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FILE NAME Brakes BRK DATE 1950 DOC BRK223 DOCUMENT DESCRIPTION Public Health Technical Monograph No. A Methodology for Environmental and 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 INTRODUCTION Environmental cancers are malignant tumors which are usually caused by prolonged exposure to exogenous agents of various types In a few instances these environmental producing factors are 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 prac- tically the only known causes of cancer in man at the present time and for this reason have considerable general significance Exposure to these factors is related to occupational activities niedicines diets cosmetics building material habits customs climate fauna contaminants of drinking water atmospheric air and foodstuffs and procedures of warfare Since prevention of cancor depends fundamentally 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 step in the development and institution of preventive cancer control measures A. THE NATURE OF THE PROBLEM Investigation into the epidemiology etiology and control of environmental 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 For example some of the environmental carcinogens such as beta- naphthylamine and benzidine scarcely ever cause toxic manifestations 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 disclose the serious danger to exposed persons Other environmental carcinogens such as benzol ionizing radia- tions rays or rays from radioactive substances will produce I 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 tissne 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 development of cancer This outcome may well appear when the affected individual has 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 physiochemical 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 precautionary period is essential in establishing standards for preventive measures and A final objective of occupational cancer surveys is the collection of specific technical information needed for the institution of adequate centrol 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 cancer hazards 1. Occupational Carcinogens Occupational carcinogens known or suspected cover a wide range of inanimate and animate agents This spectrum summarized in tablo 2 1 includes a great variety of organic chemicals both aromatic and aliphatic several inorganic chemicals various types of physical radiation and the parasite Schistosoma hematobium 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 naphthylamine benzidine anlline 7 benzol tar pitch asphalt soots domestic industrial and commercial shale oil crude paraffin oil crude anthra- cene oil creosote inbricating and fuel olls and greases syn- thetic estrogens ? 2 Aliphatic chemicals Isopropyl oll ? b Inorganic chemicals Arsenicnis chromates nickel carbonyl ? asbestos ? beryllium ? 2. Physical carcinogeus Nonionizing corpuscular radiatious radiation violet rays ionizing alpha and beta rays and electronic radiations gamma and rays 8. Parasitic carcinogens Schistosoma hematobium It must be pointed out that the various environmontal carcinogeus differ considerably in their potency not only from each other but also among members of the same type The carcinogenic potency of different types of tar varies greatly house and coke tar being the most potent Similar variations seem to exist regarding the carcinogenicity of the various types of soot and the different kinds of natural and processed petrolouins many of which are noncarcinogenic naphthylamine appears to be much moro carcinogenic than benzidine The 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 froin the recorded observations Sinco it is often difficult to establish the occupational causation of cancer re- sulting from exposure to known eareinogens often many years previously 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 the spectrum of industrial carcinogens may be growing oven wider 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 table 1 the fact is indicated that many of these carcinogens 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 Method ofexposure and carcinogen Potential sites of cancer HABITS Smoking tar ? or chewing of tobacco khaini Betel tobacco quid chewing . Chewing of tar paraffin etc. ? Lip tongue oral larynx lung cavity 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 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 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 with 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 Table 2. Recognized and suspected sources of nonoccupational environ- mental Continued Method of exposure and carcinogen Potential alles of cancer HOBBIES AND HOME ACTIVITIES Use of chlorinated aliphatic hydrocarbons in cleaning fluids with hepatotoxic proporties modifying metabolism of endogenous and exogenous carcinogens ? Liver internal organs MEDICINES AND MEDICAL DEVICES Arseni 2 c e a ol n es ne e_ ee Tar impure vaselino and mineral oil 2... IIepatotoxic chemicals chlorinated aliphatic hydrocarbons cinchophon otc ? Hematoloxic chemicals bonzol sulfonamides ? aromatic organic chomioals ? Ultraviolet radiation rays . eee eee Radioactive chomicals ionizing radiations Skin internal organs Do. Liver Leukemia Skin Skin bone leukomia ? Skin bono lung ? leukemia 7 liver 7 DIETARY FACTORS Dictary iodine deficiency 2... -- a-- Dietary protein and vitamin B complex deficiency Dietary vitamin B complex deficiency Arsenical contaminants in food drinking water air Iloated mineral oil as fat substitute in bakod goods ? Thyroid Liver Laryngopharynx Skin internal organs Internal organs COSMETIC FACTORS radiation for depilation Ultraviolet lamp oxposure for tanning ... Arsenicals in hair lotions and tonics ? Lamp black 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 dye intermediates ? Skin Do. Do. Do. Do. Breast Bladder OTHER ENVIRONMENTAL FACTORS Tar and soot in atmospheric air ... Dry and sunny climato with oxcessive solar irradiation Parasitic infections schistosomniasis Ionizing radiation in water and air in regions with radioactive ores ? Lung skin ? Skln Bladder liver intestine Lung bono tissue hematopoietio 3. Industrial and Public Health Hazards At the present time environmental cancer appears primaril industrial problem although it extends into many nonindustria pations Fully 90 percent of the known environmental carci never existed in dangerous concentrations until the developn industrial processes which brought workers into frequent an contact with them As the injurious agents have made their & ance with the growth of various industries eancers have de among exposed workers Perhaps one of the most striking ex of this pattern is the appearance of bladder cancers among