Document KzzM3vGYwEmgQ400My5XXdyX2

Occupational Diseases and Industrial Medicine Rutherford T, Johnstone, M. D. CONSULTANT IN INDUSTRIAL. MEDICINE, CLINICAL PROFESSOR OF PREVENTIVE MEDICINE AND public health AND CLINICAL PROFESSOR OF MEDICINE, UNIVERSITY OF CALIFORNIA AT LOS ANGELES Seward E. Miller, M. D. DIRECTOR. INSTITUTE OF INDUSTRIAL HEALTH PROFESSOR OF MEDICINE, MEDICAL SCHOOL PROFESSOR OF INDUSTRIAL HEALTH, SCHOOL Of PUBLIC HEALTH UNIVERSITY OF MICHIGAN, ANN ARBOR W. B. Saunders Company PHILADELPHIA * LONDON i960 Tj/treart many diverse forms of neoplastic growths constituting a group of disorders rather than a specific disease entitv. Ewing, years ago. defined a neo plasm as an autonomous new growth of tissue. C'owdry offers this definition ot cancer; ''Cancer is a condition manifested by a wide variety of ceils of chc body from before birth to the point of death in more or less remote response to the action of hundreds of influences. . . The over-all incidence of cancer has been increasing steadily lor more than a century. Despite tremendous amounts of study and research, the etiology of cancer remains a mystery. Such diverse agents as the various forms of ionizing radiations, ultraviolet light and a few chemicals ranging from complex organic structures to metallic salts can initiate the develop ment of cancer in man. Exposures to cancer-producing agents occur in many occupation? and are not limited to manufacturing industries. The farmer, sailor and outdoor worker suffer a high incidence of skin cancer from exposure to the ultraviolet portion of sun light. Within industry, there is exposure to chemical cancer-producing agents and to Some types of ionising radiations. Cancer-producing agents arc called car cinogens. Most occupational cancers occur in chc skin and rhe respiratory system, since they arc directly exposed to the various carcinogenic agents (oils, waxes, coal tar, pitch, soot and asphalt). Inhalation of chromium dust, nickel dust and nickel carbonyl, coal tar fume, "isopropyl oil" vapors, and radioactive dusts and gases may cause cancer of the respirarorv tract. In addition, inhalation and ab sorption of /J-naphthylamine or benzidine dust or vapors cause cancers of chc urinary bladder, the tissues affected being those undergoing the greatest intensity of exposure to the carcinogenic material. Cancer does not appear at once upon exposure to i carcinogen nor among all individuals exposed. Ln general, it is believed that the greater the incensxey of Page 322 the exposu Apparently disconrinu: who have 1 jobs, have no signs o some time been dem< As wi dinarily, t is imp3$i vironmeni teristics. 1 alcncc in in an cm] occupatioi non. In vi tional car is not astIn I?54. tional Car exposure cancers. < skin cane History Aid: among d Percival cancer, f phasized assemble dates, rej Eck much lax skin can as adequ carcinog< She the wint mg a group fined a ncoicimiuon o* of the body ions? to the :cr has been fl of Study jr --nts as w heals the develop- i and are not vorker suffer rnon of sunLicing agents re called car. arory system, (oils, waxes, :kd dust and ivc dusts and irion and abancers of the itest intensity n nor among ic intensity of OCCUPATIONAL CANCER m the exposure and the more porenc the carcinogen, the sooner cancer will develop. Apparently, once sufficient exposure has been incurred in a susceptible individual, discontinuing the exposure does not prevent the development of cancer. Workers who have been exposed a few or a number of years to a carcinogen and then changed jobs, have been known to develop cancer many years later. In the intervening years, no signs or symptoms appeared. Perhaps a microscopic cancer in situ existed for some time prior to the development of overt cancer, but such lesions never have been demonstrated in connection with an occupational exposure to a carcinogen. As with all occupational diseases, occupational cancer is poorly reported Or dinarily, the establishment of a specific case of cancer as occupational in origin is impossible until a carcinogenic substance has been identified in the work en vironment. Moreover, the occupational cancer has no specific identifying charac teristics. The problem of skin cancer is particularly difficult because of its prev alence in the general population. Scrotal cancer and bladder cancer, developing in an employee who has been exposed to a carcinogen, readily are recorded as occupational because of the low incidence of these cancers in the general popula tion. In view of the inherent difficulties in establishing a diagnosis of an occupadonal cancer and rhe paucity of materials established as carcinogenic to men. it is not astonishing that the total recorded cases oi' occupational ameers is small. In 1954. Huepcr collected all such cases. He has recorded 750 cases of occupa tional cancer in the United States. About half of these are bladder cancers from