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ST 0852967 PLAINTIFF'S EXHIBIT DOW-1649 OCCUPATIONAL TUMORS AND ALLIED DISEASES By W. G HUEPER, M.D. ASSISTANT DIRECTOR AND PRINCIPAL PATHOLOGIST WARNER INSTITUTE FOR THERAPEUTIC RESEARCH new york ary 1942 CHARLES C THOMAS PUBLISHER SPRINGFIELD ILLINOIS BALTIMORE MARYLAND cr c5 t ip f S . ' / H ST 0852968 All rights reserved, including the right of reproduction in whole or in part, in any form. COPYRIGHT, I942, BY CHARLES C ThOMAS Published by Charles C Thomas 220 East Monroe Street, Springfield, Illinois First Printing Printed m the United States of America ST0852969 -CP> PREFACE HE amount of factual information and the scientific as well as practical Tsignificance of tumors of occupational origin have increased rapidly ` during the past two decades. This development, however, so far has not found an adequate and comprehensive presentation in the medical textbooks dealing with industrial diseases or with cancerous growths. There is thus a place and a need for a separate and detailed treatise on occupational blastomas and related diseases. It is the principal aim of this book to furnish an extensive source of informa tion concerning the various aspects and the different types of these neoplastic disorders which have come to claim an ever-increasing importance as a part of the problem of cancer in general. A reference book is now offered in which the pertinent data, often not readily accessible and widely scattered in journals, books and separate communications of a diverse character, have been compiled. Ah attempt is made to analyze critically and to integrate the evidence obtained . from different sources, and to correlate and evaluate the various observations made and theoretical conceptions advanced, so as to form a well balanced and, when possible, coherent picture of the subject under discussion. The treatise may appeal and serve, therefore, as a guide to all those directly or indirectly interested in and charged with the supervision of industrial and public health hazards or concerned with the diagnosis and treatment of neo plastic diseases. The book is addressed to the a) medical profession, particularly those of its members who are engaged in the clinical management and scientific study of cancer and of occupational diseases, including their medico-legal aspects. b) governmental agencies charged with the safeguard of public health, the supervision of working conditions in industry and commerce, and the sanitary control of the various types of merchandise, especially foodstuffs, wearing ap parel, drugs, cosmetics and the innumerable chemicals contained in articles used in the household, agriculture, etc. c) legislative bodies formulating the laws which regulate the activities of the above mentioned governmental agencies, and of the private parties con cerned with occupational hazards causing the production of industrial cancers. d) workmens compensation boards, industrial commissions, etc. e) legal and judicial profession, f) industrial managers and engineers, g) life insurance and accident insurance companies, h) research workers in biology, chemistry and physics. ST0852970 viS OCCUPATIONAL TUMORS AND ALLIED DISEASES An appreciable unevenness exists in the presentation of the various aspects of the individual occupational neoplasms. This is in part due to the fact that marked differences exist regarding the amount of information available for any particular type of tumor, and in part to the irregularity with which our knowledge has progressed at different times and at various points. The ap parent great complexity of the subject matter, the existence of an appreciable number of disconnected or controversial observations, and the rapid and con tinuous expansion of the borders of our knowledge, may necessitate not only modifications in the interpretations of observations recorded, but also demand that final judgment must be suspended on certain points until some future time. The extensive bibliographies conform to the reference character of the book. A fairly complete list of references is offered for the majority of in dustrial neoplasms discussed. A restricted number of publications, selected according to their relative scientific or practical value or because of some special feature, is given with those industrial tumors for which a very abundant lit erature exists. The bibliographies, in these cases however, are also of great fullness and representative in character. No attempt has been made to cover the literature comprehensively, which has been accumulated concerning the traumatic causation of neoplasms, as a great number of publications dealing with the subject are of little value. It is obvious that in the difficult task of collecting data from many sources and about widely differing aspects, errors or omissions may have occurred. The indulgence of the reader is asked in this matter and the hope is expressed that his suggestions and criticisms may assist in remedying such defects and in improving the work in the future. I wish to express my sincere gratitude to William R. Warner & Company, Inc., and especially to Mr. G. A. Pfeiffer, President, and Dr. Marvin R. Thompson, Director of the Warner Institute for Therapeutic Research, for the continued interest shown in the progress of this work and for the en couragement extended to it until its ultimate publication. January r, 1942 W. C. H. Scarsdale} N.Y. ST085297I ACKNOWLEDGMENT OF CITATIONS PAGE 3 6 Hugaaoi, C. D.: An Exhibit of Im portant Books, Piper* and Memora bilia Illustrating the Evolution of the Knowledge of Cancer. Am. J. Cancer i***. 1933- 50 Orfjorae, E. D.: Microchemical Stndiea of Arsenic in Arsenical Pigmentation and Keratoses. Arch. Dermat. & Syph. 1 *:773 I9*i74. Kennaway, E. L.: On Cancer-Producing Tart and Tar Fraction!. J. Indust Hyg. 5:461, 1913-19*4. 119 Kennaway, E. L.: Further Experiments on Cancer Producing Substances. Biochem. J. 14:497, 1930. 135 Barkmeyer, A. D.: Karzinom nnd Schweiz. Unfallverticherung. Rfv. mine des acdd. du tnv. 17:81, 171, 1933135 Tentachlaender, O.: Neue Untersuch- ungen ueber die Wirkungsweise von Teer und Peeh bei der Entstebung bemicher Hautkrebse. Ztsch. f. Krebsforsch. 30:373-310, 1930. 144 Heller, I.: Occupational Cancers. J. Indust. Hyg. 11:169, 1930. 145 Leitch, A.: Paraffin Cancer and its Ex perimental Production. Brit M. J. 1:1104-1106, 1911. 145 Rost, H. C: Occupational Cancer, J. Cancer Research 3:311, 191*. 149 Twort, C. C. and Twort, J. M.: The carcinogenic potency of mineral oil*. J. Indust Hyg. 13 :104, 1931. 149 Lyth, R.: Relation of carcinogenicity of mineral oils to certain physical and chemical characteristics of these oils. J. Indust. Hyg. 15:216, 1933. 151 Bridge, J. C. and Henry, S. A.: Indus trial Cancer*. Report of International Conference on Cancer. London, 191$, John Wright & Sons, Ltd., Bristol. 159 Henry, S. A. and Irvine, E. D.: Cancer of Scrotum in Blackburn Registration District, 1*37-1919. J. Hyg. 36:310, 1936. 163 Kennaway, E. L.: The anatomical dis tribution of the Occupational Cancers. J. Indust. Hyg. 7:69, 1925. FACE 164 Scott, A.: On the Occupational Cancers of the Paraffin and Oil Workers of the Scottish Shale Oil Industry. Brit. M. J. .2:110S, 191a. 179 Twort, C. C. and Twort, J. M.: The Carcinogenic Potency of Mineral Oils, J. Indust. Hyg. 13:204, 1931. 3*1 Stewart, M. J.: Preancerotu lesions of alimentary tract. (Croonian Lecture). Lancet 2:565, 617, 669, 1931. 3*1 Weller, C. V.: Pathology of primary carcinoma of lung. Arch. Path. 7: 47, 19*9390 Boycott, A. E.: Cancer of Lung. Lancet, *:9J9> 93*531 Scheele, K.: Verhsndl. d. deutich. Geiellsch. f. Urol. 7:343, 1916. 536 Ibrahim, A. B.: The Problem of Bil- harziasis in Egypt. J. State Med. 35:701, 1917. 673 Schwartz, L., Knowles, F. L., Britten, R. H. and Thompson, L. R. Health Aspecti of Radium Dial Painting) Scope and Findings. J. Indust. Hyg. 15:361, 1933. 6* 1 Martland, H. S.: Occupational Poison ing in Manufacture of Luminous Watch Diala J.A.M.A 91:466, 552, 1919. 691 Stewart, E.: Radium Poisoning. Month ly Labor Review, U. S. Dept. Labor Bull. 2*:6, 10-61, 1929. 6*9 Schwartz, L., Knowlei, F. L., Britten, R. H. and Thompson, L. R.: Health Aspects of Radium Dial Painting) Scope and Findings. J. Indust. Hyg. 15:361, 1933. 773 Kretschmer, H. L.: Multiple Primary Cancers. Tr. Am. Assoc. Genito urinary Surg. 31:161/1938. 811 Marrack, J. R.: The Chemistry of Anti gens and Antibodies. Spec. Rep. t Series 194 and 230, H. M. Sta. Off., London, 1934 and 1938. 828 Carozzi, L.: Cancer profesiionel et Or ganiction Internationale du Travail. Acta union internat. contre cancer, *!3l 1937. 817 International Labour Conference, 18th STD852972 X OCCUPATIONAL TUMORS AND ALLIED DISEASES PACE Session, Report V, Geneve, 1934. Workmen'* Compensation for Occu pational Diseases. Geneva. Interna tional Labour Office, 19]}. 