Document 9Jq6EYmoxXYJQgV4mqVRGy09q

FILE NAME: Packings and Gaskets (PAG) DATE: 1950 DOC#: PAG061 DOCUMENT DESCRIPTION: Public Health Tech Monograph # - A Methodology for Environmental & Occupational Cancer Surveys Public Health Technical Monograph No. 1 A Methodology for Environmental and Occupational Cancer Surveys By W. C. Hueper, M. D. Chief, Cancerigenic Studies Section, National Cancer Institute of the National Institutes of Health, Public Health Service, Federal Security Agency CONTENTS I ntroduction A. Tun N ature of the P roblem-----------------Occupational carcinogens--------------------------------Nonoceupational carcinogens---------------------------Industrial public health hazards----------------------B. Types of E nvironmental Cancer Survey. Analysis of death certificates---------------------------Occupational history study of cancer deaths-----Industrial plant surveys---------------------------------C. Special Aspects-------------------------------------- ----------------Contact-site relations of carcinogens--------------------- --------Environmental cancer pattern-------------------------------------------Identification of occupational cancers---------------------------------Age factors in occupational cancer...........---------- -----------------Appendix A. Occupational and nonoceupational groups sug' gested for survey--------------------------- ------------------------------Appbnmx B, Occupational cancor record-------------------------Appenmx C. Occupational hazard code Appenuix D . Plant survey record.......... Page 1 1 2 4 6 7 7 9 10 14 15 16 19 25 26 31 33 37 n INTRODUCTION Environmental cancers are malignant tumors which are usually caused by prolonged exposure to exogenous agents of various types. In a few instancesj these environmental cancer-producing factors are well-defined physical or chemical agents; in others they are variable and undetermined mixtures of chemicals; while in a third group tho cancerigenic exposure is represented by contacts or conditions of a rather vague nature. The different environmental carcinogens which form a part of our natural or artificial environment are prnctically the only known causes of cancer in man at tho present time, and for this reason have considerable general significance. ^Exposure to these factors is related to occupational activities, medicines, diets, cosmetics, building material, linbits, customs, climate, fauna, contami nants of drinking water, atmospheric air and foodstuffs, and proce dures of warfare. Since prevention of cancer depends fund amentally on adequate information as to its etiology, the study of environmental cancers, which may bring vastly increased knowledge as to the causes of all types of cancers, is one of the most important approaches to a future control of cancer. Environmental cancer surveys which are directed at this goal represent, therefore, a basic stop in tho develop ment and institution of preventive cancer control measures. A . THE NATURE OF THE PROBLEM Investigation into the epidemiology, etiology, and control of en vironmental cancer depends upon the application of knowledge and approaches peculiar to this special type of hazard. Often these factors may not bo adequately considered in the usual studies of toxic indus trial hoalth hazards and differ in some respects from those used in epidemiologic investigations of infectious diseases. For example, some of the environmental carcinogens, such as betanaphthylamine and benzidine, scarcely ever cause toxic manifesta tions. In most instances, the carcinogenic process olieitod by these aromatic amines in the bladder is symptomatically silent during a latent period that lasts from 5 to 25 years. Industrial health surveys limited to the demonstration of acute or chronic toxic reactions and disregarding the peculiar nature of these carcinogenic hazards would fail to diseloso the serions danger to exposed persons. _ ( Other environmental carcinogens, such as benzol, ionizing radia tions (X -rays or rays from radioactive substances), will produce l severe degenerative and necrotizing reactions in the tissues as the result ol brief but intense exposure. This more striking effect can obscure the fact that less severe but more prolonged exposure may produce cancerous responses in the same type of tissue after a long latent period. When these two different types of reaction are seen in members of a surveyed occupational group, their etiologic kinship may not be apparent. . Moreover, the long latent period characteristic of environmental cancer formation tends to hinder the recognition of causal relations between the exposure to carcinogenic agents and the subsequent de velopment ef cancer. > t This outcome may well appear when the affected individual lias long since left the employment in which the effective exposure occurred. One purpose of environmental cancer surveys is to collect data on the occurrence, incidence, types, and causes of these malignant tumors and their precancerous manifestations, on the routes and types of exposure to the carcinogenic agents involved in their production, and on the physiocbemical states and properties of these agents. Only through such information is it possible to establish the principles upon which effective measures for the prevention and control of en vironmental cancers must be based. ^ _ Another purpose of occupational cancer surveys is to determine which persons may be effectively exposed to environmental carcino gens and thus become potential victims of environmental cancer. Since the development of such cancers depends on a number of asso ciated factors, environmental cancer surveys must obtain reliable data for an adequate number of cases on age, sex and race, as well as the degree, nature and duration of exposure, and the length of latent period. Information on the approximate minimal effective exposure to any particular environmental carcinogen and on the expected latent period is essential in establishing standards for precautionary and preventive measures. ' _ A final objective of occupational cancer surveys is the celleetion of specific technical information needed for the institution of adequate control measures. These data call benefit industry by aiding in the design and introduction of effective technical measures for protection of their personnel. The evidence acquired through such surveys should also provide a sound and appropriate basis for drafting proper and uniform industrial disease codes, food and drug legislation, and workmen's compensation laws covering the varied and complex fea tures of environmental and occupational cancer* hazards. 1. Occupational Carcinogens Occupational carcinogens, known or suspected, cover avvide range of inanimate and animate agents. This spectrum, summarized in table 1 1, includes a great variety of organic chemicals, both aromatic and aliphatic, several inorganic chemicals, various types of physical radia tion, and the parasite, Schistosoma hamatobium, the only generally recognized animate carcinogen, which attacks outdoor workers in Egypt and other tropical countries, inducing a form of bladder cancer. Table 1, Recognized and suspected occupational carcinogens 1, Chemical carcinogens: (a) Organic chemicals: (1) Aromatic chemicals: Betn-naplitliylaminc, benzidine, aniline (?), benzol, tar, pitch, asphalt, soots (domestic, Industrial, and commercial), sliuio oil, crude paraffin oil, crude nutliracenc oil, creosote, lubricating and fuel oils and greases, syn thetic estrogens (?). (2) Aliphatic chemicals: Isopropyl oil (?). (b) Inorganic cheinicais: Arsenlculs, chromates, nickel carbonyl (?), asbestos (?), beryllium (7). 2. Pliyslcnl carcinogens: Nonionizing rndintion-ultrn violet rays, ionizing radlatoiis-corpnscular riuliallous (alpha and beta rays) unci electronic radiations (gamma and X-rays). 8, Parasitic carcinogens: Schistosoma liematoViitm, I t must bo pointed out that tho various environmental carcinogens differ considerably in their potency not only from each other but also among members of the same typo. Tho carcinogenic potency of dif ferent types of tar varies greatly, gas-house and coko-ovon tar being the most potent. Sim ilar variations seem to exist regarding^ the carcinogenicity of the various types of soot and tho different kinds of natural and processed potroloums, many of which aro noncarcino genic. Beta-naphtliylamino appears to bo much moro carcinogenic than benzidine. Tin* data on occurronco and incidence of occupational cancers, as they appear in published reports, are very inadequate. Tho actual number of cancers which are occupational in origin is undoubtedly much higher than is apparent from tho recorded observations. Siuco it is often difficult to establish tho occupational causation of cancer re sulting from exposure to known eareinogons (often many years pre viously), and because the medical profession is to a certain extent insufficiently awaro of the existence of occupational cancers, even cancers produced by recognized occupational carcinogens ofton escape recognition as such. Furthermore, it seems highly probable that many occupational carcinogens are still unknown, and, in view of the fact that new industrial compounds are being synthesized and manu factured every year, tho spectrum of industrial eareinogons may bo growing oven wider. 3 2. Nonoccupational Carcinogens Occupational cancers belong to the larger group of environmental cancers produced by contact with exogenous agents. Contact with carcinogens may also be related to habits, hobbies, diet, medicinal agents and devices, and other nonoccupational environmental factors. The known nonoccupational carcinogens are summarized in table 2. They include many agents peculiar to certain cultural and geographic groups not found in the United States (such as the hwtigvi and ohutta,) as well as such almost universal agents as solar radiation, soot, and arsenic. As in table 1, the fact is indicated that many of these car cinogens are not yet proved but are only suspected on the basis of limited evidence. Collection of additional ovidence in these fields may not only point out hazardous habits or usages, but may also reveal hitherto unsuspected occupational carcinogens. Data provided by occupational cancer surveys are the only source of reliable informa tion on the minimum effective exposure, maximum and minimum lengths of latent period as related to degree of exposure, and on other important aspects of environmental carcinogenesis. Table 2. Recognized and suspected sources of nonoccupational environ mental cancer jUiffiiod of exposure and carcinoyen Potential tiles ofcancer HABITS: Smoking (tar) (?) or chewing of tobacco (khaini), Betel nut'lirae-tobacco quid chewing,___ _ Chewing of tar, paraffin, etc. (?) --------- _ - Lip, tongue, oral cavity, larynx, lung. Lip, tongue, oral cavity, cheek. Oral cavity. CUSTOMS: Carrying of apodal heating devices beneath clothing near abdominal skin (kairo, kangri), or sleeping on hot stoves (kang), causing burns and exposure to tar and soot. Smoking of cigars with lighted end in mouth (ohutta) (tar and burn injury). Skin. Oral cavity. HOBBIES AND HOME ACTIVITIES: Gardoning with oxpoaure to solar rays, and arsenical and other chemical pesticides (soot, etc,), Sailing, fishing, golfing and other forms of out door sports with exposure to solar radiation. Home-engineering with contact with mineral oil derivatives (?). Use of paints and paint removers containing benzol, chrome pigments, asphalts, carbon blacks (?). Skin, Internal organs. Skin. Do. Leukemia, lung, skin. 4 Table 2. Recognized and suspected sources of mmccnpational environ mental cancer--Continued Method of t i p p l e and carelnoen 1 . Potential sites of cancer HOBBIES AND HOM E ACTIVITIES--Con. TJso of chlorinated aliphatic hydrocarbons in cleaning fluids with liepatotoxio properties modifying metabolism of endogenous and exogenous carcinogens (?). Liver, infornai organs. M EDICINES AND MEDICAL DEVICES: Arscnicals................. ........