand indicates that (1) tumors were not caused directly by the 8 £ ?■> several food and cosmetic dyes are probably chemical, but by a chronic irritative effect y o S'; ■ human carcinogens; (2) that others are exerted by the. stones, which were found’ in ctr o 3-sf"" potential carcinogens; (3) that many addi­ all animals with tumors. Although poly­ tional ones have not adequately been in­ oxyethylene (8) stearate is converted by this i~ g < O „ tiJ . vestigated, (4) that contact of members of allegation from a direct carcinogen into an 2 9 CO o Q ^ 2■ the general population and of special worker indirect carcinogen, the fact remains, even % . O " § y ^ COgroups with some of these and many related if this scientifically unsound argument is dyes exists for other reasons, and (5) that adopted, that the oral consumption of this f— * < a; £ ifl o £ all dyes which may give rise to the forma­ chemical is follcnfed’ by a carcinogenic re­ (r. uj tion of orthohydroxyamines should be sus- sponse in the bladder o$ some of the rats -» IQ - pected of possessing carcinogenic properties and thus must be considered as potentially r? 00 **■ 2 (Oayson; Walpole, Williams and Roberts; dangerous and objectionable to man. The O rj uj scientific validity of the argument that Badger). gpc*°Jy>L7J.-A*r-J961 20/360 f alt & ■pBB 002044*_i ' g E 8J ^£SZm££%£% . spaas*..gps^ Cf ■ ■ ---- CARCINOGENS IN HUMAN ENVIRONMENT chronic irritation of the bladder mucosa by various cydamate compounds (calcium and the stones was the direct cause of cancerous solium cyclo-hexysulfamate) gave negative reactions must, moreover, seriously be results. doubted, since neither observations on rats E. Flavoring agents. No comprehensive and mice nor on man support the view that information is available concerning potential bladder stones are involved in the causation carcinogenic properties of the approximately of bladder cancer as a primary causal factor 300 flavoring agents employed. Lemon oil, (Zeppa and Womack; Willis; Gruber; however, has recently been reported to be a Fodilchak; Angrist; Capurro and Mourn gis; cocarcinogen (Roe). While as a rule, such Dalton, Morris, and Dubnik). It may be chemicals are present in foodstuffs in very pointed out, moreover, in this connection, small amounts, this condition does not ex­ that the Food and Drug Administration has clude the possibility of cancer hazards from prohibited at a former occasion the further such sources, since experimental investiga­ use of diethylene glycol as a humectant in tions as well as experiences made with a tobacco because this chemical when fed to few occupational carcinogens have estab­ rats produced benign and malignant tumors lished the fact that prolonged exposures to of the bladder in addition to bladder stones. minute amounts of potent carcinogens may C Synthetic mucilages, thickeners, and result after a long latent period in the stabilizers. The recent demonstration of development of cancers in exposed experivarious cancerous responses in rats by the mental animals and workers. The advisa- ~ parenteral introduction of water-soluble, bility of such investigations is indicated ■ . ■ ■>*"• polymerized compounds, such as because of the demonstration of liver tumors high*" yl pyrrolidoae, carboxymethylcellu- in rats fed red pepper (Capsicum) (Hochand dextran (Hueper, Lusky, and Ligeti) and Senecio alkaloids which are Nelson)*, should provide an indication for used by South-Africans as home remedies an extensive and competent investigation (Schoental; Cook, Duffy, and Schoental) into potential similar responses elicited by and which have given rise to chronic poisons some of the chemically similar synthetic ings among the population of South Africa polyglucoses (methyl cellulose), polyvinyl due to the consumption of bread contami-"-””.-. compounds (polyvinyl alcohol), and poly­ nated with seeds of Senecio plants. Such -”1~ silicones employed-as. substitutes for gelatine - .cases. of—‘‘bread .poisoning'.-- exhibited* -at—— and cream in some foods and food prepara­ necropsy* degenerations and cirrhosis of ther-*lri“; tions in this and other countries (Hueper). liver with ascites (Steyn). Similarly, ergot Since such products have no nutrient value, alkaloids which are contaminants of rye __ .-’-I it would be wise to eliminate them for the flour, and which are used medicinally, have *time being from the list of permitted food not only caused poisonings in persons and additives (Eichholtz), if they should be groups of people resulting in vascular and v ;ri found to have carcinogenic properties upon gangrenous lesions of extremities, but when : parenteral introduction into experimental ' fed to rats, caused the development of I.vv animal* neurofibromas of theear (Fitzhugh, Nelson, , . -C D. Synthetic sweeteners. The sweetening and Calvery). agent Duldn (^-phenetyhirea), which for' F. Surfactants. Surfactants are employed * many years was commercially available, was in foodstuffs as antifoaming agents, emulsi- ! recently found to elicit cirrhosis and tumors fiers, and dispersants or may be introduced *;. of the liver and bladder in rats given this unintentionally into them as residues of ■' cbemial by mouth (Fitzhugh and Nelson, detergents used for cleaning cooking utensils . Lettre; Griepentrog), necessitating its with- and dinnerware. In experiments on animals ' from the open market in the United it has been shown that some chemicals of Similar studies made on saccharin this type exert a cocaranogenic or weakly (k^-dihydro-S-oxobfpj^s^g^n^i^ and carcinogenic on the action ^of known *wr 2UU\. ~—S-AND cannot - .' NOT COME FRG.iVi i’PG FILES'"”""1 wrMmuer polycyclic aromatic hydrocarbons given by mice when implanted into the bladder lumen mouth and facilitate the penetration of these (Boyland and Watson) and has produced . agents through the mucosa of the alimentary uterine cancers when introduced into their u tract and the skin (Setala, Shubik; SafSoti vaginas. Hoch-Ligeti noted also that a and Shubik; Shubik and Sice; Della Porta, contraceptive containing this chemical when fed or intravaginally applied to rats kept bn et aL; Umeda; Setala et aL; Eckardt; Horton et aL). Special attention in this a protein-deficient diet produced cancers of respect should be given to the various different types in several organs including polyoxyethylene sorbitan fatty add com* the uterus and the brain. Its use in Ameri­ ' pounds (Tweens) used as dispersants and can dairy products was recently discontin­ emulsifiers (Lusky .and Nelson). A definite ued by voluntary action of the industry amount of caution, therefore, should be concerned. ' exercised in the choice of such agents for I. Petroleum Derivatives Used as Pol­ the purposes mentioned and in the amounts ishes, Glazes, Fat Substitutes, and Coating - which may be permitted in foodstuffs (can­ of Food Containers. Liquid paraffin (min­ dies; soft drinks, dill pickles, vitamin prep­ eral oil) and solid paraffin are employed as arations,^ ice.scream, cream whip,_cakes, polishes and glazes* of candy. Liquid paraf­ *4- V* *' *- “» * • ’ • Jv fin and petrolatum-like materiai have been" "bread,''rolls)'. ' ~ " I . _ G. Humectants. Humectants are incor- employed in the past at various times and .-■i * * U, / v-/ in different countries as substitutes for f, porated in marshmallows, pastilles, shredded coconut, confections, ice cream, chocolates, vegetable and animal fats and oils during and jelly-like candies, as well as cigarette periods when these nutrients were in short !&*»• tobacco. Diethylene glycol, a humectant supply, in reducing diets, and in pan meases. . formerly used in tobacco, when fed to rats They are ingested also as laxatives, ingested over many months, elicited the formation and inhaled when used as vehicles in nose - of stones, fibropapiUomas, and one carci­ drops and throat sprays, as well as when c noma of the bladder (Nelson, Fitzhugh, present as air pollutants for occupational ij reasons in exposure to sprayed or nebulized and Calvery). H. Preservatives. Thiourea, thioacetam- cooling and cutting oils. While the former practice of injecting - ide, acetamide, and various thiouradl deriva­ tives find extensive use for various purposes paraffin into breasts, noses, penis, etc, for (prevotives of orange decay, antithyroid cosmetic purposes has now been discon-, - . drugs, rubber accelerators, plastics). Thiou- tinued, such deposits have given rise not and thiouradl fed to rats caused the only to the production of paraffinomas, but q ,S Q development of thyroid adenomas (Biel- occasionally also to oncers, such as of the •XiKW Q § ^ schowsky; Purves and Griesbach), while the scrotum and breast (Hueper, Bauer, q $ oral administration of thiourea and thioacet- Schmahl and Reiter; Baader; Roe). Sim­ p ' -amide, like that of acetamide (Dessau and ilar carcinogenic effects on the lungs have U/ ry- - ‘ . Jackson), to this species was followed by been recorded in a few cases from the in­ the appearance of hepatomas (Fitzhugh and halation or ingestion of paraffin oil used Nelson; Dupta). The use of the last 2 in laxatives and throat and nasal sprays. mentioned chemicals in processing citrus ' (Wood; Sante). Foodstuffs such as milk, cream, cheese, fruits, therefore, has been prohibited in butter, margarine, and citrus fruit have, this country. r2*=■ -t-^% Another of the various preservatives of moreover, contact with paraffin and petro­ :c v. ’foodstuffs, 8-hydraxyqtiinoline, is present leum . waxes ■ (microcrystalline wax) used $ : for the* impregnation of food containers, also in contraceptives, ointments, hair lo­ tions, and rectal suppositories and used in wrapping paper, and coatings of cheeses, fruits, vegetables, as well as in cosmetics Germany as a tobacco fungicide: This chem­ q,Q uj ~ B er ical has shown carcinogenic properties for and medicines. Fat-containing foods may « « <» w K 293S CARCINOGENS IN HUMAN ENVIRONMENT either extract fat-soluble constituents pres­ ied might contain carcinogenic chemicals. ent in these paraffins and waxes, or may In subsequent analytical studies it was become contaminated with them through established spectrophotometrically that the scaling of wax -.from the walls of such "dirtiest" wax contained about 45/ig. of containers. In the home manufacture of 1,2,5,6-dibenzanthracene, a known carcino­ dtros fruit marmalade not only the dye genic hydrocarbon, in 100 grams of wax often used for coloring the rind of citrus (Falk, Kotin, and Miller; Lijinski and fruits but also the wax employed for delay­ Shubik). A possible cancer hazard to the ing evaporation of water may become in­ consumer of foodstuffs from waxed con­ corporated in the finished product. The tainers may result from the elution of the depilation of fowl is. commercially accom­ carcinogens into the contents as well as plished by dipping the birds into liquefied from the desquamation of the wax or its penetration into foodstuffs such as cheese paraffin. The urgent need for the establishment of or fruits. The apparent reality of this danger to adequate safety, standards on paraffins and waxes used by the food processing indus­ human health from such sources is indicated tries was recently demonstrated by the by recent observations of Falk, Miller, and chemical study of 24 different dairy waxes Kotin, who were able to elute 3,4-benzpy­ (Flemming). It was noted that some of these rene adsorbed to carbon particles (soot) by waxes were not white in color but distinctly plasma proteins and succeeded in subse­ greyish or yellowish, suggesting that they