exposure to specific aromatic amines. Coal tar and pitch accounted for 110 skin cancers, chromares for 75 lung cancers and a few heavier petroleum oils for 70 skin cancers. History Although in 1531 Paracelsus noted the prevalence of a deadly lung disease among the Schnecbcrg miners, it is unlikely that he recognized it as cancer. Sir Percival Pott, in 1775, identified and described the first recorded occupational cancer. His description of scrota] cancer from soot among chimney sweeps em phasized both .severe prolonged exposure and the latent period. Eckatdt (1959) has assembled the htsmrical data on a world-wide basis in an interesting table including dates, reported agent, site and number of cases repotted (Tabic 15.1). Eckardt properly points our chat the actual number of cases is undoubtedly much larger due to inadequate reporting and lack of recognition. Particularly in skin cancers is this true Wc have not accepted arsenic, saltpeter, and asbestos as adequately proved carcinogens and believe that they probably act only as co carcinogens. Shecphcrtkrs in the Balkans and outdoor workers in Kashmir, who during the wintec carry beneath their clothing, next to the skin, pots of coals to keep ;ec r\ _r may ranging the :hc scrotum that the in* cvelopment 67 per cent the general third, nasal aloyee until arional cananccr in the in increased it. Pairustak- td this well. unlv on sta* tain rvpe or iv the most tile those of been recog- in *i'~ popuc ix, or c-. , from cate an incinay discover 3roup. Once work group nost helpful cally useless. s referred to the Council Occupational lent material ulation. Cra1 by intrinsic igencs might cr, the mate- with an inlould be less OCCUPATIONAL CANCER 327 Occupational Carcinogens There arc three categories of carcinogenic materials to consider. First, the established occupational carcinogens that have been proved beyond doubt as caus ing occupational cancer. Second, materials that arc suspected of causing occupa tional cancer but not proved. Third, materials in use in industry rhat have been established as carcinogens foe some types of animal in the laboratory but which have not been implicated as producing occupational cancer in man. Agents fall ing into the first two categories arc presented in Tables 13.2 and 15.3. Table 13.2 presents the generally accepted and established carcinogens and the sites character istically affected. Table 13,2, Established Occupational Cancer Producing Agents, with Sites* AGENT TISSUE 4-Aminodiphcnyl (xenylamine) Bladder Anthracene, crude Asphalt Benzidine and derivatives Skin Skin Bladder, ureter, kidiivy L Chromates Creosote ' Respiratory system Skin Lip Ionizing radiation (all types) Skin Lungs Blood forming organs Bone Eye Isopropyl Oil Larynx and sinuses Mineral oil, crude Skin Nnphthylaminc-bcta Bladder, ureter, kidney Nickel and nickel carbonyl Respiratory tract Paraffin, crude Skth Pitch Skin Shale oil Skin Soot Skin Spindle oils, aromatic Skin Tar. coal Lip Skin Ultraviolet rays Skin Eve Wax, crude from coal Skin * Modified from Occupational Cancer. i Challenge to the Physician. New Votk State Occupa- duiu 1 Career Committee. 328 Table tyy THE OCCUPATIONAL DISEASES * Suspected Occupational Canctr Producing Agents, with Sites* AGENT TISSUE Aromatic organic chemicals Arsenic Asbestos Benzol Be^llium Carbon black Chlorinated hydrocarbons Estrogens Isopropyl oil Mineral oil. crude Naphihrlamirvc-alph* Pitch Radiant heat Sodium nitrate, crude Tar. coal Liver Skin Liver Respiratory system Lung Blood forming organs Lung Skin Liver Breast (male) Lung Respiratory system up Bladder, ureter, kidney Lip Bladder Skin Skin Respiratory' system Bladder Blood forming organs * Modified from Oecupitionil Cccr. J Challenge to thv Phrskian. New York Sate Ouupntionai Cmkct Comraime. Table 15.3 presents chose materials that have been suspected of producing occu pational cancer but are in dispute or have not been proved as 3 specific carcinogen. Several points should be noted concerning Tables 15,2 and 15-3. In Table 15,2, the potency of rhe established carcinogens is not indicated. Particularly among the oils is this important, For example, shaic oil is a much more potent carcinogen thin crude mineral oil. Also, despite the high incidence of mule-spinner's cancer of the scrotum in the textile industry in Great Britain, none has occurred in the United States. The difference in the carcinogenic property of the oil in use ia the best ex it- planacion. In the United States, particularly since the studies of Braun and Truan, there is considerable conviction, that asbestosis does not predispose ro the develop* mcnc of lung cancer. Until further evidence is forthcoming, we have arbitrarily placed asbestos in the unproved or doubtful group and arsenic in the suspected group. Finally, some substances appear on both lists. This comes about because a substance may be a proved carcinogen for one