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ALICE HAMILTON, M.D. Assistant Professor Emeritus of Industrial Medicine Harvard School of Public Health, Boston, Mass. HARRIET L. HARDY, M.D. Physician to the Division of Occupational Hygiene, Massachusetts Department of Labor and Industries; Assistant in Medicine, Massachusetts General Hospital, Boston; Consultant, Los Alamos Scientific Laboratory, University of California, Los Alamos, New Mexico; Instructor, Department of Industrial Hygiene, Harvard School of Public Health, Boston, Mass. SECOND EDITION REVISED AND ENLARGED PAUL B. HOEBER, INC. MEDICAL BOOK DEPARTMENT OF HARPER & BROTHERS New York Industrial Toxicology Copyright 1934, 1949, by Paul B. Hoeber, Inc. Medical Be ok Department of Harper & Brothers. SECOND EDITION, REVISED AND ENLARGED, 1949 All rights reserved. For information address Paul B. Hoeber, Inc., Medical Book Department of Harper & Brothers, 49 East 33rd Street, New York 10, N. Y. Printed in the United States of America PREFACE TO SECOND EDITION --------------------------- This new edition of Industrial Toxicology is, of neces sity, not only rewritten but also considerably enlarged. During the years which have elapsed since the previous edition, great strides have been made in our knowledge of the long-used industrial poisons, their action on the human body, and the most efficient methods of protection against harm from their use. Such poisons as lead and mercury and arsenic have disappeared from old occupations only to reappear in new ones, often unsuspectedly. Metals such as cad mium and aluminum have been considered afresh, for we know much more about them today. Nearly every page of the book has required rewriting. While new knowledge of the long-used poisons is now available, the complexity of the problems of industrial toxicology has increased with the enormous expansion in the number of solvents, metals, and radioactive substances encountered in industry. One of the new chapters in the book is devoted to beryllium, a subject with which the junior author has been particularly concerned. There are new chemical agents belonging to the petroleum series and others to the benzene series; there are new industries of which the manufacture of synthetic rubber is the most striking example; and the substitu tion of autogenous welding for riveting in many industries has made it possible to study on a large scale the nature of the fumes evolved during the process. All this has necessitated the addition of new material throughout the text. Finally the whole subject of radioactivity, which required but 13 pages in the previous edition, has had to be rewritten in the light of our present knowledge, and the sectiorf on occupational cancer has had to be enlarged. A new chapter, "Radiant Energy," takes up ultra violet and infra-red rays, as well as radioactive substances and the new radioactive isotopes. The relationship of atomic energy to indus try is presented. As before, an attempt has been made to provide the reader with a comprehensive yet practical bibliography. Reflecting progress in the v vi Preface to Second Edition field there are almost three times as many bibliographic references as before. However, the authors make no claim to an exhaustive treatment of the voluminous records of animal experiments to test the toxicity of the newer chemicals. For these the inquirer is referred to the Industrial Research Laboratory of the National Institute of Health, Bethesda, Maryland. Industrial skin diseases have been dealt with only casually. For this class of occupational lesions the reader is referred to The Dermatergoses or Occupational Affections of the Skin by R. Prosser White, Fourth Edition, H. K. Lewis and Company, London, 1934, and to Occupational Diseases of the Skin by Louis Schwartz, Louis Tulipan, and Samuel Peck, Lea and Febiger, Philadelphia, 1947. For valuable assistance in this revision the authors wish to express their gratitude to the following: F. Koelsch of Munich; L. Teleky, formerly of Dusseldorff, now of New York; J. C. Aub; F. H. Lewey; J. H. Foulger; R. D. Evans; M. R. Mayers; H. B. Elkins; Anna Holt; and J. B. Skinner. Alice Hamilton Harriet L. Hardy CONTENTS ------------------- Preface to Second Edition v Introduction 1 1. Diagnosis of Industrial Poisoning 21 2. Alkalies, Acids 26 3. Chromium 44 4. Lead 49 5. Mercury 104 6. Arsenic 127 7. Phosphorus 138 8. Cadmium 145 9. Antimony, Metal Fume Fever, Zinc, Manganese 157 10. Beryllium 172 11. Selenium, Tellurium, Vanadium, Aluminum, Copper, Tin 188 12. Nickel and Other Metals 205 13. Asphyxiants: Carbon Monoxide, Carbon Dioxide, The Cyanides, Hydrogen Sulphide 219 14. Aromatic Series: Coal Tar, Benzene, or Benzol 268 15. Aromatic Series (Continued): Benzene Derivatives 284 16. Aromatic Series (Continued): Toluene andXylene, Derivatives of Toluene and Xylene, Naphthalene and Naphthylamines, Chlorinated Naphthalenes and Diphenyls 303 17. Aromatic Series (Continued): Arfiline Dyes 317 18. The Petroleum, Fatty, Aliphatic Series 319 19. Chlorinated Hydrocarbons, Bromine Derivatives ofHydro carbons, Methyl Iodide 356 20. Carbon Disulphide 398 21. Turpentine, Tobacco 409 vii viii Contents 22. Synthetic