dye + 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 que 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 Sueh industrial carcinogens not only provide a serious ha the exposed workers but may possibly also affect the healtl general population through various routes of contact Carci agents produced or handled in industrial operations worksho laboratories may enter the air water supply or soil after be charged as waste Persons living or working in the fume i disposal area may thus come into effective contact with the gens Contaminated clothing worn by workers in carcinogeni tions may also create a hazard when laundered without precautions in the factory home 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 tl problem as whole Since environmental cancers represent majority of those cancers whose etiology is known observati in relation to these tumors have positive and immediate valu study and possible future control of the many types of huma whose causes are still unknown 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 the 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 the exposure takes place what organ or organs develop cancerous responses and other important aspects of occupational carcinogenesis For the 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 caucer industrial medicine public relations local tumor registries and where necessary and desirable the State association of clinical pathologists and public health nurses association The over direction of such a survey should be provided by the department of health and the work should be 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 Death Certificates Working on the premise that certain occupational activities or contact 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 If 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 particularly occupational carcinogenic spectrum should reveal suggestive relations between these factors and cancer incidence By comparing the rela- 890078-50-2 7 tive 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 industries or occupations which deserve further investigation and in which protective and preventive measures are needed To establish such correlations not only the residence but also the place of employment must be noted and evaluated For the purpose of such analysis the map of the survey area may be divided into regions with more or less defined environmental patterns dustrial agriculture commercial maritime Within 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 and processors paint manufacturers distillers and refiners of petroleum products smelters refiners and users of nonferrous metals such as copper nickel zinc silver and chromium ; producers and users of radioactive substances glass and pottery manufacturers 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 obtained 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. For 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 6 By specific occupational carcinogenic hazard according to the Occupational Hazard Code appendix C. a 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 If proper consideration is given to these limitations however biostatistical 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 Using 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 of the cancers involving certain organs skin lung nasal sinuses bladder bone bone marrow are caused by occupational or environmental carcinogens Less conclusive evidence such as geographical topographical age and sex distribution implicates environmental and possibly accupational factors in the production of cancer in other organ systems gastrointestinal nervous By tracing back the onvironmental and occupational histories and where possible discovering other exogenous 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 types of cancer in different occupations and industries In planning such a study proper consideration must be given to the fact that these tumors usually result from extended exposure and appear only after long latent periods the latter ranging ordinarily from 5 to 25 years It is necessary therefore to ascertain the occupational and nonoccupational exposures for as long as possible a period preceding death Such information should include in addition to the names and locations of the various employers detailed information as to the type or types of operations in which the individual was employed the physical or chemical agents to which the individual was exposed and the length of employment in the various occupations Whenever possible information on injuries and discases sustained during the survey period should also be collected as these may indicate specific precancerous or pericancarons reactions See 2 The type of information required appears on the Occupational Cancer Record appendix B as items 17 to 30 Data on the employment history of the docensod may be obtained from a number of sources including the last attending physician hospital records employers and their insurance carriors institutions such as homes for tho aged sanitarinns mental institutions infirmaries ote which the deceased may have been an inmate After 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 the types of occupational and nonoccupational agents with which the deceased came in contact 9 whenever available information suggests the possibility of carcinogenie exposure Data on the duration intensity and type of exposure 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 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 presence of the latter will be indicated by the predominance of certain types of cancers among individuals either engaged in a specific operation 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 how they may be controlled it is necessary to know as accurately as possible the number of persons who have been exposed and the number showing effects the nature of these effects and the type 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- nal 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 carrier number of employees raw materials used and goods produced and any evidence of suspected or established carcinogenic hazards The Plant Survey Record 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 be required for tho study the 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 never spot surveys but always time surveys However the biological and epidemiologic behavior of occupational 10 cancers makes its advisable to survey establishments that have been in operation for as little as 3 years Workers in such plants may have already developed precancerous and pericancerous lesions especially if the carcinogenic hazards affect the skin bladder bone or hematopoietic 