quent experiments to elute within 55 hours were not “fully refined" but contained still almost the entire amount of 3,4-benzpyrene oily residue These waxes represent and 1,2,5,6-dibenzanthracene added to dairy of paraffins with microcrystaUine wax and contained in- paraffin films by the es for increasing the tensile strength use of milk proteins. The crude oil fraction from which paraf­ of the /end-product and for preventing fin is obtained in the processing of crude cracking of paraffin coats of waxed food containers. It is likely that the contamina­ petroleum, shale oil, or lignite oil is a po­ tion of . the waxes with oily residues mainly tent carcinogen, being the cause of the comes from the ■ crystalline waxes. These well-known - scrotal and. skin- - cancers ..of. are branched and cyclic paraffins which do paraffin presses and mule spinners. The ..not release readily alkihe. originally, present mide rrilsr moreover. - contain potent aliAtlw carcinogenic materials by the applica­ ^I ■ m -- --- - * --------- - /tTjtatrw \ 'To oily phatic cocardnogens (Horton at et a>1 aL). It is' ' *S-V"v tion of the commercially used separation noteworthy, also, that some of die mineral methods. oils sold for human consumption and ob­ When these waxes were examined under tained from catalytically cracked stocks are ultraviolet light many showed a strong highly fluorescent because they contain aro­ bluish-white fluorescence indicating the matic polycyclic hydrocarbons. It is, more­ presence of aromatic ' hydrocarbons and over, known that technical difficulties are characteristic of but not specific for carci­ encountered in freeing completely micronogenic aromatic polycyclic hydrocarbons. crystalline waxes from residues of oils -When isooctane solutions of these waxes which are long^established human carcino­ were spectroscopically studied, 4 showed gens. A competent examination of paraffins strong absorption at the 290 m/i wavelength, and waxes used for medicinal and commerwhile for 11 waxes the absorption at this tial purposes, including food containers wavelength was of. moderate degree. It is and wrapping material, is indicated because significant that the absorption maxima of of recent observations on h turnongenic most carcinogenic polycyclic hydrocarbons action of presumably purified paraffin when *ween 288 and 298 m^_ These obser- implanted into the bladder of rodents (Bon- « # -* Hutftr s"S!e!,e4 C'”’7' PPG INDUSTRIES, INC. 010 'NOTXOME FROM IT S FILES, AND CANNOT BE AUTHENTICATED BY PPG INDUSTRIES,. INC. - ^ s* — t&Kl 'v-: indicated that liquid .paraffins contribute to agents has been obtained in experimental ■'i.r-. the carcinogenic process. A similar conclu- animals by exposing them to these chemicals ■ V sion was reached by Wolff on die basis of through nonphysiologic routes and in un­ usually high amounts, the observations >. - experimental evidence. ‘ Serious consideration should also be given made, nevertheless, are of significance in .V.' ■ to the possibility that carcinogenic hydro* terms of potential human health hazards. i; carbons may be generated in originally non* Serious consideration, moreover, should be carcinogenic .paraffins and waxes when given to the fact that the great majority of • ’ " these become exposed to high temperatures the additives either have not adequately been „ _such. as those. encountered during frying. investigated for carcinogenic qualities or w~-,-; A vivid illustration of the cancer hazards have not been studied at all in this respect. It is evident,, moreover, that some carci­ • ^ - which may arise from the consumption of ) .■* food contaminated with carcinogenic mate* nogenic food additives are present in other rial present in petroleum or coal tar deriva- consumer goods or are constituents f the tives was recently reported by Burrell. It human environment with which large parts was known for many years that members of the general population have frequent and of liquor-producing and liquor-consuming intimate contact (cosmetics, drugs, house­ * ■ trades have an excessive liability to eso* hold and sanitary goods, dothing, building -phageal cancer. Some investigators had as* materials, pesticides, environmental poisons, cribed this phenomenon to the practice of occupational agents, environmental pollut­ charring liquor barrels on the inside, there- ants). 2. Food Contaminants and Products of , by producing wood tar which may be eluted Food Processing Procedures.—To the po­ by the alcohol into the liquor and thereby tential cancer hazards which may be asso­ r_ -. create an exposure to carcinogenic aromatic q 3,. t . polycyclic hydrocarbons contained in the ciated with some intentional food additives £ menting the mash in drums previously used They form another part of th total carci­ Q z: for distributing petroleum asphalt with nogenic load placed upon the general popu­ £ . o ~ S Z. t/i which the drums were still lined, thereby lation from various sources (occupational > c 2 W permitting the alcohol to dissolve carcino­ activities, air and water pollution, habits, L_ - < [£ * 2* tO O gens from the residue of the asphalt in the customs, dimate, infections, endogenous 5 ~ Q ifj' factors). # drums. In recent experiments with 4 petro­ A- Pestiqide . Residues: (a) Arsenicalsleum asphalts used for paving roads and .Among Ad various' pesticides which may obtained from different oil fields in the o y _i a 5 c gremain attached as residues to foodstuffs, Americas, it was sh wn that they display weak carcinogenic properties when applied ^especially such as fresh fruits and vegeHOat (a $Z£> 24/304 Vot. 71, Apr, 1961 i. 2941•pJB______ -- . 