Document RpjzG2peGbYgqRezKJ74OMd9k

FILE NAME: Neighborhood Exposures (NE) DATE: 1950 DOC#: NE028 DOCUMENT DESCRIPTION: Public Health Monograph - A Methodology for Environmental and Occupational Cancer Surveys Public Health Technical Monograph No. 1 A Methodology for Environmental and Occupational Cancer Surveys B y W . C. Huepei*, 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. T he N ature of the P roblem_____________ ________ 1 Occupational carcinogens------ -------Nonoccupational 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-------------------------------Ago factors in occupational cancer.............................. Appendix A. Occupational and nonoccupational groups sug gested for survey............... Appendix B. Occupational cancor record_______ Appendix C. Occupational hazard code-------------------------- Appendix D. Plant survey record_________ Page 1 2 4 6 7 7 9 10 14 15 16 19 25 26 31 33 37 li IN T R O D U C T IO N Environmental cancers are malignant tumors which are usually caused by prolonged exposure to exogenous agents of various types, In a few instances, 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 p art of our natural or artificial environment are prac tically 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, habits, customs, climate, fauna, contami nants of drinking water, atmospheric air and foodstuffs, and proce dures of warfare. Since prevention of cancer depends fundamentally on adeqnate 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 step in the 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 be adequately considered in the usual studies of toxic indus trial health hazards and differ in some respects from those used in epidemiologic investigations of infectious diseases. Eor example, some of the environmental carcinogens, such as betanaphthylamine and benzidine, scarcely ever cause toxic manifesta tions, In most instances, the carcinogenic process elicited 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 serious danger to exposed persons. Other environmental carcinogens, such as benzol, ionizing radia tions (X-rays or rays from radioactive substances), will produce X severe degenerative and necrotizing reactions in the tissues as the result of 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. This outcome may w7ell appear when the affected individual lias long since left the employment in which the effective exposure occurred. One purpose of environmental eancer surveys is to collect data on the occurrence, incidence, types, and causes of these malignant tumors and their precaneerous 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 eancer. 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 can 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 eancer hazards. 1. Occupational Carcinogens Occupational carcinogens, known or suspected, cover a wide range of inanimate and animate agents. This spectrum, summarized in table 2 1, includes a great variety of organic chemicals, both aromatic and aliphatic, several inorganic chemicals, various types oi physical radia tion, and the parasite, Schistosoma hematobiumy the only generally recognized animato 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-naplithylamlnc, benzidine, aniline (?), benzol, tar, pitch, asphalt, soots (domestic, led ustrini, and commerciai), shale oil, crude paraffin oil, crude anthra cene oli, creosote, lubricating and fuel oils and greases, syn thetic estrogens ( ?). (2) Aliphatic chemicals : Isopropyl oil (?). (b) Inorganic chemicals: Arsenicata, chromates, nickel carbonyl (?), asbestos (?), beryllium (?). 2. Physical carcinogens: Nonionizing radiatlon-ultrn violet rays, ionizing radiatons-coi'puscnlar radiations (alpha and beta rays) and electronic radiations (gamma and X-rays). 8. Parasitic carcinogens: Schistosoma hematobium. I t must be pointed out that the various environmental carcinogons differ considerably in (heir potency not only from each other but also among members of the same typo. Tho carcinogenic potency of dif ferent types of ta r varies greatly, gas-house and coke-oven tar being the most potent. Similar variations seem to exist regarding tho carcinogenicity of the various types of soot and tho different kinds of natural and processed potroJoums, many of which aro noncarcinogenic. Beta-naphtliylamino appears to bo much moro carcinogenic than benzidine. Tlio data on occurvonco 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 the recorded observations. Sinco 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 carcinogons 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 carcinogons may bo growing oven widor, 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 kangri 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. D ata provided by occupational cancer surveys are the only source of reliable inform a 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 iUffftod ofexposure and carcinogen Potential slid of cancer HABITS: Smoking (tar) (?) or cliowing 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 special heating devices beneath clothing near abdominal skin (kairo, kangri), or sleeping on hot stoves (lcang), causing bums and exposure to tar and soot. Smoking of oigava with lighted end in mouth (chutta) (tar anti burn injury). Skin. Oral cavity. HOBBIES AND HOME ACTIVITIES: Gardening with exposure 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 nonoccupational environ mental cancer--Continued M eth od o f ex p o su re find carcin ogen ...... 1 HOBBIES AND HOME ACTIVITIES--Con. Use of chlorinated aliphatic hydrocarbons in cleaning fluids with hepatotoxio properties modifying metabolism of endogenous and exogenous carcinogens (). P otential sites o f cancer Liver, internal organs. MEDICINES AND MEDICAL DEVICES: Arsenicale. ______________________ ____ Tar, impure vasclino and mineral oil----------Hepatotoxio chemicals (chlorinated aliphatic hydrocarbons, cinchophon, oto.) (). Hematotoxic chemicals (benzol, sulfonamides (?) aromatic organic chomioals) (?). Ultraviolet radiation......................................... X-rays......... .......................................................... Radioactive ehomienlB (ionizing radiations) - - Skin, internal organs. Do. Liver. Leukemia. Skin, Skin, bone, lcukomia (?). Skin, bano, lung (?) leukemia (?) liver (?). DIETARY FACTORS: Dietary iodine deficiency______________ _ Dietary protein and vitamin B complex deficiency. Dietary vitamin B complex doficienoy.^____ Arsenical contaminants in food, drinking water, air. Iloatcd mineral oil as fat substitute in baked goods (?). Thyroid. Liver, Laryngophorynx. Skin, internal organs. Internal organs. COSMETIC FACTORS: X-radiation for dpilation_____________ __ Ultraviolet lamp oxposurc for tanning (?)___ Arsenicals in hair lotions and tonics (?)_____ Lamp blaok in oyebrow pencils (tar) (?)___ Impure vaseline and mineral oils in ointments, creams, etc. Estrogens in skin creams (?)........... ................. Impure aniline dyes in lipsticks, etc., contain ing dyo intermediates (?). Skin. Do. Do. Do. Do. Breast. Bladder. OTHER ENVIRONMENTAL FACTORS: Tar and soot in atmospheric air (?)................ Dry and sunny cllmato with oxcosslvc solar irradiation. Parasitic infections (schistosomiasis)............... Ionizing radiation in water and air in regions with radioactive ores (?). Lung, skin (?). Skin, Bladder, liver, intestine. Lung, bone, hematopoietlo tissue. 5 3. Industrial and Public Health Hazards At the present time, environmental eaneer appears prim aril, industrial problem, although it extends into many noninclustrii pations. Fully 90 percent of the known environmental carci never existed in dangerous concentrations until the develop!) industrial processes which brought workers into frequent an contact with them. As the injurious agents have made their f ance with the growth of various industries, eancers have cle' among exposed workers. Perhaps one of the most striking ex of this pattern is the appearance of bladder cancers among dye i subsequent to the establishment of aniline dye industries in countries. Observations in many industries indicate that, \ known occupational carcinogen and the proper conditions of ex the appearance of occupational cancers becomes merely a qne! 