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FILE NAME Household Contact HC DATE 1950 DOC HC058 DOCUMENT DESCRIPTION Government Report Environmental and Occupational Cancer Surveys A Methodology for Public Health Technical Monograph No. 1 A Methodology for Environmental and Occupational Cancer Surveys By W. C. Hueper M. D. Chief Cancerigenic Studies Section National Cancer Institute of the National Institutes of Health Public Health Service Federal Security Agency CONTENTS INTRODUCTION ------ 0-2 -- ase ne ener A. THE NATURE OF THE PROBLEM . a Occupational carcinogens .-.~--- ne _ Nonoccupational carcinogen rrrs eee Industrial public health hazards B. Tyres or ENVIRONMENTAL CANCER SURVEY Analysis of death certificates. cane Occupational history study of cancer deaths Industrial plant surveys cee ee eee eee nee nee C. SPECIAL ASPECTSewes eee ee nee nee Contact relations of carcinogens --------------------Environmental cancer pattern .. wee ee ce eee ee Identification of occupational cancers Age factors in occupational cancer .. APPENDIX A. Occupational and nonoccupational groups sug- PagePage Page 1 1 2 4 6 7 9 26 APPENDIX B. Occupational cancer record .. --.------- heen 31 APPENDIX C. Occupational hazard codo 33 APPENDIX D. Plant survey record 37 ii ii INTRODUCTION Environmental cancers are malignant tumors which are usually caused by prolonged exposure to exogenous agents of various types In a few instances these environniental producing factors are defined physical or chemical agents in others they are variablo 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 inan at the present time and for this reason have considerable general significance Exposure to these factorsis related to occupational activities medicines diets atinospheric cosmetics building material habits customs climate fauna contami- nants of drinking water air and foodstuffs and proce- dures of warfare Since prevention of cancer depends fundamentally " on adequate information as to its otiology 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 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 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 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 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 cancerons 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 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 involvedin 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 Intent 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 preventive measures Y collection A final objective of occupational cancer surveys is the and of specific technical information needed for the institution of adequate control measures These data can benefit industry by aidingin the design and introduction of effective technical measures for protection of their personnel The evidence required through anch 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 summarizedin table 2 1 includes a great variety of organic chemicals both aromatic and aliphatic several inorganic chemicals various types of physical radia- tion and the parasite Sohistosoma 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 Organie elemicals 1 Aromatic chemicals naphthylamine benzidine aniline ? benzol tar plich asphalt soots domestic industrial and commercial shale oil crude paraffin oli erude anthracene oll creosote lubricnting and fuel olis and greases synthetic estrogens ) 2 Aliphatic chemicals Isopropyl oll 7 b Inorganic chemicals Arseniculs chromates nickel carbonyl ? asbestos ? beryllium 7 2. Physleni carcinogens Nonlonizing radiation violet rays ionizing corpuscular radiations alpha and beta rays and electronic radiations gamma and rays B. Parasitic carcinogens Schistosoma hematobium It must be pointed out that the environmontal carcinogens 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 potrolours many of which are noncarcinogenic naphthylamino appears to be much moro carcinogenic than benzidine . The data on occurronco and incidence of occupational caucors as they appear in published reports are very inadequate The actual number of cancers which are occnpational in origin is undoubtedly much higher than is apparent from the recorded observations Since it often difficult to establish tho occupational causation of cancer re- sulting from exposure to known eareinogens often many years previously and because the inedical 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 carcinogons may bo 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 medic^>nal 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 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 carcinogen Method ofexposure and . 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 bencath 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 chutta 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 outdoor 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 1 Potential altes of cancer HOBBIES AND HOME ACTIVITIES Use of chlorinated aliphatic hydrocarbous in cleaning fluids with hepatotoxic properties modifying metabolism of endogenous and exogenous carcinogens ? Liver intonal organs MEDICINES AND MEDICAL DEVICES Arsenicals ee er ene ee ee , Tar impure vaselino and mineral oil- Ilepatotoxic chemicals chlorinated aliphatic hydrocarbons cinchophan oto ? Hematotoxic chemicals bonzol sulfonamides ? aromatic organic olomfoals ? Ultraviolet radiation_ een ease radiation_ rays___ eee ann mene ean eee eens Radioactive chemicals ionizing radiations ; Skin internal organs Do. Liver Loukemia Skin Skin bono loukomia ? Skin bono lung 7 leukemia ? liver ? DIETARY FACTORS Dietary iodine deficiency 2.00. anos a-- Dietary protein and vitamin B complex deficiency deficiency Dietary vitamin B complex doficiency . Arsenical contaminants in water air food drinking Ioated mineral oil as fat substitute in baked goods ? Thyroid Liver Laryngopharynx Skin internal organs Internal organs COSMETIC FACTORS radiation for depilation Ultraviolet lamp oxposure for tanning ---- Arsenicale in hair lotions and tonics ? Lamp black in oyebrow pencils tar ? Impure vaseline and mineral oils in ointments creams etc. Estrogons in