0020W8_i 'rOGENS IN HUMAN ENVIRONMENT at,—. and the various processed foods (wine, juices, preserves, jellies, marma­ lades, dried fruits and vegetables, canned fruits and vegetables, frozen fruits and vegetables), the different arsenical and chlorinated hydrocarbon insecticides, rodenticides, fungicides, and herbicides deserve principal attention. Arsenials in foods have ben responsible for a considerable number of chronic arsenic poisonings among consumers of contaminated food­ stuffs—especially wine Recent reports from Germany indicate that vineyard work­ ers who drank wine contaminated with con­ siderable amounts of arsenical pesticides developed, more than 10 years after cessa­ tion of exposure to these agents, cancers of the skin, lung, and liver (Roth; Hess; Rockstroh; Butzengeiger). These observations on dietary arsenic cancer parallel those previously recorded from the Reichenstein region in Germany and from Cordoba Province^ Argentina (Arguello; Tello) where the consumption of drinking water with arseniols caused the deart of cancers of the skin. Such nelastic sequelae have repeatedly been observed after a medicinal consumption of arseuiols (Arhelger and Kremen; Som­ mers and McManus) as well as in workers occupationally exposed to arsenicals, partic­ ularly in the production and use of arsenical pesticides (Hill and Fining) and in the smelting of arsenical ores (Neubauer; Rogh; Liebegott; Goldblatt; Butzengeiger; Hueper). Vegetables and fruits previously sprayed or dusted with arsenical pesticides, therefore, should be thoroughly cleaned be-' fore they are eaten, and proper precautions should always be taken to prevent any undue contact with arsenicals when employing arsenical pesticides so as to keep the onavoidable exposure with arsenicals at a minimum. Air-borne arsenic in urban at­ mospheres and arsenical residues in tobacco smoke are among frequent contributors to human exposure (Satterlee; Goulden et aL; Daff and Kennaway; Holland et aL). (by Chlorinated hydrocarbons. Among the numerous newer pesticides, various ■ CD OJ *•- w * -r 14 chlorinated aliphatic and aromatic hydro­ carbons have come into extensive use (von Oettingen). Many of them have distinct j t hepatotoxic properties (Ortega et aL; Barnes). Prolonged feeding of rats with DDT and Aramite (^-prime-chlorethylr •, /?-para-frrt. -buty1-p h e n o xy-a-ethyl-mcthylsulfide) was followed by the developmert C“ of hepatomas. While DDT has a minimal C‘ tumorigenic effect when given to rats and C-:; dogs with the feed in doses highly exces­ sive to those encountered under ordinary exposure conditions (Fitzhugh and Nel­ son), Aramite causes benign and malignant . Li’ b~~ liver tumors in the majority of rats and ■'CD dogs fed this chemical in the feed at a con­ centration as low as 5,000 parts per million (Sternberg. Popper, Oser and Oser). These observations gain in significance since other hepatotoxic chlorinated hydrocarbons (chloroform, carbon tetrachloride) when administered to mice also elicit hepa­ tomas and thus may exert a synergistic action (Eschenbrenner and Miller; Rudali and Mariani; Edwards and Dalton). Men­ tion may also be made of' an observation of Gardner and Boddaert concerning the occurrence of hepatomas and testicular in­ terstitial-cell tumors in mice subcutaneously __ injected with an estrogenic chlorinated . o» ethylene compound (tri-^-anisyl-chloro- ^: J ethylene). 3 The widespread use of aliphatic and aro- _ ^ mafic chlorinated hydrocarbons in industry, agriculture and in the home (dry cleaning fluids, paint removers, solvents, degreasing agents, medicines, fire extinguishers, furai-. gants of grain, cable coating, (von Oettingcr; Hardin; Hughes), and their distribution as pesticides from airplanes, -'-7 create frequent contacts' from various -■ sources with, these hepatotoxic agents for members of the general, population, apart from those associated with the presence of pesticide residues m foodstuffs of vegetable and animal nature. Since DDT and other chlorinated pesticides (heptachlor epoxide) are excreted in the milk, even infants are bound to have some degree of exposure to these agents. They, moveover, exert a cu- THIS DOCUMENT WAS NOT A RECORD OF PPG INDUSTRIES, INC. DID NOT COME FROM 1T1’S FILES AND CANNOT BE AUTHENTICATED BY PPG INDUSTRIES, INC. ------------------------------ ic' -V , h •17' ■ " IP;' V . . ■ v-rJii 5 * .'<... * r-. *>_»k ' ■ — -» m »j\ /* n* iQipor-i;;.: ARCHIVES OF PATHOLOGY r.ra stbrfed1 ui various ^ICLE.Q%tA» tissues, particularly fat tissue (Hayes et aL; Davidow et aL; Lange et aL). Several of the chlorinated hydrocarbons (carbon tetrachloride, chlorophenothane, benzene hcxachloride) have elicited in man aplastic anemia and panmyelophthisis (Friberg- and Martensson; Straus). Considera­ tion should be given to the possibility that they may have, like other similarly acting agents, such as benzol and ionizing radia­ tion, Ieukemiogenic properties (Hueper), or that such effects are attributable to the -solvent vehicles used, which may contain benzol as an impurity (Elkins and Pag* notto).. - (c) Carbamates. Urethan (ethyl carbaJfe-* - -.'"^matep-is^ capable of - inducing-’pulmonary *, . , adenomas and carcinomas in mice and rats .'j. t- t ~^-=^(N<*ttleship and Henshaw; Guyer and _ - - Qaus; Jaffe; Mostofi and Larsen; Malm* t gren and Saxen; Orr). It also exerts, in ' ' conjunction with a cocarcmogenic, an initi- ating carcinogenic effect on the skirr of mice (Roe and Salaman: Salaman and Roe; . Berenblum and Haran). Carbamate derivatives used as insecticides, weed killers, plas­ ticizers, fish dope, medicines, textile finishes, : and resins, therefore; should be studied for ‘ carcinogenic properties (Hueper; van Each, van Genderen and Vink; Shabad and Naul). Since urethan is capable of trans­ mitting transplacentally the tumorigenic action from the maternal organism to the offspring (Larsen; Klein) of mice, popu­ lations exposed to carbamates deserve at­ tention also for the occurrence of tumors in infants of exposed mothers (Balo). Polyurethan foam implanted into rats -caused sarcomas and adenocarcinomas of the: intestine around intra-abdominal de­ posits (Hueper). . B. Plant Growth Regulators: The vari­ ous chemicals used in agriculture and horti­ culture for controlling the growth of plants can be placed into 2 classes, those which favor this process, Le., the auxins and sprouting agents, and the plant growth inhibitors, antiauxins, or antisprouting and antimaturition agents or herbicides..