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. Sueli industrial carcinogens not only provide a serious ha the exposed workers but may possibly also affect the liealtl general population through various routes of contact. Carci 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 fume < 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 either 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, observath in relation to these tumors have positive and immediate vain study and possible future control of the many types of hum! whoso causes are still unknown. 6 B. TYPES OF ENVIRONMENTAL 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. The second approach, occupational history studies of cancer deaths, involves tracking down possible occupational factors in tho etiology of individual cancer eases. The third approach, the plant survey, is essential for determining precisely which workers come into dangerous contact with carcinogens, bow 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. F or tho organization of an occupational cancer survey on a State level, it is essential that close 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 the department of health and the work should bo carried out by either 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 cancer is 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 tile 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, particularly, occupa tional carcinogenic spectrum should reveal suggestive relations be tween these factors and cancer incidence. By comparing the rela- 800078-50-----a 7 tivo 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 of 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, establishments 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 aud processors; paint manufacturers; distillers and refiners of petroleum products; smelters, refiners, and users of nonferrous metals such as copper, nickel, zinc, silver, ancl chromium; pro ducers and users of radioactive substances; glass and pottery manu facturers ; makers and users of metallic abrasives; textile makers and dyers; 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 Record 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: (a) By occupation, according to the Alphabetical Index for Oc cupations and Industries, 16th Census of the United States, 1940, Bureau of the Census. (&) By specific occupational carcinogenic hazard, according to the Occupational Hazard Code, appendix C. (o) By place (community or region) of occupational activity. Since information recorded 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 some 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, biostatistical studies of this type may yield valuable clues th a t can be followed up by other types of epidemiologic investigations, as, for example, those described below. 2. O ccupational H istory Study of Cancer D eaths Using as a basis the information obtained from death certificates, it is possible to study the occupational histories of selected cancer eases in order to discover possible causal factors. Tho available evidence indicates th at at least some of the cancel's involving certain organs (skin, lung, nasal sinuses, bladder, bone, bone marrow) are caused by occupational or environmental carcino gens. Less conclusive evidence, such as geographical, topographical, age, and sox distribution, implicates environmental and possibly oc cupational factors in the production of cancer in other organ systems (gastrointestinal, nervous). By 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 these findings, discover hithorto unknown carcinogens, and determine tho incidence of various types of cancer in different occupations and industries. In planning such a study, proper consideration must bo given to tbo fact that these tumors usually result from extended exposure and appear only after long latent periods, tho latter ranging ordinarily from 5 to SB years. I t is necessary, therefore, to ascertain tho occu pational and nonoccupational exposures for ns long as possible a period preceding death. Such information should include, in ad dition to tho names and locations of tho various employers, detailed information as to tho typo or types of operations in which tho in dividual was employed, tho physical or chemical 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 Caneor Record (appendix B) as items 17 to 30. D ata on tho 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 deceased may have been an inmate. A fter the places of employment havo thus been ascertained from one or more of these sources, it is necessary to obtain detailed informa tion as to the type of work performed and tho types of occupational and nonoccupational agonts with which tho deceased camo in contact, 9 whenever available infonnation suggests the possibility of carcinogenie 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 of 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 will 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 of operation, and liow they may be controlled, it is necessary to know as accurately us possible the number of persons who have been exposed and the number showing effects, the nature of these effects and the typo of 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 service; 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 P lan t Survey Record form, given as appendix D , shows these data as items 1 to 11. This prelim inary survey need only be approximate and is intended merely to ascertain whether n detailed survey is indicated, how many investigators will he 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 years and sometimes more than 25 years, cancer records of industrial operations should be obtained for as long a period as possible, up to 30 years or more. Occupational cancer surveys are novel* 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 ns 3 years. Workers in such plants may have already developed prccancerous and pericanccrons lesions, especially i Ihe carcinogenic hazards affect the skin, bladder, bone, or hema topoietic tissue. I t 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 nomnalignant le sions may servo as a warning signal and hasten the introduction of adequate precautionary measures, forestalling the appearance of an epidemic of occupational cancer at some later date. In surveys of this type, the chief effort should be expended on dis covering and analyzing personnel currently or formerly employed in operations with appreciable recognized or suspected carcinogenic hazards. Those persons are the actual test subjects winch may demonstrate the type and degree of hazard through significantly ele vated cancer incidence rates. Only when these studies demonstrate the exisleiico of an occupational carcinogen is it advisable to extend the 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 be 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 records. To obtain reliable incidence figures, Iho present health status or causo of death should be determined whenever feasible for all workers currently or formerly employed for an adequate period in operations with carcinogenic hazards. Since occupational cancers have a latent period that is usually more than years, if the plant lias a fairly rapid labor turn-over, it may bo found that no workers in apparently carcinogenic operations are suffering from cancer or even from prccancerous lesions. Indeed, the medical records of the plant or its insurer may show no occupational cancel* Lhroughoul the entire period of oporation. However, it may bo discovered, by following up former employees, that some persons liavo dovclopcd occupational caucors possibly attributable to the carcinogenic agent to which they were exposed from 2 to 30 years earlier, Tabor tum-ovor may, thoroforo, totally obliterate any ovidonco of cancerous