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Conference cn Envlrc:;-.sntal Careinnrrs During the Hay 7 - S, 1955 meeting cf the Cancer Control Committee, & special conference on Environmental Carcinogens was authorised to be financed from the Chairman's Grant at a cost not to exceed v3,000. It vas proposed that a limited number of individuals interested in this field, including grantees, past and present, other investigators and staff members of the National Cancer Institute be assembled: "to outline the present knowledge of environmental carcinogens, and to indicate the need and direction of additional research in this field for the guidance of the National Cancer Institute and the Cancer Control Committee.1* - ,^ A preliminary discussion with staff members ofvthe National Cancer -Institute was held Kay 10 and it v:a.s decided to cilltho first'meeting of _ the subcommittee during the annual American Medical Association convention _ in Atlantic City! Notices of the impending^conference also were sent-out - - to the grantees, past and present, to insure their participation. The meeting in Atlantic'City on 'June 6, 1955 was attended by Dr3. Kcore, Vorwald, Williams, Kaiser, Hon and Phair. It was decided immediately that additional members of the Cancer Control Committee should join in this enterprise, giving particular attention to the number of years of membership remaining in order that whatever conclusions were reached would serve to guide the Committee for as long as possible. Accordingly, Drc. Gowen, Griswold, McCavran and Spellman were invited to participate. Other participants were reviewed and it was decided to limit the total number to 25 exclusive of National Cancer Institute staff workers; The final list of participants is appended to this report. Eh*. Hon again took the responsibility of issuing invitations innediat'el7 to the other investigators. - It was-planned -that the -conference discussions follow this general pattern: (a) The discussion of each individual or category of carcinogens would be opened by a discussion leader with a ten_to 15 minute prepared statement. Selected discussants would be prepared to follow this presentation and then the subject would be opened to all participants-. (b) 'Hie objectives of the discussions were to seek agreement upon the evidence required - clinical, epidemiological, statistical or experimental before a material or compound can be considered hazardous to man. One secondary goal was to describe the obstacles and pitfalls likely to be encountered in such investigations and another was to describe areas where studies should be initiated or extended. The final agenda listing the topics covered and the discussion leaders is attached a3 Appendix 2. Due to lack of time, it was found nc-cessery to limit the consideration of certain materials and to omit ail reference to ultra violet radiation. At the conference, each participant was given a crude score sheet to record his impression as to the validity of the evidence, human or experimentalt available at the moment. Sixteen turned in the sheets and these have been summarized, roughly and hurriedly, in Appendix No*final" or definitive.recommendations were formulated by the Conference. All participants.seemed to appreciate the opportunity to discuss generally these problems afforded by this meeting. All believed that similar talks should be arranged periodically in the future. It was evident, also, that the experimental group should be assembled to standard isb terminology and experimental methods. Part of the confusion in this field is due to minor variations in their approaches and those differences could be readily resolved if they agree on the^samc terminology and definitions, "* % Respectfully submitted, Conference on Environmental Carcinogens Stone House Conference Rcor. A and Study Hoorn September 12, 13, 1955 Invited Guosts Dr. Donald J. L-immghan Occupational Health Field Headquarters Public Health Service lOlLi Broadway Cincinnati, Ohio Dr. William E. Poel University of Dennsylvania Schco^'of Medicine 36th^dnd-Pine Streets Philadelphia Ii,- Pennsylvania Dr .-Vi Hard -Machle - Box 887 Boca Rotan, Florida .