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 nonmalignant lesions may serve 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 These persons are the actual test subjects which may demonstrate the type and degree of hazard through significantly elevated cancer incidence rates Only when these studies demonstrate the existence of an occupational carcinogen is it advisable to extend the investigation to groups of workers exposed to a lesser degree so as to determine the wider scope and ramifications of the hazard Information on the health and on other occupational exposures of these persons may be obtained through the occupational history studies of cancer deaths as described above plant employment records plant medical records insurance companies hospitals physicians institutions and social security records To obtain reliable incidence figures the present health status or cause 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 moro than 5 years if the plant has a fairly rapid labor over it may bo found that no workers in apparently carcinogenic operations are suffering from cancer or even from precancerous lesions Indeed the medical records of the plant or its insurer may show no occupational cancer throughout the entire period of operation Ilowever it may be discovered by following up former employees that some persons havo doveloped occupational cancors possibly attributable to the carcinogenic agent to which they were exposed from 2 to 30 years carlier Labor turn may thorofore totally oblitorato any ovidonco of cancerous reactions in persons exposed unless adequate follow studies of former employees are made over a period of sufficiont longth say 15 to 80 years Consideration must be given moreover to the fact that employees with occupational cancor or with therapeutically controlled occupational cancer aro in gonoral not continued in operations with carcinogonio hazards In some establishmonts howover this practico is not 11 followed as it is held that removal from the hazardous occupation does not improve the ultimate prognosis and by continuing the cm- 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 exposed workers It is usually found that various employee groups are exposed in 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 inist represents an environmental hazard in the office area Not infrequently it is found that only relatively small groups of workers have effective contact with 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 Inter- mittent irregular or rhythmic exposures of varying intensity may be sustained by such workers as watchmen repairmen packers shippers truckers supervisors clerks control chemists guards and yardmen Consideration should also be given to workers charged with the disposal of wastes and emptied containers of carcinogenic materials as well as to those workers who may become exposed to an appreciable degree through work in noncarcinogenie 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 type and route of contact to which employees are exposed and the type and intensity of such hazards and their possible variations during different periods of operation of the plant due to changes in manufacturing methods and in raw materials used Morcover record should be made of any differences in the degree and type of exposure skin contact inhalation ingestion and the physicochemical 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 Suoli distinctions are indicated for chemical as well as physical carcinogenic agents Differences in this factor affect not only the incidence rate of occupa- 12 tional cancers among various groups of workers but may 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 with the pro- duction methods and with the materials handled and manufactured 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 b Studies should be made when the plant is in operation Conditions 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 the physical appearance of workers and with permission of the management inake personal inquiries of foremen and workers in regard to suspected hazards c Since visits of this sort may be announced well beforehand there is an opportunity for cleaning up any operation Such a procedure may result unintentionally in the obliteration of important evidence It is therefore advisable that the inspector look closely at the condition of windows corners nooks ledges surfaces and joints of pipes and ducts and other machinery for evidence of poor housekeeping Arrangement and effectiveness of exhaust ventilation should be Lested d Any survey should include the yard and adjacent buildings packing and shipping facilities and disposal of wastes and emptied containers Finally the study should be extended to the neighborhood 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 haudled or produced within the plant Whoro evidence indicates the environmental spread of an occupational cancer hazard to persons living near the plant the survey should be extended to the population living or working in the vicinity of the plant and may if feasible include an epidemiologic study of cancer among wild and domesticated animals in the arca 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 precancerous or cancerous lesions f Through careful questioning the investigator should discover any changes made in production handling and precautionary incas- 13 ures employed during the period of plant operation Such changes may have a favorable or adverse effect on the conditions of exposure The direction of this influence may sometimes be rather unexpected For example improved production methods and precautionary measures 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 careinogen may have been more finely powdered thereby causing a dust which reaches the deeper regions of the bronchial tree The consequent intensification of the carcinogenic effect causes an increased incidence and 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 chemical status of the carcinogen may result moreover in a shift of the site of the ensuing cancers See C Although it is not likely that a carcinogen present in mist form may reach the nasal sinuses unless these have become abnormally accessible 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 corresponding to the usual latent period for the type of cancer has elapsed Detailed information should be obtained on the preventive prophylactic 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 type and extent of precautionary measures taken extent of medical supervision and follow of former workers and of workers shifted from hazardous to nonhazard- ous operations Special attention should be paid to the methods employed in the disposal of carcinogenic industrial wastes since inadequate measures of waste disposal