reactions in persons exposed unless adequate follow-up studies of former employees aro made over a period of sufficient length, say IB to 30 years. Consideration must bo given, moreover, to the fact that employees with occupational caneor or with therapeutically controlled occupa tional cancer aro, in gonoral, not continued in operations with carcinogonio hazards, In some establishments, however, this practico is not 11 followed sis it is held that removal from the hazardous occupation docs not improve the ultimate prognosis, and by continuing the em ployee in the occupation the absolute number of persons so exposed is held at a minimum. This proctico, on the other hand, tends to increase primary cancer incidence among exposed workers. I t is usually found that various employee groups are exposed in widely differing degrees to any carcinogenic agent or agents th a t may bo 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 th at 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 regulargly 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 te r 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 bo given to workers charged with th e dis 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 noncarcinogcnie 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 agents; typo and route of contact to which employees are exposed; and the typo and intensity of such hazards and their possible variations during d if ferent periods of operation of the plant due to changes in m anufactur ing methods and in raw materials used. Moreover, record should bo made of any differences in the degree and type of exposure (skin contact, inhalation, ingestion) and the pliyoicochemical 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 degTee the severity of exposure to respiratory cancer hazards. Such distinctions are indicated for chemical as well as physical carcinogenic agents. Differences in this factor affect not only the incidence rate of occupa- 12 tioiml 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 such plant analyses, it may be wise to follow these suggestions. (a) The investigator should be thoroughly familiar w ith the pro duction methods and with the materials handled and manufactured in the plant. He 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 bo properly studied only u n d er working conditions. Moreover, there is an opportunity to study th e physical appearance of workers and, with permission of the management, make personal inquiries of foremen and workers in regard to suspected hazards. (o) Since visits of this sort may be announced well beforehand, there is an opportunity for cleaning up any operation. Such a pro cedure may result, unintentionally, in the 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 of pipes and duels, and other machinery for evidence of poor house keeping. A rrangem ent and effectiveness of exhaust ventilation should be tested. (d ) Any survey should include the yard and adjacent buildings, packing and shipping facilities, and disposal of wastes an d emptied containers. Finally, the study should bo extended to th e neighbor hood of the plant, noting unusual effects on color and surfaces of houses, vegetation and animals, and condition of drinking water in order to discover any possible effects on the environment of carcino genic agents handled or produced within the plant. W horo 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 the vicinity of die p la n t and may, if feasible, include an epidemiologic study of cancer am ong wild and domesticated animals in the area. (e) Contact should always be made with the plant physician and information obtained as to the type of medical supervision, the type of medical facilities available, and the employment and medical policy observed in connection with workers who have developed precancorous or cancerous lesions. (/) Through careful questioning the investigator should discover any changes made in production, handling, and precautionary meas- 13 urea 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 and a shortened latent period of the resultant cancer of the lung. 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 -l.) Although it is not likely that a 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 5 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 t ype and extent of precautionary measures taken; extent of medical supervision; and follow-up of former workers and of workers shifted from hazardous to nonhazardous 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 lend 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 Hint are reliable, significant and valuable for the con- 14 d u c t oi cancer research and for the introduction of preventive measures. 1* Contact-Site Relations of Carcinogens O bservations in the field of environmental carcinogenesis have s h o w n that the route of contact with these agents, as well ns the route n u cl nature of the metabolism and excretion or the site of their deposi t i o n plays a definite role in determining the site of the ensuing cancer. T h o se observations are summarized in table 3, which indicates the f y p e of contact (direct and primary, depository, excretory) for various carcinogen s and the site of resultant cancer. Table 3. Contact-site relations oj carcinogens S ite of cancer Type of contact Carcinogen S lc in ...... .................... L u n g , larynx, nasal m uses. B1a d d er, ureter, kidnoy. B o n and bone marrow. 'Direct, primary contact. Depository contact-- . . . .Excretory contact_____ _ Ultraviolet radiation, X-radia tion. radioactivo energy, tar, pitch, soot, processed miner al oils, greases, arsenicals. Avsonicnls. Arsenicals. Direct, primary contact.. Excretory contact-- . Radioactive gasos and dusts, fumes, dusts, mists, vapors of tar, pitch, processed minorai oils, chromates, nioltol carbonyl (?), arsonlc, asbestos (?), isopropyl oil (?). Radioactive gases. Excretory contact........... Aromatic amines, tar (?), nr sonic (?). |Depository contact__ __ Direct primary contact._ Ionizing radiations (radioactivo substances), benzol, beryl lium (?), X-radiation. D e sp ite the fact th at the tissues of the alimentary and nervous syslo m s are directly or indirectly exposed to a great number of environ m e n ta l agents--some, such as tar, petroleum derivatives, arsenic and b e n z o l, having definite carcinogenic properties--and although cancers o i th e alimentary tract, exhibit topographical features 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 sis. 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 te m , as well as those of the central nervous system, usually have a p o o r prognosis, it may be hoped th at environmental eaneor surveys will BD0678--BO--- 3 15 provide data indicating the causation of at least somo of the cancers affecting these two organ systems, and thereby help open tho way to their ultimate control. 