site, skin for example, but not be established as a carcinogen for another site, such as the lung. Anaiinc docs not appear on either list since it now has been established char it is non-carcinogenic OCC despite report arc probably < Numcro' Even potent < vironments h 3, 4-benzpyre. of motor vch other expotec The U.S. tcrials tested P-H.S. Public referred to th Chief Sites As indie, tissue it reach words, it is tl that, of the f toiy tract--ar , tract, parcicu carcinogenic r The fourth a: 4cukcmia whi Skin- the skin, witf cancer lesions cancer of occ eases occurin are treated b\ arc predentin iscics from no tions of the b> results from < vapors direct! Pigment cinogenic oils areas of skin oils arc assoc tions arc con? ject to skin c cinogenic m:i lies* cue Occupacing occuarcinogen. . In Tabic .rly among jedtxsgai j cancer ot the United 2? best ciind Truan, e.drv-eloparbitrarily : suspected t because a but not be c docs cioc ircinogcnic OCCUPATIONAL CANCER 329 despite reports co the contrary in the older literature. Some entries in Table 15.3 axe probably only cocarcinogens. Numerous materials have been established in the laboratory as carcinogens. Even potent ones in the laboratory, although appearing in some occupational en vironment have not been incriminated as causing occupational cancer in man; 3, 4-bcnzpyrenc is one example. It is known to be present in the exhaust vapors of motor vehicles, yet no increased incidence of cancer among garage workers or other exposed groups has been demonstrated. The IJ.S. Public Health Service has compiled and published a survey of ma terials tested for carcinogenic activity. The second edition appeared in 1951, P.H.5. Publication 149. The student desiring to look up any specific material Lt referred to this voluminous publication. Chief Sites As indicated earlier, the sice of action of an occupational carcinogen is the tissue it reaches in greatest concentration tor the longest period ot time. In other words, it is the tissue suffering the greatest exposure. Thus it is not astonishing that, of the four major sites of occupational cancer, two--the skin and respira tory tract--are tissues of primary contact by carcinogens. The third site, the urinary tract, particularly the urinary bladder, is the body tissue most exposed when a carcinogenic material rapidly is removed from the blood by action of the kidneys. The fourth and last chief site, the hematopoietic system, is the site of origin of leukemia which is caused bv various forms of ionising radiations and benzol. Skin. Eckardr states that over 73 per cent of occupational cancers are of the skin, with coal tar and shale oil being the chief carcinogens. Fortunately, skin cancer lesions arc rcadiiv apparent and therefore cures arc more easily effected. Skin cancer of occupational origin is particularly poorly reported. It is believed that cases OCCuring among farmers and outdoor workers due co ultraviolet radiation arc created by busy practitioners but seldom reported. Occupational skin cancers are predominantly squamous cell carcinomas, having no distinguishing character istics from nun-occupational skin cancers. As might be expected, the exposed por tions of the body--the head, neck, hands and arms--incur most such cancers. This results from direct contact with the carcinogenic materials or deposition of such vapors directly upon exposed skin surfaces. Pigmentary changes in the skin have been reported from exposure co car cinogenic oils but arc not believed to be a precanccrous skin response. However, areas of skin hypertrophy and atrophy occuring on skin exposed to carcinogenic oils are associated with skin cancers. Skin cancers developing under such condi tions arc considered occupational. Uncxposed portions of the body also arc sub ject to skin cancer, particularly if the clothing becomes saturated with the car cinogenic material. Thus, oil soaked trousers convey the oil to the scrotum 3$0 THE OCCUPATIONAL DISEASES provoking mulospinners type scrotal cancer. Generally ihc latent period in skin cancer is long. 20-40 years or longer, thus years of exposure ordinarily arc rcqrnsite for rhe development of such cancers. In this connection, regular cleansing of the skin certainly must play a part in delaying or preventing rhe occurrence of skin cancer Several materials produce skin cancer and there are probably others chat have not been identified. The presently accepted skin cancer agents include ultraviolet iight: ionizing radiations, alpha, beca and gamma; coal tar, soot, pitch, creosote, crude anthracene, and crude waxes: shale oils and crude shale paraffin oils; petroleum products, lubricating oils, crude paraffin oils, fuel oils, tars, asphalr. pitch, and carbon black. The chief groups exposed to these agents arc: Ultraviolet Light. Farmers, ranchers, construction workers and espe cially outdoor workers are exposed, with greater risk in the south