may lend to a perpetuation or reintroduction of cancer hazards into operations which may have been made safe from the standpoint of 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 are reliable significant and valuable for the con- 14 duct of cancer research and for the introduction of preventive measures 1. Contact Relations of Carcinogens Observations in the field of environmental carcinogenesis have shown that the route of contact with these agents as well as the route and nature of the metabolism and excretion or the site of their deposi- tion plays a definite role in determining the site of the ensuing cancer Those observations are summarized in table 3 which indicates the type of contact direct and primary depository excretory for various carcinogens and the site of resultant cancer Table 3. Contact relations of carcinogens Site of cancer Type of contact Carcinogen Skin Skin 8 Direct primary contact ( Depository contact . Excretory contact_ . contact_ Ultraviolet radiation radia- tion radioactive energy tar pitch soot processed miner- al oils greases arsenicals Arsonfoals Arsenicals Direct primary contact Lung larynx nasal |, sinuses sinuses Excretory contact_ ~- Radioactive gasos and dusts fumes dusts mists vapors of tar pitoh processed minoral oils chromates nickel carbonyl ? arsenic asbestos 7 isopropyl oil ? Radioactive gases Bladder ureter kidney Exoretory contact ..- Aromatic amines tar ? arsenie ? Bone and inarrow bone Depository contact .. Direct primary contact Ionizing radiations radioactivo substances benzol berylHum ? radiation Despite the fact that the tissues of the alimentary and nervous systoms are directly or indirectly exposed to a great number of environmental agents such as tar petroleum derivatives arsenic and benzol having definite carcinogenic properties although cancers of the alimentary tract exhibit topographical features indicating the causal action of exogenous carcinogens there exists no definite evidence that specific exogenous and environmental factors are involved in their genesis Since cancers of the alimentary system constitute almost half of all cancers observed in males and since cancer of this organ system as well as those of the central nervous system usually have a poor prognosis it may be hoped that environmental cancer surveys will 800678-50-3 15 provide data indicating the cansation of at least some of the cancers affecting these twe organ systems and thereby help open the way to their ultimate control 2. Environmental Cancer Pattern In studying the medical histeries or symptoms of workers exposed to occupational carcinogens attention should be given not only to cancers but also to precancerous lesions proliferative conditions which are sometimes observed preceding and not infrequently leading to cancer and pericancerous lesions conditions dne to carcinogenic exposure but are unrelated to the carcinogenic process yet serving as stigmata of previously sustained specific carcinogenic exposures Proper attention should be given to the important fact that exogenous carcinogens net 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 these carcinogens may also cause degenerative necrotizing and in fact cancerous effects Such ambivalent responses to exogenous carcinogens appear in many forms and are not infrequently present in individuals with environmental precancerous and cancorous lesions In fact whenever such an environmental can- cer pattern including both aplasiogenic and hyperplasiogenic manifestations can be demonstrated in the same individual or a group of individuals exposed to the same agent it serves as valuable evidence in suppert of an exogenous causation of the cancerous responses observed in the population group Among the exogenous carcinogens which produce these ambivalent effects are arsenicals benzel ionizing radiations from radioactive chemicals and ray tubes estrogens urethane and certain nitrogen mustards Their cancerous action is utilized in the thorapy of malignant tumors while their carcinogenic action has resulted occasionally in the production of cancers when they have been used medicinally in the treatinont of nonmalignant conditions These ambivalent precancerous and pericancerous reactions to onvironmental carcinogens are summarized in table As may be noted they are found in the entire range of the carcinogenic spectrum and affect the skin nasal passagos bladder bone marrow lungs and breasts A characteristic environmental cancer pattern may be presented by the changes in the blood and hematopoietic tissues following exposure to benzol or ionizing radiations At one extreme of the scale heavy exposure is found to bring degenerative necrotizing and atrophic changes such as aplastic anemia leukopenia thrombocytopenia macrocytic anemia and severe atrophy of the hematopoietic tissues On the opposite end of the reactive range there occur leucocytotic lypor- 16 ae leucocytotic and leukemoid reactions with the appearance of immature leucocytes polyglobulia leukemia associated with metaplastic erythropoietic myeloid and leukemic proliferations in internal organs and myeloid and leukemic hyperplasia of the bone marrow Table 4. Precancerous and pericancerous reactions to environmental carcinogens Reactions Etiologic Agents SKIN Alopecia Spotty less of hair___hair___ Arsenio ionizing radiations X radioactivo radiation substances Atrophy Skin grossly thinned and glistening in | Pitol tar asphalt petroleum patches associated with keratotic radioaetivo substances areas radiation ultraviolet radia- tlon solar rays Eczema Dry seborrheic patches on skin Arsenic asphalt pitch soot tar Keratosis Flat discrete scaly area on skin with raised pearly borders Usually on parts of skin exposed to carcinogen but may occur in parts particu- unexposed | larly about sweat glands with arsenie Anthracene Anthracene arsenio asphalt Rough | paraffin pitoh soot ultravioletradio- Hyperkeratosis fissured keratotic plaques with small hard wart horns usually on hands and soles May become nodular creosote crude mineral oil radiation , radiation . and ulcerate Verrucao hyperkeratosis Horn hyperkeratosis Ulcoration Breakdown of keratotic lesions Obrome holes___ Arsenicals Chromates ohromic acid Leukoderma Pattcihoens of subnormal melanin pigmonta- melanoderma Patelies showing increased pigmentation and patches showing skin mentation of skin in subnormal pig- Most common involve of highest pigmentation and may Melanoderma Patelies of increased pigmentation Anthracone arsenic asphalt eroesoto erudo mineral oil paraffin pitel tar nonionizradiations ing ing and ionizing radiations radiations Xradioactivo substances radiation ultraviolot radla- tion selar radlation Scleroderma Dry scaly parchment skin with enlarged pores associated with louko- melanederma | Crude mineral oil paraffin oil ionizing radiations radioactivradiooactivo substances rays ultraviolet rays solar rays 17 Table 4. Precancerous and pericancerous reactions to environmental carcinogens Reactions Etiologie Agents NASAL PASSAGES PapiGlrloowmtahss and polyps in antrim Nasal ttiuornbsinates ethmoid septum cells and | perfora- Isopropyl oil nickel carbonyl chromates arsenicals BLADDER Hemorrhage submucosal Varying size with telangiectasis nainly in trigone and about orificos Located uroteral PapiPlollyopmoauss or villous pedunculated or sessile Often multiple about trigone and ureteral orifices Benzidine naphthylamine and derivatives EYES Papil omas Pedunenlated | Pedunenlated Develop mainly on lids ocensionally on eyeball Arsenic Arsenic asphalt ercosote crudo mineral oil pitch tar ionizing radiations ultraviolet raya BONE Chronic periostitis Thickoning of periosteal of bone tissue necrosis | Ionizing radiations rays radioactive substanees BONE MARROW HYPOPLASIA Blood dyscrasias Ilyperplasia and metaplasia aplastic anemia thrombocytopenia leukopenia monocytosis erythrocytosis leucocy tosis leukemoid reactions | Benzol and derivatives ionizing radiations radioactive substances rays LUNGS pneumonia | Pneumoconloses and pneumonia Asbestosis lipoid pneumonia chronic chemical . Asbestos arsenie tar soot mineral oil mist chrome salts nickel carbonyl BREAST Painful swollen breasts Glandular hyperplasia Estrogenic chomicals Intermediate degrees of exposure whether continuous or intermittent will produce mixed reactions In general it will be found that increasing exposure will result in increasing effects of both the hyperplastic and atrophic types up to a certain point From that point the increasing severity of exposure will cause a preponderantly aplastio effect overwhelming any hyperplastic reactions and leading as oxposure 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 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 cancers 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 reproduction has been achieved Conversely it is not infrequently believed that the demonstration of carcinogenic responses to an exogenous 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 naphthyl- arine 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 Age 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 female dogs naphthylamine There is controversy as to whether or not rabbits react similarly to the administration of naphthylamine 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 acetylaminofluorene and aromatic compounds amino- azotoluene toluidine On the other hand dogs fed benzidine in high and at times toxic doses for a period of more than 5 years did not develop bladder tumors rats receiving the same treatment respond with the production of cancers of the enstachian tube hepatocar- cinomas 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 ( e the bladder in man to several other tissues e liver bone marrow and probably eustachian tube The chemical analysis of the urinary metabolites of the two aroinatie amines when given to different species suggests that variations 20 in their metabolism characteristic for the species tested seem to be related to the species specific carcinogenic properties observed It thus was found that naphthylamine is excreted by the dog as hydroxynaphthalene conjugated with sulfuric acid while rats rabbits and monkeys given injections of naphtl~-ylaminein olive oil eliminate in the urine the base itself its acetyl derivative its derivative and an unidentified dihydroxyaininonaphthalene After the administration of benzidine rabbits excrete the free base and a derivative white rats eliminate a hydroxylated 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 exogenous dietary influences which through impairment of the normal liver function cause an abnormal metabolism of the carcinogenic azocompounds 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 the chemical in the rat is the riboflavin deficient diet withont which liver cancer does not develop Recent 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 While 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 results in monkoys have failed It is not unlikely that species specific factors may be responsible for 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 be possible that the generalized hair ogfraorwstehniicnaenxdpetrhiemreenbtyalloawneirmsailtss creates a highor excretory potential of action However the strikingly spotty appearance carcinogenic to the action of other mechanisms prob- arsenic cancer in man points before arsenic can ably of abnormal nature that must be present 21 produco cancerous responses even in man It is remarkable in this connection that a high percentage of all medicinal arsenic cancers have been observed in individuals with psoriasis specificity specificity carcinogenicity Another example of the great importance of species presented by the continued controversy as to the estrogenic substances in man While there can be little doubt is of that of estrogens are essentially involved in the development mammary cancer of certain inbred strains of mice of both sexes it is still q1108- tionable whether estrogens participate in the production production such tumors in man There is little likelihood that a definite decision of this con- troversy will be obtained from observations made on women However recent observations made 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 mammary cancer has been found in several males who received large amounts of stilbestrol for the control of cancer of the prostate Since normally less than 2 percent of all breast carcinomas occur in males the continued therapeutic use of estrogens in the treatment of prostatic cancer may supply conclusive evidence as to the carcinogenicity of estrogens in man The occurrence of hyperplasia of the breast in pharmaceutical workers in England and the United States engagod in the manufacture of synthetic estrogens may provide confirmatery evidence in this respect if and when mammary cancers devolop in male workers of this occupational group Briof mention may be made in this connection of two additional chemicals with potential or controversial carcinogenicity to man and definito or equivocal carcinogencity to animals Scattered occupational observations indict benzol us a leukemiogenic agent in man How- ever the experimental observations made so far ontirely on mice are contradictory Boryllium has been shown to clicit osteogenic sarcomas in rabbits only by means of intravenous injections It is an open ques- tion whether this observation indicates that this substance inay exort a similar effect in workers exposed to it by a differont route Specios specific differences exist also in tho