- Dr. Harvey W. Maguigan _ P. 0. Box 831 Hopewell, Virginia `_ Dr. Arthur J. Vorvald Department of.Industrial Medicine and Hygiene College of Medicine Vayne University 11*01 Rivard Street Detroit 7, Michigan ' Dr. Vi Ilian E. Smith Institute of Industrial Medicine.. New York University - Bellevue Medical Center Hew York 16, Nei7 York Dr. Paul Kotin Assistant Professor of Pathology University of Southern California 1200 North State Street Los Angeles 33, California Dr. Wesley Horton Kettering Laboratory University of Cincinnati College of Medicine Eden and Bethesda Avenues Cincinnati 19, Ohio Dr. Robert E. Eckardt Director, Medical Research Division Esso Research and Engineering Co. Post Office Box 51 1 Linden, New Jersey Dr. Jean S. Felton Associate Professor Deoartment of Preventive Medicine and Public Health University of Oklahoma School of Medicine 801 North East 13th Street Oklahoma City h, Cklahona Dr. Charles L. Dunham Deputy Director Division of Biology and Medicine V. S. Atomic Energy Commission Washington 25, D. C. Drl Norton Nelson Director, New York University- Bellevue Medical Center Institute of Industrial Medicine 550 First Avenue New York 16, New York * Dr. Thomas F. Kancuso Chief, Division of Industrial Hygiene State of Ohio Department of Health 306 Ohio Departments Buildings Columbus 15, Ohio Dr. Lemuel C. McGee Delaware Trust Building Wilmington, Delaware Guests invited to attend Conference on anvironnentil Carcinogens (Cont'd.) Dr. James H. Sterner Medical Director, Eastman Kodak Co. Kodak Park Rochester h, New York * Dr. Irving Tabershav" 1L5 V/est 55th Street New York 19, New York 'Dr. Kc-nneth W. Smith Medical Director,' Johns-Xanville Corp. 22 East ijOth Street - New York 16, New York - -- -- Dr. Anna M t Baetjer. Johns Hopkins School of Hygiene and Public Health 615 No. Wolfe Street Baltimore 5, Maryland . Dr. John H. Foulger Director of Medical Research E. I. DuPont de Nemours and Co., Inc. Nemours Building Room llliiOO (Medical Division) Wilmington, Delaware' Dr. Gilbert Thiessen Manager, Laboratory Section .. Research Department . Kopoers Company, Inc. Pittsburgh 19, Pennsylvania ` Dr. J. Wister Meigs^ Associate Professor of Occupational Medicine . Yale University School of Medicine Department^ of Public Health 310 Cedar Street New Haven 11, Connecticut * Dr. Paul E. Steiner Associate Professor of Pathology University of Chicago School of Medicine Chicago 37, Illinois* Dr. Lester 5reslcw Chief, Bureau of Chronic Diseases California State Department of Health 2151 Berkeley Way Berkeley, California Dr. Morten L. Levin Assistant Commissioner for Medical Services State 4? New York Department of Health - Division oT Medical'Services' 39 Columbia Streets ._ Albany 7,"New York~ Dr. -Matthew H. Griswold Chief, Division of Cancer and Chronic Diseases Connecticut State Dcaartmc.nt of Health Hartford 6, Connecticut Dr. John W. Spellman Clinical Professor of Surgery Tufts-College Medical School 1101 Beacon Street Brookline L6, Massachusetts Dr. Murray M. Copeland Professor of Oncology ~ Georgetown University Medical Center 3900 Reservoir Road Washington, D. C. Dr. John J. Phair University of Cincinnati College of Medicine Eden and Bethesda Avenue Cincinnati 19, Ohio Dr. Philippe Shubik Assistant Professor of Surgery Director, Department of Oncology The Chicago Medical School 710 South Wolcott Avenue Chicago 11, Illinois * Dr. Herman Lisco Post Office Box 299 Lemont, Illinois 1 Dr. Roy Albert Division of Biology and Medicine U. S> Atonic Energy Commission -3Guests invited to attend Conference on Environmental Carcinogens (Cont'd.) Dr. John R. Heller" Director, National`Cancer Institute Bethesda lh, Maryland Dr. C. B. Kider Assoc. Director in Charge Research National Cancer Institute Bethesda li, Maryland Dr. Michael B. Shimkin Chief, Biometry and Epidemiology Branch National Cancer Institute Bethesda 2ii, Maryland _ Dr. Harold F. Dorn Chief, Office of Bicrietry Office of the Director National Institutes of Health' Bethesda lii, Maryland Dr. Richard A. KaLngren Field Investigator Field Investigations and Demon strations Branch National Cancer Institute C/o University of Tennessee