and at high elevations where the intensity of light is greater Ionising Radiations, These agents affirct radiologists, dentists, veterinariam chiropractors. x-ray technicians, and scientists and technicians in various nuclear energy industries, Coal Products. Work groups exposed so coal tar. pitch, soot, creosote or crude* anthracene include workers engaged in handling these materials in:* Gas works Coke ovens Blase furnaces Tar distilleries Patent fuel manufactories Lens industry' duringpolishing Building and allied trades Roofing felt preparation and handling Flooring materials Weatherproofing materials Sweeping roads Making of felt Briquette works Road building and repairing Coal-tar-pitch pipe making Battery making Cord making Paint making Electrical equipment works,making cables, carbon brushes, carbon elecerodes and insulation Work of seamen andfishermen Creosote or tar preservation of wood Working with impermeable paper and cardboard Caulking of ships Shale Products. Work groups engaged in the production of shale oils and shale paraffin oils. European mule-spinners. machinists and others who worked continuously with shale oils. Little or no shaic oil presently is being produced in this country and it appears chat little is being used in American industry. Petroleum Products. Those exposed to these agents arc workers engaged in rhe prim2ry production and refining of petroleum products, as well as "Table modified from Coal T*r and Cutaneous Catcinogcnwis in Industry. F. C. Combes. Charles C Thomas. '93< ' mu] an<j ligh izin arc lay ertit is n, iden sour ben; bon: ?ou: pytt Per' fsne> are Stats ting caus (salt ores with also wou It is acts or $3 like! radia the t inhaJ Will iod in skin / arc retjui* leansing of rurrence of $ chat haw ultraviolet i, creosote, oils; petrohalc, pitch, s and espe nd ar high ists. veteriin various x, creosote d$ in:*- iking i eiec- i wood paper f shale oils 'ho worked l produced dusrry. workers en as well as C. Combo, OCCUPATIONAL CANCER 331 mule-spinners, gunsmiths, paraffin pressmen, and a large number of varied metal and tool industrial workers. The Carcinogenic Factors. The precise mode of action of ultraviolet light in the production of cutaneous cancer is unknown. The same is true of ion izing radiation. However, in both instances, intensity and duration of exposure arc important. Also, absorption of these forms of energy by the basal proliferating layer of the skin cells appears to be necessary. In coal products, carcinogenic prop erties arc found chiefly in the heavy oils and anthracene oil. Pure anthracene itself is not carcinogenic but 1. 2-bcnzanrhracene and 3. 4-benzpyrene arc among several identified carcinogens in coal-tar and coal heavy oils. Coal products are the richest sources of carcinogenic agents yet discovered. The carcinogens in petroleum products arc closely related carcinogens to the bemanthraccnc and benzpyrene found in coal products, the benzenoid hydrocar bons. Petroleum oils vary greatly in their carcinogenic ability depending upon the source, with shale oils being the more potent. Arranged in order of carcinogenic potency, depending upon their source are oils from: Venezuela. Borneo, Rumania. Persia. California. Mexico, Mid-continent. Texas. Pennsylvania and Russia. Re fined oils arc the least carcinogenic and the suifonared oils used as detergents arc harmless. Pure mineral oil and vegetable oils arc innocuous. In the United States, carcinogens are not found in rhe mineral oil fraction of lubricating or cut ting oils. The chlorinated hydrocarbon present in lubricating and cutting oils can cause a folliculitis but never produces cancer. Suspected Skin Carcinogens. These include arsenic, sodium nitrate (saltpeter), radiant heat, chemical and physical trauma. Among those exposed to arsenic are workers engaged in mining and refining ores containing arsenic and workers engaged in the production of and working with arsenic alloys. Nursery and agriculture workers using arsenical insecticides also are exposed. Arsenical skin cancers are exceedingly rare, if they exist. Such a diagnosis would depend upon: 1. History of prolonged exposure. 2. Characteristic arsenical skin manifestations. 