* The ormone-Uke action of these chemi­ cals is related to their influence upon the cellular proliferative mechanisms, Le., they have a mitotic or antimitotic effect Sprout­ ing agents are benzotriazote, p-chTorophenoxy acid (CIPA), 3-indolacetic arid (LA.) and a-cyano-y3-(2,4-dichlorphenyi)-acrylic arid (Ethyl-214), while antisprouting agents are maleic hydrazide, e-naphthalene acetic acid, 2,4,5-trichl rophenoxyacetic acid (2,4,5 T), 2,4-dichlorophenoxyacetic arid (2,4-D), £-naphthylalanine, 0-indolylalanine (trytophane), and others. Some of these agents (maleic hydrazide) are ex-, creted in cow’s milk, and are retained in ■ organs. . ' ■ A few have been tested for long-term effects in experimental animals for‘possible1 carcinogenic action. Truhauf and Vernes injected a-naphthylacetic arid into mice over many months without obtaining tumors. Maleic hydrazide fed to rats also gave nega­ tive results concerning abnormal tumor formation. Tumors also were not observed in dogs fed for one year with this particular chemicaL While these few observations are reassuring to some extent, they scarcely represent an adequate study of the many chemicals' used for the purposes stated in regard to potential cancer hazards to man, especially since Fukui et aL, who calculated the electronic structure of a number of plant growth compounds, such as benzoic arid derivatives, have found that the electronic distributions of some special positions in the molecule are intimately correlated with the auxine activity of the compounds and show a strong resemblance to carcinogenic polycondensed aromatic hydrocarbons. Re­ cent experimental studies on rats given by mouth large amounts of the herbicide; 3-amino-l,2,4-triazote, which is taken up into fruits, have shown, moreover, that this herbicide causes the development of thyroid cancers (Editorial: Flemming).' In performing such tests in the future, consideration also should be given to the fact that the active ingredients are solu­ bilized by the addition of surfactants (triethyiamine, diethylolamine, Triton X100, 2943 VoL 71. A^ 1961 mmm XOGEXS IN HUMAN ENVIRONMENT -m+.f l&Or*; ' able and not essential or justified, appear to be objectionable, even if it is still contro­ versial whether or not estrogens cause can­ cers in man (uterus, breast). It is well established that often prolonged anatomic and functional reactions to medicinal, oc­ cupational, and environmental hyperestrinism have been attributable to such contacts and have affected male and female adults and children (Watrous and Olsen; Scarff and Smith; Fitzsimons; Fisk; Pagani; Klavis; Katzenellenbogen; Kloprain and Bartini; Green; Stoppelman and Van Valkenburg). The view of a primary or contributory role of estrogens in the causation of cancers m both women and men is being held by an increasing number of competent investiga­ tors and clinicians (Eller and Wolff; Corscaden; Terp; Juptner; Gusberg, Burrows and Horning; Bromberg et al.; Muhlbock; Meissner and Sommers; DeWaard; Hertz; Speert; Novak; Hueper), Reports on the occurrence of endometrial carcinomas following a prolonged treatment of estrogens have become more frequent in recent years (Riehm and Stoll; Vass; Stokes; Emge); so have the observations on the development of uterine adenocarcinomas in coexistence with estrogen-producing gianulosa-cell ovar- ’' ian tumors (Ayre; Corbet, Miller and Tod;: Walz)’ as well* as those concerning' an ^ cessiyefrequency of cancers of the breast i»men given large amounts of estrogens '-farmedical reasoils (Hueper), or suffering from hyperestrinism because of functional and/or anatomic impairment of the liver (hepatic cirrhosis) (Symeonidis; Davies; . Coodley and Molle). • It is rather remarkable that biologically potent chemicals which are obtainable for medicinal reasons only on prescription by a licensed physician can be used freely in large quantities by persons without any proper training concerning the potential, health hazards associated with the handling' and consumption of large quantities of these hormonal substances. Such practices are ficult to control adequately on a nation-wide ■ basis in foodstuffs handled in interstate and intrastate commerce by thousands of * inTH1S DOCUMENT WAS NOT~A RECORD OF Dreft; Triton B19S6), in fuel oil, diesel oil, or other petroleum oils, which may be cardnogeiic by themselves. Negative obser­ vations made an livestock exposed to contaminated vegetation do not provide any valid evidence as to the innocuousness of these agents, since such animals are only rarely kept alive for a sufficiently long period to show any cancerous effects. C Estrogens: The growing use of estro­ genic chemicals, especially diethylsdlbestrol, tor an accelerated fattening of food animals (fowl, hogs, catde, sheep) in the form of pellets either subcutaneously implanted or' added to the feed, deserves consideration because estrogens are recognized carcinogens for several spedes, causing upon prolonged administration cancers of various organs and tissues (breast, uterus, testis, kidney, hematopoietic tissue, bladder). Practical ex­ perience has shown that farmers and poultry men do not always follow the instructions regulating