Rubber, Plastics, Welding 23. Oil Folliculitis 24. Occupational Cancer of the Skin 25. Occupational Cancer of the Lung 26. Occupational Cancer of the Bladder 27. Radiant Energy 28. Stilboestrol Bibliography Index 415 425 427 443 450 455 491 493 569 oo -H O oo cn GO cn 4T* cn ST 08 53646 CHAPTER TWENTY-FIVE ----------- ----------- Occupational Cancer of the Lung That there has been a decided increase in the incidence of pulmonary cancer in recent years is asserted by physicians in all in dustrial countries. This increase affects both sexes, but is distinctly greater in men. Hueper quotes Boycott as saying: "In looking for the cause of the increase of pulmonary malignancy one should look for a change in environmental conditions which took place toward the end of the last century." As Hueper points out, the tissues of the respiratory tract come in contact with the gases and dusts of industrial work more often and more intimately than do any other body tissues except the skin. It is also true that in our day there is an enormous increase in industrial workers and in the exposure of these workers to harmful dusts and fumes. Therefore the apparent increase in the incidence of cancer of the lungs is probably real. One must not ignore, however, certain nonoccupational fumes and dusts, whose prevalence has been greatly increased in our day and whose cancer-producing character is cer tainly not ruled out. Hueper places under this head: cigarette smok ing, paraffin oil spraying of nose and throat, x-ray examination of the chest. Dorn (236) of the Public Health Service presented in 1943 a statis tical survey of the incidence and prevalence of cancer of the lung in the United States, based on the mortality records from 1914 to 1940. The very rapid increase in this form of cancer when the death rate from other forms is falling, suggests some cause connected with mod em modes of life. The pollution of city air has been suggested as a factor, but Dorn found that the incidence of lung and respiratory cancer in men is less in Pittsburgh, with its great air pollution, than in any of the large cities surveyed, except Denver. The apparently striking increase in incidence is due certainly in part to improvement in diagnosis and the greater frequency of post- 443 ST0853647 444 Industrial Toxicology mortem examinations. Arkin and Wagner stated in 1936 that twenty years earlier, of all lung cancers discovered at autopsy only 5 per cent had been discovered during life, in contrast to 50 per cent in 1936. Peters reported that from 1905 to 1909, 3.8 per cent were clinically diagnosed, whereas for 1927-31 the per rent was 44.2. (See Hueper [538].) In a review of 100 cases of cancer of the lung in Australia, 43 of which were proved by autopsy, 12 by biopsy, Harvey (473) notes a distinct increase in recent years, for the cases were collected over a twenty-five-year period but almost half occurred in the last five years. An occupational influence is suggested by the large percentage of victims who were exposed to noxious gases, 38 per cent, or to sun light, 25 per cent. Teleky (1164) recognizes only two proved causes of occupational lung cancer: (1) chromate dust, and (2) radium-containing dust in the Schneeberg and Joachimsthal mines. (For the latter, see page 481). Carcinogenic Action of Chromates. For many years the convic tion was general among industrial toxicologists that the chro mates had no carcinogenic action. Legge stated that chrome ulcers never undergo carcinomatous degeneration and American experience seemed to bear this out. Lehmann in 1932 wrote an answer to the question "Is there any ground for special uneasiness concerning lung cancer in chromate workers?" Two cases which might be attributed to the action of chromates were referred to him and led him to a careful review of the literature of chromate poisoning up to 1932, which he found to be quite devoid of any mention of lung cancer. That chronic bron chitis, sometimes purulent, was common among chromate workers he had frequently observed and he had been able to produce it in animals made to iqhale droplets of chromate solution, but as to pul monary carcinoma, his conclusion was that the cases so far reported were too few to be significant, that isolated cases occur in all classes of workers, and that the increase of cancer of all kinds is due partly to better diagnostic methods, partly to the increased proportion of the elderly in the population and the successful lowering of other causes of death, especially tuberculosis. ST 08536U8 Cancer of the Lung 445 Of late, however, information coming from Germany shows that pulmonary carcinoma has occurred frequently enough in chromate workers to attract the attention of the Government Sickness Insur ance Department. We are indebted to L. Teleky for the following information. In 1936 the law concerning insurance against industrial accidents and diseases was extended to cover pulmonary carcinoma occurring in men who produce chromates from chrome ores and residues and those who use chromates in tanning, plating, and similar procedures. The grounds for this measure were given by Koelsch (Arbeit und Gesundheit, Heft 29, Berlin, 1937). He states that