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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. Manuscript Editor -- Lorice Ede. J.D. U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE Public Health Service Center for Disease Control National Institute for Occupational Safety and Health For tale by the Superintendent of Document*. U.S. Government Prlntin* Office. Washington. D.C. 20402 OCCUPATIONAL DISEASES DEPOSITION There are four major factors that influence the site of the ultimate toxicologic response to inhaled particulates: 1) the anatomic arrange ment and physical dimensions of the respiratory system, 2) the physio logic character of breathing rate and depth, 3) the physical nature of the particle-size, surface area, "solubility," and hygroscopicity, 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 ^m 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 particle such as uranium dioxide with a high density of 10.9 and diameter < 0.5 ^m will behave as a unit-density spherical particle of 1.65 nm, 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 ^m. 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 particles greater than 6 /am were deposited at this site at all breathing rates. Thus, the major site of deposition of the smaller par ticles is 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 /am) 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. Hygroscopicity, however, seriously affects deposition of smaller, highly water-soluble particles by increasing their size as they travel down the respiratory tract in its 95% humidity. Thus, in some instances, it is possible for a small size particle in an atmosphere of low humidity to ncrease Us *35*11 patted ^As is true vm be expected. Cl lung where ve: thC Another fact commonly associa Ci.e., nneew-l.y g= eneral deposition. clearance an In evaluatin bined physio-cht ment, 2) phagopenetration, and Respiratory chioles. Particle from the termin are transferred posure of the re the intestinal tr; the nasal passa; from the trachc Phagocyio particulates fre the appearanci increase the ra from the lung lymph nodes r dust burden f Direct in of variable m activity of thi rous protein, be cleared b' Obvious for particles dusts, such ; in a matter > certain type: sequent clea inorganic cc tions has bt day to 10 clearance, pressed as BCCG333 LAM021549 6113 18245 imate angeysiof the the and odv- the for xly- >arind 'tn>si0.9 cle at >er li nt :i- ROUTES OF ENTRY 15 increase its size in the respiratory tract as to alter considerably the ^ "sition pattern characteristic of the entering particle size. As is true with all generalizations, differences in deposition patterns be expected, and indeed have been demonstrated, particularly for t^n [ung where ventilation among the five lobes is normally variable. 1 Another factor which alters deposition patterns is electric charge, mmoniy associated with particle sizes less than 0.1 urn 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 takes place from the terminal bronchioles upward to the throat where the particles are 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 particles 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 lymph nodes represents 2 to 10 'A of 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, and biologic activity of the dust. Thus, a particle that is not readily coated with se rous protein, or other lung constituent, would penetrate the cell and then be cleared by this mechanism more readily than one that is coated. Obviously solubilization 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). BCG^300 LAM021550 6113 18246 DERMATOSES 83 Rowing groupings comprise the majority of the occupational derma- joSCS. (1) Acute contact eczematous dermatitis characterized by ery thema. edema, papules, vesicles or bullae, crust, scale, and finally, des quamation. These are the signs of an inflammatory eczematous derma titis caused by contact with a primary irritant or a sensitizer or a photosensitizer. (2) Chronic eczematous dermatitis characterized by erythema, lichenification, scaling, dryness, and fissuring 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 chloronapthalenes. (4) Neoplastic (benign and malignant) types as keratoses, papil lomata, epitheliomas, and carcinomas 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 in 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 hydroquinone; and certain phenolics 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 trioxide, calcium compounds, cement and concrete, chromic acid, burns 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) porphyria cutanea tarda caused by a certain chlorinated hy drocarbon intermediate. B0C2301 84 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 pro. ducing a dermatosis. Additional agents for the 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 acid 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 Animal Handlers antibiotics bacteria cleaners & detergents deodorants feeds fungi germicides insecticides medicaments parasites pesticides viruses Artists (Painters) acrylics epoxies paint removers pigments plasticizers solvents Artists (Sculptors) dusts plaster of Paris pneumatic tools polishes Athletes adhesives antibiotics bacteria lime medications protective gear soaps Automobile Workers adhesives asbestos antifreeze brake fluids brake linings flame retardants gasoline hydraulic fluids oils rubber solvents B0C^302 automobile Work abrasives adhesives alkalis lead paints rubber compc 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 depilatories detergents dyes fungi LAM021552 6113 18248 