833 Barkmeyer, A. D.: Karzinom und Schweiz. Unfallversicherung. Rev. mine des acdd. du trav. iT.ti, 171, 193 3 846 Flinn, F. B.: Radio-active Material an PACE Industrial Hazard? JAMA. (7: >07!, 1916. 846 Henry, S. A.: The Study of Fatal Cate* of Cancer of the Scrotum from 1911 to 1935 in Relation to Occupation, with Special Reference to Chimney Sweeping and Cotton Mule Spinning. Am. J. Cancer 31:1*, 1937. ACKNOWLEDGMENT OF TABLES PACE za Cancer death rate* for variou* aodal cli we* in England Young, M. and Russell, W. T.: An Investigation into the Statistic* of Cancer in Different Trade* and Profession*. Special Report Series $99, London, His Maj. Sta. Off., 1916. 13 Deaths from cancer of male generative organs in U.S. Hoffman, F. L.: The Occupational Incidence of Cancer. Newark, N.J., Prudential Press, 1931, p. ti. 27 Relation of social class to cancer inci dence based on statistical analysis of cancer mortality in Bavaria Cramer, W.: Importance of statistical investigations in campaign against Cancer. Am. J. Cancer *9:1, 1937. 72 Influence of origin of coal on chemical composition of tar Jambon, A.: Traitement des Eczema* par le Coaltar. Ann. de dermat. et Syph. 10:22, 1909. 73 Proportional relations of different frac tions of tar Jambon, A.: Traitement des Eczfma* par le Coaltar. Ann. de dermat. et Syph. 10:22, 1909. 90 Incidence of pitch papilloma and can cer among patent fuel workers Downing, C. C. R.: Cutaneous papil lomata among patent fuel workers in relation to malignant' disease. J. Indust. Hyg. 14:235, 193*. 97 Sites of tar epitheliomas Bridge, J. C. and Henry, S. A.: In dustrial Cancers, Report of the International Conference on Can- PACE cer, London, 192s, John Wright A Sons, Ltd., Bristol, 19a!. 99 Sites of pitch epithelioma* Bridge, J. C. and Henry, S. A.: In dustrial Cancers, Report of the International Conference on Can cer, London, 19*8, John Wright k Sons, Ltd., Bristol, 192!. 101-102 Deaths from tar and pitch cancer Bridge, J. C. and Henry, S. A: In dustrial Cancers, Report of the Internet. Conf. on Cancer, London, 1928, John Wright & Sons, Ltd., Bristol, 1928. 1 oa Age distribution of pitch warts Downing, C. C. R.: Cutaneous papil lomata among patent fuel worker* in relation to malignant disease. J. Indust. Hyg. 14:255, ijj*10a Age distribution of pitch and tar epi thelioma* Downing, C. C. R.: Cutaneous papil lomata among patent fuel workers in relation to malignant disease. J. Indust. Hyg. 14:253, 1932. 103 Incidence of pitch cancer among bri quette workers in relation to age Sladden, A. F.: Pitch Cancer. Report of Internet. Conf. on Cancer, Lon don, 1928, p. 284, John Wright A Sons, Ltd., Bristol. 103 Duration of exposure and pitch warts Downing, C. C. R.: Cutaneous papil lomata among patent fuel workers in relation to malignant disease. J. Indust. Hyg. 14:255, 93. 103 Duration of exposure and pitch and tar cancer Downing, C. C. R.: Same as above. ST 0852913 ACKNOWLEDGMENT OF TABLES xj PACK 104. Inflame of exposure on susceptibility to pitch cancer Sladden, A. F.: Pitch Cancer. Rep. of Internal. Coni on Cancer, Lon don, 191I, p. 284, John Wright & Son*, Ltd., Bristol. 117 Effect of duration of tarring upon inci dence of cancer Bang, F.: Essai de rapprochement entre lei experience* du cancer du goodron et ceilei du cancer de* riiHri/f- Ball Assoc. frans- p. l'ftnde du cancer, 17:6(9, 19a!. 150 Refractive indicea and ip. gr. of varioui oil* Twort, C. C. and Lyth, R.: Selection of Non-carcinogenic from Carcino genic Oil*. J. Hyg. 33:464, 1935159 Incidence of mule ipinnen' cancer and oil cancer Annual Report of the Chief Inspector of Factoriel and Workihopi for the Year 1919, Hit Maj. Sta. Off., London. Same for the Yean 1931 and 1937. 160 Incidence of scrotal cancer in mule ipin nen Henry, S. A.: Study of fatal caae* of Cancer of Scrotum from 1911 to 1933 in Relation to Occupation, with especial reference to Chimney Sweeping and Cotton Mule Spin ning. Am. J. Cancer 31:28, 1917. 161 Local distribution of mineral oil cancers Bridge, J. C. and Henry, S. A.: In dustrial Cancers, Report of the Internet. Conf. on Cancer, London, 1928, John Wright & Son*, Ltd. BristoL 173 Age distribution of Paraffin carcinoma} age distribution of mineral oil can cer. Scott, A.: Cancers in Mineral Oil Re fineries. Rep. International Confer ence on Cancer, London, 1928. Bristol, John Wright & Sons, Ltd. 174 Number of deaths in decennial groups from mule spinners' cancer. Age at death from scrotal and non-scrotal ea. in mule spinners. Henry, S. A.: Study of fatal cases of Cancer of Scrotum from 1911 to 1933 in Relation to Occupation, FACE with --reference to Chimney Sweeping and Cotton Mule Spin ning. Am. J. Cancer 31:28, 1937. 176 Exposure time of mulespinners' cancer Henry, S. A.: Study of Fatal Cases of Cancer of Scrotum from 1911 to 1933 in Relation to Occupation, with especial reference to Chimney Sweeping and Cotton Mule Spin ning. Am. J. Cancer 31:28, 1937. 176 Exposure time of mineral oil cancers Bridge, J. C. and Henry, S. A.: In dustrial Cancers, Rep. of the Internet. Conf. on Cancer, London, 19*8, John Wright & Sons, Ltd., BristoL 194 Incidence and distribution of chimney sweeps' cancer Kennaway, E. L.: The Anatomical Distribution of the Occupational Cancers. J. Indust. Hyg. 7:69, 1923. 197 Analysis of soot from various sources for tar content Kenneway, E. L.: The Anatomical Distribution of the Occupational Cancers. J. Indust. Hyg. 7:69, 1923. 200 Age distribution of sweep's cancer Butlin, H. T.: Three lectures on can cer* of the scrotum in chimney sweeps and others. Brit M. J. 1 :i34t) 2:1, 66, 1892. 200 Age distribution of sweep's cancer Henry, S. A.: Study of Fatal Cases of Cancer of Scrotum from 1911 to 1933 in relation to Occupation, with especial reference to Chimney Sweeping and Cotton Mule Spin ning. Am. J. Cancer 31:28, 1937. 201 Age distribution of scrotal and extrascrotal sweeps' cancer Henry, S. A.: Same as above. 230 Age distribution of solar cancers Dubreuilh, W.: pitheliomato*e d'origine solaire. Ann. de dermat et Syph. 8:387, 1907. Sutton, R. L.: The symptomatology and treatment of seborrheic kera tosis, J.A.M.A. 64:403, 1915. 231 Age distribution of therapeutic Roent gen-Cancers Holthusen, H. and Englemann, K.: ST 0852974 lii OCCUPATIONAL TUMORS AND ALLIED DISEASES PACE Die Gefahr die Roentgenkarzinoms mil Folge der Strmhlenbehandlung. Strahlentherapie 4.1:514, 1951. 155 Sites of therapeutic Roentgen Cancers Holthnsen, H. and Englmann, K.: Same as above. 31} Gastric cancer mortality in different social groups in Bavaria Cramer, W.: Importance of Statistical Investigations in Campaign Against Cancer. Am. J. Cancer 19:1-19, 1937314 Site of cancer in unskilled workers hav ing contact with tar Peller, S.: Die Rolle des Reises in der Pathogenese des menschlichen Krebses. Klin. Wchnschr. 15:117, 1936. 337 Age distribution of intestinal polyps Kollsiek, H. E.: Multiple polyposis of colon. Surg., Gynec. & Obst 47:3*, 9**343 Relation of primary liver cancer to cir rhosis of liver Stewart, M. J.: Precancerous lesions of alimentary tract. Lancet 1:565, 617, 669, 1931. 351 Experimental production of cancer of liver with 1.1.5.6-dibenzanthracene Andervont, H. B.: Susceptibility of 5 inbred strains of Mice to Liver Changes Induced by Subcutaneous Injection of a-amino-5-azotoluene. Public Health Rep. 54:1986, 1939. 371 Lung'cancer incidence Cole, P. P.: The Cancer Problem-- Present Position with Regard to Prevention. J. State Med. 43:171, l935Stocks, P. Distribution in England and Wales of Cancer of Various Organs. Brit. Empire Cancer Cam paign, Ann. Rep. 13:157, 1936. Kennaway, N. M. and Kennawzy, E. L.: Study of incidence of can cer of lung and larynx. J. Hyg. 36:136, 1936. Weller, C. V.: Pathology of primary carcinoma of lung. Arch. Path. 7: 47*, 1919. Simons, E. J.: Primary Carcinoma PACE of the Lung. Chicago, The Year book Publishers, Inc., 1937. 385 Age incidence of lung cancer McCrae, Tn Funk, E. H. and Jackson, C.: Primary carcinoma of bronchi. J.A.M.A. 89:1140, 1917. 386 Age Incidence of Bronchiogemc Car cinoma Matz, P. B.: Incidence of primary bronchiogenic carcinoma. J.A.M.A. 111:1086, 1938. 397 Post-mortem exam, of miners Reports of the Miner's Phthisis Medi cal Bureau of South Africa, 193a and 1935. 397 Incidence of pulmonary tumors--exam ined in Saranac laboratory Vorwald, A. J. and Karr, J. W.: Pneumoconiosis and pulmonary carcinoma. Am. J. Path. 14:49-58, 193*. 399 Pulmonary tumors in experimental ani mals after inhalation of silica dust Vorwald and Karr: Same as above. 411 Soot in air Kennaway, E. L.: The Anatomical Distribution of the Occupational Cancers. J. Indust. Hyg. 7 =69, 19J. 411 Relation between degree of bituminosis and incidence of lung cancer Schnurer, L.: Further studies on rela tion of pneumoconiosis to respira tory diseases in Pittsburgh district J. Indutt. Hyg. 10:14, 1938. 