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in the Chemical laboratory Edrfed by NORMAN V. STEERE, 1 4 0 Melbourne Ave., S.E. Minneapolis, Minn. 5 5 4 1 4
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CXXVIII. Occupational Cancer Control and Prevention (Concluded) Winfred F. Malone, Ph.D., Prevention Branch, Division of Cancer Control and Rehabilitation. National Cancer Institute. Bethesda, Maryland
There is also available to scientists and researchers Cancerline, which is a cornputer-based system for the retrival of ongoing information and abstracts of published materials an cancer. These report9 can he viewed a t remote terminals or printed out and sent t o users by mail. A center for world-wide information on ongoing activities in the areas of carcinogens is planned as part of this activity. The Chemical, Environmental, and Physicel' Careinagenesis and Epidemiology Information Analysis Center being developed as part of Concerline will include information on eareinogens and chemical careinogenesis; environmental and occupational eareinogenesis; radiation earcinogenesis; epidemiology of human cancer and similar studies of animal populations; and caneer prevention information. This d s t s bank is part of the International Cancer Research Data Bank Program of the National Cancer Institute. Sizeable contributions in time and effort are made to caneer control by other Federal agencies. The National Institute for Occupational Safety and Health pursues studies concerned with standards and control of carcinogens in the work environment. The Department of Labor's Occupational Safety and Health Administration is concerned with enforcing standards for levels of carcinogenic materials in the workplace. The Environmental Protection Agency has legislative mandates with regard to controlling carcinogens in the general environment. The Nuclear Regulating Agency and the Energy Research and Development Agency, formerly the Atomic Energy Commission, because of the relationship between caneer and radiation, have conducted a full spectrum of research and control activities. Because of their responsibilities involving servicemen and veterans, the Department of Defense and the Veterans Administration conduct control activities, including the outstanding pathology effort of the Armed Forces Institute of Pathology.
tional exposure to carcinogenic materials. One group is comprised of uranium miners from the Colorado plateau, and the other consists of workers from the Tyler, Texas, area who have had exposure to asbestos. These are population studies on groups a t high risk to the development of occupaThe Department of Health. Educntion, tional cancers. and Welfare is in the process of dwelop~ng A screening test is not intended t o he disrnndards fur all its own laboratory opera. agnostic but is performed on apparently tions involving carcinogenic compounds. healthy people. I t is used on a mass basis, These standards will be mandatory for all may not be extremely accurate and is relaDHEW laboratory operations when they tively inexpensive. A diagnostic test, in are adopted. The DHEW standards will he contrast, is only performed when there are prepared in two sections: (1) Carcinogen indications. I t is used an an individual safety standards and (2) carcinogen safety basis and is usually both more accurate and monographs. The standards will define the more expensive than the screening test. responsibilities of each DHEW agency, the Several research investigations in the area laboratory supervisor and worker. They of metabolic epidemiology are undergoing will establish requirements far instituting a study and evaluation. They may be imporeomprehe&ve safety management protant for identification of high-risk groups gram, and they set forth general safety and pre-malignant conditions. principles which are tb be employed in the Although certain chemical carcinogens handling and use of chemical carcinogens. have been shown to he cancer-producing The documents will be available to the without structural modification, many othpuhlic and ought t o he of great assistance ers require structural changes before their t o private laboratories involved in carcinoultimate active forms are realized. Whether gen research, synthesis, or handling. cells of a particular tissue hecome eonvertControl activities to reduce the risks ased into tumor cells would appear t o desociated with the use, distribution, and dispend, perhaps, on whether the appropriate oosal of ootential carcinoeens can he eltabenzymes needed to convert a carcinogen to ii$hed th;ouyh the application i,f the sqrund its ultimate active farm are present in or principles of toxicology, industrinl hyg~enr. can he induced in the cells. An example of and occupational medicine (Olishifski and such a n enzyme is sryl hydrocarbon hyMcElroy, 1971). While probably none of droxylase which is involved in the activathem is sufficient for complete control, extion of certain hydrocarbons. Aryl hydrocept the unrealistic one of absolute prohicarbon hydroxylase is one of the