Document DDX6eZVJvRwk0jNLr2N5eb49N

FILE NAME: Oil Industry and American Petroleum Institute (API) DATE: 1959 DOC#: API112 DOCUMENT DESCRIPTION: Book Excerpt - Occupational Cancers & Industrial Carcinogens i ^o^oo^:M c(oo^ w * ^octocJpjocxjoJcoJ] R T I. :en a book de Jolie of Poiciflemper ; and he diforders to ziers, and the : : but there is iet of people, owledge, been .he chimney- nakes its firft e in, the infe it produces a -looking fore, " trade call it inder the age of Mo d e r n M o n o g r a p h s in In d u s t r ia l Editor in C h ie f: ANTHONY J. LANZA, M.I). i.on&uiting E ditor: KJCHAUD II. OKU, M.D. Med icin e > * i Industrial Carcinogens ft vJ fly K. E./ECKAUDT, M.D., Ph.IL, F.A.E.P. ' tn , , .. Director, Medical Research Divisionf'Esso Research and Engineering Company, Linden, N. j.; Associate Clinical Professor of Industrial Medicine, Mew York University, Postgraduate Medical School; Instructor in Medicine, Cornell University, Medical School ofTHE COO- x MfcDICJAf Or 'r GRUME & STRATTON 1959 NEW YORK and LONDON 4 INDUSTRIAL C A R C IN O G E N S to the crude saltpeter. At best it can probably be said at this time that this occupation requires further inlensive study. In 1929, Marlland reported on bone sarcomas among radium watchdial painters. These cases have received so much publicity and attention, that it suffices here only to mention litem in their historical perspective. fn 1932, Grenfell reported the occurrence of lung and sinus cancer cases among workers in the Mond nickel works. It is believed by most people today that these cases resulted from long continued exposures to low concentrations of nickel carbonyl, a highly toxic gas in higher con centrations; bul ibis is not definitely established as yet. In 1935, Lynch and Smith reported lung cancers among asbestos workers who had developed asbestosis. Although there arc still those who do not agree thoroughly that asbestos was the cause in these cases, most authorities believe that the incidence of lung cancer among asbes tosis cases is higher than would lie anticipated. Finally in 1952, Weil el al. reported nasal sinus cancers among work ers in isopropyl alcohol manufacture. Although a waste product called isopropyl oil is stispeel as the specific agent, considerable doubt exists as to the exact eliologic agent. In reviewing the historical aspects of occupational cancer, it is essen tial to realize that cancer of the scrotum occupies a unique position. This is so because cancer of the scrotum is such a rare disease that it is easy to associate it with a given occupation if more than one or two cases are idiserved. Only about, 15 cases of scrotal cancer occur per 100,000,000 males per year. Thus, whenever cancer of the scrotum is observed, it should he considered occupational in origin until it is proven otherwise. Even in eases reported as having occurred among occupations not usually associated with exposure to carcinogens " I'such ns commercial, finance and insurance occupations) a complete and careful occupational history from childhood to the development of the disease seems warranted. Such a history, if carefully taken, may disclose earlier occupational contacts which really were responsible for the development of the disease. Thus, many individuals who enter more sedentary occupations as an adult, may have engaged in strenuous and dirty occupations in adolescence. Thus, a few years ago, a prominent New York newspaper featured a pic ture of the son of the Governor of the State of New York engaged in a summer occupation of road-building. He was pictured working, hare- * See page 37 of Reference 3. INS u the bronchial epithelium jorily ol cases. However, iese cancers is available, jy the end ui 1950. Earl) ubtedly will be the most n ui dust respirators may :se cases. Thus, the Chief ameers, and only 2 lung lymeut started after 1921, In addition, no eases have . out both in Canada and esc eases has not yet been jest that it is nickel car : nature ol this compound, difficult to devise experire of animals without pro ved fine!) divided nickel, ds with the. production of y decomposes on contact monoxide, it has always as, such as the lung and ' divided nickel. Although ie theory that nickel earbe accepted as conclusive /ere not involved. In view1 'arious commercial cheml-seed oil to make edible er alcohols Irom hydrnnite answers about nickel adily formed from nickel tions ol temperature and used to Hush out units 0% of carbon monoxide. I carbon)1 have occurred s in which nickel was the nickel carbonyl may he ring if nickel carbonyl is O CCUPATIO N AL CAN CERS 99 responsible for the cancers observed in the nickel refining industry in England--and if so--in what amounts.