Institute of Pathology 858 Madison Avenue Mcnphi^vLO, Tennessee -> Dr. John E. Dunn, Jr. Field Investigator Field Investigations and Demcrr-' strations Branch National Cancer Institute C/o California State Department of Public Health ?151 Berkeley Veyn Berkeley h, California Mr. William N. Haenszel Chief, Biometry Section National Cancer Institute Bethesda lii, Maryland Dr. A, G. Gilliam Chief, Epidemiology Section National Cancer Institute Bethesda lii, -Maryland- - %- -. Dr. Maurice L. Sicvors Field Investigator Field Investigations and Demon strations Branch National'Cancer Institue C/o Washington University School of Medicine Kingshighvay and Euclid Avenue - St. Louis 10, Missouri Dr. Harold L. Stewart ~ Chief," Pathologic Anatony Branch- National Cancer Institute Bethesda lii, Maryland Dr. Samuel C. Ingraham Head, Field Studies Section Field Investigations and Demonstrations Branch , National Cancer Institute Bethesda lii, Maryland Mr. Pooe Lawrence Field Studies Section Field Investigations and Demonstrations Branch National Cancer Institute Bethesda lii, Maryland i Dr. John Vender Field Investigator Field Investigations . and Demon strations Branch National Cancer Institute C/o Department of Health, Education and Welfare 123 Lincoln Street Framingham, Massachusetts Dr. James W. Egan Field Investigator Field Investigations and Demon strations 3ra.nch U. S. Public Health Service Fivld Station Division of Occuoational Health Box 2537, Fort Douglas Station Salt lake City, Utah -b Guests invited to attend Conference on environmental Carcinogens (Ccr.t'd.) Miss Marian Erjnvcc Dr. N. 3. Hen Se-.nior f.'urse Officer Head, Grants Section Aset. Field'.Investigator Field Investigations and Demon Field Investigations and Demon- strations Branch stratiens Branch National Cancer Institute National Cancer Institute' Bethesda lb, Maryland Occupational Health Field Station Division of Special Health Services Dr. Eenno K, Milnore Bex 2537, Fort Douglas Station Biometrics and Epidemiology Branch Salt Lake City, Utah National Cancer Institute Bethesda lb, Maryland Dr. Miriam Manning ' Field Investigator Dr. Willisa A. Welters Field Investigations ana Demon- - Eicaetrics and Epidoaiolcgy Branch strations_Br.anch_ _ _ _ National Cancer Institute National Cancer Institute - _ BetheaSa lb, Maryland " '~ Children's Cancer Research Foundation 35 Binney Street Miss Rosalie I. Peterson Boston 15, Massachusetts Head, Nursing Section Field Investigations and Demon Dr. Paul Ortega strations Branch Field Investigator National Cancer Institute Field Investigations and Demon Bethesda lb, Maryland strations Branch - National Cancer Institute Hiss Ruth Kahl Cancer Investigation Unit Nursing Section 3 North Dunlap Street _ _ Field Investigations and Demon Memphis 10, Tenncsseo strations Branch ' Dr. George Z. Williams Chief, Clinical Pathology-Department National Cancer Institute Bethesda lb, Maryland Clinical Centef, Nat. Inst, of Health Hiss Hary-M. Bouser Bethesda lii, Maryland _ Nursing Section ' Field Investigations and Demon Dr. Wilhelm C. Hueper strations-Branch Head, Environmental Cancer Section National Cancer Institute National Cancer Institute Bethesda lb, Maryland Bethesda lb, Maryland Dr. Raymond F. Kaiser Chief, Field Investigations and Demonstrations Branch National Cancer Institute Bethesda lb, Maryland Dr. William Baum Assistant Chief, Field Investigations and Demonstrailons Branch National Cancer Institute Bethesda lb, Maryland 1 NOTEt Did net attend Conference Conference on Environmental Carcinogens Stcne House Conference Keen A and Study Room September 12, 13, 195o ACi.ivDA ' I. Opening Remarksi ' Purpose of the Conference---- Chairman, Dr. John J. Phair II. Discussion Leaders Discussants 1; ^ Incrganio Compounds - -- _ 't _ '* --- ^ -- a. Arsenic Dr. Donald J. Birrlnghan, Dr. Norton Nelson, Drr Thomas F. Mancuso b. Chromates Dr. Willard Machle, Dr. Anna M. Baetjer, Dr. Thomas r. Mancuso, Dr. Norton Nelson c. , Nickel Dr. Wilhelm C. Hueper, Dr. Lemuel C. KcCee Dr. James H. Sterner, Dr. Robert E. Eckard d. Beryllium Dr. Arthur J. Vorvald, Dr. Willard Kachle, Dr. Irving Tabershaw - _ e. Asbestos. Dr.' William -E. Smith, Dr. Kenneth W.. Smith, Dr. .Arthur J. Vorv/ald 2. Organic Compounds. ' a. -Aliphatic Dr. Paul Kotin, Dr. Norton Nelson, Dr. A. Wesley Horton, Dr. Robert E. Eckardt b. Polycyclic (1) Petroleum Products - Catalytic and Thermal Cracked Dr. A. Wesley Horton, Dr. Robert E. Eckardt, Dr. Philippe Shubik, Dr. Paul Kotin * (2) Petroleum Cutting Oils (Additives) Dr. Robert E. Eckardt, Dr. A. Wesley Horton, Dr. Norton Nelson, Dr. John H. Foulger (3) Coal Tar Dr. William E. Poel, Dr. Philippe Shubik, Drj Gilbert Thiessen * 2- - .22 Organic Compounds (cont.) c. Dyes and Intermediates Dr. Harvey V, Haguigan, Dr. J. Wister Meigs, * Dr. Jar.es H. Sterner, Dr. John H. Foulger 3. Physical Agents. a. Ultra Violet Radiation Dr. Jean S. Fcltcyr^ Dr. Paul Steiner ,, _ `A _ b. Radioactive Materials _ _ Dr. Charles Tunhan, Dr. Hermann Lisco PROGRAM - CRDZR CF DISCUSSION September 12 ' 9:00 12:30 - _ _ 2:05 5:30 6:30 - 12:30 AK Working Session 2:00 PM Lunch 5:00 PM _ Working Session 6:30 PM Dutch Hospitality Hour 8:Q0 PM Subscription Dinner September 13 - 9:00 - 12:30 AM . Working Session - 12:30 -- 2:00 PM- Lunch.2:00- 500 PM Working Session i Appendix 3 v Semotion' of Score Shcc-t3 1 INORGANIC Arsenic Chromates Ezi derioloeical Skin Lung Other Organs 00 0 i' 0* 11 Zxperir.cr t.31 Mice Rabbits Rats Others Site 0 70' 0 0 - Skin paci-llcma 0 0 Nickel Beryl1 i um 0 0 Asbestos ' : + 0. Nasal cancer 0 - --7 ' -- 0 - 7- *" 0 ** ' V * --- - -- V '_0 Lur.g sarcoma Adcno and squamous cancer 0_ ORGANIC Aliphatio Polycyclic Petroleum Products 0 -f Cutting Oils * . Coal Tar ---- + Dyes and ' 0 Intermediates -- - 0 -0 -- 00 0 - + 0- 0 0 ' o' ' 0 - Bladdercarcinema 4 b . + -f- - 4 - - Lur.g adenoma Squamous cancer - Papillomas _ Squamous cancer Dog Bladder" tumor PHYSICAL AGENTS Ultra Violet Radioactive t * . -- Not Di: ussed Bone, * Thymus, + Blood Leukemia I "1j 1. Arsenic A. Epidemiological Evidence Skin - squamous cell carcinoma and hyperkeratotic lesions. All sixteen reporting believed that the association particularly Kith inorganic- arsenic, such as As2 O3 was valid. Some expressed doubt about the relationship with contact or industrial exposures. Ingestion was generally conceded as proved^ ** \ Lungs - Bronchogenic Carcinoma ' All expressed doubt'about the-data to-date in _ regard tothe hazard of lung cancer following either industrial or community exposures. The strongest affirmative opinion given was that the observations were suggestive. Other Organs No one felt that any "evidence,' clinical or epidemiological, was available to show a _ relationship to cancer of other organs. B. Experimental Evidence Ra"bbits Topical application of arsenical" compounds on the akin of rabbits has produced papillomas. - About half of the reporting participants felt that these observations at the best were only suggestive. The others accepted without question the results as reported. C. General Aspects. a. We have no knowledge of the action of As in the akin or other tissues. In the light of the discussion this would seem to be a useful avenue to explore. b. There.Is no real understanding of the dosage and kind of exposure required,. This is true also as to the importance of various arsenic compounds. 1 7, Chromates A. Epidemiological Evidence Skin Have a narked association between exposure to chromium and akin and nasal ulcers. However, no skin cancers have been reported. All of the participants reporting accepted this observation without question. All sixteen score sheets recorded bhat the evidence of -relationship between industrial exposures (chrome production). _ and bronchogenic_carcinoma seemed good. Community exposure - is a different question and there 3-S no acceptable evidence " available at this tine._. Other Organs ' No evidence. Other Occupations '- Suggestive evidence in occupations using chromates, i.e., painting and welding. Will require an enormous amount of - week due to_need to determine_the precise exposure, both in kind and degree, and the particular compound. B. - Experimental Evidence " C57 Mite, rabbits, guinea pigs and rats have been exposed, by inhalation, intravenous and subcutaneous injections and by ekin