the first cases of carcinoma of the lungs in chromate workers were observed in 1911 and from that date until the end of 1936, some 25 cases were recog nized in Germany. The latent period ran from about twenty to forty years, and in some cases the new growth did not appear until several years after the victim had ceased working with chromates. A special idiosyncrasy is evident, since very few of those exposed develop such tumors. Age certainly plays a part. Teleky notes the fact that no reports of cases of pulmonary car cinoma in chromate workers have come from countries other than Germany and he believes the reason is that in Germany workers are much more likely to stay in the same kind of work, even the same job, all their lives and the time required for such growths to develop is twenty years or more. It is also true that German workers are likely to spend all their lives in one place, so that their records in the Sick ness Insurance Office are complete. In this personal communication Teleky states that he saw a case of pulmonary carcinoma in a chromate worker in 1932 and that Pfeil saw 2 cases (later on, 5 more), but all PfeiTs cases developed some years after exposure had ceased. He also quotes Alwans, Bauke, and Jonas as having reported, in 1936, 6 caes of lung cancer following exposure to chromate dust and 9 additional cases in which the x-ray picture showed the tumor above the diaphragm on the right, also a slight degree of fibrosis and a few honeycomb markings. Teleky quotes from Baaders book, Recent Developments in the Field of Cancer, the chapter on industrial cancers in which Baader says that up to that time 28 cases of "bronchial carcinoma" had been discovered in five chromate factories. In addition he says that in ST 0853649 446 Industrial Toxicology older chromate workers the x-ray picture often showed a distinct swelling of the lymphatic glands on one side. Whether this was an inflammatory process or, because it was limited to one side, a pre cancerous process, could not be determined without following up the cases. Teleky adds what he believes to be the first reported American case. This was in a factory in Baltimore. The man worked from 1939 to 1945 in a plant producing chromates from chromate ores. He spent part of the time in production, part in the shipping department, where probably there was a great deal of dust He died in 1945 at the age of 31 years and the autopsy revealed bronchiogenic carcinoma with metastases in the liver. Recently Machle and Gregorins (756a) have published the results of the first extensive study so far made to determine the incidence of cancer of the lung in workers exposed to dust in the course of pro ducing chromates, bichromates, and chromic acid. This study was made at the suggestion and with the full cooperation of the five com panies in the United States which are now extracting chromates from ore in seven plants employing 1445 men. It was found possible in six of these plants to secure records of 11,019 man-years employment with 156 deaths, among which were 46 from all cancers, and of these 32 were cancers of the respiratory system. The seventh plant, without adequate employment records, yielded 20 deaths from cancer of which 10 were from lung cancer. This means a total of 42 deaths from pulmonary cancer. These figures left no doubt of the influence of occupation on the occurrence of cancer of the lungs. Since no less than 28.8 per cent of all deaths in the chromate in dustry were reported as being due to cancer of the respiratory system, the ratio is 16 times the expected ratio of 1.3 per cent. The crude death rate for cancer of the lung averaged 25 times the normal, run ning from eighteen- to fifty-fold. The rate was higher in the groups 50 years of age and under (20 to 70 times that for a comparable in dustrial group) than for the age groups over 50 years (10 to 40 times). The rate for cancers other than of the lung was 12.4 per cent, slightly lower than the 15 per cent for a comparable industrial group. Several other facts of great importance were revealed in the course of this study. The incidence of nasal irritation and perforation does ST 0853650 Cancer of the Lung 447 not run parallel with that of lung cancer, but may occur in plants with no records of lung cancer. In two plants belonging to the same company there was a marked difference in the occurrence of lung cancer although the plant populations were similar with regard to location to race, color, age groups, length of exposure. But in plant D117 per cent of all deaths were from lung cancer while in plant D2 there were no deaths from that cause. The difference apparently lay in the nature of the compounds handled. Plant D1 handled chromite, sodium chromate and sodium bichromate. Plant D2 only sodium bichromate, chromic acid, and basic chromic sulphate, a trivalent chromium compound. This suggests that the monochromates may be the compounds responsible for lung cancer. Association of Lung Cancer with Silicosis and Asbestosis. Klotz (615) and also Anderson and Dible (13) have demonstrated a possible causal relation between silicosis and lung cancer but in both re ports the evidence is presented as tentative only and