3. Demonstration of arsenic in the skin, hair and urine. It is the firm belief of those who have studied the evidence carefully thac arsenic acts essentially as a cocatcinogen but is not in itself carcinogenic. An excessive rate of skin cancer has been reported among the sodium nitrate or saltpeter workers in Chile, However, it is believed by many that this high rate likely ts due to some factor other than the sodium nicratc. possibly ultraviolet radiation. Radiation heat, chemical and physical traumas are not carcinogens, at the most they act only as cocarcinogens. Respiratory Tract Cancers. Soluble gases and particulate matter from inhaled air are deposited in the thin film of fluid covering the respiratory tract. With continuous respiration, these materials accumulate on the wails of the re- Si. lOgcnic ma> 55ucs would ract cancers sthal raincs. lung cancer $c and gases ies provided between 40 tor cbe total at this time fthe mines, ics of radio ? unknown, some radon cs also have itry. Ouud* [ung cancer. United States by the Pub t --from , .rion, udy in 1948, ;crs engaged seven chro:rrutc work>es of cancer lung cancer i in the gen>mate plants mna Baecjer $ chromates, omas in rats the environxnium causnpound and pear to exist the refining g and workof lung can- OCCUPATIONAL CANCER 333 Nickel. First from Great Britain, and more recently from Norway, have come reports and convincing studies implicating nickel as a respiratory tract car cinogen. The evidence for its being the agent responsible for cancer of the nasal sinuses is overwhelming. Also, the evidence indicates with certainty that it is a lung cancer carcinogen. Study of the work population in a Mond process plant has shown that the groups suffering the greatest exposure are those engaged in calcining the ore and those engaged in the extraction process using sulfuric acid upon the calcined material. In rears past, much dust wi< produced and good dust suppressive measures were not used. However, the gas nickel carbonyl produced in the Mond process of refining nickel originally was believed to be the only carcinogenic agent. Recently five cases of lung cancer have been reported from a small Norwegian nickel refinery utilizing an electrolytic process, not the Mond process, and so not producing nickel carbonyl. Thus the risk of cancer is not con fined to nickel carbonyl but is probably inherent in both solid 2nd gaseous forms of nickel. Prolonged inhalation experiments with animals have produced adenom atoid changes in the lungs of rats and guinea pigs but no carcinomas. `'Isopropyl Oil." In the manufacture of isopropyl alcohol using con centrated sulfuric acid, small amounts of impurities called "isopropyl oil" arc formed. As this process was used originally, four cases of cancer of the sinuses, one cancer of the larynx and one cancer of the lung occurred in the work group. With a change in process, "isopropyl oil" is noc formed and no further cases of cancer have occurred. Experimentally, "isopropyl oil" has produced skin cancers and there is no doubt chat it produces sinus and larynx cancer. Perhaps it is capa ble of producing lung cancer but this remains to be established. Among the chief constituents of "isopropyl oil" arc isopropyl sulfates, isopropyl ethers, and some polypropylene#. Precise chemical identification of the carcinogen has not been accomplished. Coal Tar. Lung cancer arising from industrial contact with coal tar has occurred with certainty only among coal gas workers. Generally, only workers em ployed in the rceort house, having cxrcnsivc prolonged exposure to the vapors and fume, have developed lung cancer. These cases have occurred when workers suffered direct exposure to the fume while working over or about the old style horizontal retorts. Operation of the modern rvpe retorts may or may not be attended with some risk of lung cancer. It will take time and detailed investigations to set tle this problem. Suspected Respiratory Tract Carcxnocens. As with skin, arsenic must be iisccd as a possible carcinogen. However, from the evidence, this is true only when the individual has been grossly overexposed to inorganic arsenic for a long period of time and exhibits gross chronic arscnicism. Probably such an ex posure could occur only when working with inorganic arsenical materials with little or no effort to control the arsenical dust in the work atmosphere. Three cases of lung cancer associated with pulmonary berylliosis have been reported. Also, Vorwald has produced carcinomas in rats following rhe inhalation 334 THE OCCUPATIONAL DISEASES of beryllium. Although beryllium may be a carcinogen, evidence that ir is the agem producing lung cancer in man is lacking. As a precautionary measure beryl lium dust should be carefully removed from the work atmosphere. Urinary Bladder Cancer. As previously pointed out. bcta-naphthylamine and benzidine produce cancer of the biadder. Alpha-naphrhylaimoe is suspected of this, but it has not been proved. Aniline definitely does not produce bladder tumors and should be cleared of this implication. Beta-naphthyiaminc is me tabolized in the body to 2-amino-1-naphthol and has been indicted as the car* cinogen. Less dear is the carcinogenicity of the metabolite of benzidine, but per haps 4, 4-diammo-3-diphenyl hydrogen sulphate is rhe culprit. The uncertainty arises because benzidine is a much less potent cancer producing agent, and the carcinogenic metabolite probably produced in much smaller quantity. One other compound, xenylaminc, or 4-aminodiphcnyl. has proved to be a potent agent in producing bladder cancer. Studies of its