Document 2jXrE3D56922vpNDZJBrrNdLr

OCCUPATIONAL DISEASES A Guide to Their Recognition Revised Edition June 1977 Editors -- Marcus M Key, M D. Austin F. Henschel, Ph.D Jack Butler, M D Robert N Ligo, M D Irving R Tabershaw, M.D Xfanuscrtpt Editor -- Lonce Ede. J D I VS. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE Public Health Service Center for Disease Control Nattonal Institute for Occupational Safety and Health r iai by tie* tf Oteuntiu, U I Onrin--iu Printlaf Offie*. VafthinctaB, b.C 1+403 RSV0033741 14 OCCUPATIONAL DISEASES DEPOSITION There are four major factors that influence the site of the ultimate toxicologic response to inhaled particulates: I) the anatomic arrange ment and physical dimensions of the respiratory system, 2) the physio logic character of breathtng rate and depth, 3) the physical nature of the particle-size, surface area, "solubility," and hygroscoptcity, and 4) the biochemical reactivity of the soluble components of the particle. The knotty problem of handling particles of all sizes, shapes, and densities has been resolved by relating all particles to a median aerody namic diameter. This is the diameter of a unit-density sphere with the same settling velocity as the particle of concern. The cut-off point for respirable size is conventionally taken as 5 urn expressed as an aerody namic diameter. The aerodynamic diameter of particulates determines which par ticles will or will not present exposure to the respiratory system and gives some indication of the degree of impaction in the various com partments of the respiratory system, and hence the site of particle deposi tion. Thus, a panicle such as uranium dioxide with a high density of 10.9 and diameter <. 0 5 pm will behave as a unit-density spherical particle of 1 65 M>n. and can be expected to settle out of undisturbed air at the rate of a larger diameter particle, and impact more in the upper respiratory passages than its measured size would indicate. The sedi mentation rate of fibers depends on their diameter and is independent of length Fiber geometry is also important in relation to certain toxi cologic properties, for example, in the induction of mesotheliomas. To simplify calculations of the deposition pattern of the aerosol of concern, the manifold compartments of the respiratory system are re duced to three: the nasopharyngeal, tracheobronchial, and pulmonary (2). If the particulates are assumed to be present as log-normal dis tributions and three tidal volumes are used, a table can be developed showing the amount of particles deposited in each of the three compart ments according to unit-density sizes, ranging from 0.01 to 10 pm. As might be expected, no particles less than 0 6 pm were deposited in the nasopharynx at any of the three breathing rates, whereas practically all of the panicles greater than 6 pm were deposited at this site at all breathing rates. Thus, the major site of deposition of the smaller par ticles ts the lung; deposition in the tracheobronchial compartment never exceeded 25 to 30% of the total particles inspired even at the smallest sizes (around 0.01 pm) and the slowest breathing rate (3). Although various degrees of mouth-breathing would upset the calculations of deposition in the upper respiratory tract, it is not believed to affect ser iously pulmonary deposition. Hygroscoptcity, however, seriously affects deposition of smaller, highly water-soluble panicles by increasing their size as they travel down the respiratory tram in its 95 % humidity. Thus, in some inmnr**, it is possible for a small size particle in an atmosphere of low humidity to ,, essse; deposition. clearance an In evaiuatin bined Phy51^ menu 2) penetration, and Respiratory chioles. ParticU from the terrain are transferred posure of the re the intestinal tr. the nasal passrn from the trachc Phagocyto particulates fre the appearance increase the ra from the lung lymph nodes r dust burden f Direct ir of variable rr activity of the rous protein, be cleared b> Obvious for panicles dusts, such i in a matter i certain types sequent clea inorganic cc uons has b< day to 10 clearance, pressed as BCC~399 6113 18245 RSV0033742 mate ingeysiof the the and Ddythe for xiy- iarrnd m>a19 cle at 'er fi at if -v 1 ROUTES OF ENTRY 15 so increase its