_...................... ......... Tar, impure vasclino and mineral oil____ _ liepatotoxio chemicals (chlorinated aliphatic hydrocarbons, oinchophon, otc.) (?). Hematotoxic chemicals (bonzol, sulfonamides (?) aromatic organic chomioals) (?). Ultraviolet radiation......................................... X-rays__________________ _____,,____ _____ Radioactive chomicals (ionizing radiations) - . Sitin, internai organa, Do. Livor. Loubemia. Slcin, SIdn, bono, leukomia (?). Sbiy, bono, lirng (?) leucemia (?) livor (?). DIETARY FACTORS: Dietary iodine deficiency............... ........... ____ Dietary protoin and vitamin B complex donoioncy. Dietary vitamin B complex deficiency............ Ai sonical contaminants in food, drinking water, air. Iloatcd mineral oil as fa t substitute in bakod goods (?), Thyroid. Liver, Laryngophnrynx. Skin, internal organs, Internal organs, b COSMETIC FACTORS: X-radiation for dpilation....... ......................... Ultraviolet lamp oxposurc for tanning (?)___ Arsenicals in hair lotions and tonics (?).......... Lamp black in oyebrow pencils (tar) (?)......... Impure vasclino and mineral oils in ointments, creams, etc. Estrogens in skin creams (?)_........................... Impure aniline dyes in lipsticks, etc., containing dye intermediates (?). Skin, Do. Do. Do, Do. Breast. Bladder, OTHER ENVIRONMENTAL FACTORS: Tar and soot in atmospheric air (?)................. D ry and sunny cllmato with oxccsalvo solar irradiation. Parasitic infections (schistosomiasis)............... Ionizing radiation in water and air in regions wJtb radioactive ores (?). Lung, skin (?). Skin, Bladder, liver, intestine. Lung, bone, hematopoietic ti6sue. 1 5 3. Industrial and Public Health Hazards At the present time, environmental cancer appears primaril, industrial problem, although it extends into many noninclusti'k pations. Fully 90 percent of the known environmental card never existed in dangerous concentrations until the develop]] industrial processes which brought workers into frequent an contact with them. As tire injurious agents have made their i ance with the growth of various industries, cancers have dor among exposed workers. Perhaps one of the most striking es of this pattern is the appearance of bladder cancers among dye r subsequent to the establishment of aniline dye industries in countries. Observations in many industries indicate that, j known occupational carcinogen and the proper conditions of e? the appearance of occupational cancers becomes merely a qn time, i. e., of sufficient latent period since the start of the op Clearly such hazards constitute an industrial problem den intensive study and control efforts. Such industrial carcinogens not only provide a serious h s the exposed workers but may possibly also affect the liealtl general population through various routes of contact. Card agents produced or handled in industrial operations, workalu laboratories may enter the air, water supply, or soil after be charged as waste. Persons living or working in the fum e < disposal area may thus come into effective contact w ith th e gens. Contaminated clothing worn by workers in carcinogen] tions may also create a hazard when laundered w ithout precautions in the factory, homo, or commercial laundry, possible extension of industrial hazards to the general popu the incorporation of carcinogens into goods for general cons cither as essential parts or as contaminants. Of course, t or similar extrinsic carcinogens which appear as industrial may also be part of the general artificial or natural environm independent of any industrial operations. Information and conclusions drawn from occupational ca veys, therefore, will have applications that are not restrict industrial or occupational field, but may have relevance to t) problem as a whole. Since environmental cancers represent majority of those cancers whose etiology is known, observatu in relation to these tumors have positive and immediate vale study and possible future control of the many types of liumi whoso causes are still unknown. 6 B, TYPES OF ENVIRONM ENTAL CANCER SURVEY To attain the objectives discussed above, several approaches may be used in environmental cancer surveys. The first method suggested, analysis of death certificates, provides a preliminary or exploratory approach which may give valuable clues and point to fruitful fields for further investigation. Tito second approach, occupational history studies of cancer deaths, involves tracking down possible occupational factors in tho etiology of individual cancer cases. The third approach, the plant survey, is essential for determining precisely which workers come into dangerous contact with carcinogens, how many may be affected, through which route tho exposure takes place, what organ or organs develop cancerous responses, and other important aspects of occupational carcinogenesis. For tho organization of an occupational cancer survey on a State level, it is essential that closo cooperation be established between various State agencies (department of health with its divisions of cancer control, industrial hygiene, and vital statistics, and department of labor) and that contacts be made with the State medical society (committees on cancer, industrial medicine, public relations), local tumor registries, and, where necessary and desirable, the State asso ciation of clinical pathologists and public.health nurses association. The over-all direction of such a survey should be provided by tho department of health and tho work should bo carried out by eithei the division of cancer control or the division of industrial hygiene, depending upon which one of these two agencies appears best suited and equipped for the work. Since occupational c a n c e ls mainly a biological phenomenon, it appears reasonable to place in charge of the project, a physician experienced in cancer, industrial medicine, or both. 1. Analysis of D eath Certificates W orking on the premise that certain occupational activities or con tact with various occupational or environmental agents result in an abnormally high incidence of total cancer deaths, as well as in an abnormal distribution of cancer as to sites, the effects of such factors on local cancer mortality might be demonstrated through a critical analysis of data recorded in death certificates. I f such environmental carcinogenic influences are sufficiently pronounced and specific in a certain area, and the worker population is relatively stable, it might be profitable to plot the local distribution of cancer deaths as to total number and as to sites. Comparison of these data with data from an area having a different environmental and, p a rtic u la rly , occupa tional carcinogenic spectrum should reveal suggestive relations be tween these factors and cancer incidence. By comparing the rela- 890078-SO-----2 7 live frequency of cancer cases for various sites in the region under study against the normally expected frequency, it may be possible to locate regional foci of carcinogenic exposure--plants, industries or occupations which deserve further investigation and in which pro tective and preventive measures are needed. To establish such correlations, not only the residence but also the place o f employment must bo noted and evaluated. For the purpose of such analysis, the map of the survey area may be divided into regions with more or less well-defined environmental patterns--in dustrial, agriculture, urban-commercial, maritime. W ithin the industrial regions, establishmente should be noted which provide known or suspected carcinogenic hazards. Such industries may include tar, pitch, asphalt, and creosote producers and con sumers; organic chemical, dye, and pharmaceutical manufacturers; rubber producers and processors; paint manufacturers; distillers and refiners of petroleum products; smelters, refiners, and users of non ferrous metals such as copper, nickel, zinc, silver, and chromium; pro ducers and users of radioactive substances; glass and pottery manu facturers ; makers and users of metallic abrasives; textile makers and dyers j and others. Appendix A provides a more extensive, although by no means complete, listing of occupations in which carcinogenic influences may be suspected. In addition to name, residence, age, sex, cause of death, and place of death, information on individual cancer cases which may be ob tained from death certificates will include occupation, industry or business in which the deceased was employed, and social security number. These data appear as items 1 to 16 on the Occupational Cancer Kecord blank given as appendix B. F or purposes of analysis, it will be necessary to code this infor mation and transfer it to punch cards. Whenever the nature of the information makes this possible, item 11 (industry or business) should be coded in three ways: (<*) By occupation, according to the Alphabetical Index for Oc cupations and Industries, 16th Census of the United States, 1910, Bureau of the Census. (6) By specific occupational carcinogenic hazard, according to the Occupational Hazard Code, appendix C. (o) By place (community or region) of occupational activity. Since information recoixlecl in death certificates is known to be often unreliable, and because death certificates do not give any data on length of residence, length of employment in last occupation, or previous occupational employments, any conclusions drawn from a statistical analysis of this nature must be merely suggestive. In somo instances, they may even prove misleading, and any report based on such an analysis should emphasize the limitations of the technique. 8 I f proper consideration is given to these limitations, however, bio statistical studies of this type may yield valuable clues that can be followed up by other types of epidemiologic investigations, as, for example, those described below. 