skin creams - Impure aniline dyes in lipsticks etc. contain- ing dye intermodiates ? Skin Do. Do. Do. Do. Breast Bladder OTHER ENVIRONMENTAL FACTORS Tar and soot in atmospheris 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 ? Skin Bladder liver intestine Lung bono tissue hematopoletio 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 t 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 1 known occupational carcinogen and the proper conditions of ex the appearance of occupational cancers becomes merely a ques time i e of sufficient Intent period since the start of the op Clearly such hazards constitute an industrial problem den intensive study and control efforts Such industrial carcinogens not only provide a serious 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 t problem as whole Since environmental cancers represent majority of those cancers whose etiology is known observatio 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 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 cancer 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 both 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 occupa- tional carcinogenic spectrum should reveal suggestive relations be- tween these factors and cancer incidence By comparing the rela- 800678-50- 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 eccupations 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 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 noted 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 consumers 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 ; 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. 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 Occupations 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. .. 0 By place community or region of occupational activity _ Since information recorded in death.certificates 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 consideration is given to these limitations however bioIf proper studies of this type may yield valnablo clues that can be sftoaltlisotwiecdalup by other types of epidemiologic investigations as for example those described below 2. Occupational History Study of Cancer Deaths basis the information obtained from death certificates Using as histories of selected cancor it is possible to study the occupational 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 careina- Less conclusive evidence such as geographical topographical gens environmental and possibly oc- age and sex distribution implicates cupational factors in the production of cancer in other organ systoms gastrointestinal nervous By tracing back the onvironmental and occupational histories and whore possible discovering other oxoge- nous agents to which the cancer patient was exposed it may be possible to substantiate further these 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 in- dividual 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 information on injuries and discases sustained during the survey period should also be collected as these may indicate specific precancerous or pericancerons reactions See C The type of information required appears on the Occupational Caneer Record appendix B as items 17 to 30 Data on the employment history of the decensed 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 the aged sanitariums mental institutions infir- mmaries etc. in 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 agonts with which tho deceased came in contact 9 whenever available information suggests the possibility of carcino- Data on the duration intensity and type of ex- genic exposure From a critical posure should complete the information required 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 us 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 bo required for the 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 . nover spot surveys but always time surveys However the biological and epidemiologic epidemiologic behavior of occupational 10 cancers its advisable to survey establishments that have been in operation for as little us 3 yours Workers in such plants may have already developed precancerous and pericancerons lesions especially if the carcinogenic hazards affect the skin bladder boneor hema- topoietic tissue It is unlikely that within such a short period cancer attributable to occupational exposure will occur in statistically signif- icant numbers but the timely recognition of these nommalignant 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 ele_ vated cancer incidence rates Only when these studies demonstrato 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 plaat omployment rec- ords plant medical records insurance companies hospitals physi- cians 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 more than 5 years if the plant has a fairly rapid labor over it may bo found that no workers in apparently carcinogenic operations operations are suffering from cancer or even froin precancerous lesions Indeed tho medical records of the plant or its insurer may show no occupational _ eancer throughout the entire period of oporation Ilowever it may bo discovered by following up foriner employees that some persons lavo doveloped occupational cancers possibly attributable to the carcinogenic agent to which they were exposed from 2 to 30 yours earlier Labor ovor may thorofore totally oblitorato any ovi- donco of cancerous reactions in persons exposed unless adequate follow studies of former employees are made over a period of sufficiont length any 15 to 80 years Consideration must be given moreover to the fact that employees with occupational cancor or with therapeutically controlled occupational cancer aro ^finganoral not continued in operations with carcinogonio hazards In some establishments 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 employee 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 mist 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 operations practically all production workers are exposed to carcinogenic cs ngents to some degree The investigations should be extended not only to individuals rogu- largly employed in hazardous