size m the respiratory tract as to alter considerably the deposition pattern characteristic of the entering particle size. As is true with all generalizations, differences m deposition ntc~K can be expected, and indeed have been demonstrated, particularly for the lung where ventilation among the five lobes is normally variable. Another factor which alters deposition patterns is electric charge commonly associated with particle sizes less than 0 ] in diameter,' i e. newly generated fume. Such particles have enhanced nasopharyngeal' deposition. clearance and retention In evaluating the health hazards from inhaled aerosols, four com bined physio-chemical actions must be considered: 1) ciliary move ment, 2) phagocytosis and lymphatic drainage. 3) direct intercellular penetration, and 4) solubilization or leaching. Respiratory tract cilia do not extend beyond the terminal bron chioles Particle clearance by upward ciliary movement cakes place from the terminal bronchioles upward to the throat where the panicles ate transferred to the gastrointestinal tract by swallowing. Thus, ex posure of the respiratory tract to particles may also involve exposure of the intestinal tract With the exception of soluble panicles impacting in the nasal passages and being absorbed there, clearance by solubilization from the tracheobronchial passages is not important Phagocytosis represents the major mechanism for clearing most particulates from the lung. Moreover, the presence of dusts stimulates the appearance of phagocytes at the site, so that repetitive exposures increase the rate of phagocytosis and hence the rate of clearance of dust from the lungs Lymph drainage of the dust-filled phagocytes to the ivmph nodes represents 2 to 10of the clearance of the total pulmonary dust burden for certain insoluble oxide dusts. Direct intercellular penetration offers another clearance mechanism of variable magnitude depending on the solubility, shape, ani biologic activity of the dust Thus, a particle that is not readily coated with se rous protein, ot other lung constituent, would penetrate the ceil and then be cleared by this mechanism more readily than one that ts coated. Obviously solubilizauon represents the dominant clearance factor for particles readily soluble in respiratory tract fluids. Highly soluble dusts, such as the chromates of the alkali metals, pass through the lungs in a matter of minutes, and even grossly insoluble mineral dusts, such as certain types of asbestos, are subject to leaching of their metals and con sequent clearance of these elements from the lung. A partial listing of inorganic compounds according to three pulmonary clearance classifica tions has been attempted for those compounds cleared in less than one day to 10 days, those requiring more than 10 days to 100 days for clearance, and those greater than 100 days, clearance time being ex pressed as biologic half-life (2). BCC-900 6113 18246 RSV0033743 I ty "e ie 15 e tl is n v \ it h e it o 3 -1 DERMATOSES 3 following groupings comprise the majority of the occupational derma toses. (1) Acute contact eczematous dermatitis characterized by ery thema. edema, papules, vesicles or bullae, cruit, scale, and finally, des quamation These are the signs of an inflammatory eczematous dermatttis caused by contact with a primary irritant or a sensitizer or a photosfnsttizer. (2) Chronic eczematous dermatitis characterized by erythema, ucbenificatton, scaling, dryness, and ftssunng resulting from contact with substances which dehydrate the skin as alkali, liquids and dusts, solvents, soaps and detergents. (3) Folliculitis and acneform dermatoses including chloracne char acterized by plugged sebaceous follicles and nodular and suppurative le sions. Chloracne also shows multiple cystic lesions which contain strawcolored material. These dermatoses are caused by contact with insoluble oils, greases, tars, waxes, and certain chlorinated hydrocarbons as the chioronapthalenes. (4) Neoplasnc (benign and malignant) types as keratoses, papil lomata. epitheliomas, and carctnomas of the exposed areas. These us ually are caused by certain petroleum products, coal tar and certain derivatives, sunlight, and ionizing radiation (5) Pigmentary disturbances characterized by an increase or de crease