metabolite excreted in the urine indi cates the presence of 4-aminodiphenyl and 4-amino*3*diphcnyl hydrogen sulphate, which later increases in quantity and hydrolyzes to 3-hydroxy-4-ammodiphenyl. Thus rhe orthohydroxy amine conjugates have been isolated in high concentra tions as urinary metabolites from bladder cancer agents bcta-naphthylamine and 4*aminodiphenyl. A much weaker bladder cancer agent, the orthohydroxy me tabolite of benzidine, is present in the urine in a lower concentration. Work Groups Exposed. In places where the primary aromatic amino beta-naphthyiaminc, benzidine, xenylaminc. and perhaps alpha-naphthyiamine arc used, workers run the risk of developing bladder tumors. The men actually en gaged in handling these materials ate most exposed when scraping or cleaning filters, or when materials being worked produce dusts, or vapors. In modem plants with built-in protection, perhaps the maintenance men constitute the most ex* posed group. Workers employed in the manufacture of basic dyes, the manufacture of some rubber anti-oxidants where ilpha-naphthylamine or xenylaminc are used in the process, and where benzidine is used tu harden rubber, may be exposed to bladder cancer agents. Adequate protection should be provided foe textile workers and employees in the priming industry where alpha-naphthyiamine and benzidine are used. Bcta-naphthylamine also has been demonstrated in small amounts in coal car from gzs works, and so workers in this industry should be adequately pro tected. Prevention Good engineering control of dusts and vapors, the use of closed systems, and observance of meticulous personal hygiene arc required. Es timations of the amount of free amine in the urine have been reported as useful in checking the adequacy of protective measures, The Hematopoietic System. Ionizing radiations, particularly gamma or x-rays and benzol, are the agents most incriminated in rhe production of occupa tional leukemias. Whether these agents are true carcinogens or merely act as co- catcinogens is unknown. O IONIZ is discusscto gamma clinics, ph is used to tcrials. Ai not be cm the equip; not be ex The i there is c. duced in x exposures The Cobalt150. places, ga forgings, arc well f industrial thorium with the been indi Ben discussed tem arc ] cion of cl kocytosi: intoxicat referred i marrow t aplasia ? and fina. observed or subar chat perl As of long sure to velop at SUMM The and this tcryl- mine cctcd udder me* : car:per* iiincy d the other tic in indi cate, icnyl. entrae and f me- mines ne are ly cn- \ >st ex- fsome in the ladder rs and ne are n coal T p- use of cd. Esuseful ima or iccupa: as CO- occupational cancer 335 Ionizing Radiation, The action of various forms of ionizing radiation is discussed in Chapter 20. It is sufficient to state here chat occupational exposure to gamma and x-rays occurs in the nuclear energy industry, hospitals, medical clinics, physicians' offices, research laboratories, and in some industries where x-ray is used to detect flaws in metal castings or to examine a variety of other ma terials. All workers with these agents should observe adequate precautions and not be careless or indifferent concerning personal exposure. In many industries, the equipment is installed in such a manner that when in operation a worker can* not be exposed. The incidence of leukemia among radiologists has been reported as high and there is experimental evidence to support such reports. Leukemia has been pro duced in mice by x-rays, with small repeated doses being mote effective than larger exposures over a shorter period. The use of radioactive isotopes emitting gamma rays in industry (particularly Cobalt60, Iridium1*1, Cerium1*1, and Thulium170) has been increasing. In some places, gamma radiography is replacing x-rays as a means of examining castings, forgings, etc., and no doubt will find increased uses in industry. Such materials arc well guarded and shielded and so far no cases of leukemia associated with the industrial uses of radioactive isotopes have been reported. Although radium and thorium have considerable use in industry, cases of leukemia in those working with these substances have nor been reported. As yet, these materials have not been indicted as the causative agents of occupational leukemia. Benzol (benzene). The many industrial uses of benzol as a solvent are discussed in Chapter 11. Tliert its depressant effects upon the hematopoietic sys tem are presented, but not its production of leukemia. The gradual transforma tion of the bone marrow from apJasia to hyperplasia has been reported. Also, leu kocytosis' has been reported as a transitory finding in the early stages of benzol intoxication. The varied peripheral blood findings in benzene workers have been referred to as the "Icukemoid condition." This reaction is only one of many bone marrow reactions to benzol intoxication. Among such reactions arc complete