* Asbestos and Asbestosis Clinical Features--The lung cancers seen in cases of asbestosis are generally squamous cell carcinomas arising from the bronchial epithe lium. In addition to the eaneers observed, squamous metaplasia of the epithelium in various adjacent and distant regions of the bronchial epithelium is observed. The most complete analysis of a large series of these cases is contained in the Annual Report of the Chief Inspector of Factories of England for the year I954.:1 In this report, a total of 544 asbestosis deaths was analyzed, of which 205 were men and 139 women. Cancer of the lung was observed in 55, or 16%. Among the men, 41 lung cancers, or 20%, were observed while 14 were seen in women, or 10.1%. This makes the male female ratio for lung cancer approximately 2:1, which compares with a malerfernale ratio in the general population of 5:1 or greater. 4 he mean age at death of men with lung cancer and asbestosis was 55 years, while Ihc mean age in women with lung cancer and asbestosis was 45.6 years. This compares with a mean age of 53.7 years for men with asbestosis without lung cancer and 42.8 for women with asbestosis without lung cancer. The mean age at death for asbestosis complicated by tuberculosis was 45.2 years in men and 35.1 years in women- These data suggest that asbestosis, uncomplicated by lung cancer poses a greater threat to longevity than when lung cancer is present. Thus, the control of asbestosis should eliminate this occupational cancer. No case of lung cancer developed in an individual, male or female, who had less than 2 years exposure, although 7 eases, all in women, of asbestosis without lung cancer or tuberculosis, and 5 cases, again all in women, of asbestosis with tuberculosis developed with exposures of less than 2 years duration. The first cases of lung cancer in women de veloped when they were between 30-39 years of age, whereas in men the first cases appeared in the 40-4-9 year age group. The diagnosis of occupational cancer in asbestos workers is consider ably simplified in comparison with other occupational cancers because * In a recenL private cuiiiniuiiicatioii Irom l)r. J. GWynne Morgan, Chief Medical Officer of the Clydach works of the Moud Nickel Company, Lid., calcined dust, rather than nickel carbonyl was proposed as the etiologic agent. Dr. Morgan has prepared a complete manuscript of his observations which is now in press. 100 INDUSTRIAL C A R C IN O G E N S of llie requirement of the pre-existence of asbestosis. Tliis dironic fibros ing disease of the lung could hardly be missed at the autopsy table. Another factor which supports the occupational origin of this typo of cancer is [he presence of asbeslos bodies. These bodies have been well described by Lynch,'1 but a review of [heir charaelerislies rnav be help ful. They vary from 10 lo more than 100 microns in length, and from about 1 to 12 microns in thickness. They have, a central translucent fiber, presumably asbestos, surrounded by a shiny, golden or brownish sub stance. They may have knobs at one or both ends. The shaft may fre quently be headed. Spherical forms of various sizes may also he seen, although these, may be the longer-knohbcd-eml structures seen on end under the microscope, or broken oil from the shaft. Characteristically, they give a Prussian Blue reaction for iron. In cases of asbeslosis, they are seen usually in the bronchial tract, the adjacent alveoli and the peri bronchial connective tissues and lymph nodes. In the alveoli, they may be enclosed by mono- or multi-nuclear phagocytes or foreign body giant cells. Tu the connective tissue they may cause some surrounding fibrosis. They may fie louiid in the sputum, hut. their presence there is not essen tial, since they are not lound in the sputum of some advanced cases of asbeslosis. It would seem that a ease ol lung cancer in an asbestos worker should not he diagnosed as occupational in origin unless asbestosis and/or asbestos bodies have been found. It should he remembered, how ever, that asbeslos bodies may he absent from advanced cases of asbes losis or present in individuals with no evidence of asbeslosis. Their presence is only an indication of exposure lo asbestos. Their absence has no significance. Lung cancer in asbestosis eases seems not to vary from lung cancer in general. The prognosis and treatment are identical, although flic embarrassment of pulmonary reserve by the fibrosis in the lungs may limit the eases in which pneumonectomy can he performed. Etiologic A('em--It is not clear at present whether these cancers result from the asbestos per sc, or whether they arise as a result of some other mineral impurities contained in certain forms of asbestos. Although this may seem academic, if is of importance for two reasons. First, it may help us understand carcinogenic mechanisms, and second, if some forms of asbestos do not load to lung cancer formation, this may lie extremely important from a practical and medico-legal standpoint. A recent study by Braun and Truan ' denies the existence of a lung cancer hazard in the Canadian asbeslos