further study is urged. Teleky (1165), reviewing the subject in 1939, found that the con nection between silicosis and lung cancer is very dubious as shown by statistics. On the other hand, the incidence of cancer of the lungs among asbestos workers is fairly high. Le Coeur (679), discussing lung cancer of occupational origin, says that in a lung with asbestosis it takes some twelve years for a cancer to develop. Islands of cancer cells are deeply embedded in fibrous tissue, which also surrounds the lymph glands, and contain particles of asbestos. The process is a "chronic interstitial indurating pneumonitis with cancerous change." The course is slow, the tendency to metastasis less than in chromate cancer. Lynch and Smith (See 538) have described 2 cases of pulmonary cancer associated with asbestosis and 1 case of squamous metasplasia of the bronchial epithelium with asbestosis, which they tentatively present as a precancerous condition, since the above-cited cases were of cancer predominantly squamous in type. In their series of 2308 necropsies the rate of primary lung cancer is 0.21 per cent; among 35 cases of asbestosis it was about 6 per cent. Welz (1235) attributes to the irritating action of asbestos 2 cases of lung cancer which were complicated with asbestosis. ST085365I 448 Industrial Toxicology Another case of lung cancer in an asbestos worker was reported in 1941 by Linzbach and Wedler (538). The patient had been followed radiologically from 1934 to his death in 1940. By 1938 there was stage III of asbestosis, in 1940, a tumor. Autopsy revealed changes charac teristic of asbestosis and a squamous-cell carcinoma. The Saranac Laboratory group admits the possibility of asbestos dust, which is mechanically irritating, setting up a squamous-cell cancer, but similar changes in the epithelium occur in other chronic inflammations of the lung, notably tuberculosis, and, in their very wide experience, tuberculosis is not attended with an increased inci dence of primary cancer of the lung (see Vorwald [1202]). Association of Lung Cancer with Other Irritants. Hueper finds some proof of a connection between pulmonary siderosis and cancer. English statistics show that metal grinders have 2.25 times as many cases of cancer of the lungs as does the general population. He cites some 6 scattered cases, but holds that the connection has not yet been proved. Teleky says that in Germany cancer of the lungs is two and one-half times as frequent among metal grinders as in the general population. Among the many causes that have been suggested to account for the apparent increase in lung tumors in recent years is the dust from asphalt-paved roads, which is undeniably a feature of modem life and one of constantly increasing importance. Leiter and his col leagues (700) produced sarcoma in mice by subcutaneous injection of tar extracted from dust collected in streets of five cities. Kling et al. (613) tested the various tars used in road-paving and urge the use of those produced at low temperatures, or those with asphalt base, or bitumens known to be free from carcinogenic elements, to obviate possible danger from street dust. Hueper is skeptical as to such causes as these. It is true that there are more cases of, lung cancer in city populations than in rural, but diagnosis is more accurate in cities and more post-mortem exami nations are made. That exposure to hot, tarry gases may give rise to lung cancer is claimed by Kawahata and Kuroda (651) who encountered, during a six-year period, 21 cases of lung cancer among men working in a Japanese steel mill where illuminating gas was generated. The men ST0853652 Cancer of the Lung 449 were continually exposed to dust, flames, and hot gases containing tar. The ages of the affected men ran from 35 to 65 years, their ex posure from nine to seventeen years. The upper lobe of the right lung was most often involved; metastases occurred with relative frequency in the brain and spinal cord. Lovelock (744) describes a complicated and difficult case in a Welsh miner, employed for twenty-two years in coal mines. The patient died, apparently from carcinoma of the liver, but the lungs contained over eight times the normal silica content (a guinea pig injected with substance from the lungs died of generalized tuber culosis), and there was carcinoma of the right lower lobe bronchus. The theory that severe infectious respiratory disease may predis pose to pulmonary cancer is apparently refuted by statistics, for the latter has been on the increase while pulmonary tuberculosis has been decreasing, and the influenza epidemic of 1918 had no demon strable effect. English statistics (Kennaway and Kennaway [See 538]) show that there has been an increase not only of lung cancer but of cancer of the larynx. Between 1921 and 1932 these tumors increased 1.4-fold in men and 1.75-fold in women. This may possibly be attributed to cigarette smoking; it would hardly be occupational, or men would be affected more than women. ST0853653 CHAPTER TWENTY-SIX ----------- ----------- Occupational Cancer of the Bladder An interesting and long unexplained manifestation of slow chronic poisoning by coal-tar derivates is the so-called aniline tumor