aplasia, aplasia with leukemoid reaction, acute leukosis without peripheral leukocytosis, and finally acute leukemia. All forms of acute and chronic leukemia have been observed among workers suffering from benzol intoxication. However, the acute or subacute myeloid types of leukemia appear to dominate. Vigliani has suggested that perhaps many cases of aplastic anemia actually were aleukemic leukemias. As stated in Chapter It, we are not inclined to give credence to the reports of long delayed eases of benzol intoxication developing even years after the expo sure to benzol has ceased. However, it seems possible that leukemia might de velop at some time after a prolonged exposure to benzol had ceased. SUMMARY Thousands of chemicals have been examined as to their carcinogenic powers and this information is contained in the previously mentioned Public Health 336 THE OCCUPATIONAL DISEASES Service publication. Numerous materials established as, or suspected of being, car cinogenic agents are used in industry, ye: today it is astonishing how seldom we see a true occupational cancer. This can be attributed to the institution of strict controls, chiefly engineering, through closed sysrems. ventilation, personal protec tive devices, and others, which serve to prevent exposure. As more workers in the older age groups continue to work in industry, more eases of so-called "naturally" occurring cancer will be found among these older employees. At this time it is believed that we have established as carcinogens only the mote potent of these agents. Moreover, it is known that marked variation exists between individuals as to cancer susceptibility. Theoretically, the weaker carcino gens should be able to produce cancer only in the more susceptible individuals. Awareness of all these facts makes it dear that detecting the weak carcinogens is next to impossible solely upon a clinical basis. Studies to establish a weak car cinogen of necessity must be of the epidemiological-statistical type embracing large groups of people who have been exposed for long periods of time. Although these studies arc arduous, they are needed to clarify the status of doubtful or dis puted cancer-causing agents, and to uncover presently unknown environmental carcinogens. We should recognize the woefully weak and inadequate status of our present knowledge of cancer etiology and the means by which carcinogens produce can cer. It appears certain that some or many materials we now accept as carcinogens are in reality only cocarcinogcns. However, this makes little difference, If. as a result of its presence in the work environment, workers develop cancer, such a material muse be entirely eliminated from the work environment. If it is con tinued in use. it must be so completely controlled that no worker may be expected to develop cancer. The possibility of a non-cardnugenic material being metabolized in the body and a carcinogenic metabolite being produced always must be recognized. Also, the long latent period is characteristic of weak carcinogens. Particularly in cancer of the internal organs are these factors of importance. Every physician should be alert to the possibility of occupational cancer arising from new materials not now suspected of being carcinogenic. Finally, w would be remiss in closing this chapter wirhour making a plea foe the keeping of full medical records on all employees, not only as to diseases diagnosed within the industrial clinic, but on all cases diagnosed and treated out side, thus making complete medical records available for all employees. Such rec ords are indispensable when work groups are under study for an occupational dis ease. particularly cancer. BIBLIOGRAPHY L .M.: PulmoMfv Oreiwxfl* ifl Chromate W<kcn. 1. A Rfv.r* ni the Utemuct tod Hepnn ol A.hLA, Arch. Indw. R.rMffT. ipso. Bcpr. A M Pulmoniry Cirpnom* ifl Chfonww Workm. I!. Inider on BaU of Hospital Rfie- ores. a.m.a, inUw,,. n.. *-**. iw. ;cu oeing, car* how seldom we nitution of strict personal proteex workers in the railed ''naruraily'' inogens only the i variation exists ; weaker caicinocible individuals, ak carcinogens is alish a weak car- cvpc embracing if time. Although t doubtful or disn environmental rus of our present ens produce can* :pc as carcinogens lifferencc. If, as a op '-*ncer, such a i ' " it is conru . jCexpected )li2ed in the body recognized. Also, ncularly in cancer ivsician should be materials nor now >ut making a plea snly as to diseases d and treated ouciployees- Such rec* l occupational dis- ' Cstfinom* *n Chmmitc u Buts of Hospital Reci. H..2.6Q1.1950. OCCUPATIONAL CANCER 33 7 > Bidnrup. P. L.: Occupational Cause* of Lung On. ccf. Transactions of the A*m. of Industrial Medical 0fleets, 9:2.195V. *, Biosmtp, P. T... and Case. R. A. M.: Carcinoma of the Luna in Workmen in the Bichrcmates-Predue inf indattiy in Great Britain. Brit J. Indust. Med. li.260.1950. 