of pigment m the epidermis Increased pigmentation can result from contact with coal tar compounds, certain petroleum oils, vegetables, fruits, sunlight, and trauma. Decreased or absent pigmentation may re sult from burns; forceful trauma; chronic dermatitis; monobenzyl ether of hydroqumone; and certain phenoiics as tertiary butyl catechol, tertiary amyl phenol, and tertiary butyl phenol. (6) Granulomatous dermatoses characterized by chronic indolent focal inflammations which tend to heal with scar. These lesions can re sult from bacterial, viral, fungal or inanimate agents as asbestos, beryl lium. and silica (7) Ulcerative lesions characterized by a loss of tissue on a cutan eous or mucous membrane surface leading to necrosis Ulcerations can be caused by arsenic rnoxide, calcium compounds, cement and concrete, chromic actd, bums and trauma. They may also result from purposeful or unconscious manipulation. (8) Miscellaneous lesions. Some occupational dermatoses, because of their unusual nature, do not fit into the above classifications. Among such miscellaneous lesions are; (a) alopecia induced by chloroprene; (b) acro-osteolvsis, with or without Raynaud's; (c) sclerodermoid changes believed due to vinyl chloride poly merization, (d) discolorations of the hair, skin, and nails due to various chem icals; (e) porphyna cutanea tarda caused by a certain chlorinated hy drocarbon intermediate. B0C2301 RSV0033744 14 occupational diseases OCCUPATIONS AND AGENTS The following is a list of occupations each accompanied by certain agents frequently associated with that occupation and capable of pm. ducmg a dermatosis. Additional agents for he occupations listed as well as additional occupations will be found in other sections, principally the one on chemical hazards. Abrasive Wheel Makers carborundum emery resin glues Agricultural Workers See Farmers Aircraft Workers adhesives (resins) alkalis bichromates chromates chromic add cutting fluids cyanides epoxy resins flame retardants glass fibers hydraulic fluids hydrofluoric acid lubricants nitric acid oils paints plastics rubber solvents thinners ultraviolet light vibrating tools X-rays imal Handlers antibiotics bacteria cleaners & detergents deodorants feeds fungi germicides insecticides medicaments parasites pesticides viruses Artists (Painters) acrylics epoxies paint removers pigments plasticizers solvents A rtists (Sculptors) dusts plaster of Paris pneumatic tools polishes Athletes adhesives antibiotics bacteria lime medications protective gear soaps Automobile Workeri adhesives asbestos antifreeze brake fluids brake linings flame retardants gasoline hydraulic fluids oils rubber solvents BC02302 i Automobile Work abraves adhesives alkalis lead paints rubber com p< solder solvents Automobile Won acids adhesives alkalis antifreeze brake fluids brake linings cleansers epoxy resins gasoline hydraulic flui lubricants rubber solvents thinners Bakers benzoyl pero cinnamon dough dusts flavors (oils flour fungi heat moisture spices sugar Barbers ammonium antiseptics bacteria cosmetics depilatones detergents dyes fungi RSV0033745 I Iveolap 'dcnce l *n the sis One r reac- 1 in i hyads the y disJr adodules h fine zymes sd by potent roccss lv afimam gether vever. : and essed supirman the it tu rn ary ce of duces d gas coal lages AIRWAYS 115 around respiratory bronchioles surrounded by a halo of dilated airspaces (101 In addttton to the accumulations of coal tn the macule, there is a slight increase in reticulin fibers and, to a lesser extent, collagen fibers. The presence of coal macules around the walls of the respiratory bron chioles mat lead to atrophy or even to disappearance of the smooth muscle, this leading to a permanent dilatation of these small airways commonlv called focal emphysema In about 1 to 2 percent of miners with simple dust accumulation, large, solid, black masses develop which represent accumulations of coal dust within macrophages and between reticulin and collagen fibers These lesions are commonly formed in the upper lobes and differ from silicotic conglomerate masses m that the masses are not composed of discreet compressed nodules. The cause of the large lesions ("progressive massive fibrosis") in coal workers is not known. They are probably not due to coexisting