of the bladder, a papillomatous growth which undergoes carcinomat ous degeneration. The German dye industry, since it is the oldest and much the most extensive, was the first to discover that men in contact with certain dye intermediates suffered in abnormal proportion from cancer of the bladder. By 1920 the reported cases numbered 177, and each year new ones were added. It was soon established that what ever was the elimination product in the urine responsible for these tumors, it belonged to the amino group, not the nitro, although in other respects the latter is the more toxic group. Description of an interesting case is to be found in the German factory inspection report for 1929. A man who had worked six years with trinitrotoluene died of cancer of the bladder, and compensation was at first refused on the ground that nitro compounds have never been known to produce such cancers. Further consideration of the case, however, resulted in a reversal of the verdict on the ground that trinitrotoluene is excreted in the urine not as such but as an amino derivative. Animal experiments have not thrown much light on the question of just which compounds are responsible. Hueper and his colleagues succeeded in producing neoplastic lesions of the bladder in nine of sixteen dogs treated with beta-naphthylamine. Morigami and Nishimura (845) had a like success with orthotoluidine and benzidine. The list of amino compounds which have been incriminated is long. Koelsch (621) lists aniline, toluidine, xylidine, cumidine, anisidine, naphthylamines, benzidine, and tolidine, and says it is extremely diffi cult to pick out one single compound because through the years of employment (usually twenty or more) the victim has come in con tact with many different ones. Muller (857) thinks benzidine the most important; Wignall (1246) in his study of English chemical workers, 450 S T 0 853654 Cancer of the Bladder 451 found alpha-naphthylamine exposure in the larger number of cases, but he also notes the uncertainty arising from the variety of exposures encountered in these cases. Other apparently cancer-producing chem icals in his experience are meta-phenylendiamine, T.N.T., benzidine, diphenylamine, triphenylmethane dyes, and azo dyes. In Britain the mortality rate from cancer of the bladder was thirtyeight times as high among chemical workers in general as for the insured male population in 1928-32. The causative agents were held to be aniline, benzidine, alpha- and beta-naphthylamine and their de rivatives. American experience narrows the list down to benzidine, betanaphthylamine, and alpha-naphthylamine which contains as much as 5 per cent of beta. In England the first cases of aniline tumor of the bladder appeared much later than in Germany because the dye industry is of more recent origin in the former country (Wignall, Macalpine [753]). According to Legge (686), 23 fatal cases were reported in England up to the end of 1931. In the United States the manufacture of coaltar dyes did not amount to much before the outbreak of the First World War shut off the supply from Germany. Twenty years later, in 1934, the first American publication on aniline tumors of the blad der appeared in the shape of a number of articles by the group of physicians associated with the E. I. du Pont de Nemours Company (Ferguson and associates [315]). This very important collection of papers revealed for the first time the occurrence of so-called aniline tumors of the bladder among Amer ican workmen, which had made their appearance in the United States, as they did in England, in less than twenty years after the . great expansion of the coal-tar industry. This was to be expected, since it was only a repetition of the German and Swiss experience. Since the foreign literature has been fully reviewed many times, it seems useful to summarize this American contribution rather fully. Ferguson and Anderson (315) both deal with the history of bladder tumors since 1895 when Rehn first demonstrated the causal relation ship of aniline to them. For a long time the reports of these tumors were practically confined to Germany, long the leader in the dye and chemical industry and the leader in research for the carcinogenic ST 0853655 452 Industrial Toxicology agent, since it was soon found that other substances than aniline might give rise to bladder tumors, especially benzidine and the naphthylamines. Experimental studies have been negative with rare excep tions such as the production of carcinoma of the bladder in rabbits by prolonged inhalation of naphthylamines (Schar [1028]) or by in jection of b-naphthylamine and aniline (Perlman and Staehler [935]). Of late, attention has been turned to the changes in the blood caused by coal-tar derivatives and Ferguson hazards the suggestion that the carcinogenic agent may not be in the urine, affecting the mucosa directly, but in the circulating blood, exerting its harmful effect in the terminal capillaries of the mucosa of the bladder. According to Anderson, a white man employed in the nitrobenzidine department of the dye works in the Wilmington area was found by cystoscopic examination in December 1931 to have a tumor of the bladder. This was the