2. Environmental Cancer Pattern Tn studying tho medical histories or symptoms of workers exposed to occupational carcinogens, attention should bo givon not only to cancers, but also to procancorous lesions (proliferative conditions which aro sometimes observed preceding and not infrequently leading to cancer), and pericancorous lesions (conditions dno to carcinogonie exposure, but are unrelated to tho carcinogenic process, yet sowing as stigmata of previously sustained specific carcinogenic exposures). Proper attention should be givon to tho important fact th a t 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 tivo conditions of exposure, those carcinogons may also cause degenera tive, necrotizing and, in fact, anti-cancerous effects. Such ambivalent responses to exogenous carcinogens appear in many forms and aro not infrequently present in individuals with environmental prccancerous and cancorous lesions. In fact, whonovor such an environmental can cer pattern, including both aplnsiogenic and liyporplasiogonic mani festations, can be demonstrated in tho samo individual or a group of individuals exposed to the same agont, it serves as valuable cvidonco in support of an exogenous causation of the cancorous responses ob served in the population group. Among tho exogenous carcinogens which produco those ambivalent effects aro arsenicals, benzol, ionizing radiations from radioactivo chemicals and X-ray tubes, estrogens, urethane, and certain nitrogen mustards. Their anti-cancerous action is utilized in tho therapy of malignant tumors, while their carcinogonie action lias resulted oc casionally in tho production of cancers whon they hnvo been used modicinally in the treatment of nonmalignant conditions. These ambivalont precancerons and pericancorous reactions to en vironmental carcinogens aro summarized in table 4. As may bo noted, they are found in tho entire rango of the carcinogonie spectrum and affect the skin, nasal passages, bladder, bono marrow, lungs, and breasts. A characteristic environmental cancer pafctorn may be presontod by the changes in the blood and hematopoiotic tissues following oxposuro to benzol or ionizing radiations. A t ono oxlromo of (he scalo, heavy exposure is found to bring degonerativo, nocrotizing and atropine changes, such as aplastic anemia, leukopenia, thrombocytopenia, mac rocytic anemia, and severo atrophy of the hematopoietic tissues. On the opposite end of the reactive rango thovo occur loucooytotic, hyper-. 16 leueocytotic and leukemoid reactions with the appearance of 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. Table 4. Precancerous and pericancerous reactions to environmental carcinogens Reactions Etiologie Agents SKIN Alopecia; Spotty less of hair...... .................................. Arsenio, io n i z in g radiations ( r a d i o a c t i v o substances, X-radiation). Atrophy: Skin grossly thinned and glistening in patches, associated with keratotlc areas. Pitch, tar, asphalt, petroleum, r a d i o a c t i v o substances. X-radiation, ultraviolet radia tion, solar mys. Eczema: Dry seborrlxeio patches on skin ................ Arsenio, asphalt, pitch, soot, tar. Keratosis: Flat, discrete, scaly area on skin with raised pearly borders. Usually on parts ef skin exposed to eareinogon, but may occur in uncxposed parts, particu larly about sweat glands, with arsenic. Hyperkeratosis: Rough, fissured keratotio plaques with small, hard, wart-like horns usually on liandB and soles. May become nodular and ulcerate. Anthracene, arsenio, asphalt, creosoto, crude mineral oil, paraffin, pitch, soot, tar, radio activo substances, uilmviolot radiation, X-radiation. Vomicae: Horn-likc hyperkeratosis............................. Uleoration: Breakdown of keratotie lesions_________ Arsenicale. Cbrome holes.-______________________ Chromates, ohroraic aeid. Leukoderma: Patches of subnormal melanin pigmenta tion. Lsuko-melanoderma: Patches showing increased pigmentation and patches showing subnormal pig mentation of skin. Most common m areas of highest pigmentation, and may involve oral mucosa. Melanoderma: Patches of increased pigmentation___ Anthracene, arsenic, asphalt, creosoto, crude mineral oil, paraffin, pitch, tar, nonioniz ing and ionizing radiations ( r a d i o a c t i v o substances, X-radiation, ultraviolet radia tion, solar radiation). Scleroderma: Dry, sealy, parchment-like skin, with enlarged pores, associated with loukomelanederma. Crude mineral oil, paraffin oil, ionizing radiations (radioactivo substances, X-rays, ultraviolet rays, solar rays). 17 Table 4. Precancerous and pericanestons reactions to environmental carcinogens--Continued Reactions Etiologie Agents n a sa l PASSAGES Papillomas and polyps: Growths in antrum, ethmoid cells and turbinates. Nasal septum perfora tions. bladder Hemorrhage, submucosal : Varying size, with telangiectasis. Located mainly in trigone and about uroternl orifices. Papillomas: Polypous or villous, pedunculated or sessile. Often multiple about trigone and urotoral orifices. EYES Papillomas: Pedunculated. Develop mainly on lids, occasionally on eyeball. BONE Chronic periostitis: Tliiekoning of periosteal tissue, neorosl3 of bone. BONE MARROW HYPOPLASIA Blood dyscrasifts: Hyperplasia and metaplasia, aplastio anemia, thrombocytopenia, leukopenia, monocytosis, orythrooytosia, leucocytoais, leukemoid reactions. LUNGS Pneumoconioses and pneumonia: Asbostosis, "lipoid" pneumonia, ehrouic chemical pneumonia. BREAST Painful, swollen breasts: Glandular hyperplasia. Isopropyl oil, niokel carbonyl, chromates, arseni cals. Benzidine, beta-naphthylamino and derivatives. Arsenic, asphalt, ereosote, orudo mineral oil, pitch, tar, ionizing radiations, ultraviolet rays. Ionizing radiations (X-vays, radio active substances;. Benzol and derivatives, ionizing radiations (radioactive sub stances, X-rays), Asbestos, arsenie, tar, soot, min eral oil mist, chrome salts, nickel carbonyl. Estrogenic eliomieals. Intermediate degrees of exposure, whether continuous or in term it tent, will produce mixed reactions. In general it will be found th a t increasing exposure will result in increasing effects of both the hyper plastic and atrophic types up to a certain point. From th a t point, the increasing severity of exposure will cause a preponderantly aplastio effect, overwhelming any hyperplastic reactions and leading, as ex posure increases, to death of the organism by destruction of tissues. Thus, a prim arily hyperplastic phase may be followed by an aplastio phase, or vice versa, depending upon the degree and rhythm of exposure. 18 A Identification of Occupational Cancers Occupational carcinogenic agents and cancers do not, in themselves, possess any characteristic properties that distinguish them Ivoin agonts and cancers of lionoocupntional linturo. The occurrence of cancer in an oxposed person of! a tum or characteristic for the particular car cinogen and typo of exposure is not, tlicroforo, absoluto proof that the cancer is of occupational origin; anatomically and histologically identical eancors aro found in persons who apparently have had no contact with tho occupational carcinogen in question. However, there is ofton sufficient associated ovideuco present, which, whon critically analyzed, provides adequate and accoptnblo proof as to tho occupa tional naturo of tho cancer. Such ovidonco is represented by tho prcsonco of typical precaneerous and pcricancorous lesions, such as radiation, lav, oil, paraffin, pitch, solar and arsenic derm atitis; radiation osteitis; and pre-leukemic leukopenias and leuketnoid reactions after exposure to benzol and ionizing radiations. Additional supporting evidence is tho demon stration of oxposui'o of adequate length and intensity to the carcino genic agent. Howovor, consideration must bo given in this connection to tho possibility th a t affective carcinogenic exposure may he tlio result of contact with tho carcinogen sustained in different employments or for olhor environmental reasons, or exposure to different carcinogens having additive action. Thus, a critical analysis of tho entire occu pational history and nonoccupational exposures is indicated for all casos in which tho initial evidence shows that tho exposure sustained in any single employment appeared insufficient or sufficient to account for tho cancer. Identification of cancers found in a particular survey area or plant may bo made by statistical methods whon individual cancers cannot be accurately identified as to etiology. This identification will not apply to any specific case, but may provido a strong suggestion of occux>aiional or environmental etiology. Those criteria of identifi cation are: (a) Significant variations in total and organ incidence of cancer in different environmental or occupational subdivisions after the data hftvo been proporly adjusted and standardized ns to race, age, sex, and othor possiblo factors. (&) S hift in organ incidence, sex distribution, froquoncy of multi plicity and ago rango of cancor during different parts of tho survey period, especially if thoso developments should follow upon the estab lishment of industries with known or suspocted cancer hazards in tho area. (o) Differences in tho inoidcnco rale and