operations or constantly in contact with carcinogenic agents but also to those entering the hazardous area or coming into contact with carcinogens at irregular intervals Intermittent 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 yardmon 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 dif- ferent periods of operation of the plant due to manuifn amacnutfauctrur-- ing methods and in raw materials used | . Moreover record should be made of any differences in the degree and type of exposure skin contact inhalation ingestion and the physicochemical status of the agents dust fumes inist 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 Such distinctions are indicated for chemical as well as physical carcinogenic agents Differences in this factor affect 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 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 tho physical appearance of workers and with permission of the management make personal inquiries of foremen and workers in regard to suspected . hazards o Sinco 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 tested 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 neighbor- hood of the plant noting unusual offects 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 Whore evidence indicates the environmonial 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 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 precancerous or cancerous lesions f Through careful questioning the investigator should discover any changes made in production handling and precautionary incas- 13 ares 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 meusures 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 my 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 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 cancerons 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 lead to a perpetuation or reintroduction of cancer hazards into operations which may have been made 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 site of their deposi- tion plays a definite in determining the site of the ousuing 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 cancor Table 3. Contact relations of carcinogens Site of cancer Type of contact Carcinogen Skin ... Direct, primary contact ewe ol Depository contact Excretory - contact_ Ultraviolet radiation , radia tion radioactive radioactive tion radioactive energy tar pitch soot processed miner- al oils greases arsenicals Arsonicals Arsenicals Lung larynx nasal sinuses sinuses Direct primary contact] ) | Excretory contact -- Radionetiva gasos and dusts fumes dusts mists vapors of tar pitch processed mineral oils ohromates nickel carbonyl ? arsenic asbestos ? isopropyl oil ? Radioactive gases Bladder ureter | Excretory contact kidney Depository contact___ -- Bono and marrow bone Direct primary contact Aromatic amhics tar ? ar sonio 7 Ionizing radiations radioactivo substancos benzol beryl- : lium ? radiation Despite the fact that the tissues of the alimentary and nervous systoms are directly or indirectly exposed to a great number of environ- montal agents such as tar petrolonm 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 observed in males and since cancer of this organ half of all cancers as well as those of the contral nervous system usually havo a spyosotrepmrognosis it may be hoped that environmental cancer surveys will 15 800678-50- 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 histories 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 aro not infrequently present in individuals with environmental precancerous and cancorous lesions In fact whenever such an environmental cancer pattern including both aplasiogenic and hyperplasiogenic mani. - festations can be demonstrated in the same individual or a group of individuals exposed to the same agent it serves as valuable evidenco in support of an exogenous causation of the cancorous responses ob- sorved in the population group Among the oxogenous carcinogens which produco those ambivalent effects aro arsenicals benzol ionizing radiations from radioactive chemicals and ray tubes ostrogens urethane and certain nitrogen mustards Their cancerous action is utilized in the therapy of malignant timers while thoir carcinogenic action has resulted oc- casionally in the production of cancers when they have been used medicinally in the treatment of nonmalignant conditions ' These ambivalent precancerous and pericancerous reactions to en- vironmental carcinogens are summarized in tablo 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 atrophio changes such as aplastic anemia loukopenia thrombocytopenia macanemia and severo atrophy of the hematopoietic tissues On the opposite end of the reactivo range there occur leucocytotic hyper- 16 | a Loo leucocytotic 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 bone marrow Table 4. Precancerous and pericancerous reactions to environmental carcinogens Reactions Etiologic Agents SKIN Alopecia . Spotty loss of haier en ee -| Arsenio ionizing radiations raraddiioaaticotnive substances - Atrophy glistening Pitol | Skin grossly thinned and glistening in patches associated with keratotle Pitol tar asphalt petroleum radioactivo substances areas radiation ultraviolet radia- tion solar rays Eozema Dry seborrheio patches on skin Arsenio asplinit pitch scot tar Keratosis : Flat discrete scaly area on skin with raised pearly borders Usually on parts of skin exposed to carcinogen but may occur in unexposed parts partien- larly about sweat glands with argente Hyperkeratosis Anctrheroascoteono craudresenio asphoaillt mineral small hard wart horns usually on hands and soles May become nodular and ulcerate radiation Xradiation . Verrucas . Horn hyperkeratosis cue .. . Uleoration Breakdown of keratotic lesions 0.0.4 Obrome holes nennneeueeunueen a.