415 Age distribution of lung cancer in gas planti Kawahata, K.: Ucber die gewerblich hervorgerufenen Lungenkrebse bei Generator-Gas-Arbeitern in den Stahlwerken. Gann 31:367, 1938. 431 Effect of cutaneous tarring on incidence of pulmonary tumors Bonne, C.: Ueber Geschwuelste bei Teertieren. Ztschr. f. Krebsforsch. 15:1, 1927. 444 Age incidence of lung cancer in miners Uhlig, M.: Ueber den Schneeberger Lungenkrebs. Virchow's Arch. 130: 76, 1921. ST0852975 ACKNOWLEDGMENT OF TABLES xiii PAGE 44j Age incidence Ublig, M.: Seme u above. 454 Age distribution of pulmonary cancer --Joachimsehal Sickl, H.: Ueber den Lungenkrebs der Bergieute in JoachimsthaL Ztichr. f. Krebsforsch. 31:609, 1931. 496 Incidence of bladder tumor after period of exposure Evans, E. E.: Causative Agents and protective measures in Anilin tumor of bladder. J. Urol. 38:211, , 9J7497 Chemical character of compounds and neoplastic response Engel, H. in Martineck, Arbeit und Gesundheit. Dritte Verordnung ueber Ausdehnung der Unfall versicherung auf Berufskrankheiten vom 16 Dezember 1936. Heft 29, Leipzig, George Thieme, 1937. Evans, E. E.: Same as above. 504 Aniline series, grade of hist, malignancy Gay, D. M.: Pathology of Aniline Tumor of Bladder. J. Urol. 38: 221, 1937. PAGE 591 Hematic responses with several chemi cals Fitz-Hugh, T.: Sensitivity Reactions of the Blood and Bone Marrow to Certain Drugs. JAMA 111: 1643-46 (Oct.) *938. 744 Incidence of traumatic mammary cancer in various countries Lane-Claypon, J. E.: Cancer of the Breast and its Surgical Treatment. Rep. on Public Health and Medical Subjects, No. 28, London, His Maj. Sta. Off., 1924. 755 Maturation time for malignant growth in various species by action of radioactive energy Uehlinger, E.: Experimentelle Geechwulsterzeugung mit radioaktivtn Substanzen. Schweiz. Ztichr. f. allg. Path. u. Bakt. 1:44a, 1938. 828 Carcinogenic agents and compensation laws in various countries Carozzi, L.: Cancer professionel et Organisation internationale du Travail. Acta union internat. contre Cancer 1:3, 1937. I wish to express my appreciation to the various publishers and authors whose works have been used in the preparation of this book and who have not been specially mentioned in the above list. W. C. H. ST0852976 TABLE OF CONTENTS PREFACE ........................................................................................................ ACKNOWLEDGMENTS.................................................................................. vii xr CHAPTER I CONCEPT AND SIGNIFICANCE OF OCCUPATIONAL TUMORS ............................................................................................................. i. The New Artificial Environment................................................................. 3. Definition and Classification of Occupational Tumors................................ 3. Historical, Industrial and Geographical Aspects............................................ 4. Statistical Relationship Between Occupation and General Cancer Inci dence .................................................................................................................... 3 3 10 14 19 CHAPTER II OCCUPATIONAL AND ACCIDENTAL TUMORS OF THE SKIN AND ITS APPENDAGES................................................................................. 3. General Anatomical and Etiological Considerations................................ 3. Chemical Agents ............................................................................................... A. Inorganic Chemicals .................................................................................. a. Arsenic .................................................................................................... I. Chemical and TechnologicalAspects............................................ jl Exposure .......................................................................................... HL Incidence ........................................................................................ iv. Symptomatology ............................................................................. v. Site of Arsenical Epitheliomas..................................................... vi. Sex and Age.................................................................................... vn. Time of Exposure........................................................................ vm. Biological Behavior ................................................................... ix. Pathology ........................................................................................ x. Histo-Chemistry ............................................................................. xi. Experimental Arsenical Cancer ....................................... xn. Causative Mechanism ................................................................. XHL Therapy........................................................................................ xiv. Preventive and Sanitary Measures......................................... xv. Public Health Aspects ................................................................. xvi. Medico-Legal Aspects ............................................................... b. Salpeter--Sodium Nitrate ................................................................... 31 31 33 33 33 33 34 36 43 46 46 47 48 48 49 52 S3 57 57 58 60 65 ST0852977 xvi OCCUPATIONAL TUMORS AND ALLIED DISEASES B. Organic Chemicals--General Chemical and Technological Aspects.. 66 a. Coal, Asphalt, Mineral 03> Oil Shale............................................. 67 l. Coal ................................................................................................. 67 n. Lignite ........................................................................................... 68 m. Oil Shale ...................................................................................... 69 iv. Asphalt........................................................................ 69 V. Petroleum .................................................................... ................. 70 vi. Comment ...................................................................................... 71 b. Pitch, Tar and Asphalt.................... 71 1. Chemical and Technological Aspects......................................... 71 XL Historical and Geographical Aspects........................................... 79 in. Exposure and Incidence................................................ 87 iv. Symptomatology ........................... 94 V. Site ................................................................................................. 97 VI. Multiplicity.................................................................................... 100 vn. Prognosis...................................................................................... 101 vm. Age ............................................................................................. 102 rx. Duration of Exposure.................................................................. 103 x. Sex ................................................................................................. 104 XL Constitution ................................................................................. 105 xn. Latency Period ...................................................... 105 xnL Acute Traumatic Tar Cancer................................................ 105 xiv. Histo-Pathology ........................................................................ 106 xv. Experimental Tar and Pitch Cancer....................................... 108 Historical Aspects ............................................................................... 109 Constitutional Factors........................................................................ 109 Sex ........................................................................................................ 114 Age ..................................................................................................... 114 ' Extrinsic Factors ............................................................................... 114 Type of Tar; Concentration of Tar; Interval Between Tarrings; Duration of Tarring; Type of Contact; Trauma; Site; Size of Tarred Area; Solar Radiation; Roentgen-rRay* and Radioactive Substances; Arsenic; Nature of Solvent and Preparation of Skin Pathology ............................................................................................. 123 Macroscopical Changes; Microscopical Changes xn. Causative Mechanism............................................... xvn. Technical, Sanitary, and Medical Protective and Precau tionary Measures .................................................................................. 