applications. All results have been essentially negative. - "The participants uniformly recorded that no -experimental evi dence has been produced to support the epidemiological findings. C, General Aspects a. It was brought out that we cay be dealing with a carcino genic industrial operation rather than exposure to a single element or conpund, b. The variation in tissue uptake, both in degree and kind of conpund, offers an interesting avenue of study. Retention also differs. c. Here we have reasonably good epidemiological evidence but no experimental studies to support the observations. Can control be based on' such results, particularly, if only certain compounds nay be involved? Nickel A. Ec^dcciioIoeic=l Evidence Skin No evidence presented. Lung (Including nasal passages) Carcinoma cf the nasal passages and lungs has been related to plant exposures and a causal relationship suggested particularly with metallic nickel ar.d .follows inhalation'. Exactly half of the participants considered the evidence available as suggestive but - 2 ~ "not entirely convincing< -The others felt.that the hazard had been demonstrated. - Other -Organs' No evidence. B. Experimental Evidence Mice \ Inhalation experiments with metallic nickel dust was followed by "a higher-incidence of lung-carcinoma than in the controls. (Significance?). Sarcomas were found only in the test animals. It was reported that nickel dust in embryonic lung tissue transplants was followed - by_ah adenoma in one_ animal. Other Animals - No evidence presented-. C. General Aspects a. Hay be dealing with an "operation exposure" rather than exposure to a single compound and similar to the chromium experience. b. Nickel carbonyl has been considered but apparently the hazard is more closely related to metallic nickel, c. A very long latent period is present, 8-30 years, if the epidemiological evidence is accepted. I ylliua Enidenlological Evidence Skin No evidence of huxan hazerd presented. . Lung Acute pneumonitis and chronic berylliosis have been shown to follow various kinds of berylliua exposures. Three or four cases of lung corcinoxa have been seen in individuals with Be exposure hf^tones but evidence .at the moment cannot be considered acceptable.' There is no relationship between the amount of Be'in the Z tissucs~and the pathologic reaction. ._ Other Tissues No evidence presented. Exoerim'ental Evidence Rats . Inhalation exposures (intratracheal) with beryllium oxide dusts have been followed by squamous and adeno carcinoma of the lungs. Also-scirrhous types and metastasis have been demonstrated. Be SO^ has not given such'results.' - Rabbits- .' __ Intravenous injections have produced bone lesions, both adenocare Inara and osteosarcoma. General Aspects a. All of the participants concluded that the evidence for a human hazard was insufficient. b. All accepted the rat studies but one or two questioned the work with rabbits. c. One or two had definite reservations about the desirability of extrapolating the results of these experimental studies to man. d. Attention was called to the extent of the hazard if a causal relationship is established due to the presence of Be in the soil of a Large part of Virginia and the Carolinaa. Asbestos A. Epidemiological Evidence Skin No evidence. Lung English reports are very suggestive - 132 of asbestccis deaths had carcinoma compared to 1.3% of silicotics. Canadian v;orkers - 6 cases of lung cancer in 52 autopsies (112). All cf the participants were^ir.presscd but on the whole felt-that core studies in grclier detail were * needed.' The tumors generally found were adenocarcinoma, _ . .squamous .and oat cell anaplastic. Other Organs. ' No evidence. ' 3.. Experimental Evidence Hats and Kice "~ Intratracheal' exposures have given negative results but the studies are obviously inadequate. The general consensus of .the conference group reporting was that the evidence was inconclusive and much more work was needed in this area. _ C, General Aspects a. Worker studies have been very-suggestive but no gTeat reliance can be'placed on the data assembled- to date.. - Additional studies are needed. b. The laboratory investigations reported do not confirm the human experience although only scanty observations are available. c. Widespread hazard if a causal relationship is established due to cany uses of this material under various conditions. i 6. Alir'-atic Or rani c Compounds A. Epidemiological Evidence' Ko evidence vas presented for any kind of exposures. 