| Arsenicals Arsenicals ohromic Chromates ohromic acid * Leukoderma Patcthioens of subnormal melanin pigmenta- 4 melanoderma Patelies showing increased pigmentation and patches showing mentation of skin pig- subnormal Most common in areas of highest pigmentation and may involve oral mucosa Melanoderma Patelies of increased pigmentation____ Anthracone arsenic asphalt eroesoto erudo mineral oil pIanrg afafinnd pitch tar lonizing nonioniz radiations radioactive substances radiation ultraviolet radia- tion solar radiation Scleroderma Dry scaly parchment skin with enlarged pores associated with louko- melanederma Crude mineral oil paraffin oil ionizing radiations radioactive substances rays ultraviolet rays solar rays 17 Table 4. Precancerous and pericancerous reactions to environmental carcinogens Reactions Etiologie Agents NASAL PASSAGES Papillomas and polyps - Growths in antrum ttuirobnsinates Nasal ethmoid septum cells and perfora- Isopropyl Isopropyl oil nickel carbonyl chromates arsenicals ; , BLADDER Hemorrhage submucosal Varying size with telangiectasis mainly in trigone and about orifices Located uroteral Papillomas Polypous or villous pedunculated or sessilo Often multiple about trigone and ureteral orifices Benzidine naphthylamine and derivatives - EYES ' Papillomas Pedunculated Develop mainly on lids occasionally on eyeball . BONE Arsenic asphalt ereosote orudo mineral oil pitch tar ionizing radiations ultraviolet raya Chronic periostitis Thickoning of periosteal tissue of bone BONE MARROW HYPOPLASIA Blood dyscrasias necrosia rays | Ionizing radiations active substances radio- Hyperplasia anemia and metaplasia aplastic | Bonzol and derivatives ionizing thrombocytopenia loukopenia monocytosis crythrocytosis leueocy- radiations radioactive sub- tosis leukenoid reactions stances rays LUNGS Pneumoconloses and pneumonia pneumonia Asbestosis lipold lipold chemical pneumonia BREAST Painful swollen breasts Glandular hyperplasia | ehronie Asbestos arsenie tar soot minnoriaclkeloiclarmbiosnytl chrome salts Estrogenic chomicals Intermediate degrees of exposure whether continuous will produce mixed reactions In or intermit- tent general it will be found that increasing exposure will result in increasing effects of both the plastic and atrophic types up to a certain hyper- the increasing severity of exposure will causepaopirnetponFdreroamnttlhyaatplpaositnito effect overwhelming any hyperplastic reactions and posure increases to death of the leading as ex- Thus a primarily hyperplastic organism organism by destruction of tissues phase or vice phase may be followed by an aplastio exposure versa depending upon the degree and rhythm of 18 3. Identification of Occupational Cancers Occupational carcinogenic agents and cancers do not in themselves possess any characteristic properties that distinguish distinguish them from and cancers of nonoccupational naturo agonts agonts The occurrence of cancer in an exposed person of a tumor characteristic for the particular car- cinogen and typo of exposure is not therefore absoluto proof that the cancer is identical of occupational origin anatomically and histologically cancers are found in persons who contact with the apparantly have had no occupational carcinogen in question However there is ofton sufficient associated ovidence present which when critically analyzed provides adequate and acceptable proof as to the tional nature of the cancer occupa- ~ Such ovidonco is represented by the presence of typical precancer- ous and pericancerous lesions such as rudiation tar oil paraffin pitch solar and arsenic dermatitis radiation osteitis and lenkomic loukoponias and leukemoid reactions after after axposure to benzol and ionizing radiations Additional supporting evidence is the demon- stration of exposure of adequate length and intensity to the carcinogonic agent However consideration must be given in this connection to the possibility that effective carcinogenic exposure may be tho result of contact with the carcinogen sustained in different employments or for other ouvironmental reasons or exposure to different carcinogens having additive action Thus a critical analysis of the entire ocenpational history and nonoccupational exposures is indicated for all casos in which tho initial evidence shows that the exposure sustained in any single employment appeared insufficient or sufficient to account for the cancer Identification of cancers found in a particular survey area or plant may bo made by statistical methods when 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 occupationaolr onvironmental etiology These critoria of identifi- cation are a Significant variations in total and organ incidence of cancer in differont onvironmental or occupational subdivisions after the data have been properly adjusted and standardized as to other possible factors raco ago sex and b Shift in organ incidence sex distribution frequency of multi- plicity and ago range of cancor during differont parts of the period especially if theso developmonts should follow survey the estab- lishment of industries with known upon or suspocted caneer hazards in the area c _ Differences in the incidenco rato and localization of within one cancer organ system exposed and unoxposed skin alimontary 19 tract etc. among porsons living in various parts of the survey aron Different types of exposure to the same carcinogen as well as contact with different carcinogens have a direct influence cu 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 epidemiologie 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 re- production has been achieved Conversely it is not infrequently believed 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 properties they may possess for man Howevor 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- amine 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 sex and heredity do not seem to have any appreciable influence in this respect The experimental reproduction of these bladder cancors 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 rondily 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 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 o liver bone marrow and probably eustachian tube - . The chemical analysis of the urinary metabolites of the two aro- matic amines when given to different species suggests that variations 20 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 naphthylamine in olive oil eliminate in the urine the base itself its