mierosombition of exposure t o carcinogenic hazards, al mixed-function oxidases found in many the balancing of controls with reduction of tissues in the body, including the liver and exposure will reduce risks. Substitution of lungs. Following exposure t o polycyclic hyless hazardous materials and processes, drocarbons, such as BAP, the enzyme acscreening, prevention education. and mot,. vatimal programs. as urll as m a n n ~ c r ~ s l tivity of aryl hydrocarbon hydroxylase is rommmnent to make the total syslrm rerapidly increased. Evidence indicates that BAP and other polycyclic aromatic hydrosponsive to these controls, will contribute substantially towards reduction of human cerbons initially undergo metabolic activacancer incidence. tion to reactive intermediates, possibly epoxides, by this enzyme system. The eporThe WHO Expert Committee on Early ides formed during the metabolism of these Detection of Cancer indicated that more compounds may then interact with DNA to than 5096 of all cancer patients could he cured if the disease were diagnosed in its cause eytotoricity, mutations, or malignant earliest stages and appropriate treatment transformations (Brsun, 1974). were given. Two large studies are underway Kellermann and associates (1913) were on the development and detection of canalso able to demonstrate genetic variation cer in individuals who have had oecupsContinued on page A510) Volume 52. Number 11, November 1975 / A509
in aryl hydrocarbon hydroxylase enzyme inducibility by using cultured human lymphocytes. The normal white population showed three separate groups having low, intermediate and highly inducihle aryl hydrocarbon hydroxylase activities. The frequencies were 49.7%, 45.9%, and 9.4%, respectively. Fifty patients with bronehogenic carcinoma were studied and the frrquencirs of carcinoma in the three groups were 4% ior the low. 66% ior the intermediate and R(rb fur thr highly indurihle group. This data indicates i h i t susceptibility to hronchogenic carcinoma might be associated with higher levels of inducible aryl hydrocarbon hydroxylase activity. At present there are problems with the reproducibility of the test. However, these are mainly difficulties related t o lymphocyte culture techniques, and i t is hoped they will be worked out shortly. If this work can be further substantiated, then i t seems likelv that future screenine.. nrograms inrlude d~terminationof aryl hgdnrcnrhm hgdro*g.ase inducibility and a c t i w ty in certain high risk populations. Another example of the possible use of metabolic epidemiology in detection is the presence of elevated levels of polyamines; i.e., putreseine, spermidine, and spermine in the urine using gas chromatography and fluorometric analyses. These compounds are present in urine in the case of certain tumors (Russell, 1971) and i t might be passible ta utilize this technique for screening high risk populations. I t might also he possible a t same point to utilize immunological techniques such as radio-immuna-assay. Immunological techniques have not been used before for occupational cancer screening; however, such procedures may ultimately find their way into more sophisticated diagnostic programs. Recent developments in the field of sputum cytology have refined the techniques so that i t can be used to identify the lung cancer risk of small population groups. This is done by identifying the number of workers with abnormal cytological findings. Persons with the most severely abnormal cells in their sputum (marked atypical cells) have a considerably elevated risk of lung cancer. Though only a relatively small number of workers with abnormal findings will ultimately develop cancer, the propartion of abnormal cytological findings is proportional to the ultimate cancer risk (Nasiell, 1968), (Saccomanno, e t al, 1963). Several aspects of developing a caneer control program including identification of the active agent, and identification of those a t risk, have been discussed. I would like to turn t o a consideration of how to prevent those actions which add t o tumor burden. Occupational exposures generally involve higher concentrations of the agent than is true for environmental situations, are more frequent, exist for more extended periods of time, and generally the routes (through the skin or inhalation rather than diet) are different than general public exposures. Partly because of these differences, the industrial exposures can be better monitored and controlled and the industrial worker trained with regard to appropriate preeau-
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A510 / Journal of Chemical Education