fick of physical carcino- gens and produce uncertaintios and problems thore identical with those encountered in connection with primary chemical carcinogens Epidemiologic ovidence strongly indicates that an excessive exposure to solar rays may result in cancer of the exposed skin among indi- viduals especially predisposed by their light complexion Observa- tions made ou mice and rats subjected to intonsive treatment with ultraviolet rays seem to confirm this causal relation between exposure to solar actinic energy and cancer development However all attempts to produce experimentally ultraviolet cancer of the skin in guinoa pigs and rabbits have failed Thus observations on two species seem to negate any relationship of solar irradiation and cancor Such a 22 conclusion however is a fallacious one as far as man mice and rats are concerned The inability of ultraviolet rays to elicit skin cancers in guinea pigs and rabbits rather may be due to species specific differences in the photochemical reactions and reaction products produced in these 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 eausing primary direct cellular mutations The available evidence favors the idea that physical earcinogenic 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 reproduce 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 nan 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 an entirely reliable one 3. In the experimental study of carcinogens which affect humans the selection of a suitable species represents the fundamental prerequisite for obtaining results that can be applied to man The planning preparation and technical execution of animal ex- periments on occupational carcinogens present certain special aspects and considerations which may be worth mentioning since they may influence decisively the outcome of the experiment Given a suitablo test species applied experimental occupational cancer research must aim to duplicate or at least closely approach in its experimental con- ditions the circumstances of exposure that are believed to lead to the development of cancer in man Experimental evidence 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 be studied it is essential to ascertain first the physical status of the carcinogen under the existing working conditions i c 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 It is especially important to ascertain 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 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 undergoes several changes in its physical state when passing through various plant processes For instance chromite ores reach 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 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 the smaller dust particles will remain suspended in the air longer than the coarser ones and that the main exposure of the workers results from the inhalation of the 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 the penetration of the dust chosen into the bronchial tree In view of the narrow respiratory passages of small animals such as mice it is not likely that these species offer favorable anatomical conditions for administering effec tive exposures to carcinogenic dusts when the action of these dusts is dependent on direct contact 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 been collected and recorded by industrial 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 conditions 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 It is for these reasons that special occupational groups enployed within a carcinogenic operation often exhibit a particularly high incidence of occupational cancer as they are exposed intermittently to highly increased concentrations of the carcinogenic agent In the experimental approaches to occupational cancer such observations deserve adequate considerations as the use of insufficient doses calculated from averaged concentration figures may produce misleading negative results Data on the concentration of radioactivity in the 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 far as carcinogenic concentrations are concerned should be measured inore in peak values than in averaged values Therefore the proper appli- 24 cation of observations on exposure in the field seems to be an important part in experimental studies on occupational carcinogenesis carcinogenesis Since there is an almost complete lack of reliable information as to the minimal effective doses for man of the various occupational car- cinogens and in view of the fact that the great majority of experi- mental reproductions of occupational cancers have been done with doses appreciably exceeding those encountered under working conditions in industry it does not seem wise to attach too much significance 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 area 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 advisable to restrict the evaluation of data in a study of occupational cancer to persons of the age group above 25 years Although female workers 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 luminous dial painting spinning and weaving ray and laboratory work Many environmental carcinogenic factors on the other hand act on the human organism at a much earlier age than the occupational carcinogens For instance cpidemiological studies on the incidence of penile cancer in circumcised and noncircumcised population groups indicate that the first 10 years of life are of definite importance in determining the occurrence and age of appearance of penile cancer It is conceivable that even prenatal maternal influences exerted on 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 in the following publications by W. C. Hueper Occupational Tumors and Allied Diseases C. C. Thomas Springfield Illinois 1942 p 896 Environmental and Occupational Cancer 209 1948 Pub Health Rep Supp 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 and its derivatives naphtbol aromatic amines toluol xylol with possible relation to leukemia lymphosarcoma and myeloma Alrplane workers Airplane hangar employees Alcohol denatured workers Amiline workers glass workers products impregnators Battery dry makers Beauty parlor operators Belt scourers Benzol purifiers Benzol workers Brake ing makers Bronzers Burnishers Cau rubber gasket manufacturers Can rubber gasket sealers Carbolle aeld makers Chemists Chlorodiphenyl makers Cluteb Impregnators Coal tar still cleaners Coal tar workers Cobblers Color makers Coke oven tar workers Compositors Degreasers Disinfectant makers Dry cleaners Dye makers Dyers Electroplaters Electroplate casi scrubbers Enamelers Enamel makers Engravers Explosive makers Feather workers Fertilizer makers Flavoring extract makers Galvanizers Gas house workers Gasoline blenders