2. Occupational History Study of Cancer Deaths U sing as a basis the information obtained from death certificates, it is possible to study the occupational histories of selected cancer cases in order to discover possible causal factors. The available evidence indicates that at least some o f the cancers involving certain organs (skin, lung, nasal sinuses, bladder, bone, bone marrow) are caused by occupational or environmental caicinogens. Less conclusive evidence, such as geographical, topographical, age, and sex distribution, implicates environmental and possibly oc cupational factors in the production of cancer in other organ systems (gastrointestinal, nervous). B y tracing back the environmental and occupational histories, and, whore possible, discovering other exoge nous agents to which the cancer patient was exposed, it may be possible to substantiate further theso findings, discover hitherto unknown carcinogens, and determine the incidence of various typ es of cancer in different occupations and industries. In planning such a study, proper consideration must be given to tho fact that these tumors usually result from extended exposure and appear only after long latent periods, tho latter ranging ordinarily from 5 to 25 years. I t is necessary, therefore, to ascertain the occu pational and nonoccupational exposures for as long as possible a period preceding death. Such information should include, in ad dition to the names and locations of the various employers, detailed information as to the typo or types of operations in which tho in dividual was employed, tho physical or ohcmical agents to which tho individual was exposed, and tho length of employment in the various occupations. Whenever possible, information on injuries and diseases sustained during the survey period should also be collected, as these may indicate specific precancerous or poricancorons reactions. (See C-2.) Tho type of information required appears on tho Occupational Caneer Kccord (appendix B ) as items IT to 30. Data on the employment history of tho deceased may he obtained from a number of sources, including the last attending physician; hospital records; employers and their insurance carriers; institutions such as homes for tho aged, sanitariums, mental institutions, infir maries, ote., in which the doceasod may havo been an inmate. A fter the places of employment havo thus beon ascertained from one or more of these sources, it is necessary to obtain detailed informa tion as to the typo of work performed and tho types o f occupational and nonoccupational agonts with which tho deceased camo in contact, 9 whenever available inform ation suggeata. the possibility of earcinogenie exposure. D ata on the duration, intensity, and typo of ex posure should complete the information required. From a critical evaluation of the information collected for each case, it is usually possible to appraise whether or not one or several occupational factors might have played an essential role in the production o f a particular cancer. (See C-3.) Through this approach it is possible to ascertain not only the extent of known occupational cancer hazards in a given area but to uncover also new industrial carcinogenic agents and foci. The pres ence of the latter w ill be indicated by the predominance of certain types of cancers among individuals either engaged in a specific opera tion or coming in contact with some particular agent present in and common to different operations. 3. Industrial Plant Surveys The individual plant survey is necessary to determine precisely the location and nature of suspected carcinogenic exposures. In order to discover whether such hazards actually exist in a particular plant, their nature and mode o f operation, and how they may be eontrolled, it is necessary to know as accurately ns possible the number of persons who have been exposed and the number showing effects, the nature o f these effects and the type o f the contact. For the efficient planning and conduct of such plant surveys, it is desirable to start by obtaining some basic information on the individ ual industrial establishments within the study area. These data should include plant location; duration of operation; type of medical sei vice $names of plant manager, plant physician, and insurance car rier; number of employees; raw materials used and goods produced; and any evidence of suspected or established carcinogenic hazards, The Plant Survey Keeord form, given as appendix D , shows these data as items 1 to 11, This preliminary survey need only be approximate and is intended merely to ascertain whether a detailed survey is indicated, how many investigators will be needed, the length of time to bo required for tho study, tlie type and degree of assistance and cooperation available from the management, and the availability of employment, medical, and insurance records. Since several years of contact with the carcinogenic agent are usually required for effective exposure and since the latent period is seldom shorter than 5 3reara and sometimes more than 25 years, cancer records o f industrial operations should be obtained for as long a period as possible, up to 30 years or more. Occupational cancer surveys are never spot surveys but always time surveys. Howover, the biological and epidemiologic behavior of occupational 10 cancers makes its advisable to survey establishments that have been in operation for as little us 3 yours. Workers in such plants may have already developed prceancerous and pericanccrous lesions, especially if ilie carcinogenic hazards affect the skin, bladder, bone, or hema topoietic tissue. It is unlikely that within such a short period, cancer attributable to occupational exposure will occur in statistically signif icant numbers, but the timely recognition of these nonraalignnnt le sions may servo as a warning signal and hasten tho introduction of adequate precautionary measures, forestalling the appearance of an epidemic of occupational cancer at sonic later date. In surveys of this type, the chief eil'ort should be expended on dis covering and analyzing personnel currently or formerly employed in operations with appreciable recognized or suspected carcinogenic hazards. These persons are the actual test subjects which may demonstrate the typo and degree of hazard through significantly ele vated cancer incidence rates, Only when these studies demonstrate tho existence of an occupational carcinogen is it advisable to extend tho investigation to groups of workers exposed to a lessor degree so ns to determine the wider scope and ramifications of the hazard. Information on the health and on other occupational exposures of those persons may bo obtained through the occupational history studies of cancer deaths, ns described above; plant employment rec ords; plant medical records; insurance companies; hospitals; physi cians; institutions; and social security rceoids. To obtain reliable incidence figures, the present health status or causo of dentil should be determined whenever feasible for all workers currently or formerly employed for an adequate poiiod in. opciations with carcinogenic hazards, Since occupational cancers have a lntout period that is usually more Hum fi years, if tho plant 1ms a fairly rapid labor turn-over, it may bo found that no workurs in apparently carcinogenic operations are sillier mg from cancer or oven from procancorons lesions, Indeed, the medical records of the plant or its insurer may show no occupational cancer Lhroughoul the entino period of operation. However, it may bo discovered, by following up former employees, that aomo persons havo dovclopcd occupational cancors possibly attributable to tho carcinogenic agent to which they were exposed from 2 to 30 years earlier. Labor tum-ovor may, thorofore, totally oblitralo any ovidonco of cancerous reactions in persons exposed unless adequate follow-up studies of former employees are mado over a period of sufficient length, say IB to 80 years. Consideration must bo given, moreover, to the fact Unit employees with occupational caneor or with therapeutically controlled occupa tional cancer aro, in gonoral, not continued in operations with earcinogonio hazards. In some establishments, howover, this practico is not 11 followed as it is held that removal from the hazardous occupation docs not improve the ultimate prognosis, and by continuing th e em ployee in the occupation the absolute number of persons so exposed is held at a minimum. This practice, on the other hand, tends to increase primary cancer incidence among axposod workers. It is usually found that various employee groups are exposed m widely differing degrees to any carcinogenic agent or agents that may be present. Office workers, for example, are not as a rule significantly exposed to industrial carcinogens unless the administrative quarters form an integral or closely related part of the production zone, thereby establishing direct contact; or unless the disposal of carcinogenic wastes, such as fumes, dust, vapors, gases, mist, represents an environ mental hazard in the office area. Not infrequently it is found that only relatively small groups of workers have effective contact w ith carcinogens. In some industries, however, such as chromate opera tions, practically all production workers are exposed to carcinogenic agents to some degree. > The investigations should be extended not only to individuals rogu- largly employed in hazardous operations or constantly in contact with carcinogenic agents, but also to those entering the hazardous area or coming into contact with carcinogens at irregular intervals. In ter mittent, irregular, or rhythmic exposures of varying intensity m ay be sustained by such workers as watchmen, repairmen, packers, shippers, truckers, supervisors, clerks, control chemists, guards, and yardmen. Consideration should also ho given to workers charged with th e d is posal of wastes and emptied containers of carcinogenic materials as well as to those workers who may become exposed to an appreciable de gree through work in noncarcinogonie operations located near the hazardous one, and thereby possibly becoming exposed to carcinogenic gases, vapors, fumes, dusts, etc., originating from the latter. Through investigations within the plant, exact information should be obtained as to the nature of the suspected carcinogenic agen ts; typo and route of contact to which employees are exposed; and the type and intensity of such hazards and their possible variations during d if ferent periods of operation of the plant due to changes in manufactur ing methods and in raw materials used. Moreover, record should be made of any differences in the degree and type of exposure (skin contact, inhalation, ingestion) and the pliyoico- chemicnl status of the agents (dust, fumes, mist, spray, vapor, gas) in different parts of the same operation and in different parts of the plant. Special attention should be paid to ascertaining the particle size of dust, fumes, mist, etc., as this factor determines to a certain degree the severity of exposure to respiratory cancer hazards. Suoh distinctions are indicated for chemical us well as physical carcinogenic agents, Differences in this factor affoct not only the incidence rate of occupa 12 tional cancers among various groups of workers but m ay also be of distinct influence in determining the site of resulting cancers. To assay cancer hazards in