133 xvm. Therapy ........................................................................ 136 xix. Medico-Legal Aspects ............................................................. 136 c. Fractionation and Distillation Products of Mineral Oils, Oil Shales, Lignite and Coal Tar (Processed Oils and Paraffins) ................... 143 1. Chemical and Technological Aspects......................................... 143 128 ST0852978 CONTENTS rvii Petroleum Oils...................................................................................... *43 Shale Oils............................................................................................... 144 Lignite Oils .......................................................................................... *45 Coal Tar OUs........................................................................................ 146 Parafins ................................................................................................. 146 n. Carcinogenic Properties of Oils and Paraffins.......................... 147 4 m. Exposure.......................................................................................... 151 iv. Geographic Distribution and Incidence ................................... 153 v. Symptomatology ............................................................................ 164 vl Sites and Local Distribution ....................................................... 166 VTL Multiplicity ................................................................................... 169 m Course and Prognosis................................................................. 170 ix. Sex.................................................................................................... 172 Age ................................................................................................... 173 xl Exposure Time ............................................................................ 175 xil Histology........................................................................................ 177 xra. Experimental Oil and Paraffin Cancer................................ 178 XIV. Causative Mechanism ................................................................. 180 xv. Therapy.......................................................................................... 182 xvi. Precautionary Medical, Sanitary, and Technical Measures . . 182 xvn. Medico-Legal Aspects.............................................................. 184 d. Creosote ................................................................................................. 187 e. Anthracene ............................................................................................ 189 f. Soot ........................................................................................................ 192 L Chemical and Technological Aspects.......................................... 192 n. Historical Aspects .......................................................................... 192 m. Geographical Distribution and Incidence ................................ 193 iv. Exposure ........................................................................................ 196 v. Age ------:......................................................................................... 199 vl Symptomatology and Pathology ................................................. 201 vn. Predisposing Factors ......................................................... 202 vm. Experimental Soot Cancer.............................................. 203 ix. Precautionary Measures .............................................................. 204 x. Medico-Legal Aspects..................................................................... 204 g. Aromatic Hydrocarbons, Coal Tar Dyes, Intermediates and Re lated Substances.......................................................................... 207 1. Chemical and Technological Aspects............................................ 208 n. Exposure, Incidence and Causative Chemical of Dermatoses . . 208 in. Carcinogenic Relations................................................................. 212 h. Chemical Traumatic Carcinomas..................................................... 217 3. Physical Agents................................................................................................. 218 A. Actinic Agents .............. 218 a. Solar and Ultraviolet Rays................................................................... 218 ST0852979 jcviii OCCUPATIONAL TUMORS AND ALLIED DISEASES i. Physical and Technological Aspects........................................... 218 n. Exposure ......................................................................................... 219 m. Geographical and Occupational Distribution and Incidence .. 219 rv. Experimental Solar and Ultraviolet Cancer........................... 222 v. Predisposing Factors: Sex; Race; Exogenous Sensitizing Agents....................................... 223 vr. Age ................................................................................................ 229 vn. Latency Period ........................................................................... 230 vm. Causative Mechanism .............................................................. 232 ix. Symptomatology ........................................................................... 237 x. Histology ......................................................................................... 238 xi. Preventive and Precautionary Measures.................................. 241 xn. Medico-Legal Aspects................................................................ 241 b. Roentgen-Rays and Radioactive Substances .................................. 244 1. Technological and Historical Notes.............................................. 244 n. Exposure ......................................................................................... 245 nx. Geographical Distribution and Incidence of Roentgen- and Radium-Cancers .................................................................................. 247 iv. Age ................................................................................................ 251 v. Site .................................................................................................. 252 vi. Multiplicity.................................................................................... 253 vn. Occupational Distribution ......................................................... 254 vxn. Sex................................................................................................ 255 ix. Exposure Time and Latency Period......................................... 255 x. Symptomatology............................................................................. 257 Acute Roentgen-Dermatitis ............................................................. 257 Chronic Roentgen-Dermatitis ......................................................... 257 xi. Histology: Acute Roentgen-Dermatitis................................................................ 261 Chronic Roentgen-Dermatitis........................................................... 264 Roentgen-Cancer ............................................................................... 265 xn. Susceptibility ............................................................................... 266 xm. Prognosis .................................................................................... 267 xiv. Experimental Roentgen- and Radium-Cancer ..................... 268 xv. Causative Mechanism.................................................................. 270 xvi. Therapy ............................................. i...................................... 274 xvn. Preventive, Protective and Sanitary Measures.................... 275 xvm. Medico-Legal Aspects.............................................................. 277 B. Physical Trauma--Benign Pseudotumors............................................. 281 a. Traumatic Epithelial Cysts................................................................ 281 1. Occupational Relations.................................................................. 282 n. Incidence......................................................................................... 282 ST0852980 CONTENTS tox m. Type of Trauma.......................................................................... IV. Site.................................................................................................. V. Latency Period................................................................................ VL Age .............................................................................................................. vn. Symptomatology .......................................................................... vm. Histology ..................................................................................... ix. Causative Mechanism................................................................... x. Malignant Potentiality................................................................... Malignant Neoflasms--Traumatic Carcinomas of the Skin .... b. General Traumatic Carcinomas.......................................................... c. Special Traumatic Carcinomas.......................................................... X. Callosities ......................................................................................... n. Frost-Bites....................................................................................... m. Thermic Burns.............................................................................. Causation; Incidence; Site; Sex; Race; Age; Latency Period; Causative Mechanism; Symptomatology; Histology; Prognosis; Treatment; Experimental Burn Scar Cancer; Radiating Heat iv. Scars................................................................................................ v. Varicose Ulcers................................................................................ vi. Osteomyelitic Fistulas................................................................... vn. Melanomas .................................................................................. vm. Medico-Legal Aspects of Traumatic Epitheliomas................ 28a 282 283 283 283 284 284 285 286 287 289 289 290 291 299 301 302 304 307 CHAPTER III OCCUPATIONAL TUMORS OF THE ALIMENTARY SYSTEM 312 1. Anatomical and Etiological Considerations................................................... 312 2. Statistical Investigations in Different Occupational Groups......................... 312 3. Tumors in the Various Organs of the Alimentary System......................... 314 1 a Lips ................... 314 1. Chemical Agents............................................................................... 315 ' n. Habitual Aspects.............................................................. 317 ' m. Physical Agents ................................................................... 318 1 b. Oral Cavityand Pharynx...................................................................... 319 * 1. Occupational Aspects........................................................................ 319 5 n. Habitual Aspects............................................................................... 320 m. Trauma ................................................................................ 323 > iv. Experimental Cancer of the Oral Cavity.................................... 324 7 c. Esophagus .............................................................................................. 325 1 i. Stomach ................................................ '............................................... 326 1 L Occupational Aspects....................................................................... 326 2 n. Intrinsic Factors ........................................................................... 327 2 m. Extrinsic Factors............................................................................ 328 !| ST085298I xr OCCUPATIONAL TUMORS AND ALLIED DISEASES iv. Trauma ........................................................................................ 329 v. Experimental Cancer of the Stomach......................................... 331 Tar and Crude Oil; Synthetic Carcinogenic Hydrocarbons; Alumi num; Radioactive Substances; Parasites e. Intestine .............................................................................................. l. Occupational Aspects .................................................................... n. Distribution and Causative Mechanism...................................... m. Precancerous Lesions.................................................................. 334. 334 335 337 Congenital Polyposis; Infectious Polyposis; Melanosis iv. Trauma ........................................................................................ v. Experimental Cancer of the Intestine......................................... vi. General Comment ...................................................................... / Liver .................................................................................................... l. Functional Aspects ........................................................................ n. Liver Cirrhosis and Its Relation to Cancer............................... m. Etiology of Liver Cirrhosis......................................................... 340 340 341 342 342 342 345 Phosphorus; Arsenic; Lead; Manganese; Copper; Alcohol; Chlorinated Aliphatic Hydrocarbons; Coal Tar iv. Experimental Production of Liver Cancer............................... Aromatic Chemicals; Parasites; Physical Agents........................... v. Trauma.......................................................................................... vl Racial Aspects............................................................................... /. Gallbladder.......................................................................................... h. Pancreas .............................................................................................. 348 357 357 3^7 359 360 CHAPTER IV OCCUPATIONAL CANCERS OF THE RESPIRATORY SYSTEM 1. Anatomical and Etiological Considerations.................................................. 2. Incidence of Pulmonary Neoplasms............................................................. 3. Symptomatology ............................................................................................ 4. Pathology.......................................................................................................... 5. Therapy............................................................................................................ 369 369 370 374 378 382 6. Causation of Increased Frequency............................................................... 382 A. Factors of Technical and Statistical Nature........................................... a. Improvement in Diagnosis................................................................. b. Change in the Ratio of Lung Cancers to All Cancers.................... c. Overaging of Population and Its Effect UponStatistical Data . . B. Endogenous Factors . . .......................................................................... a. Hereditary and Congenital Predisposition ...................................... b. Sex ........................................................................................................ C. Exogenous Factors................................................................................... 383 383 384 384 387 387 389 390 a. Bacteriotoxic Agents.......................................................................... 390 b. Chemical Agents................................................................................. 391 ST 0852982 CONTENTS xii I. Bl-Defined Occupational and Non-Occupational Chemical Agents (Pneumoconiosis in General) ................................................. n. Chemical Agents of Defined Type................................................ 392 39^ Silicosis ...................................................................................................... 396 Asbestosis .................................................................................................. 399 Chemical and Technological Asfects............................................... 399 Exposure............................................................................................... +00 Symptomatology: Cutaneous Lesions............................................... 4 Pulmonary Asbestosis...................................................................... +01 Asbestosis and Pulmonary Cancer............................................... 403 Medico-Legal and Social Asfects..................................................... 45 Sanitary Measures................................................... Siderosis .................................................................................................... 45 Arsenic ...................................................................................................... 406 Chromates................................................................................................. 48 Chemical and Technological Asfects.............................................. 48 Toxicological Asfects.......................................................................... 49 Lung Cancer........................................................................................ 410 Incidence ............................................................................................. 