tuberculous infection, but may represent an immunological reaction to the accumulated dust load. See Figure 5. Caplan described the appearance of multiple rounded nodules in the lungs ot coal miners with rheumatoid arthritis that subsequently proved to be necrobiotic nodules resembling those seen in rheumatoid arthritis (II) Microscopically, these lesions demonstrate a pale, ne crotic center surrounded by granulomatous tissue having a typically "palisaded" appearance at the periphery of the nodule. Typical Caplan nodules have subsequently been reported in other occupations than coal mining, suggesting that they are not specifically related to coal dust ex posure MIXED DUST PNEUMOCONIOSIS Tn the mixed dust pneumoconioses the pathology depends to a large extent upon the relative proportion of free silica or quartz present in the airborne dust Those with a quartz content of less than about 0 1 per cent tend to develop small nodular areas in the lungs in almost direct prooortion to the total amount of dust deposited, but little m the way of reticulin or collagen fibrosis, and very little emphysema The patho logical lesions more nearly resemble those found in coal miners. On the other hand, dusts in which the quartz content ranges from about 2 percent to about IS or 20 percent of the total dust tend to pro duce lesions that more nearly resemble those seen in classical silicosis. Some examples of dusts that contain almost no free quartz are ka olin. talc, iron oxide associated with welding, coal, and coke used in making carbon electrodes. DIFFUSE INTERSTITIAL FIBROSIS There are a number of pneumoconioses that tend to produce diffuse interstitial fibrosis as their characteristic pathological lesion (6). Among these are berylliosis, aluminosis, Shaver's disease, and asbestosis. It ap pears likely that certain slowly dissolving constituents in the dusts give B0C2903 I RSV0033746 ic 1.r -t e >t \ AIRWAYS U7 CATEGORY Profusion refers to the number of small opacities per unit area. Thus, the lung fields are divided into three zones on each side, and the number of opacities within each zone is graded Standard radiographs are avai able for comparison which divide the profusion into categories 0. 1,2, and 3 Category 0 refere to the absence of opacities or the pres ence of less profuse opacities than in category 1, category 1 shows small rounded opacities present, but few m number, and the normal lung markings are usually visible; category 2 shows numerous small rounded opacities, and the normal lung markings are still visible; category 3 shows very numerous small rounded opacities, and the normal lung markings are partly or totally obscured. Actually, there is a continuum of changes from normality to the most advanced category and, to recognize this, the British National Coal Board developed a 12-point scale (13). This scale permits subdivisions of profusion into finer grades and is useful tn epidemiological studies where progression of pneumoconiosis is important. The radiograph is classified into one of the four categories tn the usual way by comparison with the standard midcategory films If, dunng the process, the category above or below was considered as a serious alternative, this is also recorded. Thus if a category Vz is recorded, it means that on comparison with standard radiographs the radiograph most nearly matched the category 1, but category 2 was seriously considered as an alternative. The extent of pneumoconiosis is recorded by noting which of the lung zones are involved Each lung is divided into three roughly equal zones by imaginary lines drawn at approximately one-third and twothirds of the vertical distance between the apex of the lung and the dome of the diaphragm. Thus, each lung is divided into upper, mtddle, and lower zones for the purposes of recording the extent of pneumoconiosis. IRREGULAR OPACITIES Small irregular opacities are classified in much the same way as the small regular opacities, by type, profusion, and extent. Irregular opacities characteristically occur in asbestosis, but also occasionally tn the other pneumoconioses The variability, however, of these opacities in shape and width makes it virtually impossible to provide quantitative dimensions as is done in the rounded opacities; therefore, the