industry, the plant must be surveyed by a trained observer as only such a person can detect the potential danger points. In carrying out sucli plant analyses, it may bo w ise to follow these suggestions. (a) The investigator should be thoroughly familiar w ith tire pro duction methods and with the materials handled and manufactured in the plant. H e should be able to note any irregularities or exceptions from usual procedures and readily detect areas in which carcinogenic hazards may exist. (&) Studies should bo made when the plant is in operation. Con ditions of exposure and observance of precautionary measures by workers and management can be properly studied only under working conditions. Moreover, there is an opportunity to study tho physical appearance of workers and, with permission of the management, make personal inquiries o f foremen and workers in regard to suspected hazards. ( o) Since visits of this sort may bo announced w ell beforehand, there is an opportunity for cleaning np any operation. Such a pro cedure may result, unintentionally, in tho obliteration of important evidence. I t is, therefore, advisable that the inspector look closely at the condition of windows, corners, nooks, ledges, surfaces and joints o f pipes and ducts, and other machinery for evidence o f poor house keeping. Arrangem ent and effectiveness of exhaust ven tilation should be tested. (d ) Any survey should include tho yard and adjacent buildings, packing and shipping facilities, and disposal of wastes aucl emptied containers. Finally, tho study should bo oxtended to th e neighbor hood of tho plant, noting unusual effects on color ancl surfaces of houses, vegetation and animals, and condition of drinking water in order to discover any possible effects on the environment o f carcino genic agents handled or produced within the plant. Whoro evidence indicates the environmental Bprcad of an occupational cancer hazard to persons living near the plant, the survey should bo extended to the population living or working in tho vicinity of the p lan t and may, if feasible, include an epidemiologic study of cancel* am ong wild and domesticated animals in the area. (e) Contact should always bo made with the plant physician and information obtained ns to the typo of medical supervision, tho type of medical facilities available, and tho employment and medical policy observed in connection with workers who have developed precanccrous or cancerous lesions. 1 ( / ) Through careful questioning the investigator should discover any changes made in production, handling, and precautionary mcas- 13 m'es employed, during the period of plant operation. Such changes may have a favorable or adverse eifect on the conditions of exposure. The direction of this influence may sometimes be rather unexpected. For example, improved production methods and precautionary meas ures which may reduce the concentration of carcinogenic dust in the atmosphere may also increase rather than diminish the degree of exposure. In order to obtain better yields in production, the car cinogen may have been more finely powdered, thereby causing a dust which reaches the deeper regions of the bronchial tree. The con sequent intensification of the carcinogenic effect causes an increased incidence ami a shortened latent period of the resultant cancer of the lung. A corresponding result may follow when a mist hazard is converted into a vapor hazard, or dust hazard into a fume or vapor hazard. Changes in the physico-chemical status of the carcinogen may result, moreover, in a shift of the site of the ensuing cancers. (See C-T.) Although it is not likely that n carcinogen present in mist form may reach the nasal sinuses (unless these have become abnormally acces sible through operative procedures, such as are performed for the relief of chronic sinusitis), cancerous reactions of the sinus lining may be anticipated if the carcinogen appears in the form of a vapor or gas that can enter the sinuses and be trapped, condensed, and retained in the cavity. In investigating the effects of such changes in production methods, the investigator must constantly bear in mind that, as a rule, effects do not become evident until a lag period of at least 6 years, correspond ing to the usual latent period for the type of cancer, has elapsed. Detailed information should be obtained on the preventive, prophy lactic, sanitary, and medical measures taken by plant management for reducing or eliminating the cancer hazard and of the dates upon which such measures were introduced, The type and extent of precautionary measures taken; extent of medical supervision; and follow-up of former wrorkers and of workers shifted from hazardous to nonhazurdous operations. Special attention should be paid to the methods employed in the disposal of carcinogenic industrial wastes, since in adequate measures of waste disposal may lead to a perpetuation or rintroduction of cancer hazards into operations which may have been made safe from the standpoint o f production. C SPECIAL ASPECTS The conduct of occupational cancer surveys presents a series of special problems which must be taken into proper consideration to assure results that aro reliable, significant and valuable for the con- 14 c lu c t o i cancer research and for the introduction of preventive M easures. 1- Contact-Site Relations of Carcinogens O bservation s in the field of environmental carcinogenesis have s h o w n that the route of contact with these agents, as well as the route u n c i nature of the metabolism and excretion or the site of their deposi t i o n plays a definite role in determining the siLe of the ensuing cancer. T h o s e observations are summarized in table 3, which indicates the t y p o o f contact (direct and primary, depository, excretory) for various ca rcin o g en s and the site of resultant cancer. Table 3. Contact-site relations oj carcinogens S ite of cancer Type of contact Carcinogen S k in 'Direct, primary contact_ _____ _____ Ultraviolet radiation, X-radia tion. mdioactivo energy, tar, pilch, soot, processed miner al oils, greases, arsonicals, Depository contact-- - - - ArsonioalB, .Excretory nontact-------- - Arsonicals. L u n g , larynx, nasal sinuses. Direct, primary contact-*fP.v#>vAfnrv rcmi+iJlttl. . _ Radioactive gases and dusts, fumes, dusts, mists, vapors of tar, pitch, processed mineral oils, chromates, niclcol carbonyl (?), arsenic, asbestos (?), isopropyl oil (?). Uadioactivo gases. B l a d d e r , ureter, kidnoy. B o n o and bone m arrow , TT.vnv/tnrv nfiritfMvfc^ ^ ,, Depository con tact ,, . - - [Direct primary contact-- Aromntio amines, tar (?), ar senic (?), Ionizing radiations (radioactive substances), benzol, beryl lium C7). X-radiation. D e s p it e the fact that the tissues of the alimentary and nervous sys t e m s are directly or indirectly exposed to a great number of environ m e n t a l agents--some, such as tar, petroleum derivatives, arsenic and b ou K ol, having definite carcinogenic properties--and although cancers o f t h e alimentary tract exhibit topographical foalures indicating the c a u s a l action of exogenous carcinogens, there exists no definite evidence t h a t specific exogenous and environmental factors are involved in their g e n e s is . Since cancers of the alimentary system constitute almost o n e - h a lf of all cancers observed in males and since cancer of this organ s y s t e m , as well as those of the contra! nervous system, usually have a p o o r prognosis, it may be hoped that environmental cancer surveys will 690678--80---- 3 15 provide data indicating the causation of at least sonic of tho cancers affecting these two organ systems, and thereby help open the way to their ultimate control. 2. Environmental Cancer Pattern In studying tho medical histories or symptoms of workers exposed to occupational carcinogens, attention should bo given not only to cancers, but also to procancorous lesions (proliiorativo conditions which aro sometimes observed preceding and not infrequently leading to cancer), and pericancorous lesions (conditions duo to carcinogonic exposure, but are unrelated to tho carcinogonic process, yet serving as stigmata of previously sustained specific carcinogonic exposures). Proper attention should bo givon to tho important fact Unit exoge nous carcinogens not only elicit hyperplastic and benign neoplastic cellular proliferations preceding, preparatory to, or simultaneously with, cancerous reactions. Depending on the quantitative and qualita tive conditions of exposure, those carcinogens may also causo degonorative, necrotizing and, in fact, anti-cancorons effects. Such ambivalent responses to exogenous carcinogons appear in many forms and aro not infrequently present in individuals with environmental procancorous and cancerous lesions. In fact, whenever such an environmental can cer pattern, including both aplasiogenic and hyperplasiogonic m ani festations, can be demonstrated in tho samo individual or a group of individuals exposed to the same agont, it serves as valuable evidence in support of an exogenous causation of the cancerous responsos ob served in the population group. Among tho exogenous carcinogens which produco these ambivalont effects aro arsenicals, benzol, ionizing radiations from radioactive chemicals and X-ray tubes, estrogens, urethane, and certain nitrogen mustards. Thoir anti-cancerous action is utilized in tho thorapy of malignant tumors, while thoir carcinogonic action 1ms resulted oc casionally in tho production of cancers whon they lnivo boon used modiciimlly in the treatment of nonmaligmuit conditions. These ambivalent prccancerous and pericancorous reactions to en vironmental carcinogens aro sum marizod in tablo <1. A s may bo noted, they are found in tho entire rango of the carcinogonic spectrum and affect the skin, nasal passages, bladdor, bono marrow, lungs, and breasts. A characteristic environmental cancor pattorn may be presontod by the changes in the blood and hematopoiolic tissues follow ing oxposuro to benzol or ionizing radiations. A t ono oxlromo of the acalo, heavy exposure is found to bring degoncralivo, necrotizing and atropliio changes, such as aplastic anemia, loulcopenia, thrombocytopenia, mac rocytic anemia, and severe atrophy of the hematopoietic tissues. On the opposite end of the reactivo range thoro occur loucooytotic, hypor- 16 leucocytotic and leukemoid reactions with the appearance o f immature leucocytes, polyglobulia, leukemia associated with metaplastic eryth ropoietic, myeloid and leukemic proliferations in internal organs, and myeloid and leukemic hyperplasia of the hone marrow. T a b le 4. Precancerous and pericancerous reactions to environmental carcinogens Reactions Etiologie Agents SKIN Alopecia: t Spotty less of hair------------- --................. A rseni o, i oni z i ng radiations ( r a d i o a o t i v o substances, X-radiation), Skin ^grossly thinned and glistening in patches, associated with keratotlc areas. Pitch, tar, asphalt, petroleum, r a d i o a o t i v o substances, X-radiation, ultraviolet radia tion, solar mys. Eczema: Dry seborrheic patches on skin------------ Arsenic, asphalt, piteh, soot, tar. Keratosis: , . ... Flat, discrete, scaly area on skin with raised pearly borders. Usually on parts of skin exposed to caremogen, but may occur in unexposed partB, particu larly about sweat glands, with arsenic. Hyperkeratosis: ... Rough, Assured keratotio plaques with small, hard, wart-like horns usually on hands and soles. May become nodular and ulcerate. Anthracene, arsenio, asphalt, creosoto, crude mineral oil, paraffin, pitch. Boot, tar, radio activo substances^ ultmvlolot radiation, X-radiation. Vemieao: . Horn-likc hyperkeratosis............................ Uleoration: ,, , , Breakdown of keratotie lesions--------- - Arsenicals. , Cbrome holes---------------------------------- - Chromates, oliromic acid. Leukoderma: .. , Patches of subnormal melanin pigmenta tion. Lsuko-melanoderma: Patches Bhowing increased pigmentation and patches showing subnormal pig mentation of skin. Most common in areas of highest pigmentation, and may involve oral mucosa, A nthracene, arsenic, asphalt, 'creosoto, crude mineral oil, paraffin, pitch, ta r, nonioniz ing and ionizing radiations ( r a d i o a c t i v o substances, X-radiation, ultravlolot radia tion, selar radiation). Melanoderma: . Patelios of inereased pigmentation-- .-- Seleroderma: ... Dry, scaly, parchment-like ekm, wivn enlarged pores, associated with louke rnel anedorm a. Crude mineral oil, paraffin oil, ionizing radiations (radioactivo substances, X-rays, ultraviolet rays, solar rayB). 17 Table 4. Precancerous and pericancertis reactions to environmental carcinogens--Continued Reactions Etiologie Agents NASAL PASSAGES Papillomas and polyps: Growths in antrum, turbinates. Nasal tions. ethmoid septum cells and perfora . Isopropyl oil, nickel carbonyl, chromates, arseni cals. bladder Hemorrhage, submucosal: Varying size, with telangiectasia. Located mainly in trigone and about urotoral orificos. Papillomas: Polypous or villous, pedunculated or sessile. Often multiple about trigone and urotoral orifices. Benzidino, beta-naphthylamino and derivatives. EYES Papillomas: Pedunculated. Develop mainly on lids, occasionally on eyeball. Arsenic, asphalt, creosote, orudo mineral oil, pitch, tav, ionizing radiations, ultraviolet rays. BONE Chronic poriostitls: Thielsoning of periosteal tissue, neorosla of bone. Ionizing radiations (X-rays, radio active substances;. BONE MARROW HYPOPLASIA Blood dyscrasias: t Ilyporplasia and metaplasia, aplastic anemia, thrombocytopenia, leukopenia, monocytosis, orythroeytosis, leueocy- tosis, leukemoid reactions. Benzol and derivatives^ ionizing radiations (radioactive sub stances, X-rays). LUNGS , Pneumoconioses and pneumonia: Asbcstosis, "lipoid'' pneumonia, ehroutc chemical pneumonia. Asbestos, arsenic, tar, soot, min eral oil mist, chromo salts, nickel carbonyl. BREAST Painful, swollen breasts: Glandular hyperplasia. Estrogonic chemicals. Intermediate degrees of exposure, whether continuous or interm it tent, will produce mixed reactions. In general it w ill be found that increasing exposure will result in increasing effects of both the hyper plastic and atrophic types up to a certain point, From that point, the increasing severity of exposure will cause a preponderantly apla&Lio effect, overwhelming any hyperplastic reactions and leading, as ex posure increases, to death of the organism by destruction of tissues. Thus, a primarily hyperplastic phase may be followed by an aplastic phase, or vice versa, depending upon the degree and rhythm of exposure. . 18 3. Identification of Occupational Cancel's Occupational carcinogenic agents and cancers do not, in themselves, possess any characteristic propcrl/ios that distinguish them Iroin agents and cancers of nonocciipational 1ultimo, The occurrence of cancer in an oxposed person oC a tumor characteristic for the particular car cinogen and typo of exposure is not, thcroforo, absoluto proof that the cancor is of occupational origin; anatomically and histologically identical cancors aro found in persons who apparently have had no contact with tho occupational carcinogen in question, Howovcr, there is ofton sufficient associated evidence present, which, whon critically analyzed, provides adequate and uccoptablo proof as to the occupa tional naturo of tho cancer. Such ovidonco is represented by tho prcsonco of typical procancer ous and pcricanccrous lesions, such as radiation, tav, oil, paraffin, pitch, solar and arsenic dermatitis; radiation osteitis; and pre-leukemic leukopenias and leukemoid reactions after exposure to benzol and ionizing radiations. Additional supporting ovidonco is tho demon stration of exposuro of adequate length and intensity to the carcino genic agent. Howovor, consideration must be given in this connection to tho possibility that effective carcinogenic exposure may ho tlio result of contact with tho carcinogon sustained in different employments or for othor ouvironmonlul reasons, or exposuro to diAeronl carcinogens having additive action. Thus, a critical analysis of tho entire occu pational history and nonoecupational exposures is indicated for all casos in which tho initial evidence shows that tho exposure sustained in any single employment appourod insufficient or sufficient to account for tho cancer. Identification of cancors found in a particular survey area or plant may bo made by statistical methods when individual cancers cannot be accurately identified us to etiology. This identification will not apply to any specific case, but may provido a strong suggestion of occupational or environmental etiology. Thcso critoria of identifi cation aret (a) Significant variations in total and organ incidence of cancer in different onvironmontal or occupational subdivisions after the data havo been proporly adjusted and standardized as to race, ago, sex, and othor possiblo factors. t (&) S h ift in organ incidence, sex distribution, frequency of multi plicity and ago rango of cancor during diAorcnt parts of the survey period, especially if thcso developments should follow upon the estab lishment of industries w ith known or suspoclod cancor hazards in tho area. (o) DiAoroiiccs in tho inoidenco rate and localization of cancer within one organ system (exposod and unoxposod skin, alimentary 19 tract, etc.), among persons living in various parts of the survey area. Different types of exposure to the same carcinogen, as well as contact with different carcinogens, have a direct influence on the incidence rates and localizations of cancer within one particular organ system. For a conclusive demonstration of the occupational or environ mental nature of cancers suspected on the basis of statistical and epidemiologic evidence, it is usually necessary to reproduce identical cancel's in experimental animals by means of the suspected agent. In fact, it is held by many investigators that the actual cause of a particular occupational cancer is not proven until experimental re production has been achieved. Conversely, it is not infrequently be lieved that the demonstration of carcinogenic responses to an exoge nous agent in animals is evidence that this agent may exert a similar action in man. On the basis of this assumption, chemicals produced and used in industry and consumed by the general public are screened and tested in experimental animals for potential carcinogenic prop erties they may possess for man. However, existing facts indicate that neither a successful reproduction of cancer in animals nor the bioassay of chemicals for potential carcinogenicity in man fulfill entirely the requirements that must be placed on such tests. For instance, under proper conditions of exposure botn-naphthylainine and benzidine elicit bladder cancer in man. Such tumors are produced in 100 percent of the individuals after sufficiently intense and prolonged contact with theso chemicals. Ago, sex, and heredity do not seem to have any appreciable influence in this respect, The experimental reproduction of these bladder cancers was successfully achieved by feeding male or fomalo dogs beta-naphthylamino, There is controversy as to whether or not rabbits read, similarly to the administration of beta-naplithylamine; it is established that rats and mice do not respond with the development of bladder cancer when given this chemical by various routes,, although they readily show this response upon the introduction of related aromatic amines (2-acetylaminofluorene) and aromatic azo-compounds (O-aminoazotoluene, o-toluidino). On the other hand, dogs fed benzidine in high and at times toxic closes for a period of more than years did not develop bladder tumors; rats receiving the sumo treatment, respond with the production of cancers of the eustachian tube, hepatocarcinomas, and leukemia. The two aromatic amines found to bo carcinogenic to man cause species specific, cancerous responses which in the rat are complicated by a shift, of the carcinogenic shock organ (i. e., the bladder, in man) to sovoral other tissues (i. e,, liver, bone marrow and, probably, eustachian tube). The chemical analysis of the urinary metabolites of the two aro matic amines when given to different species suggests that variations 20 ill their metabolism characteristic for the species tested seem to be related to the species specific carcinogenic properties observed, It thus was found that beta-naphtliylainine ie excreted by the dog a9 2-ainino-l-hydroxynaphtlialene conjugated with sulfuric acid, while rats, rabbits, and monkeys given injections of beta-naphthylamine in olive oil eliminate in the urine the base itself, its N-acetyl derivative, its N-acetyl-6-hydroxy-derivative and an unidentified dihydroxyami- nonaphthalone. A fter the administration of benzidine rabbits excrete the free base and a hydroxy-derivative, white rats eliminate a hydrox- ylatcd compound and an acylate derivative, Workers exposed to chemicals containing benzidine excrete hydroxy-derivatives, while acyl derivatives and free benzidine have not yet been demonstrated in man, Various aromatic azo compounds produce cancer of the liver in rats but not in rabbits. Observations suggest that this species specificity is not entirely of a constitutional nature, but depends in part on exoge nous dietary influences which, through impairment of the normal liver function, cause an abnormal metabolism of the carcinogenic azo compounds, W hile a constitutional factor which causes a rapid excretion of butter yellow may account for the resistance of rabbits and guinea pigs to the carcinogenic action of butter yellow, the exogenous dietary factor that ie essential for the carcinogenic action o f file chemical in the rat is the riboflavin deficient diet, without which liver cancer does not develop. Recent experiments showed that rats kept on an adequate diet and given 2,3 azotolueiie excrete 2,1 aminophenol in the urine while rats given a riboflavin deficient diet in addition to the chemical eliminate aniline in the urine and develop bladder tumors. Another example of the species specific quality of carcinogens is offered by tar. W hile it has been possible to elicit