Gilders Glue makers Ink makers Lacquerers Lacquer makers Leather makers artificial and patent Linoleum workers Lithographers Metal washers Milnery workers Mirror silverers Mordanters Nitrobenzol inakers Nitrocellulose workers Oil extractors Paint remover manufacturers Painters Parafin makers Pencil makers Perfume mukers Petroleum distillery and refinery workers Pharmaceutical workers Phenol mukera Photoengravers Photographic chemical makers Pierle acid makers Plastic textile makers Polish makers Polishers Pottery decorators Printers Putty makers Pyroxylin plastic workers Rotogravure workers Rubber buflers Rubber cementers Rubber cement mixers Rubber compounders Rubber dippers Rubber driers Rubberized asbestos board Rubber mixers Rubber pressroom workers Rubber reclaimers makers Rubber tire builders Rubber treaders Rubber workers Shade cloth workers Shellaekers Shellac makers Shoe flnlsbers Shoe fuctory workers Shoe wood coverers Smokeless powder makers Soap makers Tar distillery workers - Tar pitch oll etc. tank cleaners Textile fullers Tobacco seedling treaters Trinitrotoluol makers Type cleaners Varnishers Varnish makers Varnish remover manufacturers 26 War gas makers Waterproof fabrle makers Wax makers Welders Wire insulators Window shade makers 2. Exposure to aromatle amines aniline dyes and related aromatic chemicals with possible relation to cancers of the bladder ureter and kidney a Occupational exposure Agricultural Inborers Blue print makers Candle makers Candy colored makers Cosmetic manufactures colored Ipstick powder cream eyebrow pencil skin tan lotions Citrus fruit dyers Dye handlers packers mixers Dye makers anlline naphthylamine henzidine xylidine toluldine etc. Fur dyers and workers Gardeners aromatic pesticides Ink makers Leather dyers and workers Lithographers Margarine eolored makers Marmalade and jelly colored makers Ore flotation workers betanaphthylamine cresyllc acid etc. Painters Paint makers Paper dyers and manufacturers Pharmaceutical workers Photographers a Occupational exposure Continued Photographic chemical workers Printers Rubber workers antoxidants naphthylamine phenyl- naphthylamine butyl- naphthylamine etc. Shoe manufacturers Soft drink turers colored manufac Textile dyers Textile printers Wax pencil makers b Nonoceupational exposure Consumers of colored foodstuffs Users of colored cosmetics Users of dyed textiles and lenihergoods that bleed excess dye when coming in contact with swent and sebuma Users frequent of medical preparations containing aromatle amino groups antihistamines- allergles hayfever etc anal- hendache neuralgia dysmenorrhea arthritis in- graine medielnes liquids tablets capsules ointments colored with aniline dyes 8. Exposure to tar pitch oil soot asphalt creosote carbon blacks parafilu anthracene with possible relation to cancers of the skin lung bladder and leukemia Artificial makers Asbestos goods workers Asphalt workers Anthrneeae manufacturers Battery dry workers Brick layers Brickyard workers Briquet makers Brush makers Cable makers and layers Carbon black makers and users Chimney sweepers Coal carbonization workers Conl still cleaners Coal workers Coke workers Cordage workers Corkstone makers and carpenters Coltoa spinners Oreosoting plant workers Diesel engine attendants Electrical equipment manufacturers Electrode makers Engineers Foundry workers Fishermen Flue cleaners Fuel oil suppllers truck drivers Furnace workers Gas house workers Gas Illuminating workers Generator stokers Grease monkeys Grease pit workers Ink makers Insulators Lamp black makers and users Machinists Mechanics Metal workers Oilers Oil refinery workers Oll well workers Optical lens grinders Ore flotation plant workers Paint sprayers Parufin distillery workers Paraffin plant workers Pavers Pharmaceutical workers Pitch workers Plastle cement workers Printers Road repairers 27 Roofers Roofing workers Rope makers Rubber workers Sanitary pipe makers Shipyard workers Soap makers Shale oil workers Stokers Tank cleaners Tar painters Tar paint munufacturers Tar workers Texille workers Waterproofers Water proof paper makers Wood plcklers Wood preservers 4. Exposure to chromium and chromium compounds chromium metal dust chromates chromium pigments chromle acid chromium carbonyl with pos- sible relation to cancer of the lung and nasal sinuses a Occupational exposure a Occupational Continued Abrasive makers Abrasive workers and polishers factory workers Mordanters Asphalt refinery workers Paint manufacturers Battery dry makers Painters Bleachers Blueprint makers Candle colored makers Coal tar workers Chromate chromtum pigments ehromle actd and leather Paper dyers Paper makers Paper money makers Paper waterproofers Photoengravers Photographle workers tanning turers compound manufac- Chromlum ore miners and miners of other metal ores with chro- Photogravure workers Pottery glaze makers Pottery makers Printers mium admixtures cobalt Refractory brick makers and Orayon and makers pencil colored masons Rubber vulcanizers Dock workers unloading chro- mite ore Soap makers Stainless steel workers Electroplaters Electrolytical chromium metal Tannery workers Textile dyers manufacturers Enamelers Enamel makers Textile printers Textile waterproofers ornament workers Explosive manufacturers Welders Furniture polishers Wood stainers Glass and pottery frosters Ink makers Linoleum workers b Nonoceupational exposure Persons living or working in fume and dust zone of chromate Lithographers plants 5. Exposure to nickel and nickel compounds nickel metal dust nickel carbonyl vapors nickel oxide nickel sulfide nickel alloys with possible relation to cancer of the lung and nasal sinuses Abrasive manufacturers Ceramic glazers Chemical workers in operations using nickel catalysts Coln makers Electroplaters Etnamelers Enamel makers German silver manufacturers German silver sinlths Hydrogen manufacturers Monel metal inakers Nickel alloy makers copper sil- ver aluminum chrome turers alloy manufae- chrome wire manufac turers Nickel extractors Nickel ore miners Nickel ore smelter and refluery workers Nickel polishers Nickel workers O refinery workers Storage battery manufacturers Tale manufacturers 28 6. Exposure to arsenic and arsenicals arsenic metal arsenious oxide calcium arsenate sodium arsenate lead arsenate cupric acetoarsenite Paris green London purple Scheele's green Schweinfurt green Wolman salts realgar orpiment Fowler's solution Donovan's pills arsphenamine cacodylates Lewisite Aslatic pills etc. with possible relation to cancer of skin lung bladder liver a b Occupational exposure a Occupational Continued Arsenic roasters Artificial flower makers Book bluders Pelt and hair lactory workers Penell makers colored Pharmaceutical workers Bronze workers Cannery workers peeling frult treated