the commercial use of these Ul ‘■ally ‘'ally highly potent substances, i.e., jJ not always insert the estrogen peii«3*~ m parts of animals (neck) which usually are discarded, but in parts which are eaten; they implant more than one pellet of 15 mg. of estrogenic chemical, and they sell their animals for human consumption before the safety period of- 6 weeks after mplantation has elapsed, while cattle estx<>_ ^enized byibotb routes are slaughtered,, as a ■ole, without observing a 60-hour estrogenfree waiting period. It is noteworthy, more­ over, that at least one synthetic estrogen, lamely tri-^-anisoldiloroethylene, is stored n the ■ human fat tissue after oral adnmi stration and thus appears to be most objectionable from a carcinogenic viewpoint iccause of its prolonged effect (Greenblatt ind Brown). Since members of the general population nay have appreciable contacts with exogeious estrogens from other sources (medcines, cosmetics, production of estrogens, landling of estrogenic preparations, prepa-ation and handling of estrogenic feed), uch exposures or the possibility of such s, especially when they are avoid- 2?. -PPG t.-iDUSTftiES, INC. DID NOT COivlc FROM ■IT'S FILES AND CANNOT BE AUTHENT1CA1 ED xmjLiuf, IWilS * i' (> fct-Tr -i- , ‘iHJI *" .. 5"cm 3HL .53?. NOTE: OME friOM Fi'u FILES ARCHtVES OF PATHOLOGY NOT Cu:v.;: ir dividual producers in quantities of several the water. So far only the use of hexmillions of animals. It is, therefore, com­ adecanol, but not of cocarcinogenic dodecmendable that the food processing industry anol, has been approved for.this purpose has agreed to. discontinue voluntarily the (Hollis). There is no published evidence further production of estrogen pellets for that either one has been studied for unto­ ward effects upon human health for other implantation into fowl. ■' . D. Water and Soil Pollutants: Since than toxic aspects. In view of th fact that water is the most important foodstuff, the dodecyl compounds are in part cocardnogens. possibility of cancer hazards from this or weak carcinogens .this new practice of source deserves serious •consideration, inas­ chemicalizing the human food supply is in much as natural or industrial carcinogenic urgent need of thorough and competent in­ pollutants may enter the drinking water sup­ vestigation for delayed carcinogenic sequelae ply as well as be absorbed by and ac­ among consumers. . cumulated In vegetables, fruits, and food Mention may also be made of the practice animals using water contaminated with such introduced during recent years of employing materials (arsenicals, selenium, radioactive chemicals, such as sodium arsenite, orthodi­ substances, wastes from coke ovens, tar re- chlorobenzene, trichlorbenzol, dichlorbenzol. \-: / .i^^ifineriesjoil refineries.,textile dyeing plants,...naphtha,'. 24;DJ2,4,5-T, and copper-.sulfate* ' paper manufactures, cellulose factories, do- as algiddes (Bartsch). Sodium arsenite is r-M^rmestic.and industrial detergents and others). considered as one of the cheapest and, Tarry and oily materials, moreover, may “safest" products for such purposes because ~ - be washed by rain into bodies of water; of its “toxicity"; its use in water supply ■■ so may radioactive fall-out and pesticides reservoirs, however, should be considered dusted and sprayed on fields and orchards, with extreme care, according to Bartsch, wh 1 ‘ and atmospheric effluents from industrial failed to mention and to consider the likely establishments containing carcinogenic mat- cancer hazards which would result from .. ter (soot, arsenicals, chromates, aliphatic such a practice. V hydrocarbons, beryllium, asbestos, etc) Selenium, a soil contaminant in the United (Hueper; Hueper and Ruchhoft; Tello; States and South Africa (Steyn) causing Goldbiatt and Goidblatt). chronic selenosis (alkali disease) among In fact, experimental investigations have livestock characterized by liver cirrhosis, demonstrated the presence of carcinogenic elicits, when fed to rats, liver cirrhosis, matter in water serving as sources of drink­ hepatic adenomas and carcinomas (Nelson, ing water or food supply (cancer of the skin Fitzhugh and Calvery). It is at present not - § *** o ' in mice painted with carbon adsorbates of known whether similar neoplastic sequelae effluents of an oil refinery) (Hueper and occur in populations consuming seleniferous O £E s; ; : o o m.. Ruchhoft)., sarcoma in mice receiving sub­ food. o: o 3: •. cutaneous implants of a polycyclic aromatic It is at present purely speculative but c h- {r . : hydrocarbon fraction of barnacles growing worth investigating whether the marked dif­ 2= '£ ‘ O — 0/ ; in waters polluted with ship fuel oil. ferences in gastric cancer mortality among Z 9 £0 O (Shimkin, Koe, and Zechmeister), demon­ different countries of similar racial and cul­ stration of several carcinogenic polycvlic tural nature and among different areas of 5 9 ^ ®> aromatic hydrocarbons in extracts of oysters the same country (England and Wales, obtained from similarly contaminated waters Netherlands) (Tromp; .Daires and Griffith) 5 y\ o k (Cahnmann and Kuratsune). are in part^causally related to local dietary most recent addition to the spectrum factors (Torgensen and Petersen). The 3 tr> < £ y 31/) — E. Wrapping and Coating Materials: of industry-related pollutants and additives O A U DijCJ to water serving as reservoirs for drinking Various chemicals either obtained from materials carcinogenic to man and animals, §=££>. water are the evaporation retardants form­ ing a monomolecular film on the surface of such as crude petroleum, shale and lignite h 3 a. A pof T1 % , ■ •** ngif&r * w •mrTmzw* ♦- a. tr aj 28/368 . | BB 0020452 I Vot. 71, Atr mi NOGENS in humas environment oils used m the production of paraffins