types are divided on the basis of thickness The s type refers to fine irregular, or linear, opacities; the t type refers to medium irregular opacities, and the u type refers to coarse (blotchy) irregular opacities. Standard radio graphs of the three types of irregular opacities are available for com parison Profusion of irregular opacities is graded in exactly the same way as is done in the rounded small opacities. PLEURAL CHANGES Certain pleural changes have recently become recognized as ac companiments to the parenchymal changes referred to above as part of BGC2304 $ i RSV0033747 AIRWAYS 119 Agent, pathotogy, anil impairment associated with pnesmoconiosas. A tent Type ot Pathology Type of Respiratory Impairment 1 Silica Simple Complicated 1 Hematite Nodular fibrosis Conglomerate nodular fibrosis Nodular fibrosis Restrictive, diffusion Restrictive, obstructive. diffusion Restrictive, diffusion 3 Mixed dusts Iron and silica 4 Silicates Talc Kaolin Bentonite Diatomite Tripoli Fuller's earth Mica Sillimantte Cement N Coal Simple Complicated 6 Graphite - Aluminum 8 Asbestos 9 Beryllium 10 Tungsten carbide 11. Barium 12. Cenum 13 Iron 14 Tm 15. Titanium Nodular fibrosis i Rarely conglomerate nodular fibrosis) Nodular fibrosis (Rarely conglomerate nodular fibrosis) Restrictive, diffusion Restrictive, obstructive Nonspecific bronchitis Obstructive Peribronchiolar macules..Obstructive (small focal emphysema airways) Conglomerate nodular Obstructive, restrictive, fibrosis diffusion Peribronchiolar macules. Obstructive (small focal emphysema airways) Interstitial fibrosis Restrictive, diffusion Interstitial fibrosis Restrictive, diffusion interstitial fibrosis (granulomata) Restrictive, diffusion Interstitial fibrosis Restrictive, diffusion Simple dust accumulation None known Simple dust accumulation None known Simple dust None known accumulation Simple dust accumulation None known Simple dust accumulation None known EGC2305 6113 18251 RSV0033748 12* OCCUPATIONAL DISEASES The simple forms of classical silicosis, coal workers' pneunuxonu osis, and the mixed dust pneumoconiosis, generally demonstrate mild obstructive impairment; whereas, the complicated forms (PMF) usually present mixtures of obstruction, restriction, and abnormalities of gjj exchange. RESTRICTIVE IMPAIRMENT The restrictive pattern of physiological response is characterized by a reduction in lung volumes and ventilatory capacity, usually uitaccom. panied by an increased air flow resistance or hyperinflation. The re strictive pattern is also associated with an increased lung recoil, reduc tion in surface area for gas exchange and/or thickening of the air blood interface of the lungs. The pneumoconioses that lead to diffuse interstitial fibrosis usually present the restrictive pattern of physiological impairment. In these, the earliest impairments are those mvolvmg gas exchange and diffusing ca pacity, and may be detectable only during exercise In the later stages, gas exchange and diffusion abnormalities are detectable also at rest and are associated with a reduction in Jung volumes, such as the vital ca pacity, total lung capacity, and the inspiratory reserve volume. Again, m cases where pneumoconiosis coexists with asthma or chrome broo chtus, this restrictive pattern may be associated with some element of obstructive impairment. Asbestosis, berylliosis, aluminosis, and Shaver's disease are examples of pneumoconioses that are characteristically associated with the restric tive pattern of physiological impairment. A summary of agent and type of pathology and respiratory impair ment is given in Table 3. REFERENCES 1 International Labour Office. 1972. The definition of pneumoconiosis. Pige 1358 in Encyclopedia of Occupational Health and Safety, Voi. II, Appendix VU McGraw Mill Book Co, New York. 2 Muir. DCF 1972. Dust Inhalation, Retention, and Elimination. In: i U Rogan, ed. Medicine in the Mining Industries, p. 55 F. A. Davis Co., Phil adelphia. 3 International Commission on Radiological Protection. 1946. Deposition and retention models for internal dosimetry of the human respiratory tract. Health Phys 12 173 4 Lippmann, M , and R. E. Albert 1969. The effects of particle sir* on the regional deposition of inhaled aarosola in the human respiratory tract. Am. ind. Hyg. Assoc, i. 30:257. 