Document 6VypMYJnmJRaeZrq7qMdrX7g

FILE NAME: Oil Industry and American Petroleum Institute (API) DATE: 1959 DOC#: API165 DOCUMENT DESCRIPTION: Book Excerpt - Industrial Carcinogens i i mu"*'l 1. 4 industrial carcinogens to the crude saltpeter. At best it can probably be said at this time that this occupation requires further intensive 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 them in their historical perspective. In 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 ns yet. in 1935, Lynch and Smith reported lung cancers among asbestos workers who bad developed asbcslosis. Although there are slid those who do not agree thoroughly that asbestos was the cause in these cases, most authorities believe that the incidence of lung cancer among asbestosis cases is higher than would be anticipated. Filially in 1952, Weil el nl. reported nasal sinus cancers among work ers in isopropyl alcohol manufacture. Although a waste product called isopropyl oil is suspect ns the specific agent, considerable doubt exists as to the exact etiologie 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 arc observed. Only about 15 eases of scrotal cancer occur per 100,000,000 males per year. Thus, whenever cancer of the scrotum is observed, it should be considered occupational in origin until it is proven otherwise, liven in cases reported ns having occurred among occupations not usually associated with exposure to carcinogens fsiic.b as commercial, finance and insurance occupations) a complete and careful occupational history from childhood to the, dcvclopnie.nl of the disease seems warranted. Such a history, if carefully taken, may disclose earlier occupational ennlacls which really were responsible for the development of iho disease. Thus, many individuals who enter more sedentary occupations as an adult, 1 may have engaged in strenuous and dirty occupations in adolescence. Thus, a few veals ago, a prominent New York newspaper featured a pic j ture of the son of the Governor of the Slate of New York engaged in a ;t summer occupation of road-building, lie was pictured working, bare I * See pace 37 of R eferonrr 3. l-.nked. with a slmvcl. T In 1-ing listed as ``dn\ Inhon The sole purpose of li "upalion of an imlividi. piv-ent occupation, wlicrcn di-case such as occupatini a'o |hut i may have been "liuded of it by careful que Mlbougli it is relatively I tile scrotum u illt nrrupa i anerrs of other sites. Thin oi incidence of about 31) | l nncs greater incidence tliai I cancer of the scrotum n It- occupational origin of i nicer of the skin, or canee I i-turen the occupation am oiind to nllrilmle a given I l c established with statistic. - f c,-Hirer among employees in an employee group ennq cciipalion. To do so rrqu .imcr.s. hut also of the po f >r the occurrence of canec of occupational.cancer mm men mugful epidemiological liurM raised liv observation mlioned not to make prr.n .I'-ncr lias n high statistical the field of occupational ra .nlmonilion and hence, the li pilional cancers that cannot idciicc for their occupation The history of occupation Kvaminalioii of this lahh important to point out in or i an be kept in proper pcrspei first, over 75',-i of the o f1f these, about (i0'/, nr nh 4 INS n the bronchial epithelium jority of oases. However, lose cancers is available, jy the end of 1950. Early ubtedly will be the most ii of dust respirators may :se cases. Thus, the Chief Jancers, und only 2 lung jyment started after 1924, In addition, no cases have . out both in Canada anil ;se cases lias not yet been ;est that it is nickel carnature o! this compound, difficult to devise experire of animals without pro. .led finely divided nickel, ils with the production of y decomposes on contact monoxide, it lias always js, such ns the lung and -""^vided nickel. Although ieory that nickel caroe accepted as conclusive ere not involved. In view arious commercial chemi-seed oil to make edible :r alcohols from hydro ilite answers about nickel iclily formed from nickel tions of temperature and used to Hush out units 1% of carbon monoxide. I carbonyl have occurred s in which nickel was the nickel carbonyl may be ing if nickel carbonyl is 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 eases of asbestosis are generally squamous cell carcinomas arising from the bronchial epithe lium. In addition to the cancers 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 1954.'* In this report, a total of 344 asbestosis deaths was analyzed, of which 205 were men and 139 women. Cancer of the lung was ubserved 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 maleifemale ratio in the general population of 5:1 or greater. The mean age at death of men with lung cancer and asbestosis was 55 years, while the 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 ease 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 40-49 year age group. The diagnosis of occupational cancer in asbestos workers is consider ably simplified in comparison with other occupational cancers because * In a l-eccnl private communication from Dr. J. C.Wynne Morgan, Chief Medical Oificer of the Clydach works of the Mond Nickel Company, Ltd., 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 CARCINOGENS of the requirement of the pre-existence of ashestosis. This ehronic fibros ing disease of the lung could hardly he missed at the autopsy table. Another factor which supports the occupational origin of this type of cancer is the presence of asbestos bodies. These bodies have been well described by Lynch,17 hut a review of their characteristics may he help ful. They vary from 10 to more than 100 microns in length, and from about 1 to 12 microns in thickness. They have a central translucent fiber, presumably nsbcslos, 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 be