acetyl derivative its derivative and an unidentified dihydroxyaninonaphthalene After the administration of benzidine rabbits excrete the free base and a derivative white rats eliminate a hydrox- ' ylated compound and an acylate derivative Workers exposed to chemicals containing benzidine excrete 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 excretionof 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 cancere readily by the application of various types of tar in inan 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 reproduction 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 growth in experimental animals creates a highior excretory potential of arsenic and thereby lowers its . carcinogenic action However the strikingly spotty appearance of arsenic cancer in man points to the action of other mechanisms prob- ably of abnormal nature that must be present before arsenic cau - 21 produce 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 great importance of species specificity is presented by the continued controversy as to the carcinogenicity of estrogenic substances in man While there can be little doubt that estrogens are essentially involved in the development of mammary cancer of certain inbred strains of mice of both sexes it is still julas- tionable whether estrogens participato 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 made 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 man- mary 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 ostrogens in man The occurrence of hyperplasia of the breast in pharmaceutical workerisn England and the United States engaged in the manufacture of synthetic estrogens may provide confirmatory ovidence in this respect if and when mammary cancors devolop in male workers of this occupational group Brief 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 as a leukemiogenic agent in man However the experimental observations made so far entirely on mice are contradictory Beryllium has been shown to elicit osteogenic sarcomas in rabbits only by moans of intravenous injections It is an open ques- tion whether this observation indicates that this substance may exert a similar effect in workers exposed to it by a different route Specios specific differences exist also in the field of physical carcino- gens and produce uncertainties and problems thore identical with those encountered in connection with primary chemical carcinogons Epidemiologic evidence strongly indicates that an excessive exposure to solar rays may result in cancer of the exposed skin among individuals especially predisposed by their light complexion Observations inade on mice and rats subjected to intensive treatment with ultraviolet rays seem to confirm this causal relation between exposure to solar actinic energy and cancer developinant Howevor all attempts to produce experimentally ultraviolet cuncor of the skin in gninon pigs and rabbits have failed Thus observations on two species seem to negate any relationship of solar irradiation and cancor Such a 2 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 earcinogens which affect humans the selection of a suitable species represents the fundamental pre- requisite 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 influeneo decisively the outcome of the experiment Given a suitablo Lest 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 lend 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 dust 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 dorived from tests of longer duration Under practical working conditions however concentrations of injurious and earcinogenic 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 eniployed 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 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 car- cinogenic concentrations are concerned should be measured more in peak values than in averaged values Therefore the proper appli- 24 cation of observations on exposure in the field seems to be an important part in experimental studies on occupational 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 con- ditions 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 ad- visable 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 extensive employment of female workers in certain industries and professions with potential cancer hazards warrants their inclusion in such surveys These industries include rubber goods manufacture luminous dial painting spiuning 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 placontal barrier may bo active in eliciting cancer in the young Thus there are no definite age range limitations in general cancer surveys st 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 Pub Health Rep Supp 209 1948 These may be useful for the interpretation of the results obtained in environmental and occupational cancor surveys 23 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 leukemin lymphosarcoma and myeloma ) Airplane workers Mordanters Apinne hangar employees Nitrobenzol inakers Alcohol denntored workers Aniline workers Nitrocellulose workers Oil extractors glass workers products impregnators Palut remover manufacturers Painters Battery dry makers Paraflin makers Beauty parlor operators Pencil makers Belt scourers Perfume mukers Benzol purillers Benzol workers l'etroleum distillery and refinery workers Brake Huing makers Pharmaceutical workers Brouzers Burnishers Phenol mukers Photoengravers Onu rubber gasket manufacturers Can rubber gasket sealers Photographle elemleal makers Pieric acid makers Carbolic acid makers ChemistsChlordiphenyl Plastic textile makers Polish makers Chlorodiphenyl makers Polishers Cluteb Impregnators Pottery decorators Coal tar still cleaners Printers Coal tar workers Cobblers Color wakers Coke oven tur workers Putty makers Pyroxylin plastle workers Rotogravure workers Rubber buffers Compositors Rubber cementers Degreasers Rubber cement mixers Disinfectant makers Dry cleaners Dye makers Rubber compounders Rubber dippers tubber driers Dyers Electroplaters Rubberized asbestos board makers Rubber mixers Dlectroplate casi scrubbers Dnamelers Enamel makers Rubber pressroom workers