and cnicrocrystalHne waxes, discussed above (Hueper, Goldblatt and Goldblatt) or syn­ thesized from carbon or silicon compounds md forming' polymerization products, such is polyethylene, cellophane, polyvinyl chlo­ ride, polyacrylafes, polysilicones, polyamides, nolytetrafluoroethylene, and Bakelite, which ire carcinogenic when, implanted into rats md mice, are employed at an increasing ^ale in the manufacture of food containers, is inner linings of cans, and as wrapping md coating materials of foodstuffs, includng sausage casings which are apt to be raten (Oppenheimer et aL; Druckrey et al.; N'othdurft; Hueper). Richmond and Hadkrw et aL produced cancers in rats by the larenteral introduction of a water-soluble ron-deoran complex used as an aniianemic. Although there exist as yet no direct "ounterparts in man to the "polymer caners" elicited in... rats and mice by the »rentenl implantation of the various mac'alar plastics, this may be due to the it the industrial, commercial, and neu.cmal use of these chemicals is of rather went date. A latent period sufficiently long or the- development of cancers following He parenteral introduction of these polymers nro urn has not elapsed for most cases. Hie existence of asbestosis cancers of the ung, however, - attests to the-.fact that the iuman organism may react to -the presence >f a silicon polymer with a cancerous maniesatioo in the exposed tissue. No evidence, >n the other hand, is available from ex­ periences in man and experimental animals whether the ingestion of any one of these polymers or the ingestion of foodstuffs ring in direct contact with them entail any arduogeuic hazard. It appears to be a wise ■recantian to keep all occupational groups aving cutaneous, respiratory, and ingestive ontact with these macromolecular chemicals nder dose surveillance for any evidence uggestmg a carcinogenic action on man. Similar considerations should be extended 3 persons who have received parenteral dmrmstrations of iron-dextran complex, ic preparations, and the various synthetic macromolecular plasma extenders, Q such as polyvinyl pyrrolidone and dextran, since several polyvinyl pyrrolidones im­ planted and intravenously injected into rats produced reticulum-cell sarcomas, Kupffercell sarcomas, and carcinomas of the uterus and skin in about 30% of the animals treated. Distinct -caution is also indicated in the industrial (felt, rubber) and medical (virucidal) use of a polymer chain-termina­ tion and cross-linking agent, y3-propiolactone, since it is capable of eliciting carcinomas of the skin in mice and subcutaneous sarcomas in rats (Walpole et al.; Roe and Salaman; Roe and Glendenning). F. Incomplete Combustion Products of Carbonaceous Materials: Recent observa­ tions indicate that foodstuffs when exposed to wood smoke, such as that used in smoking meats and fishes or when subjected to high temperatures causing charring of the foodstuffs (roasting, toasting, baking) may become contaminated with a known carcino­ genic aromatic hydrocarbon, 3,4-benzpyrene (Dickens and Weil-Malherbe; Gorelova, Dikun and Lapshin; Shabad and Dikun; Kuratsune; Sula and Dobes; Vaiade; Sulman and Sulman; Bailey and Dungal). Kuratsune, and Kuratsune and Hueper re­ cently added to this evidence by demons.„v—‘: strating that the soot produced when roasting coffee beans by direct _or indirect .exposure^tiv-^tf to a gas dame contains, among other poly­ cyclic aromatic hydrocarbons, not-inappre-. riable amounts of this carcinogen, confirmTam* 11.—Rough Estimation of Polycyclic Hydrocarbons n» a Coffee Soot Produced, by the Direct Application of Heat* 'Zux*'’ ----------- -— Pm* TtaormboM Cteran B«o* («) attomn IWmM psm Umi (a) pyrn b«ub ^A“'#^,|t jfciVWri. - •WS»:I ' V ‘r. Ty:" v. /s>,Si ?a >* - - i' ■ * .2 v *-a?r* - ■ . o 9 • o 2 *■-" 2 o UJ , s: Q oq o w Q~5 5u9 - *£gi2 fe # S£ o gg?s q9 J(3 c& 0- t 00 ing thereby previous, not entirely reliable, alimentary and respiratory tracts. It was claims of Roffo, which, however, were de­ found that the population of the coastalnied by Druckrey (Table XI). villages engaged in fishing and consuming In subsequent experiments on coffee beans large amounts of fresh, salted, and smoked roasted to different degrees, it was found fish had about 3 times as much cancer of the that 3,4-benzpyrene was not demonstrable alimentary and respiratory tract as the peo­ in the watery extracts of coffee beans of ple living in inland villages, and engaged in light as well as dark roasts (Kuratsune and agricultural activities. While the villagers of Hueper; Dansi and Zanini), although very the inland villages also eat smoked meat, small amounts of this carcinogenic were those of the coastal villages are engaged in present in a special brand of black roasted smoking fish almost the whole year around coffee where the surface of the beans is and conduct such work not only in special smoking plants but also at home, since prac­ burnt tically every house has its own smoking The practical importance of these obser­ oven in which fish are smoked for domestic vations, however, remains uncertain at the use. - present time because of conflicting experi­ There exists a great deal of equivocal and mental. evidence, .concerning the - carcino­ contradictory evidence concerning the rote genicity of these soots and their effects upon experimental animals. Eichler and Vollmer of ingested heated fats and cholesterol in failed to produce cancers of the skin in rab­ the production of cancers of the stomach bits and mice painted with coffee tar. and intestine in mice and rats (Peacock; Similarly negative results were reported by Roffo; Kirby; Falk et al; Peacock et aL; Schmahl and Reiter in rats fed heavily Chalmers; Lane, Blickenstaff and Ivy). smoked bacon for up to 1,000 days. Farfc, While