4* Causative Mechanism ................................................................ 411 Contributory Factors (Individual Susceptibility, Age, Race, Heredity) ........................................................................................ 413 Symptomatology ................................................................................. 4*4 Medico-Legal Asfects........................................................................ 4x4 Sanitary and Precautionary Measures.............................................. 4x5 Nickel carbonyl........................................................................................ 415 Chemical and Technological Asfects............................................... 415 Toxicologic Asfects .......................................................................... 416 Carcinoma of the Nasal Passages and Lungs................................. 417 Various Noxious Gases and Fumes........................................................ 418 Tar, Pitchy Mineral Oil, Paraffin^ Soot and Aromatic Chemicals 420 General Aspects of Exposure....................................................... 420 Environmental Atmospheric Soot................................................ 421 Occupational Atmospheric Soot and Tar..................................... 424 Habitual Exposure to Tarry Substances.......................................... 426 Occupational Atmospheric Mineral Oil.......................................... 426 Experimental Production of Pulmonary Cancer.......................... 427 Physical Agents.................................................................. L Physical Agents of Defined Type................................................... 435 Radioactive Substances............................................................................. 435 Lung Cancers of the Miners in Schneeberg and Joachimsthal and Workers in Radium Laboratories.............................................. 435 Historical Aspects .......................................................................... 435 45 435 S v ;j 3 5 2 S'8 3 ndi OCCUPATIONAL TUMORS AND ALLIED DISEASES Lung Cancer of the Miners at Schneeberg.................................. Technological Notes.................................................................. Exposure....................................................................................... Causative Mechanism................................................................ Experimental Investigations....................................................... Incidence....................................................................................... Age................................................................................................ Time of Exposure ....................................................................... Type of Worker Affected......................................................... Heredity ................................... Symptomatology . ....................................................................... Pathology ..................................................................................... Medico-Legal and Sanitary Aspects......................................... Lung Cancer of the Miners at Joachimsthal............................. Technological Notes.................................................................. Exposure............... Causative Mechanism................................................................ Incidence ..................................................................................... Age................................................................................................ Time of Exposure....................................................................... Type of Worker Affected......................................................... Symptomatology ......................................................................... Pathology .................................................................................... Medico-Legal and Sanitary Aspects....................................... Lung Cancer of the Workers of Radium Laboratories........... Incidence .................................................................................... Experimental Production of Pulmonary Pathology by Radio active Substances and Roentgen-Rays...................................... Medico-Legal and Sanitary Aspects......................................... n. Physical Agents of Ill-Defined Type........................................ Mechanical Trauma................................. 437 437 437 438 442 443 44s 446 446 446 447 448 449 450 450 450 450 453 454 454 454 455 455 456 456 456 457 459 459 459 CHAPTER V OCCUPATIONAL TUMORS OF THE UROGENOUS ORGANS 1. Anatomical and Functional Aspects............................................................. 2. Chemical Agents--Aromatic Compounds.................................................... L Geographic Distribution and Incidence.................................................... n. Chemical and Technological Aspects...................................................... in. Etiological Agents.................................................................................... XV. Experimental Aniline Tumors................................................................ V. Causative Mechanism................................................................................ VI. Time of Exposure and Period of Latency............................................. vix. Chemical Character of Compounds and Neoplastic Response............. 469 469 469 47 477 479 483 490 496 497 ST085298U CONTENTS ndii vxn. Symptomatology ...................................................................................... - rr. Histology..................................................................................................... x. Pathological Relations (Ratio of Benign to Malignant Tumors, Multi plicity) .......................................................................................................... xl Localization and the Developmental Mechanism................................... /-xn. Treatment ................................................................................................. m Prognosis............. .................................... ............................................ ; xiv. Susceptibility.............................................................................................. xv. Occupation ................................................................................................. . xvl Protective and Preventive Measures..................................................... xvn. Medico-Legal Aspects............................................................................ xvm. Social Aspects.......................................................................................... 3. Parasites-Schistosomiasb ............................................................................ l. Historical Aspects....................................... n. Causative Agent.......................................................................................... m. Conditions of Exposure............................................................................ iv. Incidence...................................................................................................... V. Age................................................................................................................. vl Symptomatology.......................................................................................... vn. Pathology................................................................................................... vm. Causative Mechanism ............................................................................. ix. Prognosis...................................................................................................... x. Preventive Measures................................................................................... xl Infectious Papillomatosis of the Bladder in Rats................................. 4. Mechanical Trauma.......................................................................................... 500 502 512 5*4 520 520 522 523 52^ 53* 533 534 534 534 536 537 538 539 540 543 546 546 547 548 CHAPTER VI OCCUPATIONAL AND ACCIDENTAL HYPERPLASTIC AND NEOPLASTIC DISEASES OF THE BLOOD FORMING ORGANS 1. General Anatomical Considerations.............................................................. 2. Occupational Erythrocytoses............................................................................ A. General Characteristics and Classification of Erythrocytoses . ......... a. Chemical Agents................................................................................... L Erythrocytosis Following Exposure to High Altitudes (Reduced Oxygen Tension) ................................................................................. n. Erythrocytosis Caused by Carbon Monoxide Poisoning ....... m. Erythrocytosis Following Exposure to Hydrogen Sulfide, Nitrose Gases and Hydrogen Cyanide................................................. nr. Erythrocytosis Following Exposure to Aromatic Hydrocarbons and Their Nitro- and Amino-Derivatives....................................... v. Erythrocytosis Following Occupational Diseases of the Lungs vl Erythrocytosis Following Contact with Certain Metals .... Arsenic .............................................................................................. 557 557 558 558 561 561 564 568 569 571 573 573 ST0852985 xxiv OCCUPA TIONAL TUMORS AND ALLIED DISEASES Germanium...................................................................................... Manganese ...................................................................................... Iron . . ............................................................................................. Antimony ........................................................................................ Lead.................................................................................................. Mercury ........................................................................................... Cobalt............................................................................................... vn. Erythrocytosis in Phosphorus Poisoning.................................. vm. Erythrocytosis Following Introduction of Gum-Shellac .... b. Physical Agents.................................................................................... 1. Erythrocytosis Following Exposure to Actinic Agents................ n. Traumatic Erythrocytosis............................................................. 3. Polycythemia Vera........................................................................................... A. Trauma and Polycythemia Vera............................................................. B. Experimental Polycythemia Vera............................................................. 4. General Conclusions on Erythrocytotic Reactions...................................... 5. Occupational and Accidental Leukoblastoses and Leukoblastomas........... A. General Aspects and Classification......................................................... B. Occupational Leukoblastoses and Leukoblastomas.................................. a. Chemical Agents................................................................................. x. Benzol ............................................................................................. Chemical and Technological Aspects........................................... Toxicological Aspects.................................................................... Leucocytotic, Leukemoid and Leukemic Reactions.................. Etiological Aspects ........................................................................ Preventive, Precautionary, Technical and Sanitary Aspects . . H. Benzol Derivatives and Other Aromatic Compounds........... b. Physical Agents.................................................................................... f. Roentgen-Rays and Radioactive Substances............................. Hematological Reactions............................................................... Exposed Occupations ......................... .......................................... Leucocytotic, Leukemoid and Leukemic Reactions.................... Exposure Time, Age, Occupational Distribution, etc................. Diagnostic Aspects ........................................................................ Etiological Aspects ..................................................................:.. Experimental Roentgen- and Radium-Leukemia.................... Medico-Legal Aspects.................................................................... n. Trauma.......................................................................................... Leukemia (Psychic T^rauma, Mechanical Trauma).................. Aleukemia........................................................................................ Myeloma, Chloroma, and Reticular Cell Sarcoma of Bone ... C. General Conclusions of Leucocytotic Reactions.................................. 574 574 575 577 577 578 578 579 580 580 580 583 584 584 586 586 588 588 593 594 594 594 594 594 597 598 599 602 602 602 603 604 608 608 609 611 612 613 613 621 621 626 ST0852986 CONTENTS XXV CHAPTER VII OCCUPATIONAL AND ACCIDENTAL TUMORS OF THE MESENCHYMATOUS TISSUES................................................................. 637 1. Anatomical and Functional Considerations..................................................... 637 2. Fibrillar Connective Tissue ............................................................................... 638 A. Chemical Agents........................................................................................ 638 JB. Physical Agents............................................................................................ 639 a. Radiating Energy ................................................................................. r. Ultraviolet Rays.............................................................................. n. Roentgen-Rays .............................................................................. Occupational and Therapeutic Roentgen-Sarcomas.................. 639 639 640 640 Experimental Roentgen-Sarcomas .............................................. 641 m. Radioactive Substances ........................................................ 642 Therapeutic Radium-Sarcomas ..................................................... Experimental Radium-Sarcomas................................................... iv. Physical Trauma .......................................................................... Benign Tumors: Fibroma; Keloid; Dupuytren's Contracture . 642 643 644 644 Malignant Tumors: Sarcomas ..................................................... j. Muscular Tissues.............................................................................................. A. Leiomyomatous Tumors .......................................................................... 648 650 650 B. Rhabdomyomatous Tumors ..................................................................... C. Myositis Ossificans..................................................................................... D. Desmoid Tumors....................................................................................... E. Experimental Tumors of Muscle Tissue................................................ 650 651 652 652 4. Vascular Tissue ................................................................................................ 653 A. Telangiectases and Varicosities................................................................... 653 B. Traumatic Hemangiomas......................................................................... C. Angiomyoneuromas (Glomus Tumors) ................................................ 5. Adipose Tissue......... `........................................................................................ 654 655 656 A. General Anatomical Considerations and Classification......................... B. Experimental Lipomas .............................................................................. C. Traumatic Lipomas......................................................................... a. Solitary Lipomas................................................................................... b. Multiple Symmetrical Lipomatosis..................................................... c. Lipophagic Granulomas....................................................................... d. Xantheloids................................................................................ 6. Joint Capsules and Tendon Sheaths.............................................................. A. Ganglions..................................................................................................... B. Intraarticular, Synovial "Osteochondromas"......................................... C. Xanthogranulomas..................................................................................... 656 657 657 658 660 661 663 665 665 666 666 D. Synoviomas.................................................................................................. 667 7. Osseous and Cartilagenous Tissues................................................................... 667 ST0852987 rrvi OCCUPATIONAL TUMORS AND ALLIED DISEASES A. Chemical Agents.............................................................................................. 