Rubber reclaimers Rubber tire builders Engravers Rubber treaders Explosive makers Feather workers Fertilizer makers 4 Rubber workers Shade cloth workers Shellackers Flavoring extract makers Galvanizers Gas house workers Gasoline blenders Gilders Glue makers Ink makers Shellae makers Shoe nlsbers Shoe fuctory workers Shoe wood coverers Smokeless powder makere Soap makers Tar distillery workers - Lacquerers Lacquer makers Leather makers artiflelal and patent - Linoleum workers _ Lithographers Metul washers Tar plich oll etc. tank cleaners ' Textile fullers - Tobacco seedling treaters Trinitrotoluol makers Type cleaners Varnishers Millinery workers Mirror silverers Varnish makers Varnish remover manufacturers 26 War gas makers Waterproof fabrle 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 a Occupational Continued Agricultural laborers Blue priut makers Photographie chemical workers Printers Candle makers Candy colored makers Cosmetic manufactures colored lipstick powder cream eyebrow pencil skin tan lotions Citrus fruit dyers Dye handlers packers mixers : Rubber workers antoxidants naphthylamine antoxidants phenyl- naphthylamine butylnaphthylamine etc. Shoe manufacturers Soft drink colored manufac turers Dye makers aniline naphthylamine benzidine xylldine toluidine etc. Fur dyers and workers Gardeners aromatic pesticides Ink makers Leather dyers and workers Lithographers Margarine colored makers Marmalade and jelly colored makers Ore flotation workers betn- naphthylamine cresylte meld etc. , Painters Paint makers Paper dyers and manufacturers Pharmaceutical workers Photographers Textile dyers Textile printers Wax pencil makers b Nonoceupational exposure Consumers of colored foodstuffs Users of colored cosmetics Users of dyed textiles and lealbergoods that bleed excess dye when coming in contact with sweat and seburn Users frequent of medical preparations containing aromatle _ amino groups antihistamines- allergles hayfever etc anal- hendache neuralgia dysmenorrhea arthritis in- graine medicines liquids tablets capsules ointments colored with aniline dyes 3. Exposure to tar pitch off soot asphalt creosote carbon blacks parafin laenutkhermaicaen)e with possible relation to cancers of the skin lung bladder and Artificial makers Asbestos goods workers Asphalt workers | Anthraceae manufacturers Battery dry workers Brick layers Brickyard workers Briquet makers Brush makers Cable makers and Jayers Carbon black makers and users ' Chimney sweepers Coal carbonizntion workers Coal stiil cienaers Coal workers Coke workers Cordage workers Corkstone makers and carpenters Collon spinners Creosoting plant workers Diesel engine attendants Electrical equipment manufacturers Electrode makers Engineers Foundry workers Fishermen Flue cleaners Fuel oil suppliers truck drivers Furnace workers - , Qas house workers Gas Illuminating workers Generator stokers Grease monkeys Grease pit workers Ink makers Insulators Lamp black makers and users Machinists Mechanics Metal workers Ollers Oil refinery workers Oll well workera Optical lens grinders Ore flotation plant workers Paint sprayers Parnfin distillery workers Paramo plant workers Pavera Pharmaceutical workers Piteb workers Plastie cement workers Printers : : Road repairers 27 Roofers Roofing workers Hope makers Rubber workers Sanitary pipe makers Shipyard workers Soap makers Shale oil workers Stokers Tank cleaners Tar painters Tar paint munufacturers Tar workers Textile workers Waterproofers Water proof paper makers Wood pleklers Wood preservers 4. Exposure to chromium and chromlum compounds chromium metal chromates chromimu pigments chromle acid ehromlum carbonyl dust with sible relation to cancer of the hig and nasal sinuses pos- a Occupational exposure Abrasive makers Abrasive workers and polishers a Occupational Continued factory workers Mordanters Asphalt refinery workers Battery dry makers Bleachera Blueprint makers Candle colored makers _ Coal tar workers Chromate chromie tanning turerk chromtun pigments acid and leather compound manufac- Oliromlum ore miners and miners of other metal ores with chro- mtum admixtures cobalt Crayon and pencil colored Paint manufacturers Painters Paper dyers Paper makers Paper money makers Paper waterproofers Photoengravers Photographle workers Photogravure workers Pottery glaze makers Pottery makers Printers Refractory brick makers masons and makers Dock workers unloading mite ore Electroplaters Electrolytical chromium manufacturers Enamelers Enamel makers Explosive manufacturers chrometal Rubber vulcanizers Soap makers Stainless steel workers Tannery workers Textile dyers Textile printers Texille waterproofers ornament workers Welders Furniture polishers Glass and pottery frosters Ink makers Linoleum workers Lithographers . Wood stainers b Nonocempational exposure : Persons ving or working in funne and dust zone of chromate pinnts 5. Exposure to niekel and nickel compounds nickel metal dust nickel carbonyl cvaanpcoerrsonfitchkeelluonxgidaendnincakseall ssuiln^u...sdeensickel alloys with possible relation to Abrasive manufacturers Ceramic glazers Chemical workers in operations using nickel antalysis Coln makers Electroplaters Enamelers Enamel makers German silver manufacturers German silver smiths Hydrogen manufacturers Monel metal makers Nickel alloy makers copper ver aluminum sil- chrome turers . chrome alloy wire turers Nlekel extractors Nickel ore miners manufaemanufue- Nickel ore smelter and refinery workers Nickel polishers Nickel workers Of refinery workers Storage battery manufacturers Tale manufacturers 28 6. ' Exposure to arsenie and arsenicals arsenic metal arsenious oxide calcinm 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 Occupational exposure Arsenic roasters : Artificial flower makers Book bluders Bronze workers Cannery workers peeling frult treated with Insecticides Citrus fruit orchard workers Cotton plantation workers glass workers Dyers Dyestuff makers Ilectroplaters . Enamelers Farmers , Felt hat carroters silicon workers Fur handlers and preparers Galvanizers Gardeners Glass mixers Glass workers Glue manufacturers Gold refiners Ink manufacturers Insecticide manufacturers