skin cancers readily b y the application of various types of tar in man, mice, and rabbits and with some difficulty in rats and dogs, all attempts to obtain similar rosults in monkoys have failed. > I t is not unlikely that species specific factors may be responsible fo r tho equivocal results obtained in experiments aimed at a reproduc tion of arsenic cancers in animals. Since the average latent period of arsenic cancer of the skin is relatively short when compared with the latent period for oil cancers, it is improbable that the species specific differences in life span play an important role in preventing the carcinogenic action of arsenic to become manifest in animals. It may bo possible that the generalized hair growth in experimental animals creates a higlior excretory potential of arsenic and thereby lowers its carcinogenic action. However, the strikingly spotty appearance of arsenic cancer in man points to tho action of other mechanisms, prob ably of abnormal nature, that must be present before arsenic can 21 ever, recent observations mano m , ... medicinal or occupational contact wiLh synl 10 ic cs logons may soon ^rrrin fu* fin,! tn this miestion. Umlttloml or bilateral main- pharmaceutical workers in E ngland and Iho United Stales engaged in the manufacture of synthetic estrogens may provide conhrmalery evidence in this respect, if and when mammary cancers dovolop m male workers of this occupational group. B rief mention may be imulo in this connection of two additional chemicals with potential or controversial carcinogenicity to man and definil o or equivocal carcinogcnci ty to animals. Scattered occupational observations indict benzol us a leukounogonic agent m man. IIowover, the experimental observations made so far entirely on mice aie contradictory. Boryllium has been shown to elicit osteogenic sarcomas in rabbits only by moans of intravenous injections. It is an opon ques tion whether this observation indicates tlmt this substance may exert a sim ilar effect in workers exposed to it by a dilorcnfc routo. ^ Spocios specific differences exist also in Iho field of physical carcino gens and produce uncertainties mid problems 111ore identical with those encountered in'connection with primary chemical carcinogens. Epidem iologic ovidenen strongly indicates that an excessive oxposuro to solar rays may result in cancer of the oxposed skin among indi viduals especially predisposed by their ligh t complexion, Observa tions made on mice and rats subjected to intensive treatment with ultraviolet rays seem to confirm this causal relation between oxposuro to solar actinic energy and cancov dovelopmont. H o wovor, all attempts to produce experimentally ultraviolot cancer o f the skin in guinoa pigs and rabbits have failed, Tima, observations on Uvo species seem to negate any relationship of solar irradiation and cancer. Such a 22 conclusion, however, is a lallucious one ,,s far as man, mice and rate aro concerned. The inability of ultraviolet rays to elicit skin cancers m guinea pigs and rabbits rather may be clue to species specific differ ences m the photochemical reactions and reaction products produced m those species. These species specific differences in the response to ultraviolet rays, by the way, do not support tho widely held concept that actinic energy elecits cancerous responses by eausing primary direct cellular mutations. The available evidence favors the idea that physical carcinogenic agents also produce cancer through the mechanism of chemical deviations, of so far undetermined character Evaluating the evidence on the species specificity of physical and chemical carcinogens and its relation to occupational carcinogenesis the following conclusions may be reached; 1. Failure to roproduco cancers of certain sites in experimental animals, using agents which seemingly produce such cancers in man does not disprove the carcinogenicity of the particular agents for man. 2. The employment of experimental animals in the screening of exogenous agents for potential carcinogenicity in man, while behm at present the only available and practical method, is not an entirely reliable one. ^ 3. In the experimental study of carcinogens which affect humans the selection of a suitable species represents the fundamental prelequisite for obtaining results that can be applied to man, Ih e planning, preparation and technical execution of animal ex periments on occupational carcinogens present certain speeial aspects and considerations which may bo worth mentioning since thoy may influence decisively the outcome of the experiment. Given a suitable) test speeies, applied experimental occupational cancer research must ami to duplicate or at least closely approach in its experimental con ditions the ciicumstances of exposure that aro believed to lead to tho development of cancer in man. Experimental evidence obtained in this way is most useful in its direct practical application to tho existing occupational problem, For instance, when designing the experimental conditions by which an occupational hazard entailing the inhalation of a carcinogen is to bo studied, it is essential to ascertain first tho physical slaLns o( the carcinogen under the existing working conditions; i. o., whether it is a gus, vapor, mist, spray, fume, dust, or a combination of several and what its particle size is if it occurs in a dispersed form It is especially important to aseortnin the smallest particle size present and its proportion in the dispersed matter. Industrial hygienists are now paying marked attention to the determination of the particle size, since this factor is of utmost importance in determining the depth to winch the inhaled particles penetrate the rcspii^tory 23 tract, and thus in controlling the site and degree of exposure to the inhaled agent. Not infrequently tho same agent under goes several changes in its physical state when passing through various plant processes. For instance, chromite ores reaeh the fac tory coarsely ground. The particles in this state may pass a sieve of 5 to 10 mesh. After the ore has been ground in steel ball mills to a fine powder the particle size is reduced so the chromite ore passes through a sieve of 100 mesh and half of it through a 250 mesh. When this powdored material is processed in the plant and dnst is produced, it is obvious that tho smaller dust particles w ill remain suspended in tho air longer than the coarser ones and that tlic main exposure of tho workers results from tho inhalation of tho portion of chromite or chromate compounds having the smaller particle size. When applying such information to the experiment, it is necessary not only to select a dust of proper particle size but also an animal with respiratory passages that permit tho ponotration of the dust chosen into tho bronchial tree. In view of tho narrow respiratory passages of small animals such as mice, it is not likely th a t these species oiler favorable anatomical conditions for administering effec tive exposures to carcinogenic dusts when tho action of these dusts is dependent on direct contacL of the bronchial tissue to the car cinogenic ngent. When determining the dose of carcinogen to be administered, it is not unusual that data used have been collected and recorded by in dustrial engineers and represent concentrations of the offending agent obtained in a number of random spot checks or are average values derived from tests of longer duration. Under practical working con ditions, however, concentrations of injurious and carcinogenic agents may vary considerably during various phases of tho operation and especially at times of accidents, during maintenance work or during repairs. It is for these reasons that special occupational groups em ployed within a carcinogenic operation often exhibit a particularly high incidence of occupational cancer as they are exposed inter mittently to highly increased concentrations of the carcinogenic agent. In the experimental approaches to occupational cancer such observa tions deserve adequate considerations, as tlie uso of insufficient doses calculated from averaged concentration figures may produce mislead ing negative results. Data on tho concentration of radioactivity in tho Schneebarg mines, for instance, indicate that there are not only appreciable variations in the degree of average radioactivity in the different mine shafts, but that the contents of radioactive gases within tlie same mine vary considerably in different parts and at different times, thereby causing an exposure to the miners that, as fa r as car cinogenic concentrations are concerned, should be measured more in peak values than in averaged values. Therefore, the proper appli 24 cation of observations on exposure in Iho field seems to bo an important part in experimental studios on occupational carcinogenesis. Since there is an almost complete lack of reliable inform ation as to the minimal effective doses for man of the various occupational caicinogcns, and in view of the fact that the great ruajon y o oxper mental reproductions of occupational cancers have been done witii doses appreciably exceeding those encountered under working con ditions in industry, it docs not seem wise to attach too much sig nificance to negative experimental results when low doses were used. 4. Age Factors in. Occupational Cancer A survey of environmental cancer should include a ll cases in the m m , regardless oi age, sex, race, or site. The final should consider these factors separately and should make the propel adjustments for standardization, so as to obtain comparable hgures. Since occupational exposure to carcinogenic agents does not start, as a rule, before the age of 1G to 18 years, and inasmuch as the average latent period for occupational cancers is from 5 to 25 years it is ad visable to restrict the evaluation of data in a study o f occupational cancer to persons of the age group above 25 years. A lthough femn e worker's often leave industrial occupations at an early age, the ex tensive employment of female workers in certain industries and pro fessions with potential cancer hazards warrants their inclusion in.such surveys. These industries include rubber goods manufacture, lumi nous dial painting, spinning and weaving, X -ray and laboratory wor c. Many environmental carcinogenic factors,, on the other hand, a on the human organism at a much earlier ago than the occupational carcinogens. For instance, epidemiological studios on the incidence o f penile cancer in circumcised and noncircumcisod population groups indicate that the first 10 years of life are of definitei importance m determining the occurrence and age of appearance of pom e cancer. I t is conceivable that even prenatal maternal uifiuouces, exerted oil the fetus by exogenous factors penetrating the placental barrier may bo . active in eliciting cancer in the young. Thus, there are no definite age range limitations in general cancer surveys. ^ Detailed presentations of the problem of environmental and oc cupational cancers and related disorders are available m the following ^Occupational^Tumors and Allied Diseases, 0. C. Thomas, Spring- ^E nvironm ental and Occupational Cancer. Pub. H ealth Rep. Supp. These may be useful for the interpretation of the results obtained m environmental and occupational cancer surveys. 