industry, even though asbestosis may be observed. O CCUPATIO N AL CAN CERS 101 Tiiis suggests that the causative agent of ashestosis may be different from that for lung cancer. This lends some support to the eoncept of impurities present in some asbestos hut not in others. Finally, since squamous metaplasia is also observed in practically all cases, it may be that asbestos only serves to produce the squamous metaplasia, which serves simply as a suitable field for some other carcinogen to produce the malignant changes. Cancer, then, would only develop where this carcinogen was present. From a medico-legal standpoint, ol course, this may lie unimportant, since whether lung cancer is produced or only promoted hy asbestos would have little significance. Isopropyl Alcohol Manufacture In 1952, Weil, Smyth and Nale-i; reported -1 cases of sinus cancer, one case of lung cancer, one carcinoma of the vocal cord and one papil loma ol the vocal cord among a group ol men involved in the manu facture of isopropyl alcohol. This experience bus been confirmed hy another manufacturer of isopropyl alcohol, where three sinus cancers and two cancers of tile intrinsic larynx were found. From the combined experience of these two plants, it seems possible to conclude that the sinus and intrinsic larynx eases were related to occupation. The single lung cancer ease observed can hardly he said to have any relation to occupation, since it has no statistical significance. Its presence, however, should serve to alert the profession to continue carelul review ol future developments in lung cancer incidence in this operation. Enologic Agent--Despite extensive animal testing, it is not clear today W'hat the causative agent in these: cases was. In each of the, plants in volved, evidence was developed that no cancers appeared if employees began their work in the plant after a particular date. This observation suggests that wdiatever the causative agent may have been, it was removed by alterations of the manufacturing process subsequent to that date. The most significant change in the process, which occurred at about this time was a reduction of the strength of the sulfuric acid used. In brief, the process consists of bubbling propylene through sulfuricacid to form isopropyl sulfates. This is subsequently hydrolysed by water to form isopropyl alcohol and W'eak sulfuric acid. The isopropyl alcohol is distilled oil the weak sulfuric acid, and the acid reeoncentrated for re-use. When the concentration of the sulfuric acid used was high, a small amount of impurities was lormed which is called isopropyl oil. This is a complex, variable mixture of isopropyl ethers, isopropyl 132 INDUSTRIAL C A R C IN O G EN S clue l.o changes in operations or failure of control measures and would permit the early introduction of additional personal or unit control measures or maintenance. Nickel Refining H nickel carbonyl is responsible for the sinus and lung cancer cases seen in the nickel refining industry, exposure in this ease would lie to a gas. Control of this cancer would be facilitated by more precise knowl edge of the causative agent. Until such knowledge has been developed, control measures must lie general in nature, designed to contain witbin llie process by engineering methods, any inhatable materials, gaseous or particulate. Housekeeping should be of the best, and wherever gaseous or particulate materials cannot be contained or ventilated, use of respi rators should be insisted upon. Since nickel carbonyl decomposes on contact with water, advantage of this principle might be taken in design ing respirators, and other protective or control equipment. The establishment of a medical program in this industry should be designed for the detection of early nose and lung cancers. A thorough and careful examination of the nose and nasopharynx, performed prior to entry into this work and repealed at periodic intervals, should lie done. This should be done by someone thoroughly familiar with the pathology of the nose and nasopharynx, and preferably the periodic repetition of the examination should be done by the same individual in order that changes will lie evident. X-rays of the sinuses and chest should he done at the time of this examination and interpreted by some one thoroughly familiar with the problem. Any changes observed should he followed up rigorously until a definitive diagnosis has been made. It would probably be desirable to attempt to correlate urine or blood nickel levels with exposure patterns and atmospheric nickel concentra tions in an effort to provide an additional check of exposures. Wher ever exposures cannot lie controlled by other means, the men should lie provided with adequate respirators and instructed adequately in the importance of llieir use. Re-education of the men in the importance of all protective measures can be done at the time of the periodic re