tions. The education approaches, however, to primary prevention should complement but not replace or mute less stringent industrial hygiene practices. The effectiveness of controlling caneer through prevention education may be illustrated by the 30% reduction of lung cancer mortality among British male physicians during the period of 1954-1964 when many stopped smoking, compared with the 25% increase among all men in England and Wales who generally persisted in smoking during the same period of time (Doll, 1967). Many chemists are unaware of the potential carcinogenicity of some laboratory reagents or industrial compounds (Dinman, 1974). Many chemists are guided by the philosophy that all the deleterious effects of exposure to hazardous agents are found to appear within 24 hours. Laboratory work with such compounds is frequently casual and even sloppy. Common sense precautions and an increased educational effort come t o mind. These might include hut should not be limited to: 1. Clear labeling of carcinogenic or potentially carcinogenic materials. 2. An effective educational campaign including shipment of fact sheets with commercially supplied chemicals, development and publication of proven safety guidelines for the laboratory and industrial setting. 3. Familiarity with all reports on eareinogenicity on compounds with which one is working. 4. Formal training on toxicity of chemicals in academic programs. 5. An active education program as part of the activities of professional societies such as the American Chemical Society. The application of modern technology to industrv involves an ever increasine imoact most economical means of producing a useful and saleable product. In the classic approach the economic interest of investors, workers, and ultimate users were considered in that order. Science and technology have revealed a new and vital factor in individual stewardship. That factor is the effect of the manufacturing and industrial process itself on the health, safety, and welfare of the worker, the public, and the environment. The innovative process in man's quest for better and cheaper products and the proliferation of related manufacturing technologies assures that the unknowns always overshadow assessable quantities. However, it is essential that projections into the economic future through marketing forecasts, etc., be equally matched by health impact forecasts and appropriate weighting in the decision-making process. The subtlety and newly understood possibility of extended latency of cancer from chemicals must be given careful eonsideration by the industrial community a t every level. Progress in caneer control requires the effective mobilization of resources for the prevention of cancer and the development of a framework for the expansion and systematic application of these resources (Meshenberg, 1974). The planning and operation of cancer control measures are part of a broad strategy for improving the health of the Nation. They embrace medical, educational, and
environmental approaches t o health pmhlems. Translatine the stated ouroose and specific ohjret~ves uf the- Cancer Control Program lnro n wurkable approach requires the creation of a pragmatic partnership which is designed t o encourage voluntary action by everyone t o identify and limit those activities that pose risks to sofiety. It was announced recently that 11chemical omnanies have established an Insti-
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profiles for new chemicals and on older ones. This will relieve the problem of smaller companies that cannot afford t o earrv out extensive toximloeieal studies on t h e i r products. The lnsr~tute,I prriume. will nlro undertake chronic tuxicily studies on rhcmirals which appear in the industrial environment; and thus the results would he henefieial t o all chemical companies in protecting their workers. In my introductory remarks, I noted that i t was 200 years ago that Percival Pott reported occupationally related cancer in chimney sweeps. In this, the hicentennial year of the discovery, it is fitting that the American Public Health Assaeiation should choose as the theme for its annual meeting, "Health and Work in America." I t is gratifying to learn daily of the number of professional organizations, industries, and labor organizations that wish t o collaborate in the cancer control and prevention prom9m
I have touched upon several of the major aspects of occupational cancer. These problems are not merely scientific and teehnical, hut are prof&ndly human, anxiety producing, and deserving of your most serious consideration.
Fraumeni. J. F.. Jr. 1975. Chemicals in the indudion of respiratory tnd tumom. Praeedings of the Eleventh int. cane*, cong., Exeerpfs Medies. Goldberg, L., Ed. 1974. Careinopenesis testing of ehamicah. Chemical Rubber Co. Presb, Clewland, Ohio.
Hsnwell. J. L. 1951. Survey of mmpounda which have been tested for carcinogenic activity. Second d..PHS Puhl. No. 149, Wash., D.C., U S GPO, 583: Shubik, P., a d J. L.Hertwel1. 19.57. Suppl. 1 to the above, W-h., D.C., US. GPO, 388: Peterr, J. 1969. Suppl. 2 to the above, Warh.,D.C,U.S.GPO.655. Hoover. R. N., T. J. Mason. E? W. MeKay, and J. F. Frau. men;. R.. 1975. U.S. cancer mortslity: geographic and so. eio~conamiepatterns, Persons a t high risk 10 cancer: an .pprCxh to ceneer etiology and control.
Hueper, W. C.. and W. D. Conway. 1964. Chemical car& nogenesis end eencers. Charlea C Thomas. Pub!.. spring. field. 111.. 197-257.