seen, although these may be the longcr-knobhcd-cud structures seen on end under the microscope, or broken oil from the shaft. Characteristically, they give a Prussian Mine reaction for iron. In cases of nsbcstnsis, 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 he enclosed by mono- or multi-nuclear phagocytes or foreign body giant cells. In the connective tissue they may cause some surrounding fibrosis. They may be found in the sputum, hut their presence there is not essen tial, since they are not found in the sputum of some advanced cases of ashestosis. It would seem that a case of lung cancer in an asbestos worker should not lie diagnosed as occupational in origin unless ashestosis and/or asbestos bodies have been found. It should be remembered, how ever, that asbestos bodies may be absent from advanced cases of asbestosis or present in individuals with no evidence of ashestosis. Their presence is only an indication of exposure to asbestos. Their absence has no significance. Lung cancer in ashestosis cases seems not to vary from lung cancer in general. The prognosis and treatment are identical, although the embarrassment of pulmonary reserve by the fibrosis in the lungs may limit the cases in which pneumonectomy can he performed. Etiologic Agent--It is not clear at present whether these cancers result from the asbestos per se, or whether they arise as a result of some other mineral impurities contained in certain forms of asbestos. Although this may seem academic, it is of importance for two reasons, first, it may help us understand carcinogenic mechanisms, and second, if some forms of asbestos do not lead to lung cancer formation, this may be extremely important from a practical and medico-legal standpoint. A recent study by Braun and Truati n denies the existence of a lung cancer hazard in the Canadian asbestos industry, even though ashestosis may be observed. This suggests that th from that for lung a impurities present in squamous metaplasia that asbestos only se serves simply as a su the malignant cliangi carcinogen was presei may be unimportant, promoted by asbestos Isopropyl Alcohol In 1952. Weil. Sm one case of l u n g c a n e loma of the vm-al cm facturc oi isopropyl another manufacturci and two cancers of Ih experience of these t sinus and intrinsic, la lung cancer ease obs occupation, since it hi should serve In alert I developments in lung Etialogic Agent--L what the causative ai volvcd, evidence was began their work in suggests that whatev removed by allcralioi date. The most signi about this time was a In brief, the process acid to form isopro| water Ln form isoprn alcohol is distilled o trated for re-usc. Wh high, a small amount oil. This is a comple :is. This chronic fibrosut the autopsy table, origin of this type of bodies have been well cleristics may he helpis in length, and from nlral translucent fiber, den or brownish sulis. The shaft may fro/.L's muy also be seen, ructures seen on end ifl. Charncloristieally. <es of asbestosis, they l alveoli and the peri lla alveoli, they may jr foreign body giant surrounding fibrosis, ce there is not essen ce ndvuneed cases of n an asbestos worker ;in unless asbestosis >e remeiubcred, howinced eases of asbesasbestosis. Their r heir absence has y from lung cancer itical, although the is in the lungs may formed. these cancers result "csult of some other estos. Although this isons. First, it may :ond, if some forms i may be extremely int. A recent study l cancer hazard in s may be observed. OCCUPATIONAL CANCERS 101 This suggests that the causative agent of asbestosis may be different from that for lung cancer. This lends some support to the concept of impurities present in some asbestos but not in others. Finally, since squamous metaplasia is also observed in practically all cases, it may lie that asbestos only serves to produce the squamous metaplasia, which serves simply as a suitable field for some other carcinogen to produce the malignant ehunges. Caneer, then, would only develop where this carcinogen was present. From a medico-legal .standpoint, of course, this may he unimportant, since whether lung cuncer is produced or only promoted by asbestos would have little significance. Isopropyl Alcohol Manufacture In 1952, Weil, Smyth and Nale -11 reported I cases of sinus cancer, one case of long cancer, one carcinoniu of the vocal cord and one papil loma of the vocal cord among a group of men involved in the manu facture of isopropyl alcohol. This experience lias been confirmed by unolber manufacturer nf isopropyl alcohol, where three sinus cancers and two cancers of the intrinsic larynx were found. From the combined experience of these two plants, it seems possible to conclude that the sinus and intrinsic larynx cases were related to occupation. The single lung cancer case observed cun hardly be said to have any relation to occupation, since it has no statistical significance. Its presence, however, should serve to alert the profession to continue careful review of future developments in lung cancer incidence in this operation. Etiologic Agent--Despite extensive animal testing, it is not clear liiduy what 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 dale. This observation suggests that whatever 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 ill about this time was a reduction of the strength of the sulfuric acid used. In brief, the process consists of bubbling propylene through sulfuric acid to form isopropyl sulfates. This is subsequently hydrolysed by water to form isopropyl alcohol and weak sulfuric acid. The isopropyl alcohol is distilled olf the weak sulfuric acid, and the acid reconcentrilled for re-use. When the concentration of the sulfuric acid used was high, a small amount of impurities was formed which is called isopropyl oil. This