first recognized American case of aniline tumor. Since then 25 have been discovered. Family history seems to have no bearing on the incidence of these tumors. A history of pre vious attacks of cyanosis was obtained in less than half, 48 per cent, of the subjects and an equal percentage had a history of urinary dis turbances, frequency, dysuria, and hematuria, but in 42 per cent there was no such history, which shows that without a cystoscopic examination more than half the cases would not have been dis covered. Gehrmann's contribution to the du Pont symposium (315) was one of unusual interest. He was able to report on cystoscopic examina tions of 532 men and the discovery of 25 positive cases, or an incidence of 4.5 per cent. Sixteen other cases were found in which there were hemorrhagic areas in the bladder. A second group of 55 cystoscopic examinations yielded 2 positive cases, or about 3.6 per cent. The age of the men affected varied from 30 to 60 years, and the time of expo sure from four to eighteen years. Of the twenty-five tumors, fourteen were simple papillomas, eight definitely carcinomas, and three were at the moment doubtful. The men had all been exposed to either b-naphthylamine or benzidine, and only two had not been exposed to the former. The two men in the second group who showed tumors had been exposed to a-naphthylamine. Germans do not connect this last with bladder tumors, but both American and English experience ST 0853656 Cancer of the Bladder 453 incriminates it, probably, Gehrman thinks, because in these countries jt contains about 5 per cent of beta while in Germany it is beta-free. The three responsible agents, then, in the experience of the du Font Company seem to be beta-naphthylamine, benzidine, and aniline. Oppenheimer's (908) last report in 1927 deals with 40 German cases, 22 of which have already been discussed in previous papers by the author. The substances to which these subjects were exposed were all amido compounds, aniline being responsible for 16 cases, benzidine for 6, and naphthylamine for 3. The others were exposed to more than one amido compound, but aniline or benzidine were in volved in 10 further cases. The duration of employment before de velopment of a tumor ranged from one to seventeen years, with an average of eight years. A striking case was that of a man who left the aniline factory after only two years' employment and developed can cer of the bladder seventeen years later. Oppenheimer finds that irri tation of the bladder and cystitis, which are common troubles in chemical workers, do not occur in those who develop tumors of the bladder, and therefore cannot be relied upon to give warning of a precancerous state. The first report of aniline tumors of the bladder in Russia was pub lished in 1926. Three cases were described, all in users of aniline black. The victims had worked for thirty, thirty-five, and forty-five years, respectively. Prevention. Preventive measures must be directed toward the three compounds, beta-naphthylamine, benzidine, and aniline, espe cially by means of a closed system when practicable, supplemented, when not practicable, by exhaust ventilation. Even with these meas ures the problem of adequate protection for the men making mechan ical repairs is a very difficult one. Periodic medical examinations must be kept up throughout employment even if the man is shifted to harmless work, for experience has shoyvn that a tumor may develop as many as thirty-five years following exposure to the inciting agent. If the man is discharged he should be given an examination at least once a year thereafter. No applicant for such work should be accepted who is under 20 or over 45 years of age, and those taken should be physically perfect (carious teeth and diseased tonsils can be attended to), if they are to be put into hazardous work of any kind. If the job ST0853657 454 Industrial Toxicology deals with the three agents mentioned, a cyctoscopic examination must be made once a year in every case and immediately if blood ap pears in the urine. The procedure of shifting victims of bladder tumor to other work has been abandoned, on the advice of the German authorities who maintain that once a man has been exposed removal does not lessen the danger to him and only results in the exposure of a new man. Gehrman speaks of a German dye plant where there is a completely closed method of manufacture and where dust and fumes were entirely eliminated fourteen years ago. No men taken on since have developed tumors but some of the older ones have. Goldblatt (392a) also believes that the victim of "aniline" bladder tumor should be kept on the job, provided he is closely observed and cystoscoped at regular intervals. The earliest warning symptoms are low back pain, suprapubic pain, or even vague hypogastric pain. Hematuria is the first positive sign. These are important if they ap pear in a man working with beta-naphthylamine or benzidine, per haps with aniline or alpha-naphthylamine. The prognosis for "aniline" bladder cancer is fairly good, better than that for the nonoccupational kind. Neither the Germans nor English use cystoscopic examination as a routine measure, being convinced that their