Document 6bwgOOqJz8m3XbJkVr3gGrad9

FILE NAME: Exxon (EXX) DATE: 1959 DOC#: EXX044 DOCUMENT DESCRIPTION: Book Excerpt - Industrial Carcinogens Modern Mo n o g r a p h s in Industrial Medicine 4 I i h t u r 1/1 C h t c j : V Y I ' I I O I M .1. I . V , \ Z \ , M.l). ( ../i.Mj/ini- ///Ku, . H I C I I A I i l ) 11. O K U , M.D. Industrial Carcinogens l i y ]{'. K.:/i'>.C; tk VKDT, W.D., lh.l)., F.A.C.F. I)u ci im . Niceh^TTuut.'srd iih I' ii" nu-fi 11 i<a (inm|idiu. I,mien. 1-^-0 lu'M an h aiul J : A-.mu idle (liniuil 1'11111- -<)t (j| 111(1ll-.ll idl Mi-i Ik 111!'. \|'U 'lin k l in \ rl s il \ l'n-t^i diliidh- M mill d I Silio o l: 11ml i ucl< 11 in iMmluini'. F in imll l niM'i sii m Mm lit dl S i 'Ikh iI ^ e r T o r the C00/Vs , ' ,,S O t m w / u . o i n t (H r 1 4 2 9 8--6^-s)\4o;. 3 siV / i C l; l \ I. \ ST K \ TTO A 19 3 9 m :\\ H ) i: k n n i.o a d o a 4 INDUSTRIAL CARCINOGENS 1<j the crude saltpeter. At best it can probably be said at this time that this occupation requires further intensive study. In 1929, Maitland 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 eases 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: hul this is not definitely established as yet. In 1935, Lynch and Smith reported lung cancers among asbestos workers who had developed asbestosis. Although there are still those who do nol agree thoroughly that asbestos was the cause in these cases, most authorities believe Lhat Lhe incidence of lung cancer among asbes tosis cases is higher than would he anticipated. Finally in 1952, Weil et al. reported nasal sinus cancers among work ers in isopropyl alcohol manufacture. Although a wasle product called isopropyl oil is suspect ns lhe specific agcnl. considerable doubt exists as Lo the exact eliologic agent. In reviewing the historical aspects of occupational cancer, it is essen tial Lo realize tlial 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 observed. Only about 15 cases of serolal cancer occur per 100,000,000 males per year. Thus, whenever cancer of the, scrotum is observed, il should be considered occupational In origin until il is proven otherwise. Even in cases reported as having occurred among occupations nol usually associated with exposure In carcinogens Isuch as 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 lhe disease. Thus, many individuals who outer more sedentary occupations as an adull. 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 Stale of New York engaged in a summer occupation of road-building. He was pictured working, bare * See page 37 of R e feren ce 3. ' .n Led. with a 'hovel. Ilie Icing listed as l'dn\ lahorei ......li*. The sole pm pose of t ill "` upntion of an individual (>r 111 occupation, whereas. i ili'-ca-c such as occupation;! i/o that it ma; bare been f 'inded of it by carcful quest \lthoiigh it is iclalivch e I the scrotum " ilh occupali . .Hirers of other s i t e s . Thus, m incidence of about 30 pc Inins greater incidence than < .f i.'nicer of the scrotum ina tin- m i upalional origin of tl i ance! of the skin, or cancer In'twcen the occupation and imd to attribute a given l\ hr established with statistical "1 <nicer among cmplosccs i in an employee group rompa "upntion. l o d o so rrquil nnreis, but also of the pop Lit the occurrence of cancer f occupational- cancer musi liraningful epidemiological been raised In oIkcm atious autioiicd not to make prom .truce lias a high statistical lhr hold of occupational eai idimmition and hence the lit patinimi cancers lhat cannot idonee fot llioii occupation The history of occupation l'Aaminalion of ibis laidi important to point out in on an he kept in proper pcrspcc First, over 75',< of the o< Of these, about 6 0 ';. or ah OCCUPATIONAL CANCERS 99 responsible for the cancers observed in the nickel refining industry in England-- and if so-- in what amounts.* Asbestos cand 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 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 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 nrale:feinale 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 lire 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 cases, all in women, of asbestosis without lung cancer or tuberculosis, and 5 eases, 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 recent private communication from Dr. J. Gwynne Morgan, Chief Medical Officer of the Clydach works of the Mond Nickel Company, Ltd., calcined dust, rather than nickel carhonyl 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 reqtiiiemenl of the pre-existence of asbeslosis. This chronic 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 mav 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 asbestos, surrounded by a shiny, golden or brownish sub stance. They may have knobs at one or both ends. The shaft may fre quently he headed. Spherical forms of various sizes may also he seen, although these may be the longcr-knobbed-end structures seen oil end tinder the microscope, or broken olf from Ihe shaft. Characlerislirallv. 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 ihe alveoli, they may he enclosed hv mono- or multi-nuclear phagocytes or foreign body giant cells. In the connective tissue they may cause some surrounding fibrosis. They may he found in the sputum, but their presence there is nol essen tial. since they are nol found in Ihe sputum of some advanced cases of asbeslosis. It would seem that a case of lung cancer in an asbestos worker should nol be diagnosed as occupational in origin unless asbeslosis and/or asbestos bodies luue been found. It should he remembered, how ever, that asbestos bodies may be absent from advanced cases of asbes losis or present in individuals with no evidence of asbeslosis. Their presence is only an indication of exposure to asbestos. Their absence has no significance. Lung cancer in asbeslosis cast's seems nol 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 eases in which pneumonectomy can he performed. E/iologic Agent-- It is not clear at present whether these cancers result from the asbestos per so, 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 mav he 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 asbestos industry, even though asbeslosis may be observed. OCCUPATIONAL CANCERS 101 This suggests tiiat the causative agent of asbestosis may be different from that for lung eancer. 