5 Brain, i. D. 1971. The effects of inhaled particles on die numbers of alveolar macrophages. In: M. H Walton, ed. Inhaled Particles III, VoL l. p 209. Unwin Bros., Ltd., Old Woking. 6 Nagelschmidt, O. 1960. The relation between lung dust and lung pathology in pneumoconiosis. Bn. I. Ind. Med. 17:247. 7 Steele, R A 1972. The pathology of silicosis. In: I M. Rogan, ed. Medicine in the Mining Industries, p. 20. F A. Davis Co., Philadelphia. 8. Heppleslon, A. G 1969 The fibrogenic action of silica. Br. Med. BuU. 23:282. 9 Spencer, H. 1968. Pathology of the Lung, 2nd ed. Pergamon Press, Oxford. RSV0033749 2J* OCCUPATIONAL DISEASES contains 50-]00''. benxene, the remainder consisting of toluene, xylene, and other constituents which disull below 120 C. SYNONYMS Benzol, phenyl hydride, coal naphtha, phene, benxole. cyclohexatriene POTENTIAL OCCUPATIONAL EXPOSURES Benzene is used as a constituent in motor fuels, as a solvent for fats. inks. oils, paints, plastics, and rubber, in the extraction of oils from seeds and nuts, and in photogravure printing It is also used as a chem ical intermediate. By alkylation, chlorination, nitration, and sulfonation, chemicals such as styrene, phenols, and maleic anhydride are produced. Benzene is also used in the manufacture of detergents, explosives, phar maceuticals. and dyestuffs A partial list of occupations in which exposure may occur includes Adhesive makers Asbestos product impregnators Dry-battery makers Chemists Benzene hexachlonde makers Burnishers Carbolic acid makers Chlorinated benzene workers Detergent makers Dye makers Furniture finishers Glue makers Linoleum makers 'Maleic acid makers Nitrobenzene makers Petrochemical workers' Putty makers Rubber makers Styrene makers Welders PERMISSIBLE EXPOSURE LIMITS The Federal emergency standard for benzene effective May 21, 1977, is I ppm for an 8-hour TWA. with 5 ppm as a maximum peak above the acceptable ceiling for a maximum duration of 15 minutes. ROUTES OF ENTRY Inhalation of vapor which may be supplemented by percutaneous absorption although benzene is poorly absorbed through intact skin. HARMFUL EFFECTS Local-- Exposure to liquid and vapor may produce primary irritation to skin. eyes, and upper respiratory tract. If the liquid is aspirated into the lung, it may cause pulmonary edema and hemorrhage. Erythema. \esicutation. and dry. scaiy dermatitis may also develop from defatting of the skin Systemic-- Acute exposure to benzene results in central nervous system de pression. Headache, dizziness, nausea, convulsions, coma, and death may result. Z of ventricular endogenous e rhages (non-p mucous memb Chronic < changes. Beni cyte, and thrt anemia may c The bone mar ways correlate Recent ei related blood t to conclude th vincing for act. but a connectr vestigaton. Recent wr ations assodan bone marrow i exposure has and seem to is | ; MEDICAL SUR' Preplacem especially with of exposure to the blood. Pre plete blood coi white blood coticukicyte count The type ; related to the c giene studies, a Recommendatic criteria for a re cemed with oth vous system, ar SPECIAL TESTS Biologic rr benzene exposui phenol content no worker absc absorption of bt to occur at leve gravity corrects the NIOSH "C BCC2307 6113 18253 RSV0033750 411 OCCUPATIONAL DHEA9BS SYNONYMS None. POTENTIAL OCCUPATIONAL EXPOSURES Cement is used as a binding agent tn mortar and concrete (a ture of cement, gravel, and sand). Potentially hazardous exposure tnl occur during both the manufacture and use of cement ' A partial list of occupations in which exposure may occur inducfe. Asbestos cement workers Bnck masons Bridge builders Drain tile makers Heat insulation makers Oil well builders Building construction workers Silo builders Burial vault builders Cement workers Storage tank builders Tunnel builders Concrete workers Water pipe makers should be pro {long sleeved s penonal hygte encouraged clothes. pFrneshi basts. BiBUlOGRAPh' Cahwn.C I960 Kalacic. I !97' Environ He Ksltcic. I I97i Hnlth 26 g. Moms. C. E |v I J01 SaltieHre. aOlth 1A7 9. PERMISSIBLE EXPOSURE LIMITS The Federal standard for Portland cement is SO mppcf. ROUTE OF ENTRY SODIUM h Inhalation of dust. description HARMFUL EFFECTS Local-- Exposure may produce cement dermatitis