localization of cancer within one organ system (exposed and unoxposed skin, alimentary 19 I 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, oxisling 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 beta-naplithylamine and benzidine elicit bladder cancer in man. Such tumors are produced in 100 percent of the individuals after sufficiently intense and prolonged contact with these chemicals. Ago, sox, 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 fcmalo dogs beta-imphthylamino. There is controversy as to whether or not rabbits react similarly to the administration of beta-naplithylannno; 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 (0-aminoazotoluene, o-toluidino). On the other hand, dogs fed benzidine in high and at times toxic doses for a poriod of more than 5 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 be 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 several other tissues (i. e., livor, 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 tlie species tested seem to be related to the species specific carcinogenic properties observed. I t thus was found th at beta-naphthylamine is excreted by the dog as 2-amino-l-hydroxynaphthalene 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-acetyI-6-hydroxy-derivative and an unidentified dihydroxyainirtonaphthalene. A fter the administration of benzidine rabbits excrete the free base and a hydroxy-derivative, white rats eliminate a hydroxylatcd 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 tile 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. While 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 is essential for the carcinogenic action of tile chemical in the ra t is the riboflavin deficient diet, without which liver cancer does not develop. Eecent experiments showed that rats kept on an adequate diet and given 2,3 azotoluene 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 by 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 tlxe 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. I t may be 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 produco cancerous responses oven in man. It is remarkable in this connection that a high percentage of all medicinal arsenic cancers have been observed, in individuals with psoriasis, ^ Another example of the groat importance of species specificity is presented by the continued controversy as to the carcinogenicity oi estrogenic substances in man. W hile there can be lilt o doubt that estrogens are essentially involved in the development of mammary cancer of certain inbred strains of mice of both sexes, it, is still epicslionable whether estrogens participate in the production of such tumors in man. There is little likelihood that a definite decision of this con troversy will be obtained from observations niado on women, How ever, recent observations mado in males with intensive and prolonged medicinal or occupational contact with synthetic estrogens may soon provide the final answer to this question, Unilateral or bilateral mam mary cancer has been found in several males who received large amounts of stilbestrol for tbo control of cancer of the prostate. Since normally less than 2 percent of all breast carcinomas occur in males, tho continued therapeutic use of estrogens in the treatm ent of prostatic cancer may supply conclusive ovideneo os to the carcinogenicity of estrogens in man. The occurrence of hyperplasia of tho breast in pharmaceutical workers in 'England and tho United States engaged in the manufacture of syntlioiic estrogens may provide confirmatory evidence in this respect, if and when mammary cancers dovolop in male workers of this occupational group. Brief mention may be mado in this connection of two additional chemicals with potential or controversial carcinogenicity to man and deiinit o or equivocal carcinogenci ty to animal. Scattered occupational observations indict benzol as a leukomiogcnic, agent in man. How ever, tho experimental observations made so fill* entirely on mice are contradictory. Beryllium lias been shown to elicit osteogenic sarcomas in rabbits only by moans of intravenous injections. I t is an open ques tion whether this observation indicates that this substance may exert a sim ilar effect in workers exposed to it by a differout vouto. Spccios specific differences exist also in tho field of physical carcino gens and produce uncertainties and problems thoro identical with those encountered in connection with primary chemical carcinogens. Epidemiologic ovideneo strongly indicates that an excessive oxposuvo to solar rays may result in cancor of the exposed skin among indi viduals especially predisposed by their light complexion, Observa tions made on mice and rats subjected to intensive treatment with ultraviolet rays seem to confirm this causal relation between exposuro to solar actinic energy and cancor development, However, all attempts to produce experimentally ultraviolet cuncov of tho skin in guinoa pigs and rabbits have failed. Thus, observations on two species seem to negate any relationship of solar irradiation and cancer. Such a 22 conclusion, however, is a fallacious one as far as man, mice and rats aro concerned. The inability of ultraviolet rays to elicit skin cancers in guinea pigs ancl rabbits rather may be due to species specific differ ences in the photochemical reactions and reaction products produced in those species. These species specific differences in the response to ultraviolet rays, by the way, do not support the widely held concept that actinic energy elecits cancerous responses by causing 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 ancl its relation to occupational carcinogenesis the following conclusions may be reached: 1, Failure to reproduco 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 being at present the only available and practical method, is not ail entirely reliable one. 3, In the experimental study of carcinogens which affect humans the selection of a suitable species represents the fundamental pre requisite for obtaining results that can be applied to man. Tile planning, preparation and technical execution of animal ex periments on occupational carcinogens present certain speeial aspects and considerations which may bo worth mentioning since they may influenco decisively the outcome of the experiment. Given a snitablo test speeies, applied experimental occupational cancer research must aim to duplicate or at least closely approach in its experimental con ditions the circumstances of exposure that arc believed to lead to the development of cancer in man. Experimental evidonee obtained in this way is most useful in its direct practical application to the 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 the physical slaLus of the carcinogen under the existing working conditions; i. o., whether it is a gas, vapor, mist, spray, fume, dust, or a combination of several, and what its particle size is if it occurs in a dispersed form. I t is especially important to ascertain the smallest particle size present ancl its proportion in the dispersed matter. Industrial hygienisLs aro now paying marked attention to the determination of the particle size, since this factor is of utmost importance in determining the depth to which the inhaled particles penetrate the respiratory 23 tract, and thus in controlling the site and degree of exposure to the inhaled agent. Not infrequently the same agent under goes several changes in its physical state when passing through various plant processes. For instance, chromite ores resell the fac tory coarsely ground. The particles in this stato 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 Clio chromite ore passes through a sieve of 100 mesh and half of it through a 250 mesh. When this powdered material is processed in the plant and dnst is produced, it is obvious that the smaller dust particles -will remain suspended in the air longer than the coarser ones and th at the main exposure of the workers results from tho inhalation of the portion of chromite or chromate compounds having