Insectiekle sprayers and dusters Japan makers , Jewelers .Lend factory workers Lead shot makers Linoleum color workers Lithographers Miners of arsenic copper zinc silver lead ores a Occupational Continued Pell and hair iactory workers Penell makers colored Pharmaceutical workers Photographers Polson bait makers Pottery decorators Pottery plant glaze dippers and mixers Pyrites burners Rotogravure workers Rubber compounders Rubber mordant mixers Rubber pressors Rubber tire workers Sealing wax makers Seamstresses handling fabric dyed or treated with arsenicals Sheep dip manufacturers Smelters of arsenle capper zine silver lead ores Sulfur burvers Sulfuric acld workers Tannery workers carriers Taxidermists Textile printers Tinners Velvet makers Vinery workers Vineyard workers War gas manufacturers Wax ornament workers Weavers nsing yarn dyed with use of arsenicals Weed killer manufacturers refinery Oil manufacturers Paper colored makers Paper glazers Wire drawers makers Wood preserve Wood preservors Paper hangers - Paper printers ' b Nonoecnpational exposure Zine mixers Zine smelter chargers ; \ . Users of arsenic containing drinking water especially near arsenle ore smelters and mines of foodstuffs and liquor contaminated with arseni- eals . Users of arsenic containing medicines arspbenamines encodylates Fowler's solution Asiatle pilla Donovan's solution arsenious oxide in tonics antiseptics antipsoriasis or caustic olutments antispasmodics eosmetles hair lotions Persons exposed to inhalation of arsenleal dust spread from arsenic ore smelters or by dusting arsenicals from airplanes 7. Exposure to asbestos silicates containing calelum magnesiuin iron nickel and copper with possible relation to cancer of the lung Artificial manufacturers Asbestos construction workers board wallboard shingle tile mortar elinker Insulation workers | Asbestos workers crushers izers wolders earders Asbestos miners fiber- Asbestos spinders Ashestos workersworkers k~ t curtain sheets twine thread cloth blan rupes cords Electric manufacturers material manufacturers Gasket makers Asbestos weavers lluing manufacturers living workers Carpenters Dye workers acid and fireproof Insulation workersworkers pipes bollers Plumbers packing meekantes Roofers Rubber production workers 8. Exposure to solar radiation and ultraviolet radiation to caneer of the skin with possible relation Agricultural laborers Boatmen . Cnttlemen Construction workers Cowboys Drivers Farmers Fishermen Gardeners Herders Ilouse painters Lumbermen Miners working working in surface mines Nurserymen Oilfield workers Oll operators manufacturers Pharmaceutical manufacturers manufacturers of vita- min D. Railroad engineers Railroad workers Ranchers Road workers Rural mail carriers Suitors Suitors Sportsmen Stockinen Sunbathers Vine growers Welders 9. Exposure to roentgen rays and radioactive radioactive chemicals to cancer of the skin lung bone liver , and leukemia : a Occupational exposure Atomic energy plant workers Biologists with possible relation relation Chemists Gas mantle manfacturers Lahoratory technicianstechnicians and attendants NLuurmsienosus dial dial painters handlers and shippers metal serap handlers . Phaacrtmiavceeutrtaiccearlsuwborsktearnscworkeers susing radioactiveradioactive isotopes and making radio Physicists . Radioactive electrostatic eliminator manufacturers devices in textile and paperpaper plants and operators of such Radiologie technicians Radiologists Radium laboratory workers Radlum refinery workers Research workers handling handling radioactiveradioactive Roentgen and radium technicians Roentgen mechantes isotopes and tracer substances Roentgeo manufacturers Roentgenologists cal textlic art medical electric Industry aviation metallurgic chemi- and jewelry jewelry shoe shoe sales beauty parlors parlors research SUhroaenisuamledsymeenmain ikn estrosres using fluoroscopes for fitting Uranium glass makers Uranium glaze munkers tile Uranium Uranium miners and miners of etc. * radioactive radioactive ores pitch blende carnotite Uranium paint makers b Nonoccupational exposure : Customers of shoe storesstores using fluoroscopes Patlents consuming radioactive radioactive water for medicinal periods purposes over long Paltents receivingreceiving large doses of ionizingionizing radiation for medicinal medicinal People living in regions with radioactiveradioactive ores and purposes rwaadtieoracotfivreadoipoearcattiivoenssprings springs or residing in the wdraisntkeindigsposoarlodrispbosaaltahrienag oinf 20 APPENDIX B Occupational Cancer Record 1. Name 3. Residence State . City 2. Place Hospital Death CCityity Street 4. Social Security No. 5. Sex 6. Color or Race 7. Date of Birth 10. Occupation 8. Age Years Mos 11. Industry or Business Days 9. Date of Death 12. Cause of Death 14. Name of Physician 13. Method of Diagnosis Clinical ( ) Biopsy ( ) Autopsy ( ) Other ( ) 15. Street 16. City 17. Clinical Diagnosis | 18. PatMhioclroogsiceopDiicaDgiagnnosios )sisGross ( ) 19. Primary Site 20. Date of First Symptoms | 21. Dact^e>aonf First Visit to Physi- 22. Date of First Diagnosis . 23. Stage of Diesase at First 24. History of Other Illnesses of Site Affected Diagnosis 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 From To Name of Plant " Location of Plant : Type of Business or Product Mode 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 Percent ofWorking Time Describe Type Exposure and Estanate Exposed I | 28. Name any ment other important materials to which employee has been exposed Hobbies Habits Medicines ; Cosmetics Diets Environ- ; Additional Information 29. Registry etc. Obtainable at Physician Laboratory Hospital Insurance Co Plant Medical Department Clinic Tumor Name . . . Address 30. Any other information pertaining to tumor Multiplicity Sites etc. ae ae mee ea nr ne on ne a ve . Date ; NOTE More blocks should be added under Nos 26 27 and 29 on actual record form eee e Investigaor InvestigatorInvestigator Investigator ne ee : Investigator APPENDIX C Occupational Hazard Code Prepared in cooperation with Dr. H. F. Dora A. Abnormalities of air pressure : 001 Compressed air increased atmospheric 002 Altitude rarefied air decreased pressure B.B.B. Abnormalities of temperature and atmospheric humidity: pressure 010 Feat 011 Cold 012 Sudden variations of temperature O. Dampness : 020 Dampness 021 Dryness D. Defective illumination 030 Defective illuminatlon D. Dust Organle dust 040 Textlle dust 041 Flour 042 Sugar 048 Wood dust 044 Leather dust 045 Feathers 010 Coal dust 047 Tobacco dust 050 Organic dust other than specified Inorganie dust ; 060 Abrasive dust 061 Brick dust 002 Clay dust 063 Flint dust , 004 Glass dust 005 RockRock dust 060 Quartz dust . 