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 eases, 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 oidy develop where this carcinogen was present. From a medico-legal standpoint, of course, this may be unimportant, since whether lung cancer is produced or only promoted by asbestos would have little significance. Isopropyl Alcohol Manufacture fn 1952, Weil, Smyth and INaleL>li reported 4 eases ol sinus cancer, one case of lung cancer, one carcinoma 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 has been confirmed by another manufacturer of 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 can 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 ol future developments in lung cancer incidence in this operation. Etiologic 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 sulfuric acid to form isopropyl sulfates, 'fids is subsequently hydrolysed by water to form isopropyl alcohol and weak sulfuric acid. The isopropyl alcohol is distilled off the weak sulfuric acid, and the acid reconcen trated for re-use. When the concentration of the sulfuric acid used was high, a smalt amount of impurities was formed which is called isopropyl oil. This is a complex, variable mixture of isopropyl ethers, isopropyl 132 INDUSTRIAL CARCINOGENS clue lo 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 ease would he lo 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 be general in nature, designed to contain within the process by engineering methods, any inhalable materials, gaseous or particulate. Housekeeping should be of ihe 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 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 repeated 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 he done by the same individual in order that changes will be 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 be followed lip rigorously until a definitive diagnosis has been made. It would probably be desirable lo 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. Ile-educalion 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 of the prolonged inhalation < the control of the (lustiness with the provision oT exhaus dustiness. Use of w<T processi of good housekeeping roulin Elimination of all unuccessa dust may settle will also help cannot be controlled by any should be provided. Ihe use one for work clothes, seems washing or shown ing facilil rncnls in the wolking enviro arc increasing, the reasons lo Individuals selected for llii examination. This should h monary abnormalities, or an A pre-placement rlie-t X-ray inalion. Any pulmonary abn ated before the individual is examinations should be, re sputum examinations lor aof such bodies Irom the sp presence in the sputum slim bility of excessive exposen for asbestos bodies inclitdi hydroxide, followed by ectil dues are spread over seve examined. Ihe election mic bodies more carefully, but fracture. It should be icmemlxT variety of olliei oeeupalioi a way that dust can be pH permit prolonged, icpealet hazard exists. Each such the potential hazard. 1her lion in the susceptibility U while others nun have re ease, even after rnnsidrml OGENS control measures and would mal personal or unit control e sinus and lung cancer cases ;ure in this case would he to a iiInlet! h\ more precise knowtnowledge has heen developed, ire, designed to contain within inhalahtc materials, gaseous or he best, and wherever gaseous ned or ventilated, use of respiickcl carhonyl decomposes on ciple might he taken in design'onlrol eipiipment. am in this industry should he and lung cancers. A thorough tiasoplmi >nx, performed prior i periodic intervals, should lie thoroughly familiar with the t, and piclctably the periodic :lune h\ the same individual in rays oi the sinuses and chest lalion ami interpreted hy somel. Any changes observed should itive diagnosis has heen made, ipt to correlate urine or hlood atmospheric nickel concentranal check of exposures. Wherjther means, the men should he 1 instructed adequately in the f the men in the importance of t the lime of the periodic re- cancer resulting from asbestos islosis. The disease is the result PROTECTIVE PROGRAMS 133 oi 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 oi the dustiness. 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 he controlled hy any of these means, adequate dust respirators should he provided. The use ul double lockers, one lor street clothes and one lor work clothes, seems warranted in this industry, but no special washing or showering laeilities seem necessary. Periodic dust measure ments in the working environments should he undertaken and il levels are Increasing, the reasons lor this should he sought. Individuals selected for this work should have a careful pre-placement examination. This should he designed speeifically to detect any pul monary abnormalities, or any encroachment on the pulmonary reserve. A pre-phieement chest X-ray should he included as a part of this exam ination. Any pulmonary abnormalities lound should he cardutly evalu ated before the individual is permitted to work in this occupation, 'lhese examinations should he repeated at yearly intervals, at which time sputum examinations lor asbestos bodies should he done. Ihe absence of such bodies from the sputum has no special significance, but their presence in the sputum should serve to alert the physician to the possi bility of excessive exposures. The technique of examining the sputum lor asbestos bodies includes digestion oi the sputum hy warm sodium hydroxide, followed hy centrifugation and decanting. The decanted resi dues ue spread ovei 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 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 wa^ that dust can he produced, and the work is of such a nature as to permit prolonged, repeated inhalation ol the dust, a potential asbeslosis hazard exists. Each such use must he carefully evaluated in terms oi the potential hazard. There seems to he u considerable individual varia tion in the susceptibility to asbeslosis, some people developing il rapidly, while others may have comparable exposures with no signs of the dis ease, even after considerable periods ol exposure.