5. Boater. G. M.. fluid*. J. G. and Stewart. M. j.; Occupational Cancer of the Urinary Bladder in Dyestuffs Operatives and of the Lung in Asbestos Tc.vrik Workers and Iron-Ore Miners. Ad. J. Oin Path. J5.-126. 1955. 6. Braun. D. C..and Truan. T. D.: An n.pidcmwikgical Study of Lung Cancer in Asbestos Miners. A.MA. Arch. Indust. W., I 7.AJ4. 1??#. 7. Cancer of the Lung; An Eviction of the Problem. Proceeding* of the Scientific Sesiion Annual Wee ing, November J 4.1955. American Cancel Soc>er-\ Inc.. i?. A. Ccmbcr. H..and Watson. J. A.. Bronchogenic ur- rinotna from Radioactive barium Sulfwi:. A.M.A. Arch. Indust. H.. 17.2.W. l?13. 9. Combes, f. C-: Coal T*r and Curancous Circutogenesi* in Industry Charles C Thoms*. Kuhiwna. 5pringficld, Illinois. 1954. 10. Council on Industrial Health. A.M.A.: Occupa tional Oncer Methods of Fp>dfmtc'lg>ci -Study. JAMA., rdd/21'1.195#. [ 1 tawdry, Js. V ; Epidermal Ga.-eimjgcni.-Ji* In Ad vance* m Cancer Research. Vl. f. Edited by Gteensuin. I. P.. and Haddo*. A Academic Pros. It*.. New York. 191 i12. Cramer. 'V.: The Importune* ofStatistical Invest'giruinv m the Campaign agaum Oncer. Am. J. Cancer. 29.-1. ivj'. !}. Doll. R.; Motralitv from Luttf Cartier in Asiiow* Worker*. Brit J. Indust MvH.. J2.B1. 19*1 14. Doll. R.. Cancer of the hung and N<t m Nickel Workers. Brit. J. Indus;. Med.. I'-21*. W55. S> Doll. H. OcevpitioiMl Lung C'.invi, A Ae-wen. Brit. J. Indust. Med., NJ.1SI. !W. m. Erkardc, R. E . Cardnogcnieitv of Petroleum Prod ucts with Particular Reference the Aummnwr indunm. Induti. MuU. Outm* 17. Bckardt. R. E: Industrial Carcinogen*. Mcxlrm Monograph* in Intiui-triiu Medicine. Ctui'c IK Sir.ucon. New York. 1V5V 15. Editorial: Silicoets. Aabe'tosiv and Cancer of the Ung. Am./. Clin. Path., jr.if**. I?11. 19. Ewing. J.: Neoplastic Disci.**, 1'ouFTh Ed.. VC' B. Saunders Company, Phil^clphi*, 19*1 2a Federal Security Agency, P.H.S.. Health of Work er* in Chromate Producing Industry: a .Study. Prdet*l Security Agency, OivUion of Occupational Health of the Bureau of State Services. RILS.P. Nv 193, 19SJ. 21, Fischer. H. G. M,. Priestley, W.. Jr., Bby, L T.. VPark*. G G-, and Rehncr,Jr.: Properties of High-boiling Petroleum Products. A.M.A, Arch, indusc, H.. 4:M, 1951. 22. Hendricks, N. V., Betty, C M , Lionc. J. G, and Thorpe. J.J.: Cancer of the Sootum in W Press- t.ient. A.MA. Arch. Jodutr. H-. J9.-524, 1959 25. Huepex. W. C . Hrperimoinl Caidnogenk Studies on Hydrogenated Coal Oil*. I. BerguittS Oils. Ut- dust. Med Surg H.-il. 1956. 21 James. W. R. L: Primary Lung Cancer in South Wales Coal Workers with Pneumoconiosis. Brit J. Iflduit. Mod, 12.T, 1995. 25. Kaplan, 1.: Relationship of Nontoua Gam re Gar- einoma nfthe Lung in Rulrmd Wocfcera JA.MA- l7l.tW. 19. 26 Kotin, P., Fallt, H. L, and McCaauiion, CJ.: Can- ca Clinic Pulmonary Cancer with 5pecial Refer ence ro Air Pollution and Pathegenqi*. CA Bulk, rin, Manji-Apr.. 195t, page 62. 27. Lionc. J. G.. and Denholm. J. S : Cancer of the Scrotum <n Wav Presuncn, II. Clinical Obacrva- uoM. A.MA. Arab Indusc. H. 19-690, 1959. 28 Mickle. W, and Grafonm, F.: Cancer of the Re spiratory System in the U.S. Chromate-producing Industry. Pub. Health Rep- 6j.'lll4, 1941. ^ Mancuso. T. F.. Occupationii Cancer and Other Health haaurda in a Chromite Plant; A Medical Appraisal. II. Clinical and ToxicoJogk Aspect*, Indusr, Med. Surg,. 20.-993, >951- >0. Munvmatteo, E.: Cutting Oils and Squamous Cell Carcinoma. Pan I: Incidence in a Plant with a Report of $>* Case*. Brit. J. Indust. Med. 12: 240. 1955. >1. Nau.C. A.. Neal. J.. and Swnbridge.v,; A Study of rhe Physiological Effects nf Carbon Black. I. Ingestion. A.MA. Arch. Indusc. H.. 17.-21. 195B 32. PeKer. S.. ind Pick. P - Leukemia and Other Ma lignancies in Physicians. Aru. J. M Sc.. 224.154. 1952. ' .3}. Raven. R. W.. editor: Cancer. Puneiwotrh 4s Co.. I.rd., London. Volume 1, 1957, Volume >, l?9t. >4. Sampvy, J. R.: Inorganic Carcinogenic Agents, Iftduir. Med. 5uj" 1959- JJ. Sclfscr, H .ind Sartwell, P. E.: The Application of Cobalt Atulyiis to the Study of louring Ra diation and Longevity in Physician*. Am. J. Pub. Health, 49:1610. 19595& Smith. W. .. Sunderland. O A., and Sugiun, K.: Expcrunottal Analysis of the Carcinogeok Activity of Certain Petroleum Pnoduett. A.M.A Arch. InduM. H.,4,'299,1951. J7. Unsolved Cllnkal Ptobktna; in biological perapee, tivc. Volume II of Medical Research: A MIdccn- tux* Survey. Little. Brown and Co.. Bwton, 1955. i 19. ViflitAi. E. C, u*i Sojtn. G.: LcukemiM: Jroco Beiucne, d- Livoro, iv.'41, 39. Von Hum, E., *nd Malleete, F. 5.: Studio eft cite Toxicity *nd Skin Eflect* <rf Compound! U*cd in cite Rubber and Pluck Indujcriei. HI. Carcino genidcy of Carbon Black Extract*. A.M.A. Arch. lorfuit. H., 5-S27.1912. 40. VonriM. A- J.: AdcnoCUCimon* in the lUfif of Albino MO Expand to Compound? of BenUium. Proceeding of the Scientific Seuion, Am. Cancer Stxjcrt Annual Meeting. Nov. }-J, 1V5}. i(