25 APPENDIX A Occupational and Nonoccupational Groups Suggested for Survey 1. Exposure to benzol and Its derivatives, napbtbol, aromatic amines, toluol xylol (with possible relation to leukemia, lymphosarcoma, and myeloma), ' Airplane-dope workers. Airplane hangar employees. Alcohol (domitnml) workers. Aniline workers. Art-glass workers. Asbestos-products impregnators. Cattery (dry) makers. Beauty parlor operators. Belt scourers. Benzol pnfillers, Benzol workers. Brake lining makers. Brouzers. Burnishers. Gnu (rubber gasket) manufacturers. Gan (rubber gasket) sealers, Carbolic acid makers. Chemists. Chlorodiphenyl makers. Cluteb-dlsk Impregnntors. Coal tar still eleaners. Goal tar workers, Cobblers, Color makers. Coke oven ta r workers. Compositors. Degreusers. Disinfectant makers. Dry cleaners. Dye mukers, Dyers. Electroplaters, Electroplate cast scrubbers. Enamders. Enamel makers. Engravers. Explosive makers. Feather workers. Fertilizer makers, Flavoring extract makers, Onlranlzers. Gas house workers. Gasoline blenders. Gliders. Glue makers. Ink makers. Lacquerers. Lacquer makers. Leather makers (artificial and patent). Linoleum workers. Lithographers. Metnl washers. Millinery workers. Mirror sllverers. Mordaniers. Nitrobenzol makers. Nitrocellulose workers. Oil extractors. Paint remover manufacturers. Painters. Paraffin makers. Pencil makers. Perfume milkers. Petroleum distillery and refinery workers. ['harmncputieul workers. Phenol milkers. Pholoongrnvers. Photographic chemical makers. Picric add makers. Plastic textile makers. Polish makers. Polishers. Pottery decorn tors. Printers. Putty makers. Pyroxylin plastic workers. Rotogravure workers. Rubber buffers. Rubber cementers, Rubber cement mixers. Rubber compounders. Rubber dippers. Rubber driers. Rubberized asbestos board makers. Rubber mixers. Rubber pressroom workers, Rubber reclaimers. Rubber tire builders. Rubber trenders. , Rubber workers. Shade cloth workers. She! lackers. Shellac makers. Shoe finishers. Shoe factory workers, Shoe-lieel (wood) eoverers. Smokeless powder makers. Soap makers. Tar distillery workers. . Tnr, pitch, oil, etc., Lauk cleaners. Textile fullers. Tobacco seedling Lreaters. Trinitrotoluol makers. Type cleaners, Vavnlshers. Varnish makers. Varnish remover manufacturers. 26 Wnr gas makers. Waterproof fabric makers. W as makers. Welders. Wire Insulators. Window shade makers. 2. Exposure to aromatic amines, aniline dyes and related aromatic chemicals (with possible relation to cancers of the bladder, ureter and kidney). (a) Occupational exposurei (a) Occupational exposure--Continued Agricultural laborers. Photographic chemical workers. Blue print makers. Printers. Candle makers. Candy (colored) makers. Rubber workers (antoxldants: heta-nnphtliylnmlne, plienyl- Cosmetic manufactures (colored bctn-nnphthylamlne, b u t y l - lipstick, powder, cream, eye heta-naplithylamlne, etc.). brow pencil, sldn tan lotions). Shoe manufaelurers. Citrus fru it dyers. Soft drink (colored) manufac Dye handlers, packers, mixers. turers. Dye makers (aniline, naphthyl- Textile dyers. amine, benzidine, xylldine, Textile printers, toluldlne, etc.). Wax pencil makers. Fur dyers and workers. (b) Nonoeenpatlonal exposure: Gardeners (aromatic pesticides). Consumers of colored foodstuffs. Ink makers. Users of eolored cosmetics. Leather dyers and workers. Users of dyed textiles and loath- Lithographers. ergoods that hleed excess dye Margarine (colored) makers. when coming in contact with Marmalade and jelly (colored) sweat anil sebum. makers. Users (frequent) of medleal prep Ore flotation workers (beta arations containing aromatic naphthyl amine, cresyllc add, amino groups: antlhlstainlnes- etc.). allcrgles, hnyfovor, etc.'; nnal- Painters, geslcs-hendnehe, neuralgia, P aint makers, dysmenorrhea, arthritis, mi Papex* dyers and manufacturers. graine; medicines (liquids, Pharmaceutical workers. tablets, cnpsuleR, otntmenla) Photographers. colored with aniline (lyeB. S. Exposure to tar, pitch, oil, soot, asphalt, creosote, carbon blacks, paraffin, anthracene (with possible relation to cancers of the skin, long, bladder, and le u k em ia ). Artificial-stone makers. Asbestos goods workers. Asphalt workers, Anthracene manufacturers. Battery (dry) workers. Brick layers. Brickyard workers. Briquet makers. Brush makers. Cable makers and layers. Carbon blnek makers and users. Chimney sweepers. Coal carbonization workers. Con1-tar still cleaners. Coal-tar workers. Coke-oven workers. Cordage-factory workers. Corkstone makers and carpenters. Colton spinners. Oreosotlng plant workers. Diesel engine attendants. Electrical equipment manufacturers. Electrode makers. Engineers. Foundry workers. Fishermen. Flue cleaners, Fuel oil suppliers, truck drivers. Furnace workers. Gas house workers. Gas (Illuminating) workers. Generator stokers, Grense monkeys. Grease pit workers. Ink makers. Insulators. Lamp black makers and users. Machinists. Mechanics. Metal workers. Oilers. Oil refinery workers. Oil well workers. Optleal lens grind era, Ore flotation plant workers. Paint sprayers. Paraffin distillery workers. Paraffin plant workers. Pavers. Pharmaceutical workers, Pitch workers, Plastic cement workers. Printers. Itoad repairers. 27 Roofers. Roollng-pnpor 'workers. Hope mfilters. Rubber workers. Sanitary pipe makers. Shipyard workers. Soap makers. Shale oil workers, Stokers. Tank cleaners. Tar painters. Tar paint manufacturers. Tar workers. Textile workers. Wnterproofors. Water proof paper makers. Wood plcltlers. Wood preservers. 4. Exposure to chromium and chromium compounds (chromium metal dust, chromates, chromium pigments, chroinio acid, chromium carbonyl) (with pos sible relation to cancer of the lung anil nasal sinuses), (a) Occupational exposure: (a) Occupational exposure--Continued Abrasive makers. Abrasive workers and polishers. Asphalt refinery workers, JBnttcry (dry) makers. Bleaehers, Blueprint makers, Candle (colored) makers. Coal ta r workers. Match-factory workers. Mordantors Paint manufacturers. Painters. Paper dyers. Paper makers. Paper money makers. Paper waterpvoofers. Chromate, chromium pigments, Photoengravers. ehromie add and leather Photographic workers. tanning compound manufac Photogravure workers. turers. Pottery glaze makers, Chromium ore miners and miners Pottery makers, of other metal ores with chro Printers, mium admixtures (cobalt), Refractory brick makers and Crayon and pencil (colored) masons. makers. Rubber vulcnnizers, Dock workers unloading chro Soap makers. mite ore. Stainless steel workers, Eleetroplnters. Tannery workers. Blectrolytleal chromium metal Textile dyers. manufacturers, Textile printers. Enamelers, Textile waterproofers. Enamel makers. Wax-ornament workers. Explosive manufacturers. Weldors, Furniture polishers. Wood stalners. Glass and pottery frosters. (i) Nonoceupntlonal exposure: Ink makers. Persons living or working Jn fume Linoleum workers. Lithographers, and dust zone of chromate plants, 5, Exposure to nickel nnd nickel compounds (nickel metal dust, nickel carbonyl vapors, nlelcel oxide, niekel snlllde, nickel alloys) (with possible relation to cancer of Hie lung and nasal sinuses). Abrasive manufacturers. Ceramic glnzers. Chemical workers in operations using nickel eatalysis. Coin makers. Eleetroplaters. Enamelers. Euamel makers. German silver manufacturers. Germnn silver smiths. Hydrogen mamifnciurors, Monel metal makers. Nickel alloy makers (copper, sil-, ver, aluminum), Nlclcel-chrome turers, Nickel-ehrome alloy wire manufac manufac turers. Niekel extractors. Nickel ore miners. Nickel ore smelter and refinery workers. Nickel polishers. Nickel-steel workers. Oil refinery workers. Storage battery manufacturers. Talc manufacturers. 28 6, Exposure to arsenic and arsenicals {arsenic metal, arseulous oxide, calcium arsenate, sodium arsenate, lead arsenate, cupric acetoarsenlte, Paris green, Loudon purple, Selieele's green, Sclwoliifurt green, Wohnan salts, realgar, orpiment, Fowler's solution, Donovan's pills, arsplienamlne, cacodylates, Lewisite, Asiatic pills, etc,) (with possible relation to cancer of skin, iung, bladder, liver). {) Occupational exposure: Arsenic roasters, Artificial ilower makers, Book binders. Bronze workers. Cannery workers peeling fruit treated with insecticides. Citrus fruit orchard workers. Cotton plantation workers. Cut-glass workers, Dyers. Dyestuff makers. Electroplaters. Enamelers. Farmers. Felt lint enrrotem Fevro-silieon workers. Fur handlers and preparers. Gnlvanizers. Gardeners. Glass mixers. Glass workers. Glue manufacturers. Gold refiners. Ink manufacturers. Insecticide manufacturers. Insecticide sprayers and dusters, Japan makers. Jewelers. Lead factory workers. Lend shot makers. Linoleum color workers. Lithographers. Miners of arsenic, copper, zinc, silver, lead ores. Oil eloth manufacturers. Oil refinery workers. Paper (colored) makers. Paper glnzers. Pnper hangers. Paper printers. (cii Occupational exposure--Continued Pelt and hair iactory workers. Pencil makers (colored). Plmnnaceutical workers. Photographers Poison bait makers, Pottery decorators. Pottery plant glaze dippers and mixers. Pyrites burners. Rotogravure workers. Rubber compounders. Rubber mordant mixers. Rubber prossors. Rubber tire workers. Scaling wax makers, Seamstresses handling fabric dyed or treated with arsenicals. Sheep dip manufacturers. Smelters of arsenic, copper, zinc, silver, lend ores. Sulfur burners. Sulfuric add workers. Tannery workers (carriers). Taxidermists. Textile printers. Tinners, Velvet makers. Vinery workers. Vineyard workers. W ar gas manufacturers. Wax ornament workers. Weavers using yarn dyed with use of arsenicals, Weed killer manufacturers, Wire drawers. Wood preserve makers. Wood preservers. Zinc mixers. Zinc smelter chargers. (6) Nonoocnpatioual exposure: Users of arsenic containing drinking water, especially nonr arsenic oro smelters and mines, of foodstuffs and liquor contaminated with nrsenieals. Users of arsenic containing medicines (arspbenninines, cacodylftles, Fow ler's solution, Aslatlo pills, Donovan's solution, arsenious oxide in tonics, antiseptics, antipsoriasis or caustic ointments, antlspasmodies), cosmetics (hair lotions). Persons exposed to inhalation of arsenical dust spread from arsenic oro smelters or by dusting nrsenlcals from airplanes, 7. Exposure to asbestos (silicates containing calcium, magnesium, iron, nickel and copper) (with possible relation to cancer of the lung). Artificial-wood manufacturers. Asbestos-Insulation workers. Asbestos construction-material workers Asbestos-mill workers (crushers, fiber (in 111-board, wall board, shingle, tile, laers, inolders, carders). mortar, ellnker). Asbestos minors. 29 Asbestos spinners. Asbestos-textile workers (cloth, blan ket, curt aui, sheets, ropes, cords, twine, thread). Asbestos wen vers. Brake-lining manufacturers, Brake-lining workers, Carpenters. Dye workers (acid and fireproof). 