'Widespread exposure exists- in all valk6 of life but no data establishing, a bursan hazard has ever been collected.. B. Experimental Evidence u. Inhalation exposure's to synthetic* snogs and epoxides alone and adsorbed on "soot" have bden follcved by |adencmas~cf the-lung. - - - - . _ Painting experiments vith epoxides have clveri a few epithelial cancers but this vcrk is only preliminary and cannot be used vith qualifications at the ncnent. C. ` General Aspects a. Ho .human hazard has been established. b. Animal experiments are interesting but not conclusive and cannot be extrapolated to can. -1 7, Petroleum Products (Polycyclic Organic Ccmcour.ds) A, Epidemiological Evidence - Skin - - The "relationship between human skin carcinoma ar.d exposures to certain petroleum oils - particularly paraffin oils in America and shale oils in England - was accepted by all participants. The relative importance of accelerators and cocarcinogens (initiators and promoters) found in petro- leun has not- been completely established, although it is generally accepted today that they play a ca^or role. The tumors produced are.squamous or basal cell carcinoma. Scrotal cancers are a very prominent group, lur.g - - _ No evidence to date that_the incidence of lung cancer is - increased by .exposure. - _ I I * ' ~ Other Organs No evidence to date. E, Experimental Evidente Animal A wide variety of animals has been used experimentally, but mice and rabbits have been found cost_satisfactory, Some doubt was exprossed as to the ability to quantitate therelative potency of different fractior.3 by animal tests, Thu tumors produced are papillomas and scuamous carcinoma, ~ Chemical Testing - -*' .~ A considerable amount of time vas spent on a discussion of the value of precise' chemical analyses of petroleum products in-the appraisal of potency. The participants did not reach any definite conclusion but thi3 is one area where agreement among the various investigators should be sought, C, - General- A spe ct a - (a) With these materials, the epidemiological observations have been substantiated by experimental studies, (b) The differences found when the English and American studies are compared nay be due in part to personal hygiene habits and working conditions. (c) Additional studies, both in the field and laboratory are still needed. B. "Cuttins Oils (Polycyclic Organic Campounds) A. Epidemiologies! Studies Skin Carcinoma'of the skin, particularly .of the forearms, although scrotal lesions are found, has been associated with exposure to cutting oils both in America and England. The occurrence, of hyperkeratosis and neoplasias is part of the over-all picture of skin irritation which is also narked by folliculitis. The participants as a group felt that the invidence was good. - Lung No evidence of a causal relatlonship^to tumors has been presented to date. It was brought exit that there is a real hazard of oil pneumonitis in such occupational - - exposures- -_ __ _ _ Other Organs' . No evidence. "B. Experimental Evidence Animal Studies Hice and rabbits have been used and papillomas produced. It was brought out that possibly not enough attention - has been given to papillomas. The consensus of the conference, based on the score sheets, was that the evidence was-essentially good and nore^than suggestive. Chemical Studies - It-was brought out that cutting fluids vary widely in formula and that it is impossible to determine what material is at"fault. -The problem is magnified because the material is expensive and is usually recirculated and periodically recharged. As a result, the formula changeb from day to day and the fluid likewise can become contaminated with many other materials. C. General Aspects a. Epidemiological observations are well established under certain circumstances. b. The laboratory investigations will