which is usually due to primary irritation from the alkaline, hygroscopic, and abrasive proper ties of cement. Chrome irritation of the eyes and nose may occur. In some cases, cement workers have developed an allergic sensitivity to constituents of cement such as hexavalent chromate. It is not unusual for cement dermatitis to be prolonged and to involve covered areas of the body. Systemic-- | NaOH. s pellets, flakes, enne. Aqueo KOH. potacent lumps, r are known as 1 SYNONYMS Sodium dram hydrate Potassiui No documented cases of pneumoconiosis or other systemic mani festations attributed to finished Portland cement exposure have been reported. Conflicting reports of pneumoconiosis from cement dust ap pear related to exposures that occurred in mining, quarrying, or cradl ing silica-containing raw materials. MEDICAL SURVEILLANCE Preemploymec; and periodic medical examinations should stress significant respiratory problems, chest X-ray, pulmonary function tests, smoking history, and allergic skin sensitivities, especially to chromates. The eyes should be examined. SPECIAL TESTS Patch test studies may be useful In dermatitis cases. PERSONAL PROTECTIVE METHODS In areas exceeding safe dust levels, masks with proper cartridges caustic alkali. POTENTIAL 1 Sodium salts in petre duenon. and soaps, and 11 tions of then paper, explo: (ion of zinc, washing, and Potasstu a mordant fc ton, m electr in ptunt and thesis, and tl BCC~908 6113 18254 RSV0033751 na' Inst,, ''`K'tion (I 'lSur* to -studies 0f * b> e*Periagents jn Talation a). important nst.ru,e ,hg ' P^valent eP'demione individ. res There 'ty or the at a given genent and i common r)ng their -tiring the s a group By comnex posed ncreased uculation requency with that of more oulation. : may m ess nsky ncate an >o-called 'ment of nortality ers with 1 CHEMICAL CARCINOGENS 445 tons latent or l^pse times following onset of exposure may yield erroneous occlusions as to the lack of health effects of those chemicals in the work `,,vironment that are being studied. IHIMAL STUDIES In epidemiologic studies, once a chemical or exposure condition has been shown to cause cancer, preventive measures may not be adequate to protect those who have had previous exposures, but who have not lived jong enough for effects to be expressed in terms of clinical illness. A major advantage of experimental animal studies is the possibility of detecting a chemical cancer hazard earlier than if one waited for epidemi ologic evidence of cancer in man to become available. Under such circumstances, preventive acuon can be taken much sooner. To date, there are a number of instances in which data on cancer in experimental animals have been used to establish occupational health regulations in the United States. It is increasingly evident that experi ments in animals can be important indicators of cancer nsk for man. Almost all chemicals shown to be carcinogenic m man by epidemiologic studies have also been shown to be carcinogenic in appropriate animal nwdels. Although this does not necessarily mean that a positive test for cancer in animals provides incontrovertible evidence of cancer nsk for man, it does indicate that the chemical should be considered at least as a potential carcinogen for man. Experts frequently recommend testing chemicals in more than one animal species, primarily to avoid false negauve results. Nevertheless, this should not be interpreted to mean that, before a chemical can be called a carcinogen, it must be positive in two or more species tested. Naturally, however, the greater the number of studies that show that certain chemicals produce cancer in different species of laboratory ani mals. the greater the confidence in the conclusion that those substances pose a carcinogenic threat to man. POTENTIAL OCCUPATIONAL EXPOSURES The boundaries of potential occupational exposures to chemical carcinogens are ever expanding. The following occupations are some of those subject to recent investigations. Asbestos workers Auto repairmen Bakery workers Clothing pressers Coke oven workers Dairy industry workers Dental laboratory technicians Electricians Leather workers Photoengravers Roofers Rubber workers Vinyl chloride workers BCC~309 1 RSV0033752 *4* OCCUPATIONAL DISEASES .Table 4 presents a list of