the subcutaneous injection of one on the other hand, obtained tumors in 8 of type of polymerized and peraxidized vege­ 20 mice fed smoked bacon, but none in 50 table oil has been shown to produce sarcomas mice used in a repeat experiment None of - in rats, the injection of another similarly these observations is of convincing value altered vegetable oil into mice was not concerning a carcinogenic action of smoked followed by the appearance of tumors foodstuffs in man because cancers of the (Chalmers). It may be pointed out in this alimentary tract cannot consistently be connection that the physicochemical condi­ produced in rats and mice even when large tions prevailing in deep-hit frying processes amounts of 3,4-benzpyrene or other similar favor the development of oxidized and potent carcinogens are fed (Waterman; - polymerized products, especially when the Rorei and Gummd; Shay, Harris and fat or oil once heated remains in permanent ;i Grueostein; Lorenz and Stewart) unless use. A similar uncertainty exists in regard to some'cocardnogenic or procarrinogenic ve­ hicle is used in the administration of these the alleged carcinogenicity of normal choles­ carrinogais. It is moreover not definitely terol. While Hieger and Badger note that established that 3,4-benzpyrene is carcino­ cholesterol has a definite, although weak, carcinogenic potency, Fieser states that cho­ genic to man. Nevertheless, recent epidemiologic studies lesterol itself, which is so widely distributed of Voitelovich et aL on the cancer incidence in the body, could hardly have the properties among 2 population groups, one represent­ of a carcinogen of even low-order potmcy ing the inhabitants of 2 coastal villages, the but that tumors appearing at the site of the second of 6 inland villages in Latvia, provide injected, material must have been initiated important evidence supporting the view that by some transformation product of choles­ carcinogenic factors in the smoke used for terol or some unknown companion sub­ smoking foodstuffs may play a significant * stance. The extreme rarity of primary role in the production of cancers of th$ cancers of the arterial system in which cho30/370 Vol. *f W *2947 7"bb’ 002045^! 7Aa CINOCENS IN HUMAN ENVIRONMENT esterol and its esters are deposited and -etained for decades supports Fieser’s views, it least as far as man is concerned. Kirby railed to produce cancers in rats fed choesterol esters of unsaturated fatty adds is well as in mice painted with such raaerials or subcutaneously injected with them. 3i$choff et aL, on the other hand, reported hat a combination of sesame oil and certain oxidation products of cholesterol is carcino­ genic to mice, eliciting fibrosarcomas. It is toteworthy finally in this connection that he reported occasional occurrence of tumors n nanalimentary organs following the inges­ tion of carcinogens might be related to the fact that chylomicrons may act as carriers of ngested carcinogenic hydrocarbons, thereby causing their general hematic distribution, md under suitable dietary and metabolic ronditions become arrested in specific organs (Setala and Ermala). The possible existence jf such correlations is supported by obc^-’ons of Andervont and Lorenz, who ed tumors of the lung of mice by an nuLvenous injection of dibenzanthracene iispersed in lipemic dog serum. Conclusions 1. The growing pollution of the human mvironrnent with chemical and physical tgents associated with the modern industrial, ievelopment poses serious problems to medifine, public health, sociology, economy, ratuTal sciences, and technology. 2. Because of the still far-reaching lack jf factual knowledge on the carrinogenic igents already present in the human en­ vironment and the distinct difficulties en:ountered in discovering and identifying hem by epidemiologic, medical, and ex­ perimental procedures, definite efforts should pc made to-prevent, as much as possible and practicable, any further addition of new ndustry-related carcinogens to the human environment. 3. Cancer hazards associated with ex­ posure to “these agents represent a segment pf the general toxic health hazards conwith the production, distribution, and release of industrial wastes into the en­ vironmental air, water, and soil. 4. In view of the rapid growth of in­ dustrial activities and of population, the com­ plex problems created by these developments deserve serious and urgent attention by all parties concerned so as to keep them within controllable limits. 5. Cancer hazards of industry-related causation should not be considered as un­ important and unavoidable calculated risks of modem living. They are as amenable to sanitary control measures as communicable diseases have proved to be in past decades. The recently advanced argument that the prophylaxis of environmental cancers can cut us off from all our amusements and that it is best, therefore, to enjoy life and take the small risks attached to these things (Wright) reflects a philosophy which denies the best traditions of medical practice and public health, and would open the way for an indiscriminate introduction of any num­ ber of highly toxic and carrinogenic ma­ terials into the human environment While the risks to health and life resulting from such exposures would be of the "calculated" variety, distinct differences would exist be­ tween tiie. parties who would run the risks and those who would do the calculations. 9307 Rockville Pike, .Bethesda -14, MC, BIBLIOGRAPHY' Allen, ii J.; Borland, £■; Duka, C E.; Hom­ ing, E. &, and Watson, J. G.: Cancer of the Urinary Bladder Induced in Mice with Me­ tabolites of Aranatic Amines and Tryptophan, Brit J. Cancer 11:212-228, 1957. Alhnark, M. G.; Grice, HrC, and La, F. 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