workmen would never endure it, and they depend on the detection of blood in the urine. After blood has been found three times the cystoscope is used. Gross, of Elberfeld, and Simon (See Hueper [538]) of Ludwigshafen were opposed to biopsy of these tumors holding that it leads to multiple implants and recurrences. They made the diagnosis in doubtful cases after fulguration, claiming that all simple tumors respond favorably to it, malignant do not. Treatment The final article by Washburn (315) takes up the treat ment of bladder tumors, by fulguration and implantation of gold radon seeds, and by open operation. INDEX ----------- ST 0853658 Acetaldehyde, 354 Arsenic (Continued) Acetates, 334 ff. Copper arsenide Acaiju Anlydride, 338 lung cancer, as cause of, 482 Acetone, Dimethyl Ketone, 347 Lead and calcium arsensates, 130 Acetylene, 338 Skin cancer, as cause of, 438 Acetylene Tetrachloride, 372 Solid compounds, 127 Acids Trioxide, white, 127 Chromic, 44 Arsine Hydrochloric, 33 From acetylene, 339 Hydrofluoric, 40 In aniline dye works, 132 Nitric, 37 In cleaning tank cars, 132 Sulphuric, 29 Fatal dose, 136 Achoklin, 354 From ferrosilicon, 135 Acrylonitrile, 254 Hydrogen arsenide, 131-136 Alcohols, 328 ff. From storage batteries, 133 Allyl, 333 Amyl, 332 BAL, Therapy, 156,217,218 Butyl, butanol, 332 Benzene, Benzol, 268 ff. Methyl, methanol, wood acohol, 328 Acute poisoning, 269 Propyl, 334 Atypical cases, 275-280 Alkalies, 26-29 Chronic poisoning, 270, 272 Alpha Rays, 456, 465, 469, 470 Concentration in air, 269 Aluminum, 197 Diagnosis, 272-277,282 Pathology, 200, 201 Experimental poisoning, 271 Poisoning, clinical, 198-201 Industrial uses, 268,281 experimental, 200 Prevention, 283 Silicosis, use against, 197 Benzene Derivatives, 284 ff. Ammonia, 26 Hydroxy compounds, 285-289 Aniline Dyes, 317 ff. Benzine, see Naphtha Aniline Tumors, Bladder, 450 ff. Beryllium, 172 ff. Antimony, 157 Acute poisoning, 179-182 Industrial uses, 157-159 "Berylliosis," 181 Antimony Hydride, Stebine, 160 Chronic poisoning, delayed chem- Antimony Poisoning ' ical, 174 ff. Clinical, 158-160 Clinical cases, 173-183 Experimental, 159-160 Argyrosis, Arcyria, 213 Arsenic Aceto-arsenite of copper, green, 127 paris Concentration in air, 184 Diagnosis, 177, 179, 180, 182 Experimental poisoning, 184-186 Industrial uses, 172 Pathology, 176, 180, 183 569 ST0853659 570 Index Beryllium (Continued) "Pneumonitis," 174-181 Prevention, 187 BeTA-NAPHTHYLAMINE, 313, 451 ff. Beta Rays, 485 Bhass Founders' Ague, 161 ff. Brass Founding, Lead In, 54 "Brass Poisoning," 163 Brombenzene, 397 Bromine Derivatives of Hydro carbons, 390 ff. Buna S., 415, 418 Butadiene, 418 Butanone, 350 Butyl Rubber, 415 Cadmium, 145 Industrial Uses, 146 Poisoning acute, 147-150 chronic, 147, 150-153 experimental, 153-155 prevention, 155 Calcium, Cyananimide, 253 Cancer, Occupational, Bladder, 450 ff. Cancer, Occupational, Lung, 443 ff. Chromates, 444 ff. Copper arsenide, 462 "Joachimsthal lung," 482 Other irritants, 448 "Schneeberg lung," 481 ff. Silicosis and Asbestosis, association with, 447 Cancer, Occupational, Skin, 427 ff. In American industry, 430-435 Arsenical, 437--439 Briquet workers' cancer, 428-430 Chilean nitrate, 440 Chimney sweeps' cancer, 427 Experimental, 435-437 Heat, 441 Mule-spinners' cancer, 428 Cancer, Occupational, Skin (Con tinued) Nickel, 439 Oil and pitch cancer, 427 ff. Solar rays, 440 Carbitol, 336 Carbon Dioxide, 246 Carbon Disulphide, 398 ff. Poisoning, clinical, 399 ff. Poisoning, experimental, 406 Prevention, 408 Uses in industry, 397, 401 Carbon Monoxide, 219 ff. Acute gassing, 235-239 Blindness, 238,239 Blood, action on, 228, 229 Central nervous system, action on, 229-231 Chronic poisoning, 242-248 Concentrations, effects of, 222-225 Epilepsy, 241 Experimental, 246 Glycosuria, 234 Heart, action on, 232-234 In industrial gases, 219-222 "Poisoning," 226, 227 Sequelae, 238-242 Carbon Tetrachloride, Teira- chlormethane, 361 ff. Poisoning, clinical, acute, 362 clinical, chronic, 368 experimental, 361 Prevention, 369 Cellosolves, 336 Chloral, Trichloro-Acid-Aldehyde, 376 Chlohinated Diphenyls, 316 Chlorinated Hydrocarbons, 356 ff. Chlorinated Naphthalenes, 313 ff. Chlorine, 32 Chloroform, Trichlormethane, 361 Chloro-Ortho-Toluidine, 307 Chloroprene, 417 Chromates, Potassium, Sodium, 44 Chrome Ulcers, 44 Index ST 0853660 571 Cinnabar, Mercury Sulphide, 109 Fluorescent Lighting, 489 Cobalt, 208 Fluorides, 40 Columbium, 216 Formaldehyde, 351 Copper, 127, 202 ff., 482 Formic Acid, 355 "Cracked Petroleum," 320-322 Furfural, 354 Cresols, 288 , Crotonaldehyde, 354 i Cyanides, 248 ff. Gallium, 216 Gamma Rays, 457, 469, 470 Hydrogen cyanide, 248 Gasoline, see Naphtha Industrial uses, 248, 250, 254, 255, Geiceh-Mulleh Counter, 478 257 Glycerol, 336 Poisoning acute, 249-253 Glycols, 335-337 chronic, 254-261 "Hemochromatosis," 202 Sodium, potassium, 248 Treatment, 261 Hexalin, 288 Hexamethylenetetramine, 341 . Cyclohexanol, Hexalin, 288 Hexanols, 289 Hydrogen Sulphide, Sulphuretted Death Rates of Industrial Class, 1 Hydrocen, 262 ff. Diagnosis, General, 21-25 From acetylene, 339 Dichlorethane, 370 Chronic poisoning, 267 Dichlorethylene, 376 DlCHLORMETHANE, 360 Sequelae, 266 Sources in