examinations. Asbestos Handling The solution of the problem of lung cancer resulting from asbestos lies in the control of the problem of asbestosis. The disease is the result PRO! of the prolonged inhalation the control of the dustiness with the provision nl exliau? dustiness. Use of vvel process of good housekeeping roulin Elimination of all imneeessa dust may settle will also help cannot be controlled by any should be provided. I lie use one for work dollies, seems washing or showering facilil mcnls in the working covin arc increasing, the reasons fo Individuals .selected for tl\ examination. d Ills should I monary abnormalities, or at A pre-placement chest X-ray illation. Any pulmonary aln ated before the individual is examinations should he re sputum examinations for a; of such bodies Imm the s) presence in the sputum slio bilily of excessive exposen for asbestos bodies includi hydroxide, followed by ecu dues are spread over sev< examined. The electron mu bodies more candidly, bn fracture. It should he rememhei varielv of other oreupatioi a way that dust can he pr< permit prolonged, repealc hazard exists. Each such the potential hazard. I bin lion in the susceptibility l< while others nun tune e< ease, even after rnnsideral OGENS f control measures and would mal personal or unit control e sinus and lung cancer eases ure in this case would he to a dialed h\ more precise knowlnowiedge has been developed. ;re, dcsigned to contain within inhalable materials, gaseous or he best, and wherever gaseous ned or ventilated, use of respiiekel carhonyl deeoinposes ou eiple might he taken in designmntrol equipment, am in this industry should he and lung cancers. A thorough nasopharynx, performed prior l periodic intervals, should he thoroughly familiar with the and prelerably the periodic lone by the same individual in rays oi the sinuses and chest uition and interpreted by somei. Any changes observed should live diagnosis has been made, ipl to correlate urine or blood atmospheric nickel concentranal cheek of exposures. Wherither means, the men should he l instructed adequately in the the men in the importance of : the time of the periodic re- cancer resulting from asbestos stosis. The disease is the result PROTECTIVE PRO G RAM S 133 of the prolonged inhalation of asbestos dust, so that its control lies in the control of the dusliness of the operation. Enclosure of equipment with the provision of exhaust ventilation should eliminate much of the dusliness. Use of wet processes wherever possible, and the establishment of good housekeeping routines to clean up accumulated dust will help. Elimination of all unnecessary ledges, nooks and areas where asbestos dust may settle will also help control this operation. Wherever dustiness cannot lie controlled by any of these means, adequate dust respirators should he provided. The use ol double lockers, ime lor streel (dollies and one for work ( lollies, seems warranted in this industry, but no special washing or showering facilities seem necessary. Periodic dust measure ments in the working environments should be undertaken and if levels are increasing, the reasons lor lids should lie sought. Individuals selected for this work should have a careful pru-plaeemenl examination. This should he designed specifically to detect any pul monary abnormalities, or any cncroacluucnt on tlie pulmonary reserve. A pre-placement chest X-ray should he included as a part ol this exam ination. Any pulmonary abnormalities found should lie candidly evalu ated before the individual is permitted to work in this occupation. These examinations should he repealed at yearly intervals, at which lime sputum examinations lor asbestos bodies should lie done. 1he absence of such bodies from the sputum has no special significance, hut their presence in the sputum should serve to alert the physician to the possi bility of excessive exposures. The technique ol examining the sputum for asbestos bodies includes digestion of the sputum by warm sodium hydroxide, followed by centrifugation and decanting. The decanted resi dues are spread over several slides, mounted in Canada balsam and examined. The electron microscope can also he used for examining these bodies more carefully, hut great care must be exercised or they may fracture. It should lie remembered that asbestos is widely used in a large variety of other occupations ami industries. Whenever it is used in such a way that dust can be produced, and the work is of such a nature as to permit prolonged, repeated inhalation of the dust, a potential asbestosis hazard exists. Each such use must lie carefully evaluated in terms of the potential hazard. There seems to he a considerable individual varia tion in the susceptibility to asbestosis, some people developing it rapidly, while others may have comparable exposures with no signs ol the dis ease, even after considerable periods ol exposure.