be hampered by the vide variety of compounds in formulas and possible contaminants. c. The role of chronic skin irritation is very important. :1 9, Coal Tar (Polvcvclic Organic Ccrrcur.ds) A. Zridemi ologjcal Evidence Skin The participants accepted the association between exposure to coal tar and certain products. It was brought out that chronic skin.irritation has an important role and personal hygiene and plant housekeeping were also important factors. Attention was directed also to the fact that there are many compounds in various fractions ar.d that pure motcrials do . not exist. It was also noted that the number of workers in the industry itself is rather small. Lung ----- - - .. -_* v "No evidence to'date to indicate such a hazard. Other Organs No evidence. E. Experimental Evidence Animals Mice and rabbits have been used and carcinomas produced. Tests for "promoting" substances have been negative so the materials are considered essentially primary carcinogens. Chemical : The complexity of the various fractions hampers chemical studies and far the most part they have been confined to the determination of the benrpyrene concentration. Industry does not believe that extensive chemical fractionation would be fruitful. _Environmental factors probably have a large role, C. General Aspects (a) .Epidemiological evidence is apparently good for skin tumors, (b) Animal and chemical experimentation hampered by the complexity of the materials. (c) Personal hygiene and plant housekeeping are very important. i 10. Dyes and Intermediates (Polycyclic Organic Cocpounds) A. Epidemiological Evidence Skin Wo evidence presented. Lung No evidence presented. Other Organs Bladder tumors have teen definitely associated vith 3eta-nnphthylamine and benzidine. Jke participants accepted the evidence for these tvo'cexpounds but considered-the data-demonstrating *a hazard frofa other _ . caterials JLn this field as doubtful or not present. - pt vas pointed out_that Beta-naphthylamine should be - .classified as one of our most potent carcinogens. ~ B. Experimental Evidence . Animal Dogs' have been used principally and tumors have been induced by'feeding.- No one questioned these observations. Chemical Research in this area is very important." The question of contamination vith Beta-naphthyl amine Is very important and. may be the reason vhy other ccmrpcur.ds are considered hazardous. There is the possibility that ~ workers may have such-exposures- without _actually_vorking * vith this compound.- C. General Aspects ." a. Epidemiological studies seem conclusive for at least tvo compounds. b. Animal experiments have substantiated the field observations. c. Much additional vork is needed to determine if additional hazards exist. i 111. Ultrs-Violet Radiation (physical Agents) This area was not discussed due to limitation in tine. 12, Radioactive Materials (Physical Agents) A, Zcideriolorical Evidence Raciun, X-Ray, and fission products have all been associated definitely and clearly with carcinomas, sarconas and leukemias and involving bones, skin, bloocf and muccrus membranes. Radon still remains dubious because there is no direct evidence except v.-ith German experience, - All of the participants accepted the caus^T relationships which have'bcen demonstrated for actual tumor productions. Attention "was called to the'need to define the degree-and - -kind of- exposuro in more detail. Consideration should_be _ _ given also to question of cumulative effect and the latent _ - period. The problem of intra-uterins exposure was also brought up -as an example of the need for controls. B. Experimental Evidence ."Operation Greenhouse" demonstrated 100X leukemic response in mice above certain_dosages, Hany other animals have also been used successfully in similar studies'with various radioactive materials, C. "General Aspects - . - - " A. There is no question of the hazard to ran of this particular group of physical agents. B. . Co-carcinogerls needs Turther investigation. C* There is a great need for extension and application of controls die to the increasing use ana exposures to radioactive materials, both in industry and in the community. i