the smaller particle size. When applying such information to tho experiment, it is necessary not only to selecL a dust of proper particle size but also an animal with respiratory passages that permit tho penetration of tho 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 offer 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 agent. When determining the dose of carcinogen to be administered, it is not unusual that data used have beon 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 the operation and especially at times of accidents, during maintenance work or during repairs. I t 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 the uso of insufficient doses calculated from averaged concentration figures may produce mislead ing negative results. Data on tho concentration of radioactivity in tlio Schneeberg 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 the same mine vary considerably in different parts and at different times, thereby causing an exposure to the miners that, as f a r as car cinogenic concentrations are concerned, should bo measured more in peak values than in averaged values. Therefore, the proper appli- 24 cation of observations on exposure in the field seems to bo an important p a rtin experimental studies on occupational carcinogenesis. Since there is an almost complete laok of reliable inform ation as to tbo minimal effective doses for man of the various occupational car cinogens, and in view of the fact that the great m ajority of experi mental reproductions of occupational cancers have been done with doses appreciably exceeding those encountered under working con ditions in industry, it does 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 all cases in the urea, regardless of age, sex, race, or site. The final analysis, however, should consider these factors separately and should make the proper adjustments for standardization, so as to obtain comparable figures. Since occupational exposure to carcinogenic agents does not start, as a rule, before the age of 16 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 of occupational cancer to persons of the age group above 25 years. A lthough female 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 work. Many environmental carcinogenic factors, oil the other hand, act on the human organism at a much earlier age than the occupational carcinogens. For instance, epidemiological studios on the incidence of penile cancel* in circumcised and noncircumciscd population groups indicate th at the first 10 years of life are of definite importance in determining the occurrence and age of appearance of penile cancer. I t is conceivable th at oven prenatal maternal influences, exerted on the lotus by exogenous factors penetrating the placental b arrier 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 in the following publications by W. C. H ucper: Occupational Tumors and Allied Diseases, 0. C. Thomas, Springfield, Illinois, 1912, p. 896. Environmental and Occupational Cancer. Pub. H ealth Rep. Supp. 209,1918. These may be useful for the interpretation of the results obtained in environmental and occupational cancer surveys. 25 APPENDIX A Occupational and Nonoccupational Groups Suggested for Survey 1, Exposure to benzol find Its derivatives, naphtbol, aromatic amines, toluol, xylol (wH.lt possible relation to leukemia, lymphosarcoma, nrnl myeloma). Airplane-dope workers. Airplane hangar employees. Alcohol (dcniilnml) workers. Aniline workers. Art-glass workers. Asbestos-products inipregiiators. Battery (dry) makers. Beauty parlor operators. Belt scourers. Benzol pnriJiers. Benzol workers. Brake lining makers. Brouzers. Burnisbers. Gnu (rubber gasket) manufacturers. Gan (rubber gasket) sealers, Carbolic aeld makers. Chemists. Ohiorodiplienyl makers. Gluteb-dlsk tnipregnntovs. Coal tar still cleaners. Goal tar workers. Cobblers. Color makers. Coke oven tar workers. Compositors. Degreusers. Disinfectant makers. Dry cleaners. Dye makers. Dyers. Electroplaters, Electroplate cast scrubbers, Ennmelers, Enamel makers. Engravers. Explosive makers. Penthev workers. Fertilizer makers, Flavoring extract makers, Gnlvantzers. Gas house workers. Gasoline blenders. Gliders. Glue makers. Ink makers. Lacquer era. Lacquer makers. Leather rankers (artificial and patent). Linoleum workers. Lithographers. Mctnl washers. Millinery workers. Mirror sllyerers. Mordanters. Nitrobonzol makers. Nitrocellulose workers. Oil ext motors. Paint remover manufacturers. Painters. Paniilln makers. Pencil makers. Perfume milkers. Petroleum distillery and refinery workers. Pharmaceutical workers. Phenol milkers. Photocngravevs. Photographic chemical makers. Picric add makers. Plastic lexllle makers, Polish makers. Polishers. Pottery decorators. Priu tora. Putty makers. Pyroxylin plastic workers. Rotogravure workers. Rubber buffers. Rubber cemcnLers. Rubber cement mixers. Rubber compounders. Rubber dippers. Rubber driers. Rubberized asbestos board makers. Rubber mixers. Rubber pressroom workers. Rubber reclaimers. Rubber tire builders. Rubber tveaders. Rubber workers. Shade cloth workers, Shellaokers. Shellac rankers. Shoe finishers. Shoe factory workers. Shoe-heel (wood) coverers. Smokeless powder makers. Soap makers. Tar distillery workers. Tar, pitch, oil, etc., tank cleaners. Textile fullers. Tobacco seedling treaters. TrilliLrotohiol makers. Type cleaners. Yarn! fillers. Varnish makers. Varnish remover manufacturers. 26 War gas makers. Waterproof ftibrle makers. Wax 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 exposure i (ft) Occupational exposnre--Continued Agricultural laborers. Blue print makers. Candle makers. Candy (colored) makers. Cosmetic manufactures (colored lipstick, powder, cream, eye brow pencil, skin tan lotions). Citrus fruit dyers. Dye handlers, packers, mixers. Dye makers (aniline, naphthyl- amine, benzidine, xylldine, toluldlne, etc.). Fur dyers and workers. Gardeners (aromaticpesticides). Ink makers. Leather dyers aud workers. Photographic chemical workers. Printers. Rubber workers (antoxldants: hetn-nnphtliylarnine, phenylbetn-nnplitliyiamlne, b u t y l - beta-naphtliylamine, etc.). Shoe raannfaellivers. Soft drink (colored) manufac turers. Textile dyers. Textile printers. Wax pencil makers, (b) Nonoeenpatlnnal exposure: Consumers of colored foodstuffs. Users of eolored cosmetics. Users of dyed textiles nnd lenih- Lithographers. Margarine (eolored) makers. Marmalade and jelly (colored) makers. Ore flotation workers (betn- naplitliylamine, cresyiic neld, etc.). Painters, Paint makers, Paper dyers nnd manufacturers. ergaods that hlecd excess dye when coining in contact with sweat and sebum. Users (frequent) of medical prep arations containing aromatic amino groups: antllilstainlnesallergles, hayfever, etc.'; nnalgesles-liendache, neuralgia, dysmenorrhea, arthritis, mi graine; medicines (liquids, Pharmaceutical workers. Photographers. tablets, capsules, ointments) eolored with aniline dyes. 3. Exposure to tar, pitch, oil, soot, asphalt, creosote, carbon blacks, pnraflln, anthracene (with possible relation to cancers of the skin, lung, bladder, and leukemia). Artlflcla 1-stone makers. Asbestos goods workers. Asphalt workers, Anthracene manufacturers. Battery (dry) workers. Brick layers. Brickynvd workers. Briquet makers. Brush makers. Gable makers and layers. Carbon black makers and users. Chimney sweepers. Coal carbonization workers. Coal-tar still eleaaevs. Coal-tar workers. Coke-oven workers. Cordage-faetory workers. Corlcstone makers and carpenters. Colton spinners. Creosotlng plant workers, Diesel engine attendants. Eleetrical equipment manufacturers. Electrode makers. Engineers. Foundry workers. Fishermen. Flue cleaners, Fuel oil suppliers, truck drivers. Furnace workers. Gas house workers. Gas (illuminating) workers. Generator sLokors. Grease monkeys. Grease pit workers. Ink makers. Insulators. Lamp black makers and users. Machinists. Mechanics, Metal workers, Oilers. Oil refinery workers. Oil well workers. Optical lens grinders. Ore flotation plant workers. Paint sprayers. Paraffin distillery workers. Paraffin plant workers. Pavers. Pharmaceutical workers, Pitch workers, Plastic eeuient workers. Printers. Road repairers. 