Kellermann. G., M. Luyten-Kellermmn, and C. R. Shaw. 1973. Presence and induetion of exoxide hydras* in cul. turcd human leukocyte^. Rimhem. Riophyr. Re$. cammun., 52:712-71fi. Ke11ermsnn. G.. C. R. She., and M. Luyten-Kellermsnn. 1973. Alyl hydmcarbon hydrorylaso inducibility and bronehogenic carcinoma. N. Engl. J. Mad., 289:93&937. Li. F.P. 1969. Cancer mortality among chemist%J. Natl. Cancer Inst., 431159. Lilenfdd, Pederson. sad Dowd, Eds. 1967. Cancer epi. demiology: methud3 of study, Calrulation of relative risk8 from reiraspeetive studies. John Hopkinr Prear, Balto., Md.,131-140. Mantel. N.. and W. R. Bryan. 1961 Safety tastingof csrcinogenic agents. J. Natl Cancer Init., 27:155470. Msugh, T. H. 11. 1974. Chemical earcinogenesis: a longnegleefed field blossoms. Science. 183:94O-946 McMiehael. A. J., R. Spirtan, L. L. Kuppar. 1974. An epi. demiologb study of morfslity within a cohort of rubber workers. J. Occup. Mad., 16:458-644. Meshanberg. J., F. Bed, and D. R. M m n a . 1974. Health planning and the environmenf: s preventive focus, Amer. Soc of Planning Officials, 1313 E. M)thSt.,Chirago. Ill.
LITERATURE CITED Braun, C. 1974. The biology of cancer, Addiron-Wesley Pub1 Co., Reading, Me*. Bryan. W. R.. and M. B. Shimkin. 1943. Qvanfifstive analysis of dm-response dats 0bfsined with three carcino~enichydraearbons in C3H male mice. J. Nstl. Csneer Inrt.,8:SO3-631. Cancer fa& and figures. 1975. American Cancer Society, Inc.. New York. N.Y.
Nasiell, M. 1968. Sputum~cytologlcchanges in smoker$ and non-smokers in relation to chronic innammetory lung diseases. Acts Pathol. Microbioi. Scsnd., 74313. Nowill, v. A. ,974. Regulstory decision making: e seien. li.ts role. 3. Wash. Aead. Sci.. 6(:2:31-47. Olinhifski. J. B, and F. E. MeElroy. 1971. Fundsmenfalr of industrial hygiene. National Sahty Council, Chicago, 111.
Polt, P. 1963. Chirugical observation8 relative to the cancer of the scrotum. Lond., 1775, reprinted in Natl. Cancer. Innt Mono, 10:7-13. Chemicals being tested for esreinoanrity by the bioasay opawtions segment. 1975. Division af Cancer Cause
and Plevention. Natl. cancer tnrt.. Bethesda, Md. Christenpen, E., Ed. 1974. Toxic subtmees list, 1974 ed. DHEW. Natl. Inst, of Oeeup. Safety and Health. Rack"ilk Md. Dinman. B. 197h The nature of oecupstionsl cancer: a critical review and present problems. Charles C. Thoma.. SprinpcTeM, 111.
Principles for the tasting and evelverion o f drum for car. einogenicity 1969. WHO Tech. Rep. Ser.. No. 426. Progagainat cancer. Nail Advisory cancer Council. DHEW, PHS. NIH. k h n , L. 1895. Bleneneeschwulste be1 fuchr in Arheiten. Arch. Klin. Chirugle, 50:538600. R w 1 . D . H. 1971. Nature iLond.). 223.NB. 114-145.
Doll, R. 1967. Prevention of cancer Pointers from epidermioloey. N"ffidd Provincial Hospital Trust. Land., Eng.
Ssemmanno, G.. R. P. Saundors, H. Ellis, V. Archer, B. Wmd, and P. Beckler. 1963 Concentration of carcinoma andlor atypical cells in sputum. Aeta Cytol. 7305-310.
Eckardt, R. E. 1959. Industrial carcinogens. Greene and Sfratton, New York.
SEER Pmgram. 1976. Program of cancer surveillance, ep. idemiology, and end rosu1ts reporting implementefion. DHEW,PHS,.NIH.
Evsluation of carcinogenic risk of ehemieals to man. 1974. IARC Monographs, Int. Agency far Research on Cancer, WHO. Lyon, France.
Selikaff, I. J. and E. C. Hsmmond, ods 1975. Toxicity of vinyl ehloride~polyvinylchloride. Ann. Aead. Li., 246.
Evaluation of environments1 carcinwens. 1970. Ad Hoc
Shubik. P., and J. Siee. 1956. Chemical cercinogenesis a% I chronic safety tent. Cancer Res., 16:725742. The Conference Board. 1971. Industry roles in health Esrc. 845 Third Ave., New York, N.Y.
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