with insecticides Citrus fruit orchard workers Cotton plantation workers glass workers Dyers Dyestuff makers Electroplaters Enamelers Farmers Photographers Polson batt makers Pottery decorators Pottery plant glaze dippers mixers Pyrites burners Rotogravure workers Rubber compounders Rubber mordant mixers Rubber pressors Rubber tire workers and Felt hat carroters silicon workers Fur handlers and preparers Galvanizers Gardeners Glass mixers Glass workers Glue manufacturers Sealing wax makers Seamstresses handling fabric dyed or treated with arsenicals Sheep dip manufacturers Smelters of arsenie copper zinc silver lead ores Sulfur burners Sulfuric acid workers 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 arsenie copper silver lead ores Oil cloth manufacturers zinc Oil refinery workers Paper colored makers Paper glazers Paper hangers Paper printers Tannery workers carriers Taxidermists Textlle 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 WoodWood preservors preservors Zine mixers Zine smelter chargers j Nonoccupational exposure Users of arsenic containing drinking water especially near arsenie ore smelters eals and mines of foodstuffs and liquor contaminated with arseni- Users of arsenic containing medicines arspbenamines cacodylates Fow- ler's solution Astatio pills Donovan's solution arsenious oxide in tonics antiseptics antipsoriasis or caustic olutments antispasmodies cosmetles hair lotions Persons exposed to inhalation of arsenical dust spread from arsenic ore smelters or by dusting arsenicals from alrplanes 7. Exposure to asbestos silicates containing calcium magnesium iron nickel and copper with possible relation to cancer of the lung Artificial manufacturers Insulation workers Asbestos construction workers AsbestosAsbestos workers crushers board wallboard shingle tile lzers molders earders mortar ellnker Asbestos miners fiber- 29 Asbestos spinners Asbestos workers cloth blanket curtain sheets ropes cords twine thread Asbestos weavers Brake manufacturers Bruke workers Carpenters Dyc workers acid and fireproof Electric manufacturers material manufacturers Gasket makers Insulation workers pipes boilers Plumbers packing meelianies Roofers Rubber production workers 8. Exposure to solar radiation and ultraviolet radiation with possible relation to cancer of the skin Agricultural Inborers Boatmen Cattlemen Construction workers Cowboys Drivers Turmers Fishermen Gardeners Herdels Ilouse painters Lumbermen Miners working in surface mines Nurserymen Oilfield workers Oll operators Pharmaceutical manufacturers of vita- min D. Railroad engineers Railroad workers Ranchers Rond workers Rural mail carriers Sailors Sportsmen Stockmen Sunbathers Vine growers Weiders 9. Exposure to roentgen 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 Physicists Radioactive electrostatic eliminator manufacturers and operators of such devices in textile and paper plants Radiologle technicians Radiologists Radium laboratory workers Radlum refinery workers Research workers handling radioactive isotopes and tracer substances Roentgen and radium technicians Roentgen meclionies Roentgen manufacturers Roentgenologists medical electric industry aviation metallurgic chemi- cal textlic art and jewelry shoe sales beauty parlors research Shoe salesmen in stores using fluoroscopes for fitting Uranium dye makers Uranium glass makers Uranium ginze makers tile Uranium miners and miners of radionetive ores pitch blende carnotite etc). Uranium paint makers b Nonoccupational exposure Customers of shoe stores using fluoroscopes Patlents consuming radioactive water for medicinal purposes over long periods Palients receiving large 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 Occupational Cancer Record 1. Name 2. Place of Death City Hospital 3. Residence State City Street 4. Social Security No. 7. Date of Birth 5. Sex 8. Age Years 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 ( ) Other ( ) 15. Street | 16. City 17. Clinical Diagnosis 20. Date of First Symptoms 18. Pathologic Diagnosis Microscopie( ) Gross ( ) 19. Primary Site 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 31 32 26. Occupational History List occupations in chronological order beginning with last or present one Dates From To Name of Plant - Location of Plant Type of Business or Product Made Title of Job Type of Work Performed 27. Exposure Investigator will name carcinogenic substances to which employee has been exposed Name of Substance Name of Plant Date of Last Exposure Duration of Exposure Years Months Describe Type of Exposure and Estimate Working Percent of Exposed Working Time 28. any Name ment other important materials to which employee has been exposed Hobbies Habits Medicines Cosmetics Diets; Environ- 29. AddiRteigiosntarlyIentfco.rmation Obtainable at Physician Laboratory Hospital Insurance Co Plant Medical Department Cl^>nicTumor Name Address 30. Any other information pertaining to tumor Multiplicity Sites etc. TS mr re ew ne ew we meee ee Date eee NOTE More blocks should be added under Nos 26 27 and 29 on actual record form TA we ee ee ee ee ee Investigator ee ee 3. Continued 251 252 253 Soot lamp black carbon blaek gas black etc. Spindle oll Sterols 254 225 256 257 258 Sulphur chloride Sulphur dioxide Sulphuretted hydrogen hydrogen sulphide Sulphuric acid Tar and pitch artificial asphalt bitumen 250 Tellurium compounds 200 Tetrachlorethane acetylene tetrachloride 261 262 263 Tetrachlorethylene perchlorethylene Tetraethyl lead Thallium 261 Tin 265 Titanium oxide 266 Trichlorethylene 267 Trorthocresyl phosphate 208 Turpentine 260 Uranium 270 Vanadlum 271 Vinyl chloride 272 Zine brass metal fume fever 278 Styrene K. Trauma not covered in any of the above : Chemical 800 Chemical acute 301 Chemical chronic Physical 802 303 804 305 Mechanical acute Mechanical chronic Thermic acute burn Thermic chronic Scars fistulas 306 Sears 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 G J E F K B II C A D. Carcinogenicity recognized or suspected 36 APPENDIX D Plant Survey Record 1. Company. 2. Location . 3. Plant manager 11. Number of employees 4. Plant physician 8 carrier_ Insurance 5. carrier_ ee 6. In operation since __ 7. Products manufactured 8. Known or suspected carcinogens 9. Medical service_ 10. Rate of labor turnover_--percent annually_ Malea White Colored_ Female weeeenewe Colored_ Total Date___ Production Office Total 12 Operation Operations involving known or suspected carcinogenic hazards Number of employees Type of exposur~ Route of exposure Duration of exposure for worker years mittent Occasi- WC M. Male Female 9. Total WC Constant _C Inhalation Skan Ingestion Other Average Longest GOVERNMT a. b c. PRINTG Pre- or cancerons effects noted Cancers noted OFICE Site Number Dates Site Number Dates ID80 80 b C. 37