industry, 262-264 DDT, Dichloro-diphenyl-trichloroethane, 289 Toxic action, 284-266 Dichloroethyl Sulphide, 390 Dimethyl Ketone, see Acetone Dimethyl Sulphate, 342 Indium, 212 Infra-red Rays, 489 Dinitrophenols, 286 Dioxan, Diethylene Dioxide, 337 Diphenylamine, 292 Diphenyls, 291 Lead Absorption, 60 Excretion, 64, 89 History, 49 Ether, Sulphuric, Diethyl, 346 Line, 85 Porphyrinuria, 91 Ethyl Bromide, 396 Race poison, 99 Ethyl Chloride, Monochlorethane, 370 Ethylene Chlorhydrin, 387 Toxicity of Compounds, 50 arsenate, 51, 129 basic carbonate, 57 Ethylene Dibromide, 396 Ethylene Dichloride, Dichlore thane, 370 basic sulphate, 58 chromate, 51, 59 metallic, 54, 55 Ethylene Oxide, 344 Ethylene Trichloride, Trichlore- thane, 372 Ethyl-Methyl Ketone, 350 oxides, 52-56 sulphides, 59 tetraethyl, 94 Transportation and distribution, 63 ST085366 I 572 Index Lead Poisoning Arthralgia, gout, 77 Blood, 87 anemia, 89 basophilia, stippling, 87 "basophilic aggregations,'' 88 Cerebral form, 80 Diagnosis, 83-93 Gaatro-intestinal tract, 68 Kidney, 71 Liver, 70 Palsy, 78 Treatment of, 65 Vascular lesions, 75 Luminous Dial Painters, 461 ff. Magnesium, 206 Manganese, 166 ff. Industrial uses, 168 Poisoning clinical, 167-171 experimental, 169 Melanosis, Riehl's, 426 Mercury, 104 ff. Fulminate, 111 Hatters' trade, 105 Mercuric oxide, 112 Metallic, 109, 112, 115 mercury amalgam, 109, 124 Mining, 104 Nitrate, 106 Organic compounds, 113 Tests for vapors in laboratories, 124 Mercury Poisoning, 115-123 Diagnosis, 123 Prevention, 124 Psychoses, 122 . Stomatitis, 117 Tremors, 118 Metal Fume Fever, 161 ff. Methanol, see Alcohols Methyl Bromide, 390 ff. Methyl Chloride, MonochlorMETHANE, 358 Methyl Iodide, 397 Methylene Chloride, DichlorMETHANE, 360 Metol, 342 Mineral Oils, 425 Molybdenum, 215 Monochlorethane, 370 MONOCHLORMETHANE, 358 Naphtha, 312 ff. Poisoning acute, 322-325 chronic, 325-327 Naphthalene, 312 Naphthols, 312 Naphthylamines, Alpha and Beta, 312, 451 Neoprene, 415, 417 Nickel, 205 Carbonyl, 205, 206 Nicotine, 412 Nitro and Amino Compounds, 294 ff. Aniline, 295, 450 Dimethylnitrosamine, 301 Ethanolanilin, 301 Methyl-isopropyl benzene, 302 Nitranilines, 299 Nitrobenzenes, 295,298 Paraphenylendiamine, 300 Nitroglycerine, 342 ff. Nitropropane, 345 Nitrous Fumes, 37 On, Boils, 425 On, Folliculitis, 425 Osmium, 211 Oxalic Acid, 339 Oxalyl, Chloride, 36, 341 Palladium, 214 Paraldehyde, 354 Perna, Perchlornaphthalkne, 312 Petroleum, "Cracked," 320-322 Petroleum Series, 319 ff. Distillates, 320 ff. Phenol, Carbolic Acid, 285 ST 0853662 Index 573 Phosgene, 34 ff. Phosphine, Phosphorettkd Hydro gen, 143, 339 Phosphorus History, 138-141 Uses fire works industry, 140 match industry, 139 production and conversion, 141, 142 Phosphorus Sesquotjlphide, 140 "Phossy Jaw," 139 Photo-Enckaving, 53 Pickling Metal, 133 Picric Acid, 287 Plastics, 419 Platinum, 210 Plutonium, 469, 471, 472, 474 Poisons Mixed, 5 Mode of entrance, 3 Polonium, 465, 468, 480 Potassium Hydrate, 28 Prevention of Industrial PobonINC, 11-19 Printing Trades, 52, 53, 55 Antimony in, 147 Lead in, 52 Pyridine, 312 Quicksilver, see Mercury Race and Susceptibility, 6 Radiant Enercy, 455 ff. Blood, effects on, 461 ff., 483 Bone, effects on, 482 Genetic injury, 461, 483 * Industrial uses, 457, 459, 461 ff. Limits of tolerance, 471 ff. Offspring, effects on, 461, 483 Prevention, 464-467, 475-479 Skin, effects on, 458 ff., 480 Radio-Active Iodine, 467 Radio-Activity, see Radiant Energy Radio-Isotopes of Metals, 466, 469 Radium in Industry, 461 ff. Roentgen Rays, 457 ff., 469 Selenium, 188 Hydrogen selenlde, 191 Industrial uses, 188 Poisoning clinical, 188-190 experimental, 190 Sex and Susceptibility, 9 Silver, 213 Sodium Hydrate, 28 Stdlboestrol, 491 Storage Battery Manufacture Arsine from, 133 Cadmium in, 151 Lead in, 56 Styrene, 416 Sulphur Dioxide, 29 Synthetic Rubber, 415 ff. Tantalum, 216 Tellurium, 192 Industrial uses, 192 Poisoning, clinical, 192 experimental, 193 Tetrachlorethane, Acetylene Tet rachloride, 372 ff. Tetrachlorethylene, 386 Tetrachlormethane, 381 Tetralin, Tetrahydronaphthalene, 312 Tetryl, 292 Thallium, 207 Thiokol, 415, 417 Thorium, Thohon, 484 Thorium X, 461 Tin, 203 Titanium Dioxide, 214 Tobacco, 411 Toluene, Toluol, 303 ff. Blood, effect on, 304-307 Urine, effect on, 306 Toluidines, 307 ff., 450 ST 0853663 574 Index Trichlorethane, 872 Trichlobrhtlenx, 877 ff. Foisodng clinical, acute, 878, 381 clinical, chronic, 381-385 experimental, 380, 885 Trichlormethane, 361 TtacHESYL Phosphate, 290 TRINITROPHENOL, Picric Acid, 287 TRINITROTOLUENE, T.N.T., 308 ff. Tuncsten, 215 Turpentine, 409 Ultra-Violet Rays, 488 Uranium, 485 Vanadium, 194 Industrial uses, 194 Poisoning clinical, 195 experimental, 196 Viscose Rayon, 266 Carbon disulphide, 266 Hydrogen sulphide, 266 Production, 266 Welmnc, 419 ff. Carbon monoxide in, 421 Description of methods, 420,421 Experimental, 421 Gases produced in, 421-424 Lead fumes in, 54 Wood Alcohol, see Alcohols Xylene, Xylol, 303 Xyudines, 307 ff., 450 X-Rays, 457 ff., 469 Youth and Susceptibility, 6 Zinc Chloride, 166 Zinc Oxide, 161 ff., 339 Zirconium, 216 J35>-- HECEi V D | ! P O i\ <" \/ jm 28 1958 &')-< *'9 mis us* bfssiiiicat ST 0 85366U biochemical research