667 B. Physical Agents .............................................................................................. 668 *. Ultraviolet Rap ............................................................................... 668 b. Radioactive Substances............................................................................. 668 u Physical and Technological Aspects............................................... 668 n. Occupational Exposures.................................................................... 671 m. Historical Aspects............................................................................. 674 rr. Incidence ........................................................................................... 676 v.- Symptomatology............ .................................................................. 676 vi. Location .............................................................................................. 677 vn. Age . i................................................................................................ 677 nn. Causative Mechanism.................................................................... 678 ix. Demonstration of Radioactivity in Workers................................. 679 x. Pathology.............................................................................................. 681 xi. Experimental Osteogenic Sarcomas of Radioactive Genesis .. 684 xn. Prognosis . . . ..................................................................................... 686 - nn. Therapy.......................................................................................... 687 xiv. Preventive and Sanitary Measures.............................................. 688 xv. Medico-Legal Aspects .................................................................... 69a c. Roentgen-Rap ......................................................................................... 693 d. Physical Trauma...................................................................................... 694 Pseudoneoplastic Reactions: TraumaticOsteochondromatosis .. . 694 Traumatic Exostoses and Ecchondroses.............................................. 695 Traumatic Excess Callus........................................................................ 695 Giant Cellular Granuloma ................................................................... 696 Neoplastic Reactions: Benign Tumors: Chondromas; Osteomas 696 Malignant Tumors: Osteogenic Sarcomas....................................... 697 8. Notochordal Tissue ............................................................................................. 700 CHAPTER VIII OCCUPATIONAL AND ACCIDENTAL TUMORS OF THE EYE AND ITS ADNEXAE .. ................................................................................. 710 1. Chemical Agents.................................................................................................. 710 A. Inorganic Chemicals: Arsenic.................................................. B. Organic Chemicals: Tar, Pitch, Crude Oil, Lubricating Oil, Paraffin, Creosote........................................................................................................... 710 2. Physical Agents...................t........................................................................... 712 A. Radiating Energy: Solar and Ultraviolet Rays.......................................... 712 Roentgen-Rap Radioactive Substances.................................................... 712 B. Phpical Trauma: Pseudotumors..................................... `........................ 712 True Tumors ............................................................................................... 713 710 ST0852988 ?. CONTENTS xxvii '( CHAPTER IX OCCUPATIONAL AND ACCIDENTAL TUMORS OF THE VOUS SYSTEM......................................................................................... ^General Etiological Aspects..................................... .................................... ^Experimental Production of Cerebral Turnon........................................... hums and Tumors of the Nervous System................................................ jf/Turnon of the Brain................................................................................ -B2 Meningeal Neoplasms................................................................................ jC'. Turnon of the Peripheral Nerves........................................................... 716 716 7*7 718 718 727 727 CHAPTER X OCCUPATIONAL TUMORS OF THE ENDOCRINE GLANDS 73* CHAPTER XI CUPATIONAL AND ACCIDENTAL TUMORS OF THE SEX RGANS ............................................................................................................. .Occupational and Accidental Tumon of the Male Sex Organs................ A.' Prostate ...................................................................................................... jr,2L Testis........................................................................................................... a. Experimental Testicular Turnon...................................................... L Chemical Agents............................................................................. n. Physical Agents............................................................................. b. Trauma .................................... ............................................. 2. Occupational and Accidental Tumors of the Female Sex Organs A. General Etiological Aspects....................................................... B. Experimental Tumon of the Female Sex Organs.................... C. Trauma......................................................................................... D. Tumon of the Mammary Glands.............................................. a. Biological and.Experimental Aspects.................................. b. Trauma.................................................................................... 734 734 734 734 734 734 736 736 739 739 739 740 74* 74* 743 CHAPTER XII SPECIAL ASPECTS OF OCCUPATIONAL TUMORS .................... r. Age and Span of Life................................................ 2. Sex...................................................................................................................... 3. Race and Pigmentation.................................................................................. 4. Organ and Tissue Specificity........................................................................... 5. Primary Multiplicity of Tumon.................................................................... 751 751 760 762 768 772 CHAPTER XIII THE RELATION OF OCCUPATIONAL NEOPLASIA TO THE ORIES OF CANCERIGENESIS.................................................................... r. Consideration and Classification of Theories............................................. 785 785 S T 0 8 5 2 983 xxviii OCCUPATIONAL TUMORS AND ALLIED DISEASES 2. Cohnheim's and Ribbert's Theories............................................................. 3. Virchow's Theory.......................................................................................... 4. Senescence Theory.......................................................................................... 5. Chemo-Cytotoxic Theories ........................................................................... 6. Cellular Metabolic Theories.......................................................................... 7. Mutation Theories.......................................................................................... A. Inherited Mutation ................................................................................. B. Congenital Mutation................................................................................. C. Acquired Mutation................................................................................... a. Direct cellular mutation ................................................................... b. Allergic mutation ............................................................................... D. Virus Cancerigenesis................................................................................. 786 787 788 789 791 797 797 800 801 801 801 815 CHAPTER XIV MEDICOLEGAL AND PUBLIC HEALTH ASPECTS................... 1. Medicolegal Aspects........................................................................................ A. Occupational Tumors............................... B. Accidental Traumatic Tumors............................................................... 2. Public Health Aspects...................................................................................... 826 826 826 832 844 SUBJECT INDEX ........................................... 851 THE DOW CHEMICAL COMPANY TOXICOLOGY LIBRARY 1803 BUILDING