lveolar 'dence in the sis. One reac- coal lages AIRWAYS 115 around respiratory bronchioles surrounded by a halo of dilated airspaces (10). In addition to the accumulations of coal in 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 may lead to atrophy or even to disappearance of the smooth muscle, this leading to a permanent dilatation of these small airways commonly 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 in 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 of 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 In 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 proportion to the total amount of dust deposited, but little in 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 18 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 makine 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 BGC~903 LAM021553 6113 18249 AIRWAYS 117 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 available for comparison which divide the profusion into categories 0, 1,2, and 3. Category 0 refers 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 in 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 in epidemiological studies where progression of pneumoconiosis is important. The radiograph is classified into one of the four categories in the usual way by comparison with the standard midcategory films. If, during 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, middle, 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 in 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 BCCS304 AI1WAY9 119 Table 3. Agent, pathology, and impairment associated with pneumoconioses. Agent Type of Pathology Type of Respiratory Impairment Silica Simple Complicated Hematite 3. Mixed dusts Iron and silica 4. Silicates Talc Kaolin Bentonite Diatomite Tripoli Fuller's earth Mica Sillimanite Cement 5. Coal Simple Complicated 6. Graphite 7t Aluminum 8. Asbestos 9. Beryllium 10. Tungsten carbide 11. Barium 12. Cerium 13. Iron 14. Tin 15. Titanium Nodular fibrosis Conglomerate nodular fibrosis Nodular fibrosis Restrictive, diffusion Restrictive, obstructive, diffusion Restrictive, diffusion Nodular fibrosis (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 Restrictive, diffusion <granulomata) Interstitial fibrosis Restrictive, diffusion Simple dust accumulation None known Simple dust None known accumulation Simple dust accumulation None known Simple dust accumulation None known Simple dust None known accumulation EGC2305 LAM021555 6113 18251 120 OCCUPATIONAL DISEASES The simple forms of classical silicosis, coal workers' pneumoconiosis, and the mixed, dust pneumoconiosis, generally demonstrate mild obstructive impairment; whereas, the complicated forms (PMF) usually present mixtures of obstruction, restriction, and abnormalities of gas exchange. RESTRICTIVE IMPAIRMENT The restrictive pattern of physiological response is characterized by a reduction in lung volumes and ventilatory capacity, usually unaccom 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 involving 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 lung volumes, such as the vital ca pacity, total lung capacity, and the inspiratory reserve volume. Again, in cases where pneumoconiosis coexists with asthma or chronic bron chitis, 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. Page 1558 in Encyclopedia of Occupational Health and Safety, Vol. II, Appendix VII. McGraw Hill Book Co., New York. 2. Muir. D. C. F. 1972. Dust Inhalation, Retention, and Elimination. In: J. M. Rogan, ed. Medicine in the Mining Industries, p. 55. F. A. Davis Co., Phil adelphia. 3. International Commission on Radiological Protection. 1966. 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 size on the regional deposition of inhaled aerosols in the human respiratory tract. Am. Ind. Hyg. Assoc. J. 30:257. 5. Brain. J. D. 1971. The effects of inhaled particles on the numbers of alveolar macrophages. In: M. H. Walton, ed. Inhaled Particles III, Vol. 1. p. 209. Unwin Bros., Ltd., Old Woking. 6. Nagelschmidt, G. 1960. The relation between lung dust and lung pathology in pneumoconiosis. Bri. J. Ind. Med. 17:247. 7. Steele, R. A. 1972. The pathology of silicosis. In: J. M. Rogan, ed. Medicine in the Mining Industries, p. 20. F. A. Davis Co., Philadelphia. 8. Heppleston, A. G. 1969. The fibrogenic action of silica. Br. Med. Bull. 25:282. 9. Spencer, H. 1968. Pathology of the Lung, 2nd ed. Pergamon Press, Oxford. 10. Heppleston, A. G. I ming and L. B. Hun The Williams and W 11. Caplan, A. 1953. Ce coal miners suffering 12. Jacobson, G., and W classification of radio 48:65. 13. Liddell, F. D. K., ar classification of simpi bibliography Dinman, B. D. 1974. The Springfield, Illinois. Enterline, P. E. 1974. Re Med. 16:523. Gross, P., P. A. Theodos. ( 1976. The pulmonary mitlee on Environme Chest 69:216. Hendrick, D. J., and D. J Ind. Med. 34:11. Patel, R., N. Janakiraman. and coma from perchlr BGC2306 LAM021556 6113 18252 236 OCCUPATIONAL DISEASES contains 50-100% benzene, the remainder consisting of toluene, xylene, and other constituents which distill 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 Furniture finishers Asbestos product impregnators Glue makers Dry-battery makers Linoleum makers Chemists Maleic acid makers Benzene hexachloride makers Nitrobenzene makers Burnishers Petrochemical workers' Carbolic acid makers Putty makers Chlorinated benzene workers Rubber makers Detergent makers Styrene makers Dve makers Welders PERMISSIBLE EXPOSURE LIMITS The Federal emergency standard for benzene effective May 21, I 977, is 1 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, vesiculation. and