27 Roofers. Roofing-paper workers. Rope makers. Rubber workers. Sanitary pipe makers. Shipyard workers. Soap makers. Shale oil workers. Stokers. Tank cleaners, Tnr painters. Tar paint manufacturers, Tnr workers. Textile workers, Wnterproofers. Water proof paper makers. Wood plcklers. Wood preservers. 4. Exposure to chromium and chromium compounds (chromium metal dust, chromates, chromium pigments, chromic acid, chromium carbonyl) (with pos sible relation to cancer of the lung and nasal sinuses). (n) Occupational exposure: (a) Occupational exposure--Continued Abrasive makers, Abrasive workers and polishers. Asphalt refinery workers. Battery (dry) makers. Bleachers, Blueprint makers. Candle (colored) makers. Coal tar workers. Chromate, chromium pigments, ehromle acid and leather tanning compound manufac turers. Chromium ore miners and miners of other metal ores with chro mium admixtures (cobalt), Crayon and pencil (colored) makers. Dock workers unloading chro Mnteli-faetovy workers. Mordanters Paint manufacturers. Painters. Paper dyers. Paper makers. Paper money makers. Paper waterproofers. Photoengravers. Photographic workers. Photogravure workers. Pottery glaze makers, Pottevy makers. Printers, RefrucLory brick makers and masons. Rubber vulcanizers, Soap makers. mite ore. Eleetroplnters. Eiectrolytleal chromium manufacturers, metal Stainless steel workers. Tannery workers. Textile dyers. Textile printers. Enamel ers. Enamel makers. Explosive manufacturers. Furniture polishers, Glass and pottery frosters. Ink makers. Linoleum workers. Lithographers. Textile walerproofers. Wax-ornament workers. Welders. Wood stainers. (7j) Nonocenpatlonal exposnre: Persons living or working in fume and dust zone of chromate plnnts. 5. Exposure to niekel and nickel compounds (nickel meLnl dust, nickel carbonyl vapors, niekel oxide, niekel aulilde, niekel alloys) (with possible relation to cancer of the lung and nasal sinuses). Abrasive manufacturers. Ceramic glnzers. Chemical workers in operations using nickel entalysls. Coin makers. Eleetroplaters. Ennmelers. Enamel makers. German stiver manufacturers. German silver smiths. Hydrogen mamifncfurers. Monel metal makers. Nickel alloy makers (copper, sil-, ver, aluminum). Nickel-chrome alloy mamifae- turers, Nlckel-elirome wire turers. Niekel extractors. manufac Nickel ore miners. Nickel ore smelter and refinery workers. Nickel polishers. Nickel-steel workers. Oil refinery workers, Storage battery manufacturers. Talc manufacturers. 28 G, Exposure to arsenic and arsenicals {arsenic metal, arsenlous oxide, calcium arsenate, sodium arsenate, lead arsenate, cupric acetoarsenite, Paris green, Loudon purple, Selieole's green, Sehweinfurt green, Wolman salts, realgar, orplmont, Fowler's solution, Donovan's pills, arsplienamhie, cacodylates, Lewisite, Asiatic pills, etc.) (with possible relation to cancer of skin, iung, bladder, liver). (a) Occupational exposure: (O) Occupational exposure--Continued Arsenic roasters. Artificial flower makers, Book binders. Bronze workers. Cannery workers peeling fruit treated with Insecticides. Citrus fruit orchard workers. Cotton plantation workers. Cnt-glass workers. Dyers. Dyestuff makers. Electroplaters. Enamelers. Farmers. Felt lint enrroters, Ferro-slllcon workers. Fur handlers and preparers, Galvanizers, Gardeners, Glass mixers. Glass workers. Glue manufacturers. Gold refiners. Ink manufacturers. Insecticide manufacturers. Insecticide sprayers and dusters, Japan makers. Jewelers. Lead factory workers. Lead shot makers. Linoleum color workers. Lithographers. Miners of nrsenie, copper, zinc, silver, lead ores. Oil eloth manufacturers. Oil refinery workers. Paper (colored) makers. Paper glazers. Pnpcr hangers. Paper printers. Pelt and hair lactory workers. Pencil makers (colored). Pharmaeon tlcal workers. Photographers Poison bait makers. Pottery dccoralors. Pottery plant glaze dippers and mixers. Pyrites burners, ltoiogravnre workers. Rubber compounders. Rubber mordant mixers. Rubber prossors. Rubber tire workers. Sealing wax makers. Seamstresses handling fabric dyed or treated with arsenleals. Sheep dip manufacturers. Smelters of arsenle, copper, zinc, silver, lead ores. Sulfur burners. Sulfuric add workers. Tannery workers {carriers). Taxidermists. Textile printers. Tinners. Velvet makers. Vinery workers. Vineyard workers. War gas manufacturers. Wax ornament workers, Weavers using yarn dyed with use of arsenicals. Weed killer manufacturers. Wire drawers. Wood preserve makers, Wood preservors. Zinc mixers. Zinc smelter chargers. (ft) Nonoecnpatioual exposure: Users of arsenic containing drinking water, especially near arsenic ore smelters and mines, of foodstuffs and lhpior contaminated with nrsenieals. Users of arsenic containing medicines (arspbenamlnes, cacodylates, Fow ler's solution, Asiatic pills, Donovan's solution, arsenious oxide in tonics, antiseptics, antipsoriasis or caustic ointments, antlspasmoilies), cosmetics (hair lotions). Persons exposed to inhalation of arsenical dust spread from arsenic ore smelters or by dusting arsenicals from airplanes. 7. Exposure to asbestos (silicates containing cnleium, magnesium, iron, nickel nnd copper) (with possible relation to cancer of the lung). Artificial-wood manufacturers. Asbestos-Insulation workers. Asbestos construction-material workers Asbestos-mill workers (crushers, flber- (mill-board, wallboard, shingle, tile, Izers, molders, earders). mortar, ellnker), Asbestos miners. 29 Asbestos spinners. Asbestos-textile w orkers (cloth, blan ket, curtain, sheets, ropes, cords, twine, th read ). Asbestos weavers. Brake-lining m anufacturers, Briilce-lluiiig w orkers. Carpenters. Dye workers (acid and fireproof). Electric-w ire m anufacturers. Filter-m aterial m anufacturers. Gasket m akers. Insulation w o rk e rs (p ip e s, b o il e r s ) . Plum bers. Pum p-packing m echanics. Roofers. Rubber production w orkers. 8. Exposure to solnr radiation and ultraviolet ra d ia tio n (w iLh p o ssib le re la tio n to cancer of the skin). Agricultural laborers. Boatm en. C attlem en . Construction workers. Cowboys. D rivers. Farm ers. F ish erm en . Gardeners. Ilerdeis. House painters. Lum berm en. M iners w orking in su rface N urserym en. Oilfield w orkers. m ines. Oil operators. Pharm aceutical m an u factu rers of vita min D. R ailroad engineers. R ailroad workers. R an ch ers. Road workers. Rural m all carriers. Sailors. Sportsm en. Stockm en . Sunbathers. Vine grow ers. W elders. 9. Exposure to roentgen-vnys 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 maufacturers. Laboratory technicians and attendants. Luminous dial painters, handlers nrnl shippers, metal scrap handlers. Nurses. Pharmaceutlcnl workers using radioactive isotopes and making radio active tracer substances. Physieists. Radioactive electrostatic eliminator manufacturers and operators of such devices in textile and paper pinnts. Radioioglc technicians. ' Radiologists. Radium laboratory workers. Radium refinery workers. Research workers handling radioactive isotopes and tracer substances. Roentgen and radium technicians. Roentgen mechanics. Roentgeo-tuiie manufacturers. Roentgenologists (medical, electric industry, aviation, mtallurgie, chemi cal, textile, art and jewelry, shoe sales, beauty parlors, research). Shoe salesmen In stores using fiuorosoopes for fitting. Uranium dye makers. Uranium glass makers. Uranium glaze makers (tile). Uranium miners and miners of radioactive ores (pitch blende, carnotlte, etc. ). Uranium paint makers. (l>) Nonoccupationnl exposure: Customers of shoe stores using fiuorosoopes, Patients consuming radioactive water for medicinal purposes over long periods. PaLleuts receiving lnrge doses of Ionizing radiation for medicinal purposes. People living In 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 O ccupational Cancer R ecord 1. Name 3. Residence: State 4. Social Security No. 7. Date of Birth City 