007 Talc 068 Agbestos 000 Iron ore F. Infections 070 Inorganle dust other than specifled Amoeba and other unicellular organisins Bacteria and spiroclistes Fungus Rickettsia and related microorganisms Virus Worms and other multicellular parasites Other parasites G. Radlant energy 100 rays 101 Radlum 102 Radiothorium 108 Mesothorium 104 Radioactive isotopes 300 - Radioactive substances Ultraviolet and infrared rays . 110 Ultraviolet rays 111 Infrared rays other than specified Carcinogenicity recognized or suspected 33 H. Repeated motion pressure shock etc 120 Repented motion pressure shock etc. J. Poisons 130 Acetaldehyde 131 Acetone 132 Acids inorganie 133 Acids organie 134 Acridine 135 Acrolein 136 Alcohols 137 Aldehydes 138 ' Aluminum 139 140 141 142 Ammonia Amyl acetate butyl acetate Amyl alcohol Amilme and other awine compounds of henzol acetanilde naphthylamines nitraniline euwidine and its homologues; toluidine xylidine 143 Aniline dyes 141 Anthracene 145 140 147 Antimony and its compounds Arsenic and its compounds except arsenluretted bydrogen Arseniuretted hydrogen arsine 148 149 Asphalt natural Azo compounds 150 Barlun 151 Benzidlue and derivatives 152 159 Benzine gasoline naphtha Benzol benzene and its aminoazotoluene homologues toluol and xylol 154 Beryllium 155 Brownine 150 Butanone 157 Butyl alcohol 158 Undmlum 159 Calelum eyanamide cyanamide 100 Carbazoles 181 Cambolle acid phenol 162 Carbon black . ' 163 Carbon dioxide 181 Carbon disulphide 105 Carbon monoxide 106 167 168 Carbon tetrachloride Cellosolve mono ether of ethylene glycol Chloride of lime 160 Chlorinated diphenyls 176 Chlorinated hydrocarbons 171 Chlorinated naphthalenes 172 Chlorine 173 Chloroprene butadiene 174 Chromium carbonyl 175 Chromium compounds 176 Coal 177 Cobalt 178 179 180 181 182 188 Copper Creosote Cresol cresylic acid Cyanogen compounds hydroeyanle Dichlorethylene Dichlorethyl ether aeld 184 Dimethyl sulphate 185 D'ultrophenol 1-2-4 186 Dioxan diethylene dloxide 187 Estrogens synthetle 188 Estrogens natural 189 Ethyl benzene Carcinogonlelty recognized or suspected 34 Continued J. 190 Ethyl bromide and ethyl chloride 191 Ethylene dibromide 102 Ethylene dichloride dichlorethane 108 Ethylene oxide 104 Ethyl silicates tetracthyl tetramethyl sillonto 105 Formaldehyde 196 Formle acid 107 Furfural 108 Germauium compounds . 100 200 201 202 208 Glycols Halogenated hydrocarbons allpbatie eblorine bromine fluorine Halogenated hydrocarbons aromatle -- exanonemethyl butyl ketona Hexone methyl Isobutyl ketone 204 205 206 207 208 Hydrazines Hydrochloric acid Hydrofluoric acid fluorine and its compounds Iron carbonyl Isopropyl compounds 200 210 211 Ketones Lead and its compounds Lead arsenate - 212 Magnesium 213 214 215 210 217 218 210 220 221 Manganese Mereury and its compounds Methanol methyl alcohol Methyl bromide Metbyl cellosolve ethylene glycol monomethyl ether Methyl chloride Methylene chloride dichloromethane Methyl formate Mineral oil crude mineral oil processed or grease prepared by frnellonation or cracking 222 Naphthols 228 Nickel 224 Nickel carbonyl 225 220 Nicotine Nitrobenzol and other nitro compounds of benzol and its home- logues chlorodinitrobenzol chloronitrobenzol; dinitrobenzol ; nitronaphthaleno trinitrotoluol . 227 Nitroglycerin 228 Nitrous fumes and nitric acid 220 Oil shale 280 Oxalic acid 231 282 283 284 Ozona Paraflin ; paraffin oil crude Pentanone methyl propyl ketone Petroleum 235 Phenol - 280 Phenyl hydrazine 287 Phosgeno 288 230 240 241 Phosphorus Phosphuretted hydrogen phosphine Plerle neid trinitrophenol Polycyclic hydrocarbon e g benzpyrene methyleholanthrene ; carbazole various derivatives of benzanthracene 242 Porphyrins 2:43 Potassium hydroxide 244 Pyridine 245 Quinones 240 Selenium compounds 247 Silver 248 Sodium hydroxide 249 Sodium nitrate erude 250 Soot Carcinogenletty recognized or suspected 35 J. Continued 251 Soot lamp black carbon black gas black etc. 252 Spindle oll ' 253 Sterols 254 Sulphur chloride 225 256 257 258 Sulphur dioxide Sulphuretted hydrogen hydrogen sulphide Sulphuric acid Tar and pitch artificial asphalt bitumen 250 200 201 Tellurium compounds Tetrachlorethane acetylene tetrachloride , Tetrachlorethylene perchlorethylene 262 Tetraethyl lead 263 Thallium ~ ^iTin 265 Titanum oxide 206 Trichlorethylene 267 Triorthocresyl phosphate 208 Turpentine 200 Uranium 270 Vanadium 271 Vinyl chloride 272 Zine brass metal fume fever 278 Styrene K. Trauma not covered in any of the above : ; Chemical : 300 Chemical acute 801 Chemical chronic Physical : 902 308 804 . Mechanical acute ' Mechanical chronic Thermic acute burn 305 Thermle chronic Scars fistulas 300 Scars fistuins 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 D F K B II C A D - Carcinogenicity recognized or suspected APPENDIX D Plant Survey Record 1. Company . ee ee tener er 2. Location_ ene ee ce ee meen een ernie sama wane 3. Plant manager oe eee 11. Number of employees Production Office Total 4. Plant physician.. eedie 5. re ee 6. In operation sinc ----- 9e -0 7. Products manufactured..- ee- e ee- e eee- me- re - ree 8. Known or suspected carcinogens. nH percent annually 9. Medical service ~~ ne --- eee 10. Rate of labor turnover nnn reer ----- Operations involving known or suspected carcinogenic hazards : Duration of exposure for worker years 12 Operation Number of employees Type of exposure Route of exposure | | { Male Fermale mittent Occasi- | | Total U. | TF Constant Inhalation Sken Ingestion Other Average Longest SOVCANERY b2C.o PRIKTNG Pre- or cancerous effectsnoted Cancers noted OFICK Sita Number - | Dates Site Number Dates IB80 , < 37