drv, scaly 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. E of ventricular endogenous e rhages (non-p mucous memb Chronic ( changes. Ben: cyte, and thr< anemia may c The bone mar ways correlate Recent et related blood i to conclude th vincing for act but a connects vestigators. Recent wr ations associate bone marrow t exposure has a and seem to in MEDICAL SUR' Preplacem especially with of exposure to the blood. Pre plete blood cot white blood cc ticulocyte count The type ; related to the d giene studies, a Recommendatic criteria for a re cemed with oth vous system, ar SPECIAL TESTS Biologic ir benzene exposui phenol content, no worker absc absorption of be to occur at leva gravity corrects the NIOSH "C BGC2307 LAM021557 6113 18253 432 OCCUPATIONAL DISEASES SYNONYMS None. POTENTIAL OCCUPATIONAL EXPOSURES Cement is used as a binding agent in mortar and concrete (a ^ ture of cement; gravel, and sand). Potentially hazardous exposure may occur during both the manufacture and use of cement. A partial list of occupations in which exposure may occur includes Asbestos cement workers Drain tile makers Brick masons Bridge builders Heat insulation makers Oil well builders Building construction workers Silo builders Burial vault builders Cement workers Concrete workers Storage tank builders Tunnel builders Water pipe makers pr"oM' h',glC' BLIOGRAPH' ,, r 1960 Clnan' ! 197? KalaCEnv.ron. He r 197*1 2,1 *- caader. O. S n Health lAL 7` :9r PERMISSIBLE EXPOSURE LIMITS The Federal standard for Portland cement is 50 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. Chronic 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-- j NaOH. s. pellets, flakes, erine. Aqueoi KOH. potas cent lumps, u are known as 1 SYNONYMS Sodium dium hydrate. Potass iur. 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 crush ing silica-containing raw materials. MEDICAL SURVEILLANCE Preemploymem 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 t Sodium salts in petro duction, and soaps, and it tions of their paper, explos tion of zinc, washing, and Potassiu a mordant fo ton, in electn in paint and thesis, and th BGC~908 LAM021558 6113 18254 'nal. InitUtc OS,,in thl. osure to ^ studies of ; by expenagents. In ialation alimportant. nstitute the i prevalent epidetniohe individies. There ity or the lat a given data genesent and i common .ring their :uring the s a group By comnexposed increased liculation requency with that of more pulation. ; may in ess risky iicate an -.o-called 'ment of nortality ;rs with CHEMICAL CARCINOGENS 445 long latent or laps* times following onset of exposure may yield erroneous inclusions as to the lack of health effects of those chemicals in the work L vironment that are being studied. AN1MAL 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 long 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 action 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 risk for man. Almost all chemicals shown to be carcinogenic in man by epidemiologic studies have also been shown to be carcinogenic in appropriate animal models. Although this does not necessarily mean that a positive test for cancer in animals provides incontrovertible evidence of cancer risk 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 negative 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 BGC-309 UM02 7 559 6113 18255 446 OCCUPATIONAL DISEASES . Table 4 presents a list of occupational chemicals and substance which cause, or are suspected of causing, cancer and the target organ or tissue. It should be emphasized that this list is substantially incompfett in that many, if not most, chemicals in the workplace have not bee,, 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 in 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 compounds 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 chloride, 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 or 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 chloride 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 trichloroethylene produces liver cancer in experimental animals (4), and data from Russia have suggested a human carcinogenic lung and skin response to chloroprene (5). BCCG310 Kidney Larynx Liver Lung Lymp Tis Nasal Pancr pleur Prost Scror Skin Urint Bl; LAM021560 6113 18256 dances an or mplete ' been ir. the 1 in a diagduals. ionals -hemi mav 'tigate with 'ected Toxic lately ested. mtive id to -`rtain ound. 'unds more :ently long patic e to stynave i the oatic v-up lelp rker cted rices able invl nan. ices t is esis mi' in nan CHEMICAL CARCINOGENS 447 Table 4. Confirmed and suspected occupational carcinogens by target organ. ______ Occupational Carcinogen -p^roey Organ / Tissue ConfirmedSuspected Bone Brain Gastroenteric Vinyl Chloride Beryllium Tract Asbestos Hematopoietic Benzene Tissue (leukemia) Styrene Butadiene and other Rubber Manufacture Substances Kidney Larynx Liver Coke Oven Emissions Asbestos. Chromium Vinyl Chloride Lead Aldrin Carbon Tetrachloride Chloroform DDT Dieldrin Heptachlor PCB's Trichloroethylene Lung Arsenic Asbestos Bis (chloromethyl) ether Beryllium Cadmium Chloroprene Chloromethyl methyl ether Lead Chromates Coke Oven Emissions Mustard Gas Nickel Soots and Tars i Uranium Vinyl Chloride Lymphatic Arsenic Tissue Benzene Nasal Cavity Chromium, Isopropyl Oil, Nickel, Wood Dusts Pancreas Benzidine PCB's Pleural Cavity Prostate Scrotum Skin Urinary Bladder Asbestos Soots and Tars Arsenic Coke Oven Emissions Cutting Oils Soots and Tars 4-Aminobiphenyl Benzidine B-Naphthylamine Cadmium Chloroprene Auramine 4-Nitrodiphenyl Magenta .,, BGC-311 4 !