5. Sex 8. Age: Years 2. Place of Death: City Hospital Street 6. Color or Race Mos. Days 9. Date of Death 10. Occupation 11. Industry or Business 12. Cause of Death 14. Name of Physician 13. Method of Diagnosis: Clinical ( ) Biopsy ( ) Autopsy C ) Other ( ) 15. Street 16. City 17. Clinical Diagnosis 18. Pathologic Diagnosis: Microscopic ( ) Gross ( ) 19. Primary Site 20. Date of First Symptoms 21. Date of First Visit to Physi 22. Date of First Diagnosis cian 23. Stage of Diesase at First Diagnosis 24. History of Other Illnesses of Site Affected 25. History of Injury to Site Affected 26. Occupational History: List occupations in chronological order beginning with last or present one D ates Prom To N am e of P lant Location of P lan t T ypo of B usiness Or Product Mode T itle ol Job T ype of Work Performed 27. Exposure: (Investigator will name carcinogenic substances to which, employee has been exposed.) N am e of Substance N am e of P lant D ate of L ast Exposure D uration of Exposure Years M onths Describe T yp e of Exposure and E stim ate Percent of W orking T im e Exposed 2S. Name any other important materials to which employee has been exposed. (Hobbies; Habits; Medicines; Cosmetics; Diets; Environ ment.) 29. Additional Information Obtainable at: Physician; Laboratory; Hospital; Insurance Co.; Plant Medical Department; Clinic; Tumor Registry, etc. N am e Address 30. Any Other information pertaining to tumor (Multiplicity, Sites, etc.) D ate K ote: M re blocks should be added under N os. 26,27 and 29 on actual record form . Investigator APPENDIX C Occupational Hazard Code f Prepared in cooperation with Dr, H. F. Dorn) A. Abnormalities of air pressure: 001 Compressed air (increased atmospheric pressure). 002 Altitude; rarefied air (decreased atmospheric pressure) 11. Abnormalities of temperature and humidity: 010 Heat. 011 Cold, 012 Suddeu variations of temperature. O. Dampness: 020 Dampness. 021 Dryuess. D. Defective illumination: 030 D efective illum ination. ID. Dust: Organic dust: OdO Textile dust. 041 Flour. 042 Sugar. 043 Wood dust. 044 Leather dust. 045 Feathers. 010 Coal dust. *047 Tobacco dust, 0D0 Organic dust oilier than specified. Inorganic dust: 000 Abrasive dust. 001 Brlelc dust. 002 Olay dust. 003 F lin t dust. 004 Glass dust. 005 Rock dust. 000 Quartz dust. 007 Tale. *008 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 Rickettsia and related microorganisms. 004 Virus. *095 Worms and other multicellular parasites. 000 Other parasites, G. Radiant energy: *100 X-rays. *101 *102 *103 *104 *300 Radium. Radiotliorium. Mesothorium. Radioactive Isotopes, Radioactive substances other than specified. Ultraviolet and infrared rays: *110 Ultraviolet rays. *111 Infrared rays. Carcinogenicity recognized or suspected. H, Repented motion, pressure, shock, etc.: 120 Repeated motion, pressure, shock, etc. J. Poisons: 130 Acetaldehyde. 13 L 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 homologues; acetanilide; iinphlliylamines; nltvanillne; toluldlue; xylldlue; cumi dine. *143 Aniline dyes. *144 Anthracene. 145 Antimony and its compounds. *140 Arsenic and its compounds (exceiot arsenluretted hydrogen). 147 Arsenluretted hydrogen (arsine). *148 Asphalt, natural. *149 Azo compounds. 150 Barium . *151 Benzidine and derivatives. 152 Benzine; gasoline ; naphtha. *153 Benzol (benzene) and its hoinologues (toluol and xylol) : o-aminoazotolnene. *154 Beryllium. 155 Bromine. 150 Bu til none. 157 Butyl alcohol. 158 Cadmium. 159 Calcium cyanauilde (cyanamlde). *160 Cnrbazoles. 161 Cai bolle acid : lysol-phenol. *162 Carbon black. 163 Carbon dioxide. 161 Carbon disulphide. 105 Carbon monoxide. *106 Carbon tetrachloride. 167 Cellosalve (mono-ethyl ether of ethylene glycol). 168 Chloride of lime. 169 Chlorinated diphenyls. *176 Chlorinated hydrocarbons. *171 Chlorinated naphthalenes. 172 Chlorine. *173 Chloroprene (2-ehloro-butadlene), *174 Chromium carbonyl, *175 Chromium compounds. 176 Coal. 177 Cobalt. 178 Copper. *179 Creosote. *180 Cresol (eresyllc add). 181 Cyanogen compounds, liydroeyanie acid. 182 Dicliloretliylene. 183 Dlchlorethyl ether. 184 Dimethyl sulphate. 185 Diiiltrophenol (1-2-4). 186 Dloxan (diethylene dioxide), *187 Estrogens, synthetic, *188 Estrogens, natural. 189 Ethyl benzene. Carcinogenicity recognized or suspected. 34 J. Poisons--Continued 190 Etliyl bromide find etliyl chloride. 191 Ethylene dlhvomide. 192 Ethylene dlehlorlde (fllchlorotliano). 193 Ethylene oxide. 194 Etliyl silicates; tetracthyl-ortho-slllcate; tetrnmethyl-ortboslllonte, 10H Formaldehyde. 196 Formic neld. 107 Furfural. 195 Germanium compounds. 109 Glycols. *200 Ilnlogenated hydrocarbons, allpbntte (obloriue, bromine, fluorine). *201 Haiogeiuitocl hydrocarbons, aromatic. 202 Ilexauone (methyl butyl ltetono). 203 Hexone (methyl Isobutyl ketone). 204 Hydrazines. 205 Hydrochloric acid. 206 Hydrofluoric acid, fluorine and its compounds. 207 Ivon carbonyl. *208 Isopropyl compounds. 209 Ketones. 210 Lead find its compounds. *211 Lead arsenate. 212 Magnesium. 213 Manganese. 214 Mercury and its compounds. 215 Methanol (methyl nleohol). 210 Methyl bromide. 217 Methyl cellosolve (ethylene glycol monomethyl ether). 218 Methyl chloride. 219 Methylene chloride (diebloromelhane). 220 Methyl formate. *221 Mineral oil, crude; mineral oil, processed or grease prepared by fractionation or cracking), *222 Naphthols. *228 Nickel. *224 Nickel carbonyl. 225 Nicotine. *220 Nltrobenzol and other nltro compounds of benzol and its homologues; chlorodlnitrohenzol; chloi'onilrobenzol; dlnllrobenzol; nitronaphthaleno; trinitrotoluol. 227 Nitroglycerin, 228 Nllrous fumes and nitric acid. *220 Oil, shale. 230 Oxalic acid. 231 Ozono. *232 Paraffin ; paraffin oil, crude. 233 Pentanono (methyl propyl ketone). *284 Petroleum. 235 Phenol. 280 Phenyl hydrazine. 237 Pliosgeno. 288 Phosphorus. 239 Phosphuretted hydrogen (phosphine). 240 Picric aeid (trinilrophenol). *241 Polyeyellc hydrocarbon, e, g., benzpyrene; methylebolanthreno; rtibenz-earbazole; various derivatives of benzanthracene. 242 Porphyrins. 243 Potassium hydroxide. 244 Pyridine. 245 Quinones. *246 Selenium compounds. 247 Silver. 248 Sodium hydroxide. *249 Sodium nitrate, crude. *250 Soot. Carcinogenicity recognized or mispectcd. '35 J. Poisons--Continued *251 Soot (lump black, carbon black, gas black, etc.). *252 Spindle oil. *253 Sterols. 254 Sulpliur chloride, 225 Sulphur dioxide, 250 Sulphuretted hydrogen (hydrogen sulphide). 257 Sulphuric acid. *258 T ar and p itch ; artificial asp h n lt; blturaen-lignlte, 250 Tellurium compounds. *200 Tclriichlorethnne (acetylene tetrachloride). *261 Tctrachlorethylenu (pevchloreUiylene), 262 Tetraethyl lead, 20S Thallium. 204 Tin. 2(55 T itan iu m oxide, *200 Trlchlorcthylcne. 267 Ti'iorlhocresyl phosphate. 205 Turpentine. *269 Uranium. 270 Vanadium, 271 Vinyl chloride. 272 Zinc; brass, m etal funic fever, 278 Styveue, K. Trauma (not covered In any of the above): Chemical: 300 Chemical, acute. 801 Chemical, chronic. Physical; 802 M echanical, acute, 303 Mechanical, chronic. *804 Thermic, acute (burn), *305 Therm ic, chronic. Scars, fistulas; *300 Scars, fistulas, etc. If there are present more than three hazards, each of which Is from a different major hazard group, code in preference as follows: Q, J, E, F, K, U, H, 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 manufactured________ 8. Kho-wn or suspected carcinogens. 9. Medical service________________ 10. P a te of labor turnover________ .percent annually. 11. Number of employees: M ain Whlt.R Cnlnrnfl Vernata "White Colored T otal __ . ............. Production Office Total V , f . f l O V M K M I I C T P HI BT I M * O t f l C E l U I 12. O p eration Operations in volvin g known or suspected carcinogenic hazards-- N um ber o i em ployees 'Type of exposure B o a ts of exposure Duration of exposure for worker (years) x own M ale Wc Fem ale W C C onstant In te rrm ttent Occasional Inhalation 1 Skin Ingestion Other Average Longest a. b. c. Pro- or peri-cancerous eSects noted. S ite N um ber D ates Cancers noted S ite N um ber D ates a. b. c. U- jJ