8. Exposure to solar radiation nnd ultr to cancer of the skin). Agricultural laborers. Boatmen. Cattlemen. Construction workers. Cowboys, Drivers. Earners. Fishermen. Gardeners. Ilerdeis. House painters. Lumbermen. Miners working in surface Nurserymen. Oilfield workers. mines. Electric-wire manufacturers. Filter-material manufacturers. Giisket makers. I n s u l a t i o n workers (pipes, boilers). Plumbers. Pump-packing meelianlos. Roofers. Rubber production workers, violet radiation (with possible relation Oil operators. Pharmaceutical manufacturers of vita min D. Railroad engineers. Railroad workers. Ranchers. [toad workers. Rural mall carriers. Sailors. Sportsmen. Stockmen. Sunbathers. Vine growers. Welders. 9. Exposure to roentgen-rays and radioactive chemicals (with possible relation to cancer of the skin, lung, bone, liver, and leukemia). (a) Occupational exposure; Atomic energy plant workers. ' Biologists. Chemists ` Gas mantle manfacturers. Laboratory technicians and attendants. Luminous dial painters, handlers and shippers, metal scrap handlers. Nurses Pharmaceutical workers using radioactive isotopes and making radio active tracer substances. Phv^iplBis Radioactive electrostatic eliminator manufacturers and operators of such devices in textile and paper plants. ^ Radiologic technicians. ' Rndioioglsts. Radium laboratory workers. Radium refinery workers. Research workers handling radioactive isotopes and tracer substances. Roentgen and radium technicians. Roentgen mechanics. Roentgeo-Uihc manufacturers. Roentgenologists (medical, electric industry, aviation, m etallurgy, chemi cal, textile, art and Jewelry, shop sales, beauty parlors, research). Shoe salesmen In stores using fiuoroseopes for fitting. Uranium dye makers. Uranium glass makers. Uranium glaze makers (tile). Uranium miners find miners of radtoaetlve ores (pitch blende, oarnotlte, etc. ). Uranlmn paint makers. (b) Non occupational exposure : Customers of shoe stores using fiuoroseopes. Patients consuming radioactive water for medicinal purposes over long periods, ^ , ,, . , Patients receiving inrge doses of ionizing radiation for medicinal purposes. People living lu regions with radioactive ores and drinking or bathing in water of radioactive springs, or residing in the waste disposal area of radioactive operations, 30 APPENDIX B Occupational Cancer Record 1. Name 3. Residence: State City 2. Place of Death: City Hospital Street 4. Social Security No. 7. Date of Birth 10. Occupation 12. Cause of D eath 14. Name of Physician 5. Sex 6. Color or Race S. Age: Years Mos. Days 9- D ate of D eath 11. Industry or Business 13. Method of Diagnosis: Clinical ( ) Biopsy ( ) Autopsy ( ) Other ( ) 15. Street 16. City 17. Clinical Diagnosis IS- Pathologie Diagnosis: Microscopic ( ) Gross ( ) 19. Primary Site 20. Date of First Symptoms 21. Date of First Visit to Physi 22. D ate of First Diagnosis cian 23. Stage of Diesase a t First Diagnosis 24. History of Other Illnesses of Site Affected 25. History of Injury to Site Affected UK> 26* Occupational History: List occupations in chronological order beginning with last or present one Dates Iront To Name ot Plant Location of Plant TypeotBusiness OrProduct Made Title ol lob Type of Wort Performed 27. Exposure: (Investigator will name carcinogenic substances to which, employee has been exposed.) Name of Substance N $ i m o f Flout l lo+n P T jic+ TP akii rt i7 * lU U 4 lU iM lt i p 0 5 B I o Duration of Exposure Years Months Describe Typo of Exposure and Estimate Percent of Working Time Exposed 2S* NS n t ? y 0ther im p0rtant materials t0 TMUdh employee has been exposed* (Hobbies; H abits; Medicines; Cosmetics; D iets; Environ- 2* A d i^ a iia l Hdormation Obtainable a t: Physician; Laboratory; H ospital; Insurance Co.; P la n t Medical D epartm ent; Clinic; Tum or Name Address 30. Any other information pertaining to tum or (Multiplicity, Sites, etc.) Date Note: More blocks should be added under Nos. 26,27 and 29on actual recordform. Investigator APPENDIX C Occupational Hazard Code {Prepared in cooperation with I>r, H. F. DornJ A. Abnormalities of air pressure: 001 Compressed air (increased atmospheric pressure). 002 A ltitude; ravelled a ir (decreased atmospheric pressure) 1), Abnormal 1ties of temperature and humidity: 010 Heat. OH Gold. 012 Sudden variations of temperature. O, Dampness: 020 Dampness. 021 Dryness. D. Defective Illumination: 030 Defective Illumination. D, D ust: Organic dust ; 040 Textile dust. 041 Flour. 042 Sugar. 043 Wood dust. 044 Leather dust. 04B Feathers. 010 Coal dust. *047 Tobacco dust. 050 Organic dust other than specliled. Inorganic dust: 000 Abrasive dust. 001 Brick dust. 002 Olay dust. 003 Flint dust. 004 Glass dust. 005 Rock dust. 000 Quartz dust. 007 Talc. *0G8 Asbestos, 000 Iron ore. 070 Inorganic dust other than specified. F. Infections: 000 Amoeba and other unicellular organisms. 001 Bacteria and spirochetes, 092 Fungus. 003 Rickottsia and related microorganisms. 004 Virus. *000 Worms and other multicellular parasites. 000 Other parasites. G. Radiant energy: *100 X-rays. *101 Radium. *102 Radio Lhorium. *103 Mesothorlum. *104 Radioactive isotopes. *300 Radioactive substance oilier than specified. Ultraviolet and infrared rays : *110 Ultraviolet rays. *111 Infrared rays. Carcinogenicity recognized or Buspected. H. Repeated motion, pressure, shock, etc.: 120 Repeated motion, pressure, shock, etc. J, Poisons : 130 Acetaldehyde. 131 Acetone. 132 Acids, inorganic. 133 Acids, organic. 134 Acridine. 135 Acrolein. 130 Alcohols. 137 Aldehydes. . 138 Aluminum. 139 Ammonia. . 140 Amyl acetate; butyl acetate. 141 Amyl alcohol. ' ,. , *142 Aniline and other amine compounds of benzol and Its homalogues, ' acetanilide; naphlhylamines ; nltranillne; tolnldlne; xylldlue; cmui dine. *143 Aniline dyes. *144 Anthracene. 145 Antimony and its compounds. , *140 Arsenic and its compounds (except arsenlnretted hydrogen). 147 Arsenluretted hydrogen (arsine). *148 Asphalt, natural. *149 Ano compounds. 150 Darlmn. *151 Denudine and derivatives. 152 B e n z in e ; gasoline; n a p h t h a . *153 Benzol (benzene) a n d its homologues ,_ 7 , (toluol and xylol) . o-aminoazotoluene. *154 Beryllium. 155 Bromine. 150 Buttinone. 157 Butyl alcohol. 158 Cadmium. 159 Calcium cyanamide (cyanamlde). *160 Carbazoles. 161 Cal bolle acid : lysol-phenol. *162 Carbon black, 163 Carbon dioxide. 16i Carbon disulphide. . 105 Carbon monoxide. *106 Cnrbon tetrachloride. , ^ 167 Cellosolve (mono-etliyl ether of ethylene glycol). 168 Chloride of lime. 169 Chlorinated diphenyls. *176 Chlorinated hydrocarbons, *171 Chlorinated naphthalenes. 172 Chlorine, *173 Ohloroprene (2-chloro-hutndlene). *174 Chromium carbonyl. *175 Chromium compounds. 176 Coal. 177 Cobalt. 178 Copper. *179 Creosote. *180 Cresol (evesyllc ad d ). 181 Cyanogen compounds, hydroeyaulc acid, 182 DichloreLliylene. 183 Dlchlovethyl ether. 184 Dimethyl sulphate. 185 Dlultrophenol (1-2-4). 186 Dloxnn (diethylene dioxide). *187 Estrogens, synthetic, *188 Estrogens, natural. 189 Ethyl benzene. Carcinogenicity recognized or suspected. 34 J. Poisons--Continued 190 Ethyl bromide nrnl ethyl chloride. ' 191 Ethylene dlbvomide. 102 Etliyleno dlehlorlde (dicliloretliane). 103 Etliylene oxide, 191 Ethyl silicates; tetraethyl-ortho-sllicate; tctrnmetliyl-ortbosillonte. 105 Formaldehyde, 108 Formic acid. 197 Furfurol. 198 Germanium compounds. 190 Glycols. *200 Ilnlogenatod hydrocarbons, aliphatic (ohlovlue, bromine, fluorine). *201 Hnlogeufltcd hydrocarbons, aromatic. ' 2C2 Ilexnnoiie (methyl butyl ketone). 203 I-Iexnnc (methyl Isobutyl ketone). 20-1 Hydrazines. 200 Hydrochloric aeld. 208 Hydrofluoric acid, fluorine and its compounds. 207 Ivon carbonyl, *208 Isopropyl compounds. 200 Ketones. 210 Lend and Its compounds, *211 Lead arsenate. 212 Magnesium. 213 Manganese. 214 Mercury and its compounds. 215 Methonol (methyl alcohol). . 21C Methyl bromide. 217 Metbyl celiosolvo (ethylene glycol monomethyl ether). 218 Methyl chloride. 210 Methylene chloride (diehloromolbane). 220 Methyl formate. *221 Mineral oil, crude; mineral oil, processed or grease prepared by fractionation or cracking). *222 NaphUiols. *228 Nickel. *224 Nlokel carbonyl. 225 Nicotine. *220 NUrobenzol and other nltro compounds of benzol and Its homo logous; chlorodlnitrolienzol; chloronltrobeuzol; dinltrobenzol; nitronaphthalono; trinitrotoluol. 227 Nitroglycerin. 228 Nllrous fumes and nitric add. *220 Oil, shale. 230 Oxalic acid. 231 Ozono. *232 Paraffin; paraffin oil, crude. 233 Pentanone (methyl propyl ketone), *284 Petroleum. 235 Phenol. 280 Phenyl hydrazine. 237 Phosgene. 238 Phosphorus, 230 Phosphuretted hydrogen (phosphine). 240 Picric aeid (trlnitrophenol). *241 Polycyclic hydrocarbon, e. g., benzpyrene; lnethyleholnnthreno; dibenz-earbazole; various derivatives of benzanthracene. 242 Porphyrins. 243 Potassium hydroxide. 244 Pyridine. 245 Quinones. *248 Selenium compounds. 247 Silver. 248 Sodium hydroxide. *240 Sodium nitrate, crude. *250 Soot. Carcinogenicity recognized or suspected, '35 J, Poisons--Continued *251 Soot (lamp black, carbon blaelc, gas black, etc.}. *252 Spindle oil. *253 Sterols, 254 Sulphur chloride, 225 Sulphur dioxide. , ,., . 256 Sulphuretted hydrogen (hydrogen sulphide). 257 Sulphuric acid. ,w ^ .. *258 Tar and pitch; artificial asphalt; bitumen-lignite, 250 Tellurium compounds. *200 Tclvachlorethnne (acetylene tetrachloride). *261 Tctrachlorethylenu (perchlorethylene). 262 Tetraethyl lead, 203 Thallium. ' 264 Tin. 265 Titanium oxide. *206 Trlchlorcthylcne. . 267 Triorihoevesyl phosphate. 208 Turpentine. *268 Uranium. 270 Vanadium. 271 Vinyl chloride. 272 Zinc; brass, metal funic fever, 278 Styrene, K. Trauma (not covered In any of the above): Chemical: 800 Chemical, acute. 801 Chemical, chronic. Physical: 802 Mechanical, acute, 303 Mechanical, chronic. *804 Thermic, acute (burn). *305 Thermic, chronic. Bears, fistulas: *306 Scars, fistulas, etc. If there are present more than three hazards, cadi of which Is from a different major bnzard group, code In preference as follows: O, J, El, F, K, li, II, C, A, D, Carcinogenicity recognized or suspected. 36 APPENDIX D Plant Survey Record Date. 1. Company---------------------------------------------------------2. Location----------------------------------------------------------3. Plant manager------------------------------------------------------4. Plant physician-------------------------------------------------- 5- Insurance carrier.---------------------------------------------------- 6. In operation since--------------------------------------------------7. Products m anufactured------------------------------------------8. Known or suspected carcinogens------------------------------- 9. Medical service--------------------------------------------- 10. R ate of labor turnover---.---------------- percent annually. 11. iS;umber of employees: P ro d u c tio n . _ _w W flT*ft ... ___ _ PftlflTWl _ ___ T'ornai . _____ ______________ VTTiifcA ____ _ ... . ___ -- T o ta l-- .----------------------------------- Office T otal * , I. OVfftHMMY MIMMI OFflOKi 191