is a complex, variable mixture of isopropyl ethers, isopropyl 137 INDUSTRIAL CARCINOGENS due to 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 If nickel carbonyl is responsible for the sinus and lung cancer cases seen in the nickel refining industry, exposure in this case would he to a gas. Control of this cancer would he facilitated by more precise knowl edge of the causative agent. Until such knowledge has been developed, control measures must be general in nature, designed to contain within the process by engineering methods, any inhalahle materials, gaseous or particulate. Housekeeping should be of the best, and wherever gaseous or particulate materials cannot he contained or ventilated, use of respi rators should be insisted upon. Since nickel carbonyl decomposes on contact with water, advantage of this principle might he taken in design ing respirators, and other protective or control equipment. The establishment of a medical program in this industry should he 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 be 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 he evident. X-rays of the sinuses and chest should be 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 be controlled by other means, the men should be provided with adequate respirators and instructed adequately in the importance of their 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 PROT ol the prolonged inhalation i the control of the dustiness with the provision of exliaus dustiness. Use of wet process of good housekeeping roulin Elimination of all unncccssn dusl may settle, will also help cannot be controlled by any should he provided. The use one for work dollies, seems washing or showering facili iiicnls in the working covin are increasing, the reasons fi Individuals sele.rlod for ll examination. Ib is should monary abnormalities, or a A pre-placement chest X-vn matioii. Any pulmonary ah ated before the individual i examinations should lie r sputum examinnlions for a of such bodies from llie . presence in the sputum slu liilily of excessive, cxposui for asbestos bodies incltldi hydroxide, followed by e.ci dues arc spread over sew examined. The electron mi bodies more carefully, liu fracture. It should he renmnihevariety of other ne.eupntio a way thal dusl ran he pn permit prolonged, rcpcalc hazard exists. Kadi such the potential hazard. 1hri lion in the susceptibility t while others may have c< ease, even afler ennsiderd I! O SEN S f control measures and would mal personal or unit control e sinus and lung cancer cases mre in this ease would be to a lilalcd by morn precise know)nowledge has been developed, I ire, designed lo contain within iulialahlc materials, gaseous or be best, ami wherever gaseous mid or ventilated, use of respi ) ickel carbonyl decomposes on I ripie might he taken in designmntrol equipment. am in Ibis industry should be and lung cancers. A thorough nasopharynx, performed prior I I periodic intervals, should be thoroughly familiar with the J-U and preferably the periodic le by the same individual in ..ys of the sinuses and chest j lation and interpreted by somej i. Any changes observed should j dive diagnosis has been made, j ipt to correlate urine or blood j atmospheric nickel concentra* nal check of exposures. Wherdher means, the men should be J instructed adequately in the f the men in the importance of t the time of the periodic re cancer resulting from asbestos estosis. The disease is the result PROTECTIVE PROGRAMS 133 of the prolonged inhalation of asbestos dust, so that its control lies in the control of the dustiness of the operation. Enclosure of equipment with the provision of exhaust ventilation should eliminate much of the dustiness. Use of wet processes wherever possible, and the establishment of good housekeeping routines lo 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 he controlled by any of these means, adequate dust respirators should he provided. The use of double lockers, one for street clothes and one lor work clothes, seems warranted in this industry, hut no special washing or showering facilities seem necessary. Periodic dust measure ments in the working environments should he undertaken and if levels arc increasing, the reasons for this should he sought. Individuals selected for this work should have a careful pre-placcmenl examination. This should he designed specifically lo delect any pul monary abnormalities, or any encroachment on the pulmonary reserve. A pre-placement chest X-ray should he included as u pari of this exam ination. Any pulmonary abnormalities found should he carefully evalu ated before the individual is permitted to work in this occupation. These examinations should he repeated at yearly intervals, at which time sputum examinations For asbestos bodies should he done. Ihe absence of such bodies from the sputum has no special significance, hut tlteir presence in the sputum should serve to alert the physician to the possi bility of excessive exposures. The technique of examining the sputum for asbestos bodies includes digestion of the sputum hy 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 cave must he exercised or they may fracture. It should he remembered that asbestos is widely used in a large variety of other occupations and industries. Whenever it is used in such a way that dust euu lie produced, and the work is of such a nature as lo permit prolonged, repeated inhalation of the dust, u potential asheslosis hazard exists. Each such use must he carefully evaluated in terms of the potential hazard. There seems lo he n considerable individual varia tion in the susceptibility to asheslosis, some people developing it rapidly, while others may have comparable exposures with no signs of the dis ease, even after considerable periods of exposure.