occupational chemicals and subst*^ which cause, or are suspected of causing, cancer and the target organ ^ tissue, it should be emphasized that this list is substantially incomplete in that many, if not most, chemicals in the workplace have not been adequately tested for their carcinogenic potential. As such, however, the format of Table 4 attempts to organize a growing body of data in a manner that may be useful for physicians m making a differential diag. nosis of the possible occupational etiology of cancer cases in individuals Additionally, this list may lead physicians and other health professionals to become more aware of the magnitude of the growing problem of chem. ical carcinogens in the workplace. Since occupational carcinogens may effect virtually all organ systems, physicians should be alert to investigate situations where clinically evident cancer could be associated with on-the-job chemical exposures. One helpful data source for physicians is the registry of suspected carcinogens maintained by NIOSH as a subfile of the Registry of Toxic Effects of Chemical Substances (3). This Registry contains approximately 1.500 suspect carcinogens, most of which have not been adequately tested. Their inclusion on this list does not represent a process of substantive evaluation with respect to the adequacy of scientific data related to carcinogenicity. Rather, this list is a useful starting point to ascertain the extent of data regarding carcinogenic responses for a given compound. Even with these caveats, it should be evident that a number of compound in this list may be shown to be carcinogenic in man following more detailed evaluation. Observations by alert physicians and alert workers have frequently helped to identify problems of carcinogenic risk in the workplace long before they might otherwise be realized. Examples of this are hepatic angiosarcoma, a rare liver cancer caused by occupational exposure to vinyl chlonde. and leukemia among workers in the manufacture of sty. rene-butadiene rubber. A number of other occupational chemicals have been shown to produce "marker" or unusual forms of cancer, such as the pleural and peritoneal mesotheliomas due to asbestos, and hepatic angiosarcoma due to inorganic arsenic. It is likely that careful follow-up of rare cancers oi unusually high incidences of common cancers may help to uncover unsuspected chemical cancer hazards among other worker populations. Unsuspected occupational cancer problems might also be predicted on the basis of structural similarity with certain chemicals and substances already shown to cause cancer in humans or animals. For example. Table 5 lists compounds that by virtue of their structural similarity to vinyl chlonde would be suspected of posing possible carcinogenic risks to man. Surveillance by alert physicians of workers exposed to these substances might help to early identify potential future problems. Similarly, it is most important for clinicians to be aware of newer data on carcinogenesis emerging from experimental studies on animals. For example, prelimi nary data have indicated that tnchloroethylene produces liver cancer in experimental animals (4), and data from Russia have suggested a human carcinogenic lung and skin response to chtoroprene (S). BCCSDIO lOdney Laryn* Liver Lung Lymp Tis Nasal Panci Pleur Prost Scrot Skin Unni Bl. 6113 18256 RSV0033753 ,,anc(* "n or mpiete r been ir. the ima diag. duals tonah .'hem- mav -tigate with ^ected Toxic lately isted antive -d to main iund. Hinds more .ently long patic *e to stynave i the oatic v-up ielp rxer ;led ices able in yl nan. ices I is esis mi* :m nan ! 1 ! f j 1 CHEMICAL CARCINOGENS 447 TjWb 4. Confirmed and mpactad occupational carcinofant by targat organ. i Organ/Tissue Bone Brain Gastroenteric Tract Hematopoietic Tissue (leukemia) Kidney Larynx Liver Occupational Carcinogen Contimied Beryllium Vinyl Chloride Asbestos Benzene Styrene Butadiene and other Rubber Manufacture Substances Coke Oven Emissions Asbestos. Chromium Vinyl Chloride Lymphatic Tissue Nasal Cavity Pancreas Pleural Cavity Prostate Scrotum Skin Arsenic Asbestos Bis (chloromethyl) ether Chloromethyl methyl ether Chromates Coke Oven Emissions Mustard Gas Nickel Soots and Tars Uranium Vinyl Chloride Urinary RSV0033754